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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">UEG Week 2013 Oral Presentations</title></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmc">4070608</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4070608</idno><idno type="RBID">PMC:4070608</idno><idno type="doi">10.1177/2050640613502899</idno><idno type="pmid">NONE</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">000251</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">UEG Week 2013 Oral Presentations</title></analytic><series><title level="j">United European Gastroenterology Journal</title><idno type="ISSN">2050-6406</idno><idno type="eISSN">2050-6414</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader></TEI><pmc article-type="abstract"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">United European Gastroenterol J</journal-id><journal-id journal-id-type="iso-abbrev">United European Gastroenterol J</journal-id><journal-id journal-id-type="publisher-id">UEG</journal-id><journal-id journal-id-type="hwp">spueg</journal-id><journal-title-group><journal-title>United European Gastroenterology Journal</journal-title></journal-title-group><issn pub-type="ppub">2050-6406</issn><issn pub-type="epub">2050-6414</issn><publisher><publisher-name>SAGE Publications</publisher-name><publisher-loc>Sage UK: London, England</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmc">4070608</article-id><article-id pub-id-type="doi">10.1177/2050640613502899</article-id><article-id pub-id-type="publisher-id">10.1177_2050640613502899</article-id><article-categories><subj-group subj-group-type="heading"><subject>UEG Week 2013 Oral Presentations</subject></subj-group></article-categories><title-group><article-title>UEG Week 2013 Oral Presentations</article-title></title-group><pub-date pub-type="epub-ppub"><month>10</month><year>2013</year></pub-date><pmc-comment>Fake ppub date generated by PMC from publisher
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<pub-date pub-type="ppub"><month>10</month><year>2013</year></pub-date><volume>1</volume><issue>1 Suppl</issue><issue-title>21st United European Gastroenterology Week Berlin, Germany, October 12-16, 2013 Abstract Issue</issue-title><fpage>A1</fpage><lpage>A134</lpage><permissions><copyright-statement>© The Author(s) 2013</copyright-statement><copyright-year>2013</copyright-year><copyright-holder content-type="society">United European Gastroenterology</copyright-holder><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc/2.0/"><license-p><pmc-comment>CREATIVE COMMONS</pmc-comment>This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc/2.0/">http://creativecommons.org/licenses/by-nc/2.0/</ext-link>), which permits non-commercial use, distribution and reproduction in any medium, provided the original work is properly cited.</license-p></license></permissions></article-meta></front><body><p><bold>MONDAY, OCTOBER 14, 2013 8:00-10:30</bold></p><p><bold>Opening Plenary Session – Hall 1</bold></p><sec><title>OP001 RANDOMISED CONTROLLED TRIAL OF DRUG LEVEL VERSUS CLINICALLY BASED DOSING OF INFLIXIMAB MAINTENANCE THERAPY IN IBD: FINAL RESULTS OF THE TAXIT STUDY</title><p><bold>N. Vande Casteele</bold><sup>1,*</sup>, A. Gils<sup>1</sup>, V. Ballet<sup>2</sup>, G. Compernolle<sup>1</sup>, M. Peeters<sup>1</sup>, K. Van Steen<sup>3</sup>, S. Simoens<sup>4</sup>, M. Ferrante<sup>2</sup>, G. Van Assche<sup>2</sup>, S. Vermeire<sup>2</sup>, P. Rutgeerts<sup>2</sup></p><p><italic><sup>1</sup>KU Leuven Laboratory for Therapeutic and Diagnostic Antibodies, <sup>2</sup>UZ Leuven Department of Gastroenterology, Leuven, <sup>3</sup>University of Liège Systems and Modeling Unit, Liège, <sup>4</sup>KU Leuven Research Centre for Pharmaceutical Care & Pharmaco-economics, Leuven, Belgium</italic></p><p><bold>INTRODUCTION:</bold> Treat-to-target dosing based on infliximab (IFX) trough levels (TLI) has been suggested to increase efficacy, safety and cost-effectiveness of IFX treatment, although prospective data are lacking. In the optimisation phase of the TAXIT study we showed that dose intensification of IFX in CD patients with TLI <3 µg/ml resulted in a better disease control, whereas dose reduction in CD and UC patients with TLI >7 µg/ml resulted in lower drug exposure and lower IFX cost whilst maintaining disease control.<sup>1</sup></p><p><bold>AIMS&METHODS:</bold> Here we report on the subsequent long-term randomised part of this study. 251 patients entered the maintenance phase (MP) of which 123 patients (82 CD/41 UC) were randomised to the clinically based (<bold>CB</bold>) arm and 128 patients (91 CD/37 UC) to the trough level based (<bold>LB</bold>) arm. Primary end point of the MP was the rate of both clinical (Harvey-Bradshaw/partial MAYO score) and biological (CRP ≤5 mg/l) remission one year after randomisation in each group. Secondary end points included number of patients with TLI between 3-7 µg/ml and antibody to IFX (ATI) rate.</p><p><bold>RESULTS:</bold> After optimisation, median TLI and CRP were equal in the CB and LB arm (respectively 4.9 µg/ml [3.8-5.9] <italic>vs </italic>5.0 µg/ml [4.0-5.7] and 1.3 mg/l [0.6-4.5] <italic>vs </italic>1.5 mg/l [0.7-4.1]). 226/251 patients (90%) completed the MP of whom 69% of the CB <italic>vs</italic> 72% of the LB arm achieved the primary end point (P=0.7). During MP, 11 patients (4.4%) (5 CB <italic>vs</italic> 6 LB) were failures and 14 patients (5.6%) (7 CB <italic>vs</italic> 7 LB) were excluded (e.g. due to pregnancy or lost to follow-up). After one year, 56% in the CB <italic>vs</italic> 78% in the LB arm had TLI between 3-7 µg/ml (P<0.001). During MP, undetectable TLI were more frequently observed in the CB than in the LB arm (RR 3.7; 95% CI 1.7-8.0; P<0.001) which may have influenced the higher frequency rate of ATI observed in the CB <italic>vs</italic> the LB arm (RR 3.3; 95% CI 1.4-7.7; P<0.01). At the end of MP, three patients were ATI positive in the CB <italic>vs</italic> none in the LB arm (P=0.1). All three patients were ATI negative at screening and developed ATI during MP.</p><p><bold>CONCLUSION:</bold> Dose-to-target optimisation of IFX allowed to achieve TLI within the interval of 3-7 µg/ml which resulted in a more efficient use of drug. The maintenance phase did not show superiority for continued level based drug adjustment over clinically based adjustment. Treatment guided by levels resulted in less ATI formation but the proportion of patients in clinical and biological remission was similar for both groups.</p><p><bold>REFERENCES:</bold></p><p>1. Vande Casteele N, et al. <italic>Gastroenterology</italic> 2012;<bold>142</bold>(5):S211-S212.</p><p><bold>Contact E-mail Address:</bold><email>niels.vandecasteele@pharm.kuleuven.be</email></p><p><bold>Disclosure of Interest</bold>: N. Vande Casteele: None Declared, A. Gils Financial support for research from: Pfizer, Lecture fee(s) from: MSD, Pfizer, V. Ballet: None Declared, G. Compernolle: None Declared, M. Peeters: None Declared, K. Van Steen: None Declared, S. Simoens: None Declared, M. Ferrante Financial support for research from: Janssen Biologics, Lecture fee(s) from: Merck, Tillotts, Ferring, Abbvie, Consultancy for: Abbvie, Merck, Janssen Biologics, G. Van Assche Financial support for research from: Ferring, Abbvie, Lecture fee(s) from: Merck, Abbvie, Janssen-Cilag, Consultancy for: PDL BioPharma, UCB Pharma, Sanofi-Aventis, Abbvie, Ferring, Novartis, Biogen Idec, Janssen Biologics, NovoNordisk, Zealand Pharma A/S, Millenium/Takeda, Shire, Novartis, BMS, S. Vermeire Financial support for research from: UCB Pharma, MSD, Abbvie, Lecture fee(s) from: Abbvie, Merck, Ferring, UCB Pharma, Centocor, Consultancy for: UCB Pharma, AstraZeneca, Ferring, Abbvie, Merck, Ferring, Shire, Pfizer, P. Rutgeerts Financial support for research from: UCB Pharma, Abbvie, Janssen Biologics, Merck, Prometheus, Lecture fee(s) from: Abbvie, Merck, Consultancy for: Amgen, Merck, UCB Pharma, Genentech, BMS, Abbvie, Janssen Biologics, Millenium, Neovacs, Actogenics, Prometheus.</p><p><bold>Keywords:</bold> anti infliximab antibodies measurement, biologic therapy, inflamatory bowel disease, Personalized therapy, pharmacokinetics/Pharmacodynamic relationship, trough levels</p></sec><sec><title>OP002 EARLY VERSUS ON-DEMAND NASOENTERAL FEEDING IN SEVERE PANCREATITIS: A MULTICENTER RANDOMISED CONTROLLED TRIAL</title><p><bold>O. J. Bakker</bold><sup>1,*</sup> and The Dutch Pancreatitis Study Group</p><p><italic><sup>1</sup>Surgery, University Medical Center Utrecht, Utrecht, Netherlands</italic></p><p><bold>INTRODUCTION:</bold> In patients with severe pancreatitis, a routine start of nasoenteral feeding within 24 hours after admission is believed to reduce complications. However, evidence is based on observational and retrospective data.</p><p><bold>AIMS&METHODS:</bold> Between August 2008 and July 2012, 867 patients were screened for enrollment in 19 hospitals. Eventually, 208 adults with predicted severe pancreatitis were randomised to early nasoenteral feeding through a nasojejunal tube started within 24 hours of admission (n=102), or starvation for 72 hours followed by an oral diet with on-demand nasoenteral feeding whenever oral intake was insufficient (n=106). Predicted severe pancreatitis on admission was defined as an Acute Physiology and Chronic Health Evaluation II score ≥ 8, Imrie score ≥ 3, or CRP ≥ 150 mg/L. The primary endpoint consisted of a composite of mortality or infection (infected pancreatic necrosis, bacteremia, or pneumonia). The protocol of this trial has been published.<sup>1</sup></p><p><bold>RESULTS:</bold> One patient from the early feeding group and 2 patients from the on-demand group were excluded because of incorrect diagnosis of acute pancreatitis; thus 101 patients were analysed in the early feeding group and 104 patients in the on-demand group. Baseline characteristics did not differ. Median APACHE II scores at randomisation were 11 in the early feeding group and 9 in the on-demand group (p = 0.24). In the early feeding group, nutrition was initiated a median of 23 hours after admission. The primary composite endpoint occurred in 30 patients in the early feeding group compared to in 28 patients in the on-demand group (30% versus 27%; p = 0.76). Mortality was 11% in the early feeding group compared to 7% in the on-demand group (p = 0.33). There were no differences in infections (25% versus 26%, p = 0,87), persistent single-organ failure (13% versus 8%, p = 0.65) or persistent multi-organ failure (5% versus 7%, p = 0.77). In the on-demand group, 72 patients (69%) tolerated an oral diet and only 32 patients (31%) required nasoenteral tube feeding.</p><p><bold>CONCLUSION:</bold> Starting nasoenteral tube feeding within 24 hours after admission in patients with predicted severe pancreatitis does not reduce complications as compared to on-demand nasoenteral tube feeding started after 72 hours. Therefore, in contrast to what is advised in recent guidelines, routine early nasoenteral tube feeding is not necessary. Nasoenteral tube feeding can be started after 72 hours when oral intake is insufficient.</p><p><bold>REFERENCES:</bold></p><p>1. Bakker OJ , van Brunschot S, van Santvoort HC, et al. and Gooszen HG for the <bold>Dutch Pancreatitis Study Group</bold>. Pancreatitis, very early compared with normal start of enteral feeding (<bold>PYTHON</bold> trial): design and rationale of a randomised controlled multicenter trial. <italic>Trials. 2011 Mar 10;12:73. doi: 10.1186/1745-6215-12-73.</italic></p><p><bold>Contact E-mail Address:</bold><email>o.j.bakker@pancreatitis.nl</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Acute Pancreatitis, Complications, Nutrition, pancreas, randomised controlled trial</p></sec><sec><title>OP003 SUSTAINED VIROLOGIC RESPONSE 12 WEEKS POST-TREATMENT WITH INTERFERON-FREE REGIMENS OF ABT-450/R, ABT-267, ABT-333, AND RIBAVIRIN IN CHRONIC HCV GENOTYPE 1 DIFFICULT-TO-TREAT PATIENT SUBGROUPS</title><p>M. Rodriguez-Torres<sup>1</sup>, <bold>F. Nunes</bold><sup>2,*</sup>, D. Cohen<sup>3</sup>, W. Xie<sup>3</sup>, C. Marincic<sup>3</sup>, A. Khatri<sup>3</sup>, T. Pilot-Matias<sup>3</sup>, T. Podsadecki<sup>3</sup>, B. Bernstein<sup>3</sup></p><p><italic><sup>1</sup>Fundación de Investigación, San Juan, Puerto Rico, <sup>2</sup>PHGI Assoc. Ltd., Philadelphia, <sup>3</sup>AbbVie, North Chicago, United States</italic></p><p><bold>INTRODUCTION:</bold> ABT-450 is a potent hepatitis C virus (HCV) protease inhibitor (dosed with ritonavir 100mg, ABT-450/r) identified as a lead compound by AbbVie and Enanta; ABT-267 is an NS5A inhibitor and ABT-333 is a non-nucleoside polymerase inhibitor. We examined the safety and efficacy of 12- and 24-week (wk) interferon (IFN)-free 3DAA+ribavirin (RBV) regimens (ABT-450/r, 100/100-150/100mg QD; ABT-267, 25mg QD; ABT-333, 400mg BID; and weight-based RBV) in treatment-naïve (TN) patients (pts) and prior pegIFN/RBV null responders (Null) with chronic HCV genotype 1 (GT1) infection, overall and in pt subgroups with baseline characteristics associated with poorer response to pegIFN/RBV.</p><p><bold>AIMS&METHODS:</bold> Non-cirrhotic TN and Null pts received 3DAA+RBV for 12 or 24 wks. SVR<sub>12</sub> rates (HCV RNA <25 IU/mL at post-treatment wk12) were analyzed in the TN and Null cohorts overall and according to age, race, ethnicity, BMI, HOMA-IR, IL28B genotype, and baseline viral load (ITT, non-completer=failure).</p><p><bold>RESULTS:</bold> 247 pts (159 TN, 88 Null) assigned to 3DAA+RBV regimens received ≥1 dose of study drug (male: 49% and 63%; GT1a infection: 68% and 63%). Overall SVR<sub>12</sub> rates for TN and Null cohorts were 98.7% and 93.3% (12-wk) and 92.5% and 97.7% (24-wk). SVR<sub>12</sub> rates ≥90% were achieved regardless of age, BMI, race, ethnicity (Table), HOMA-IR, IL28B genotype, or baseline viral load, with no statistically significant differences in any comparisons made in the TN or Null cohorts (<italic>P</italic>>0.05, Fisher’s exact test). Most common AEs in TN and Null cohorts were fatigue (32.7% and 23.9%) and headache (31.4% and 30.7%). 4 of 247 pts (1.6%) discontinued treatment due to study drug-related AEs. 1 pt (0.4%) had a serious AE (arthralgia) possibly related to study drug.
<table-wrap id="table1-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1"></th><th rowspan="1" colspan="1"><bold>TN, n/N (%)</bold></th><th rowspan="1" colspan="1"><bold>Null, n/N (%)</bold></th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">Age ≥50 y</td><td rowspan="1" colspan="1">92/97 (95)</td><td rowspan="1" colspan="1">52/56 (93)</td></tr><tr><td rowspan="1" colspan="1">Age <50 y</td><td rowspan="1" colspan="1">60/62 (97)</td><td rowspan="1" colspan="1">32/32 (100)</td></tr><tr><td rowspan="1" colspan="1">BMI ≥30 kg/m<sup>2</sup></td><td rowspan="1" colspan="1">36/40 (90)</td><td rowspan="1" colspan="1">18/18 (100)</td></tr><tr><td rowspan="1" colspan="1">BMI <30 kg/m<sup>2</sup></td><td rowspan="1" colspan="1">116/119 (98)</td><td rowspan="1" colspan="1">66/70 (94)</td></tr><tr><td rowspan="1" colspan="1">Black</td><td rowspan="1" colspan="1">16/17 (94)</td><td rowspan="1" colspan="1">9/9 (100)</td></tr><tr><td rowspan="1" colspan="1">Non-black</td><td rowspan="1" colspan="1">136/142 (96)</td><td rowspan="1" colspan="1">75/79 (95)</td></tr><tr><td rowspan="1" colspan="1">Hispanic/Latino</td><td rowspan="1" colspan="1">10/11 (91)</td><td rowspan="1" colspan="1">8/8 (100)</td></tr><tr><td rowspan="1" colspan="1">Non-Hispanic/Latino</td><td rowspan="1" colspan="1">142/148 (96)</td><td rowspan="1" colspan="1">76/80 (95)</td></tr></tbody></table></table-wrap></p><p><bold>CONCLUSION:</bold> In this study, treatment with 3 DAAs (ABT-450/r, ABT-267, and ABT-333) plus RBV for 12 or 24 wks was well-tolerated, with high SVR<sub>12</sub> rates achieved in non-cirrhotic HCV GT1 treatment-naïve patients and previous null responders, even with baseline characteristics associated with a poorer response to pegIFN/RBV.</p><p><bold>Contact E-mail Address:</bold><email>laurinda.cooker@abbvie.com</email></p><p><bold>Disclosure of Interest</bold>: M. Rodriguez-Torres Financial support for research from: AbbVie, Akros, Boehringer Ingelheim, BMS, Gilead, GSK, Idenix Pharmaceuticals, Idera Pharmaceuticals, Inhibitex Pharmaceuticals, Medtronic, Merck, Novartis, Pharmasset, Roche, Santaris Pharmaceuticals, Scynexis Pharmaceuticals, Tibotec, Vertex Pharmaceuticals, ViroChem Pharma, ZymoGenetics, Consultancy for: BMS, Genentech/Roche, Gilead, Inhibitex Pharmaceuticals, Merck, Santaris Pharmaceuticals, Tibotec, Vertex, F. Nunes Financial support for research from: AbbVie, Merck, BMS, D. Cohen Shareholder of: AbbVie, Other: Employee of AbbVie, W. Xie Shareholder of: AbbVie, Other: Employee of AbbVie, C. Marincic Shareholder of: AbbVie, Other: Employee of AbbVie, A. Khatri Shareholder of: AbbVie, Other: Employee of AbbVie, T. Pilot-Matias Shareholder of: AbbVie, Other: Employee of AbbVie, T. Podsadecki Shareholder of: AbbVie, Other: Employee of AbbVie, B. Bernstein Shareholder of: AbbVie, Other: Employee of AbbVie</p><p><bold>Keywords:</bold> clinical trial, direct-acting agents, Hepatitis C virus (HCV)</p></sec><sec><title>OP004 KLEBSIELLA OXYTOCA OVERGROWTH AND TILIVALLINE PRODUCTION INDUCE ANTIBIOTIC ASSOCIATED HEMORRHAGIC COLITIS</title><p><bold>G. Schneditz</bold><sup>1,*</sup>, J. Rentner<sup>2</sup>, K. A. T. Herzog<sup>1,3</sup>, G. Gorkiewicz<sup>4</sup>, S. Roier<sup>1</sup>, S. Schild<sup>1</sup>, R. Breinbauer<sup>2</sup>, E. L. Zechner<sup>1</sup>, C. Högenauer<sup>3</sup></p><p><italic><sup>1</sup>Institute of Molecular Biosciences, University of Graz, <sup>2</sup>Institute of Organic Chemistry, Graz University of Technology, <sup>3</sup>Department of Internal Medicine, <sup>4</sup>Institute of Pathology, Medical University of Graz, Graz, Austria</italic></p><p><bold>INTRODUCTION:</bold> Antibiotic-associated hemorrhagic colitis (AAHC) caused by <italic>Klebsiella oxytoca</italic> is exemplary for antibiotic-driven enterobacterial dysbiosis. Alterations of the intestinal microbiota following penicillin therapy results in exclusive overgrowth of β-lactamase producing <italic>K. oxytoca</italic>, which is found in intestine of about 5% of the healthy population. AAHC patients usually report a sudden onset of severe bloody diarrhea but recover spontaneously after cessation of antibiotic prescription. To understand the virulence of <italic>K. oxytoca</italic> our work focused on an unknown secreted substance with strong toxicity towards human intestinal epithelial cell lines in vitro.</p><p><bold>AIMS&METHODS:</bold> We conducted transposon- and site-directed mutagenesis of a toxin-producing <italic>K. oxytoca</italic> strain, combined with an in vitro screen for cytotoxic effects on epithelial cells to identify toxin negative mutant strains. In parallel, the genome of a toxin-producing clinical isolate of <italic>K. oxytoca</italic> was sequenced and annotated. The toxic product was isolated from <italic>K. oxytoca</italic> conditioned medium. Preparative HPLC followed by HiRes-MS and NMR analysis of purified toxin were used to identify the toxin structure. We evaluated the toxin as a virulence factor in a mouse model for AAHC. Following inoculation per os, AAHC was triggered via administration of amoxicillin/clavulanate and indometacin. Colon tissue was subjected to histological analysis for assessment of AAHC pathologies. Toxin-induced host cell pathophysiology was investigated using an epithelial barrier model in vitro.</p><p><bold>RESULTS:</bold> We identified a cytotoxin secreted by<italic> K. oxytoca</italic> as a pentacyclic pyrrolobenzodiazepine (PBD) named tilivalline (TLV). PBDs are known as DNA-modifying metabolites of Actinobacteria, whereas TLV is the only known PBD produced by the human microbiota and by gram-negative bacteria. We showed that TLV producing strains caused AAHC, however virulence of TLV knock-out strains was strongly attenuated in the murine model. Induction of epithelial apoptosis is the dominant effect of TLV-positive strains in vivo. In vitro evidence indicates that apoptotic death progresses to disruption of the epithelial barrier.</p><p><bold>CONCLUSION:</bold> We conclude that TLV is the main virulence factor of <italic>K. oxytoca</italic> in AAHC development. TLV is the first reported PBD causing human disease - an example of a novel class of intestinal bacterial cytotoxins.</p><p><bold>Contact E-mail Address:</bold><email>georg.schneditz@uni-graz.at</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> colitis, dysbiosis, klebsiella oxytoca, Microbiota, pyrrolobenzodiazepine, toxin</p></sec><sec><title></title><p><bold>MONDAY, OCTOBER 14, 2013 11:00-12:30</bold></p><p><bold>Today's science; tomorrow's medicine: From genes to disease in IBD – Hall 2</bold></p></sec><sec><title>OP005 GENETIC AND CLINICAL CHARACTERIZATION OF 47 MULTIPLE-AFFECTED IBD FAMILIES</title><p><bold>A. Settesoldi</bold><sup>1,*</sup>, T. Billiet<sup>1</sup>, E. Hoefkens<sup>1</sup>, V. Ballet<sup>2</sup>, P. Rutgeerts<sup>2</sup>, S. Vermeire<sup>2</sup>, I. Cleynen<sup>1</sup></p><p><italic><sup>1</sup>KU Leuven, <sup>2</sup>UZ Leuven, Leuven, Belgium</italic></p><p><bold>INTRODUCTION:</bold> Although the exact pathogenesis of inflammatory bowel disease (IBD) is not known, our current understanding suggests an etiology based on an interaction among genetic, environmental and immunological factors. The genetic progress has been outstanding with 163 genetic loci identified. It is believed that multiple-affected families have a high burden of genetic risk variants although this has not been studied yet in detail.</p><p><bold>AIMS&METHODS:</bold> We collected 47 families with 3 first-degree members affected by IBD (Crohn's disease (CD), ulcerative colitis (UC) or colitis-type unclassified (IBD-U). Our aim was to characterize these families and to find to what extent the 163 confirmed genetic loci are associated with disease in these families. Clinical data (gender, diagnosis, age at diagnosis, CD location and behavior, UC extent) were obtained. Both affected and unaffected members were genotyped using immunochip and 192 independent SNPs from the 163 loci were included in plink.</p><p><bold>RESULTS:</bold> Of the 47 families, 32 were CD only, 1 was UC only, 12 were mixed CD/UC, and 2 also contained IBD-U. These families comprised 81 nuclear relations (offspring with both parents), 165 affected (138 CD, 24 UC, 3 IC) and 132 unaffected members, 132 of which were male and 165 female. The median age at diagnosis was 29 years for CD (IQR 10-70) and 32 for UC (IQR 35-54). 17 SNPs were nominally significant (p<sub>uncorrect</sub><0.05) for the combined TDT and parent TDT test statistic. The most significant association was seen for rs3172494 (<italic>IP6K2</italic>, p=5.71e-05), located in the 3p21 region close to <italic>MST1</italic>. Although rs3172494 is differentially transmitted from both heterozygous fathers and mothers to affected offspring (T:U<sub>pat</sub>=2.5:14.5, T:U<sub>mat</sub>=6.5:11.5), paternal transmission bias is most pronounced (p=3.61e-03). The next most significant SNPs were rs2227551 (p=4.91e-03) and rs4256159 (p=6.49e-03). Interestingly, the <italic>NOD2</italic> frameshift mutation rs2066847 was not significantly associated with disease, but there was a strong paternal transmission bias of the risk allele (T:U<sub>pat</sub>=13:4, T:U<sub>mat</sub>=4:4, p<sub>pat</sub>=2.91e-02).</p><p><bold>CONCLUSION:</bold> This is the largest cohort of multiple-affected IBD families studied for genetic association to date. We found nominal significance for disease association with some of the known IBD susceptibility loci, as well as paternal or maternal transmission bias. However, most risk alleles were not specifically associated with disease and many risk alleles were also carried by unaffected relatives. It will be important to also incorporate environmental factors in the family-based association studies in order to try and predict individuals at high risk for developing disease.</p><p><bold>Contact E-mail Address:</bold><email>a.settesoldi@hotmail.it</email></p><p><bold>Disclosure of Interest</bold>: A. Settesoldi: None Declared, T. Billiet: None Declared, E. Hoefkens: None Declared, V. Ballet: None Declared, P. Rutgeerts Financial support for research from: UCB Pharma, Abbvie, Janssen Biologics, Merck, Prometheus, Lecture fee(s) from: Abbvie, Merck, Consultancy for: Amgen, Merck, UCB Pharma, Genentech, BMS, Abbvie, Janssen Biologics, Millenium, Neovacs, Actogenics, Prometheus, , S. Vermeire Financial support for research from: UCB Pharma, MSD, Abbvie, Lecture fee(s) from: Abbvie, Merck, Ferring, UCB Pharma, Centocor, Consultancy for: UCB Pharma, AstraZeneca, Ferring, Abbvie, Merck, Ferring, Shire, Pfizer, I. Cleynen: None Declared</p><p><bold>Keywords:</bold> genetics, IBD</p></sec><sec><title></title><p><bold>MONDAY, OCTOBER 14, 2013 11:00-12:30</bold></p><p><bold>TSTM: From genes to disease in IBD – Hall 2</bold></p></sec><sec><title>OP006 TRANSCRIPTOMIC PROFILES FOR HUMAN INTESTINAL T CELLS REVEAL NOVEL PATHWAYS OF REGULATION AND INTERACTIONS WITH GENETIC RISK FOR BOTH GASTROINTESTINAL AND EXTRAINTESTINAL INFLAMMATORY DISEASE.</title><p><bold>T. Raine</bold><sup>1,2,*</sup>, J. Liu<sup>3</sup>, C. Anderson<sup>3</sup>, M. Parkes<sup>2</sup>, A. Kaser<sup>1,2</sup></p><p><italic><sup>1</sup>University of Cambridge, <sup>2</sup>Cambridge University Hospitals NHS Foundation Trust, <sup>3</sup>Wellcome Trust Sanger Institute, Cambridge, United Kingdom</italic></p><p><bold>INTRODUCTION:</bold> The intestinal mucosa harbours the largest accumulation of T lymphocytes in the human body. These T cells play an important role in the triggering and maintenance of intestinal inflammation but are poorly characterised in humans, whilst in the mouse there are only a handful of reports of transcriptomes generated for individual cell types, many of which lack direct human equivalents.</p><p><bold>AIMS&METHODS:</bold> CD4<sup>+</sup> and CD8<sup>+</sup> effector T cells purified from the intraepithelial (IEL) and lamina propria (LPL) layers of terminal ileal biopsies from 6 healthy female volunteers were used for expression microarrays analysis alongside reference peripheral blood populations. <italic>In silico</italic> pathway analysis, protein-protein interaction modelling, transcription factor and kinase prediction modelling were used to predict active pathways in the gut and results confirmed by <italic>ex vivo</italic> flow cytometric analysis. Genetic risk loci for a range of gastrointestinal and extraintestinal inflammatory pathologies were tested for enrichment of key gut expressed genes.</p><p><bold>RESULTS:</bold> Key pathways upregulated in gut T cells include TNF-receptor signalling, IL-17A and aryl hydrocarbon receptor signalling and 4-1BB costimulatory signalling. Genetic risk loci for gastrointestinal pathologies were significantly enriched for genes upregulated in gut T cell populations, including Crohn’s disease (CD4<sup>+ </sup>and CD8<sup>+ </sup>LPL), Ulcerative colitis (CD8<sup>+</sup> LPL) and coeliac disease (CD4<sup>+ </sup>and CD8<sup>+ </sup>IEL and LPL). Risk loci for extraintestinal pathologies with a significant microbial trigger were also enriched for gut expressed genes (type 1 diabetes, MS), whilst other inflammatory pathologies and non-inflammatory pathologies showed no such enrichment (SLE, rheumatoid arthritis, BMI, Height). Transcription factor prediction and interrogation of risk loci using published ChIP-Seq data converge on HNF4a as a key point of genetic regulation of gut inflammation.</p><p><bold>CONCLUSION:</bold> We report the first complete transcriptional analysis of all 4 major T cell populations in the terminal ileum of healthy human volunteers. We provide evidence for several gut-specific T cell signalling pathways. Risk loci for gastrointestinal inflammatory diseases are enriched for gut expressed T cell genes; this approach informs our understanding of candidate genes and causal cell populations at risk loci. We also show a surprising role of gut T cell genes in a subset of extraintestinal inflammatory pathologies with strong epidemiological links to microbial influences.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Genetic susceptibility, inflamatory pathways, mucosal inflammation, T cell</p></sec><sec><title></title><p><bold>MONDAY, OCTOBER 14, 2013 11:00-12:30</bold></p><p><bold>Paediatric IBD – Hall Helsinki</bold></p></sec><sec><title>OP010 LONG-TERM OUTCOME OF PAEDIATRIC-ONSET ULCERATIVE COLITIS: EARLY YEARS ARE SHAPING THE FUTURE.</title><p><bold>C. Gower-Rousseau</bold><sup>1,*</sup>, J. Salleron<sup>2</sup>, D. Turck<sup>3</sup>, M. Fumery<sup>4</sup>, A. Peneau<sup>5</sup>, C. Spyckerelle<sup>6</sup>, E. Laberenne<sup>7</sup>, F. Vasseur<sup>2</sup>, L. Peyrin-Biroulet<sup>8</sup>, J.-F. Colombel<sup>9</sup>, G. Savoye<sup>10</sup> and EPIMAD Group</p><p><italic><sup>1</sup>Epidemiology, <sup>2</sup>Biostatistics EA2694, <sup>3</sup>Pediatrics, UNIVERSITY AND HOSPITAL LILLE , Lille, <sup>4</sup>Gastroenterology, University and Hospital, Amiens, <sup>5</sup>Gastroenterology, Saint Philibert Hospital Catholic University, <sup>6</sup>Pediatrics, St Antoine Hospital Catholic University, Lille, <sup>7</sup>Gastroenterology, General Hospital, Seclin, <sup>8</sup>Gastroenterology, University Hospital Inserm U954, Nancy, France, <sup>9</sup>Gastroenterology, Henry D.Janowitz Division of Gastroenterology, New-York, United States, <sup>10</sup>Gastroenterology, University Hospital, Rouen, France</italic></p><p><bold>INTRODUCTION:</bold> Data on long-term outcome of paediatric-onset ulcerative colitis (UC) are scarce.</p><p><bold>AIMS&METHODS:</bold> All patients recorded by the EPIMAD Registry between 1988 and 2004 with a diagnosis of UC before the age of 17 years were included. The cumulative risks of receiving immunosuppressants (IS, including azathioprine and/or methotrexate and/or cyclosporine) and anti-TNFα therapy, as well as undergoing colectomy were estimated <italic>via </italic>the Kaplan-Meier method.</p><p><bold>RESULTS:</bold> 159 paediatric-onset UC patients with a follow-up ≥ 2 years were identified (5% of all cases of UC), including 92 females. Median age at diagnosis was 14.5 years [IQR: 11.4-16.1] and median duration of follow-up was 11.5 years [8.2-15.8]. At diagnosis 25% of children had proctitis (E1), 38% left-sided colitis (E2) and 37% extensive colitis (E3). Disease course was characterised by disease extension in 50% of patients (50 among 101 E1 and E2). Cumulative risks of colonic extension were 11% at 1 year, 48% at 5 years, 54% at 10 years and 57% at 15 years. At diagnosis 12 (7.6%) patients had extra intestinal manifestations and 40 (25%) at maximal follow-up including articular manifestations (n=27). Cumulative probabilities of receiving IS and anti-TNFα therapy were respectively 20% and 0.5% at 2 years, 28% and 4% at 5 years, 32% and 7% at 10 years and 35% and 13% at 15 years. Cumulative probabilities of colectomy were 6% at 1 year, 20% at 5 years, 21% at 10 years and 24% at 15 years.</p><p><bold>CONCLUSION:</bold> In this large population-based cohort of paediatric-onset UC disease the rate of disease extension and colectomy rapidly increased within the first 6 years after diagnosis and then remained stable. These data emphasize the need for early intervention to modify the natural history of paediatric UC.</p><p><bold>Contact E-mail Address:</bold><email>corinne.gower@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: C. Gower-Rousseau Financial support for research from: Ferring Company, J. Salleron: None Declared, D. Turck: None Declared, M. Fumery: None Declared, A. Peneau: None Declared, C. Spyckerelle: None Declared, E. Laberenne: None Declared, F. Vasseur: None Declared, L. Peyrin-Biroulet: None Declared, J.-F. Colombel: None Declared, G. Savoye: None Declared</p><p><bold>Keywords:</bold> inflammatory bowel disease, natural history, paediatrics, population-based </p></sec><sec><title>OP011 NATURAL HISTORY CONFIRMS THE VALIDITY OF SEPARATING PAEDIATRIC IBD AT 10 YEARS OF AGE IN THE PARIS CLASSIFICATION</title><p><bold>J. Van Limbergen</bold><sup>1,*</sup>, P. Henderson<sup>2</sup>, H. E. Drummond<sup>3</sup>, R. K. Russell<sup>4</sup>, J. Satsangi<sup>3</sup>, D. C. Wilson<sup>1</sup></p><p><italic><sup>1</sup>Child Life and Health, University of Edinburgh, <sup>2</sup>Dept of Paediatric Gastroenterology and Nutrition, Royal Hospital for Sick Children, <sup>3</sup>Gastrointestinal Unit, University of Edinburgh, Edinburgh, <sup>4</sup>Dept of Paediatric Gastroenterology, Yorkhill Hospital, Glasgow, United Kingdom</italic></p><p><bold>INTRODUCTION:</bold> Compared with adult IBD, paediatric IBD (PIBD) has been shown to be more dynamic and extensive at diagnosis using the Montreal classification(1). An updated and modified classification of paediatric IBD (Paris)(2) has recently been published; a key feature is an age division at 10 years. Data on the natural history of PIBD using the Paris classification are scarce.</p><p><bold>AIMS&METHODS:</bold> Our aims were to characterise the phenotype of PIBD in different age groups (A1a<10 years;A1b≥10<17 years), at diagnosis and after 2 & 4 years of follow-up, using the Paris classification. 713 patients (<17 years at diagnosis, male/female 407/306, median age (Q1-Q3) 11.5y (8.7-13.3): 473 CD / 173 UC / 67 IBDU) were analysed at diagnosis, 2 (295CD / 100UC) & 4-year (103CD / 56UC) follow-up and Chi-squared analyses were performed.</p><p><bold>RESULTS:</bold> The A1a-location of paediatric CD differs from A1b (p=0.0002). A1a CD is characterised by less ileal disease (L1+/- L4: 6/154 (38.9%) vs. 32/313 (10.2%); p=0.01 OR 0.36 (0.15-0.87)) and more limited oral+/-perianal CD at presentation (14/154 (9.1%) vs. 3/313 (0.9%); p<0.0001 OR 10.33 (2.92-36.53)). These differences persist during follow-up of A1a and A1b (p=0.0007 and p=0.02 at 2y and 4y, respectively). By 4 years after diagnosis, A1a CD is characterised by less panenteric CD (L3+L4ab: 4/67 (5.9%) vs. 18/103 (17.5%); p=0.03 OR 0.30 (0.10-0.93)).</p><p>By 2y after diagnosis, Paris location (of patients not L3+L4ab at diagnosis), changed in 20.8% (59/283). This change of location was due to ileal (from colonic to ileo-colonic disease) in 24/59 (40.7%) vs. colonic (from ileal to ileo-colonic disease (n=8) or isolated colonic extension (n=5), 13/59 (22%)) in the patients who extend (p=0.02 OR 2.43 (1.08-5.43)). 28/59 (47.4%) had extension into the upper gastrointestinal tract (L4a/b).</p><p>Whereas A1a CD remains largely inflammatory during follow-up, A1b CD behaviour progresses to intestinal penetrating complications (p<0.0001).</p><p>UC presented as pancolitis (E4) in 60% of A1a (36/60) vs 74.8% of A1b (77/103), p=0.04 OR 0.51 (0.26-1.00). 4 years after diagnosis, E4 UC was less common in A1a compared with A1b (15/30 (50%) vs 20/26 (76.9%), p=0.03 OR 0.30 (0.09-0.96)).</p><p><bold>CONCLUSION:</bold> We have demonstrated that A1a CD phenotype is characterised by less ileal disease with more oral+/- perianal disease and inflammatory disease compared with A1b CD. Childhood UC is extensive (E3/E4) at diagnosis but pancolitis is rarer in A1a than A1b UC; these differences persist during follow up.</p><p><bold>REFERENCES:</bold></p><p>1. Van Limbergen J. & Russell R.K. et al. Gastroenterology 2008;135(4):1114-22.</p><p>2. Levine A. et al. Inflamm Bowel Dis. 2011;17(6):1314-21.</p><p><bold>Contact E-mail Address:</bold><email>johanvanlimbergen@hotmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> inflammatory bowel disease, paediatrics, phenotype </p></sec><sec><title>OP012 PRIMARY SCLEROSING CHOLANGITIS IN PEDIATRICS NEWLY-ONEST CROHN’S DISEASE IS ASSOCIATED WITH MALE PREDOMINANCE, PERIANAL LESIONS AND ABBERANT SEROLOGICAL RESPONSE</title><p><bold>M. K. Sladek</bold><sup>1,*</sup>, R. B. Herman<sup>1</sup>, I. Herman-Sucharska<sup>2</sup>, K. Fyderek<sup>1</sup></p><p><italic><sup>1</sup>Department of Pediatrics, Gastroenterology and Nutrition, <sup>2</sup>Departemnt of Electroradiology, Faculty of Sciences, JAGIELLONIAN UNIVERSITY MEDICAL COLLEGE, Krakow, Poland</italic></p><p><bold>INTRODUCTION: Introduction:</bold> Primary sclerosing cholangitis (PSC) is a chronic fibroobliterative disorder of the biliary ducts strongly associated with inflammatory bowel disease (IBD) with reported predominant association with ulcerative colitis (UC). A distinct clinical phenotype has been reported in UC-PSC but for Crohn’s disease (CD) is poorly defined, especially in children.</p><p><bold>AIMS&METHODS: The aim </bold>of the study was to evaluate the incidence of PSC in IBD children and to define the clinical characteristic of pediatric-onset CD-PSC. <bold>Patients/ Methods:</bold> The study involved 585 newly–onset IBD children; 368 CD patients, 140 UC patients and 76 IBD-U patients at the ages 2 to 18 years, prospectively diagnosed in our institution according to the Porto criteria between 2004-2012. Of this cohort 16 patients were identified with concomitant PSC according to the conventional cholangio-MR criteria, results of liver tests and ultrasound imaging; 14/16 were diagnosed with CD. Therefore 2 UC patients were excluded from the analysis and CD patients were matched 1:2 to CD-PSC patients with sex and age and served as a control group. CD activity was evaluated by the Pediatric Crohn’s Disease Activity Index (PCDAI) and disease phenotype was determinate with the Paris classification. The following tests were performed: pANCA, IgA and IgG ASCA, ANA, PAB and liver tests (ALT, GGTP). For statistic analysis the chi-square and t-test were performed using Statistica 9 software.</p><p><bold>RESULTS: Results:</bold> In our IBD cohort PSC was predominantly diagnosed in CD patients (87%) and more frequently in boys than girls (71% vs. 29%; p<0.005). MRCP showed mainly extra and intra hepatic involvement (71%). CD-PSC patients more frequent presented with perianal lesion (29% vs. 19%; p<0.005). At the time of diagnosis there were no differences in PCDAI, location and behavior of the disease (p>0.05), however CD-PSC patients received more frequently steroids treatment to induce remission (p=0.001). Altered immunological response with significant higher rate of pANCA (71% vs. 21%, p<0.0002), ANA (29% vs. 4%; p<0.04) and PAB (43% vs. 21%; p=0.0003) was demonstrated in CD-PSC patients. No difference was found in ASCA rate in both groups (CD-PSC 29%, CD-32%, p>0.05), and 21% CD-PSC patients expressed overlap ASCA with pANCA. Significant higher GGTP level (92,7 vs. 18,4 U/l, p=0,0001) but not ALT was present in CD-PSC patients.</p><p><bold>CONCLUSION:</bold> Pediatric newly-onset CD-PSC patients have a unique clinical presentation with higher rate of perianal disease and male predominance. An altered serological response to microbial and autoantigens with UC-like profile was present.</p><p><bold>REFERENCES:</bold></p><p>1. Noble-Jamieson G, Heuschkel, Torrente F et all. Colitis-associated sclerosing cholangitis in children: A single center experience. JCC 2013. dx.doi.org/10.1016/j.crohn's.2013.01.016 2. Halliday JS, Djordjevic J, Lust et all. A unique clinical phenotype of primary sclerosing cholangitis associated with Crohn's disease. JCC 2012; 6:174-181</p><p><bold>Contact E-mail Address:</bold><email>misladek@cyf-kr.edu.pl</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Children, Crohn`s disease, Primary sclerosing cholangitis </p></sec><sec><title>OP013 REPEATED EXCLUSIVE ENTERAL NUTRITION IN THE TREATMENT OF PEDIATRIC CROHN’S DISEASE: EVALUATION OF EFFICACY AND LONG-TERM OUTCOME</title><p><bold>K. Frivolt</bold><sup>1,2,*</sup>, T. Schwerd<sup>1</sup>, S. Schatz<sup>1</sup>, K. Werkstetter<sup>1</sup>, A. Schwarzer<sup>1</sup>, P. Bufler<sup>1</sup>, S. Koletzko<sup>1</sup></p><p><italic><sup>1</sup>Dr. v. Hauner Children’s Hospital, University Munich Medical Center, Munich, Germany, <sup>2</sup>2nd Department of Pediatrics, Comenius University Medical School, Bratislava, Slovakia</italic></p><p><bold>INTRODUCTION:</bold> Exclusive enteral nutrition (EEN) induces mucosal healing in children with active Crohn’s Disease supporting its role as induction therapy and suggesting EEN as treatment for disease exacerbation.</p><p><bold>AIMS&METHODS:</bold> We aimed to compare short- and long-term outcome of a second course of EEN in a single center cohort. Patients with active CD treated with EEN were retrospectively evaluated for induction of remission and relapse-free duration in the study period 01/2004 to 06/2011. Patients with anti-TNF-therapy or corticosteroids 3 months prior to EEN were excluded. Analysis included changes in mathematically weighted Pediatric Crohn’s Disease Activity Index (wPCDAI), laboratory and anthropometric data. Remission was defined as wPCDAI of <12.5 and relapse as wPCDAI of ≥12.5 and/or need for anti-TNF-treatment, steroids, surgery or EEN-reintroduction.</p><p><bold>RESULTS:</bold> During the study period, 181 CD patients were seen, 94 (52%) received at least one course of EEN, but 42 children did not meet inclusion criteria (33 prior CS, 2 IFX, 7 less than 12 months follow up). Of the remaining 52 children (31 male, mean age 13.2 years) 26 (50%) received a 2<sup>nd</sup> course of EEN. Azathioprin was started in 33/52 patients during first month of EEN. The mean wPCDAI at 1<sup>st</sup>-EEN was significantly higher compared to 2<sup>nd</sup>-EEN. Remission rate 3 months after starting 1<sup>st</sup> or 2<sup>nd</sup>-EEN was 92% (48/52) and 77% (20/26), respectively. Within one year follow-up, 32/48 (67%) and 14/20 (70%) patients relapsed, respectively (median time 231 vs. 145 days). Disease severity, anthropometric data, blood and fecal inflammatory markers showed better improvement with 1<sup>st</sup> compared to 2<sup>nd</sup>-EEN. Normalized fecal calprotectin during EEN did not reduce the risk for relapse.</p><p><bold>CONCLUSION:</bold> EEN is highly effective for induction of remission in active CD but a slightly lower efficacy is observed with second course. Despite early introduction of immunomodulatory therapy with azathioprine the one-year relapse rate is high.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> exclusive enteral nutrition, pediatric IBD</p></sec><sec><title>OP014 INFLIXIMAB REGIMENS OF MAINTENANCE THERAPY IN CHILDREN WITH CROHN DISEASE - MULTICENTER RANDOMIZED STUDY</title><p><bold>J. Kierkus</bold><sup>1,*</sup>, B. Iwanczak<sup>2</sup>, U. Grzybowska Chlebowczyk<sup>3</sup>, I. Lazowska Przeorek<sup>4</sup>, E. Toporowska Kowalska<sup>5</sup>, G. Czaja Bulsa<sup>6</sup>, B. Korczowski<sup>7</sup>, M. Sladek<sup>8</sup></p><p><italic><sup>1</sup>Gastroenterology, Hepatology and Feeding Disorders, IPCZD, warsaw, <sup>2</sup>Department of Pediatrics, Gastroenterology and Nutrition, Medical University of Wroclaw, Wroclaw, <sup>3</sup>The Department of Paediatrics, Medical University of Silesia, Katowice, <sup>4</sup>Department of Pediatric Gastroneterology and Nutrition, Medical University of Warsaw, Warsaw, <sup>5</sup>Department of Paediatric Allergology, Gastroenterology and Nutrition, Medical University of Lodz, Lodz, <sup>6</sup>Paediatrics, Gastroenterology and Rheumatology, Zdroje Hospital in Szczecin, Szczecin, <sup>7</sup>Department of Pediatrics, State Hospital, Rzeszow, <sup>8</sup>Department of Pediatrics, Gastroenterology and Nutrition, Jagiellonian University School of Medici, Krakow, Poland</italic></p><p><bold>INTRODUCTION:</bold> Optimal use of biologics in Crohn’s disease (CD) requires balance between benefits and risk, and concern of serious side effects may question the concomitant immunomodulators use in pediatric patients. The study was conducted to compare the efficacy of two infliximab maintenance regiments: (1) infliximab alone and (2) infliximab with immunomodulator in pediatric patients with moderate to severe active CD.</p><p><bold>AIMS&METHODS:</bold> Patients (n=99; 14,5 mean age, 62% males) with PCDAI>30 were involved to the study and received induction therapy with infliximab 5 mg/kg at weeks 0, 2, and 6. Clinical (PCDAI score) evaluation were performed at week 10 and patients with clinical response (decrease of PCDAI≥15 AND PCDAI<30) and/or remission (PCDAI≤10) were randomized to Group l receiving infliximab 5 mg/kg every 8 weeks with immunomodulator until Week 54 (n=45) or Group II receiving infliximab 5 mg/kg every 8 weeks with immunomodulator stopped at Week 26 (n=39). Clinical assessment (PCDAI score) was performed at week 54 in both groups. Primary endpoint was loss of clinical response defined as increase of PCDAI>15 points or PCDAI>30. Secondary endpoint was: necessity to increase/change maintenance therapy.</p><p><bold>RESULTS:</bold> 84 out of 99 (85%) pts had response, and 58 (59%) clinical remission after induction therapy at Week 10. 2 out of 45 (4%) pts in Group I and 2 out of 39 pts (5%) in Group II had loss of clinical response at Week 54 (non significant-NS). The increase/change of maintenance therapy was necessary in 13 out of 45 patients (29%) in Group I and 11 out of 39 (28%) in Group II (NS).</p><p><bold>CONCLUSION:</bold> Both regimens of maintenance therapy (1.Infliximab with immunomodulator and 2. Infliximab alone) are clinically equally efficient in children aged 7-17 years with moderate to severe CD.</p><p><bold>Contact E-mail Address:</bold><email>j.kierkus@czd.pl</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> children, Crohn, infliximab</p></sec><sec><title>OP015 ENDOSCOPIC AND CLINICAL PREDICTORS OF 1-YEAR OUTCOME IN CHILDREN WITH ULCERATIVE COLITIS TREATED WITH INFLIXIMAB: RESULTS FROM THE T72 TRIAL</title><p><bold>D. Turner</bold><sup>1,*</sup>, A. M. Griffiths<sup>2</sup>, G. Veerman<sup>3</sup>, J. Johanns<sup>4</sup>, L. Damaraju<sup>5</sup>, M. Blank<sup>5</sup>, J. Hyams<sup>6</sup></p><p><italic><sup>1</sup>Shaare Zedek Medical Center, Jerusalem, Israel, Jerusalem, Israel, <sup>2</sup>HSC, Toronto, Canada, <sup>3</sup>UZ , Brussels, Belgium, <sup>4</sup>4Janssen Research & Development, LLC , <sup>5</sup>Janssen Research & Development, LLC , Spring House, Pennsylvania, <sup>6</sup>Connecticut Children’s Medical Center, Hartford, United States</italic></p><p><bold>INTRODUCTION:</bold> Infliximab is increasingly used to treat moderate to severe ulcerative colitis (UC) in children. We aimed to identify early clinical, laboratory, and endoscopic predictors of sustained steroid-free remission in this population.</p><p><bold>AIMS&METHODS:</bold> A post-hoc analysis was conducted in 51 children (6-17 years) with moderate to severe pediatric UC treated with infliximab in the 1-year T72 randomized controlled trial. The primary outcome of this analysis was steroid-free remission at both Weeks 30 and 54, determined by patient and physician global assessments. Predictors were mucosal healing, The Pediatric UC Activity Index (PUCAI) and CRP (all measured concurrently at Week 8).</p><p><bold>RESULTS:</bold> The PUCAI at Week 8 performed best in predicting 1-year sustained steroid-free remission (9/17 (53%) who had PUCAI<10 points were in sustained remission vs. 4/20 (20%) who had PUCAI>=10; P=0.036). Week-8 mucosal healing (MH) was less predictive (7/16 (44%) with MH vs. 6/21 (29%) without; P=0.34).</p><p>Area under the ROC curve to predict steroid-free sustained remission was 0.70 (95%CI 0.53-0.88) for the PUCAI, 0.56 (0.36-0.76) for MH and 0.44 (0.24-0.65) for CRP.</p><p>Using a multivariable logistic regression model, the Week 8 PUCAI was the only predictor of sustained 1-year steroid-free remission (P=0.038) while MH and CRP were not (P>0.2). The PUCAI had a high concordance with endoscopic score (33% remission rate by the PUCAI vs. 31% complete MH at week 8).</p><p><bold>CONCLUSION:</bold> We present the first data on the utility of MH to predict disease course in pediatric UC. The PUCAI, which is a non-invasive clinical index, has at least similar power as MH in predicting sustained remission and was superior to CRP. Routine endoscopic evaluation in children with UC who are in complete clinical remission by the PUCAI may not be necessary.</p><p><bold>REFERENCES:</bold></p><p>1. COI- the PUCAI is copyrighted to the Hospital for Sick Children</p><p><bold>Contact E-mail Address:</bold><email>turnerd@szmc.org.il</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> mucosal healing, prediction, PUCAI, ulcerative colitis</p></sec><sec><title></title><p><bold>MONDAY, OCTOBER 14, 2013 11:00-12:30</bold></p><p><bold><italic>H. pylori</italic> treatment – Hall 7</bold></p></sec><sec><title>OP016 MULTICENTRIC RANDOMIZED STUDY OF <italic>H.PYLORI</italic> ERADICATION AND PEPSINOGEN TESTING FOR PREVENTION OF GASTRIC CANCER MORTALITY (GISTAR). THE STUDY DESIGN</title><p><bold>M. Leja</bold><sup>1,*</sup>, I. Upmace<sup>2</sup>, J. Y. Park<sup>3</sup>, M. Plummer<sup>3</sup>, R. Herrero<sup>3</sup></p><p><italic><sup>1</sup>Faculty of Medicine, <sup>2</sup>University of Latvia, Riga, Latvia, <sup>3</sup>International Agency for Research on Cancer, Lyon, France</italic></p><p><bold>INTRODUCTION:</bold> Currently no ideal preventive modalities are available for reducing gastric-cancer caused mortality in organized population-based application. The primary objective of the study is to determine if <italic>H.pylori</italic> screening followed by eradication of positive subjects and endoscopic follow-up of those with serological evidence of atrophic gastritis reduces mortality from gastric cancer in middle-aged people in high-risk areas.</p><p><bold>AIMS&METHODS:</bold> The GISTAR study is a multicentre randomized study of <italic>H.pylori</italic> eradication and pepsinogen testing for prevention of gastric cancer mortality. Here, we report the study design.</p><p><bold>RESULTS:</bold> Altogether 30.000 individuals aged 40-64 years will be enrolled, providing 90% study power to detect at least 35% reduction in gastric cancer mortality at 15 years of follow-up; initially a pilot study by enrolment approx. 3000 individuals is planned. Participants will be randomly allocated to one of two groups. In the active investigation/management group those positive for <italic>H.pylori</italic> will be offered eradication therapy, individuals with decreased pepsinogen will be invited for endoscopy. The control group will receive standard health care. The primary endpoint for our trial will be the mortality difference from gastric cancer between the groups at 15 years or when enough cases accumulate to demonstrate a statistical difference.</p><p><bold>CONCLUSION:</bold> The study is expected to provide valuable information on the utility for reduction in gastric cancer mortality of: 1)<italic>H.pylori</italic> eradication in adults on a population-basis, including among subjects who may already have pre-malignant lesions; 2)pepsinogen testing in screening settings.</p><p><bold>Contact E-mail Address:</bold><email>cei@latnet.lv</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> gastric cancer, prevention, study</p></sec><sec><title>OP017 SEQUENTIAL THERAPY FOR 10 DAYS VERSUS TRIPLE THERAPY FOR 14 DAYS IN THE FIRST LINE TREATMENT OF HELICOBACTER PYLORI INFECTION- A MULTICENTER, OPEN-LABEL, RANDOMIZED TRIAL</title><p><bold>J.-M. Liou</bold><sup>1,*</sup>, J.-T. Lin<sup>1,2</sup>, C.-C. Chen<sup>3</sup>, C.-Y. Chang<sup>4</sup>, J.-Y. Wu<sup>5</sup>, W.-H. Chang<sup>6</sup>, Y.-C. Lee<sup>1</sup>, M.-S. Wu<sup>1</sup> and Taiwan Helicobacter Consortium</p><p><italic><sup>1</sup>Internal Medicine , NATIONAL TAIWAN UNIVERSITY HOSPITAL, <sup>2</sup>Fu Jen Catholic University, Taipei, <sup>3</sup>Internal Medicine , NATIONAL TAIWAN UNIVERSITY HOSPITAL, Yun-Lin , <sup>4</sup>Internal Medicine , E-DA Hospital , <sup>5</sup>Internal Medicine , Kaohsiung Medical Universisty Hospital , Kaohsiung , <sup>6</sup>Internal Medicine , Mackay Memorial Hospital, Taipei, Taiwan, Province of China</italic></p><p><bold>INTRODUCTION:</bold> Our recent trial showed that sequential therapy for 14 days was superior to triple therapy for 14 days in the first line treatment of <italic>Helicobacter pylori (H. pylori)</italic> infection. However, whether sequential therapy for 10 days (S-10) is superior to triple therapy for 14 days (T-14) remains controversial. Besides, whether the efficacies of sequential therapy and triple therapy vary in hospitals-based and in community-based subjects remain unknown.</p><p><bold>AIMS&METHODS:</bold> Therefore, we aimed to further compare the efficacy and tolerability of S-10 and T-14 in the first line treatment in the hospitals and in the community. We recruited adult patients with <italic>H. pylori</italic> infection naïve to eradication therapies from eight medical centers and from the community. Using a computer-generated randomization sequence, we randomly allocated patients to either sequential therapy for 10 days (S-10) or triple therapy for 14 days (T-14). Our primary outcome was the eradication rate in first-line treatment by intention-to-treat (ITT) and per-protocol (PP) analyses. Minimum inhibition concentrations were determined by agar dilution test. 23S rRNA mutation was detected by polymerase chain reaction followed by direct sequencing.</p><p><bold>RESULTS:</bold> Between Feb, 2012 and April, 2013, we enrolled 1118 patients and 651 strains were collected. The eradication rates in the S-10 and T-14 groups were 87.6% (383/437) and 87.1% (385/442) in ITT analysis (p=0.810) and were 91.6% (383/418) and 90.6% (385/425) in the PP analysis (p=0.596), respectively. The eradication rates of T-14 appeared to be lower in the community (86.6%, 149/172) than in the hospitals (93.3%, 236/253) in the PP analysis (p=0.021). However, the eradication rates of S-10 were similar in the community and in the hospitals. The prevalence of 23S rRNA mutation were 9.9% (26/263) and 7.5% (20/268) in the S-10 and T-14 groups, respectively. The eradication rates of S-10 and T-14 were both significantly affected in the presence of clarithromycin resistance and 23S rRNA mutations.</p><p><bold>CONCLUSION:</bold> Sequential therapy for 10 days was as effective as triple therapy for 14 days in the first line treatment of <italic>H. pylori </italic>infection, but the eradication rate of triple therapy appeared to lower in the community than in the hospitals. (ClinicalTrials.gov: NCT01607918)</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> community , H pylori , resistance , Sequential therapy, triple therapy </p></sec><sec><title>OP018 THE EFFICACY OF SECOND-LINE ANTI-HELICOBACTER PYLORI ERADICATION USING 10-DAY AND 14-DAY LEVOFLOXACIN-CONTAINING TRIPLE THERAPY</title><p><bold>W.-C. Tai</bold><sup>1,*</sup>, S.-K. Chuah<sup>1</sup>, K.-L. Wu<sup>1</sup></p><p><italic><sup>1</sup>Division of Hepatogastroenterology, Chang Gung Memorial Hospital, Kaohsiung, Kaohsiung, Taiwan, Province of China</italic></p><p><bold>INTRODUCTION:</bold> Large meta-analyses recommended that second line Helicobacter pylori eradication with 10-day fluoroquinolone triple therapy as one of the treatment options. Reports describing second line Helicobacter pylori eradication using 14-day of fluoroquinolone-containing triple therapy are few.</p><p><bold>AIMS&METHODS:</bold> Current study aimed to compare the efficacy of 10-day and 14-day levofloxacin-containing triple therapy as second line regimen and the clinical factors influencing the outcome.</p><p>148 patients who failed Helicobacter pylori eradication using the standard triple therapy for 7 days were enrolled and divided to a 10-day levofloxacin-containing triple therapy group (levofloxacin 500 mg once daily, amoxicillin 1 g twice daily, and esomeprazole 40 mg twice daily for 10 days, EAL-10) or a 14-day levofloxacin-containing triple therapy group (levofloxacin 500 mg once daily, amoxicillin 1 g twice daily, and esomeprazole 40 mg twice daily for 14 days, EAL-14). Follow-up to assess treatment response consisted of either endoscopy or a urea breath test, which were carried out 8 weeks later.</p><p><bold>RESULTS:</bold> Eradication rates attained by 10-day levofloxacin-containing triple therapy (EAL-10) and 14-day levofloxacin-containing triple therapy (EAL-14) treatments in the per-protocol analysis were 50/67(74.6%; 95% CI=60-84.3) and 63/69 (90.0%; 95% CI=82.2-97.8). In the intention-to-treat analysis, these were 50/74 (67.6%; 95% CI=53.5-80.4) in the EAL-10 group and 63/74 (85.1%; 95% CI=73.7-92.4) in the EAL-14 groups. The observed adverse events were 14.9 % and 21.6 % among the two groups. The drug compliance of EAL-10 vs EAL-14 groups was 100% vs. 98.6%. Levofloxacin-resistant strains occurred at a frequency of 25.7%. <italic>H. pylori</italic> eradication rates for the levofloxacin-susceptible strains and levofloxacin-resistant strains were 89.3% (25/28) and 22.2% (2/9) in the per-protocol analysis. Univariate analysis showed that previous peptic ulcer history, duration of <italic>H. pylori </italic>eradication and levofloxacin resistance are the clinical factors influencing the efficacy of <italic>H. pylori </italic>eradication therapy.</p><p><bold>CONCLUSION:</bold> A 14-day levofloxacin-containing triple therapy was more efficient than 10-day therapy. A 14-day levofloxacin-containing triple therapy approach provides a > 90% per-protocol report card with the caveat that this approach is markedly less effective in the presence of fluoroquinolone resistance.</p><p><bold>Contact E-mail Address:</bold><email>luketai1019@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Antibiotics resistent, Levofloxacin-containing triple therapy, Second-line anti-Helicobacter pylori eradication</p></sec><sec><title>OP019 ERADICATION RATES FOR HELICOBACTER PYLORI INFECTION: LESSONS FROM A SYSTEMATIC REVIEW AND META-ANALYSIS OF SEQUENTIAL THERAPY</title><p><bold>L. Gatta</bold><sup>1,2,*</sup>, N. Vakil<sup>3</sup>, C. Scarpignato<sup>2</sup>, D. Vaira<sup>4</sup></p><p><italic><sup>1</sup>Gastroenterology and Digerstive Endoscopy Unit, Versilia Hospital, Lido di Camaiore, <sup>2</sup>Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy, <sup>3</sup>Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States, <sup>4</sup>Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy</italic></p><p><bold>INTRODUCTION:</bold> The increasing prevalence of antimicrobial resistant strains of <italic>H. pylori</italic> has markedly reduced the eradication rate of the current regimens. There has been world-wide interest in sequential therapy, a new regimen administering antimicrobials in a given sequence rather than all simultaneously.</p><p><bold>AIMS&METHODS:</bold> To perform a systematic review and meta-analysis of studies comparing sequential therapy to pre-existing and new therapies. We searched Medline, Embase, the Cochrane Central Register of Controlled Trials up to March 2013, and abstract books of the major European, American and Asian gastroenterological meetings for RCTs in adults, never treated before, where sequential therapy was compared to a pre-existing or new therapies. Two reviewers independently abstracted data and appraised risk of bias.</p><p><bold>RESULTS:</bold> 40 RCTs were reviewed and analysed: 4873 patients were randomized to sequential therapy and 6749 to other (established and new) treatments. The overall eradication rate of sequential therapy was 84.1% (95% CI: 81.6 to 86.4). Sequential was superior to 7-day triple therapy (Relative Risks, RR 1.20; 95% CI: 1.16 to 1.25; I<sup>2</sup>: 18.4%), marginally superior to 10-day triple therapy (RR: 1.13; 95% CI: 1.05 to 1.22; I<sup>2</sup>: 63.2%), but not superior to 14-day triple therapy (RR: 1.00; 95% CI: 0.94 to 1.06; I<sup>2</sup>: 54.3%), bismuth (RR: 1.04; 95% CI: 0.97 to 1.10; I<sup>2</sup>: 0%) and non-bismuth therapy (RR: 1.01; 95% CI: 0.94 to 1.08; I<sup>2</sup>: 41.9%).</p><p>Data on eradication according to pre-treatment anti-microbial susceptibility testing were available in seven studies, and sequential therapy eradicated the 72.8% (95%CI: 61.6 to 82.8) of strains resistant to clarithromycin.</p><p><bold>CONCLUSION:</bold> Eradication rates with pre-existing and new therapies for <italic>H. pylori</italic> are currently sub-optimal. Regional monitoring of resistance rates should help guide therapy, while new agents for treatment need to be developed.</p><p><bold>Contact E-mail Address:</bold><email>gattaluigi@yahoo.it</email></p><p><bold>Disclosure of Interest</bold>: L. Gatta: None Declared, N. Vakil Lecture fee(s) from: AstraZeneca Pharmaceuticals; Takeda Pharmaceutical, Consultancy for: AstraZeneca Pharmaceuticals; Orexo, Takeda Pharmaceutical; Ironwood Pharmaceuticals; Otsuka , Shareholder of: Meridian Diagnostics; Orexo, C. Scarpignato Lecture fee(s) from: AstraZeneca, Consultancy for: AstraZeneca; Pfizer; Janssen-Cilag; Sidem; , D. Vaira: None Declared</p><p><bold>Keywords:</bold> Dyspepsia, Helicobacter pylori eradication, Sequential therapy</p></sec><sec><title>OP020 CULTURE BASED TRIPLE THERAPY USING LEVOFLOXACIN OR RIFABUTIN IN PATIENTS WHO FAIL INITIAL THERAPY</title><p><bold>G. Fiorini</bold><sup>1,*</sup>, N. Vakil<sup>2</sup>, A. Zullo<sup>3</sup>, I. M. Saracino<sup>1</sup>, V. Castelli<sup>1</sup>, C. Ricci<sup>4</sup>, C. Zaccaro<sup>1</sup>, L. Gatta<sup>5</sup>, D. Vaira<sup>1</sup></p><p><italic><sup>1</sup>Department of Clinical Medicine, University of Bologna, Italy, Bologna, Italy, <sup>2</sup>University of Wisconsin, School of Medicine & Public Health, Madison, Wisconsin, USA., Madison, United States, <sup>3</sup>Gastroenterology Unit, “Nuovo Regina Margherita” Hospital, Rome, Italy , Rome, <sup>4</sup>Gastroenterology Unit, University of Brescia, Italy, Brescia, <sup>5</sup>Gastroenterology and Digestive Endoscopy Unit, Versilia Hospital, Lido di Camaiore, Italy;, Lido di Camaiore, Italy</italic></p><p><bold>INTRODUCTION:</bold> Eradication of h pylori is extremely difficult when resistant strains are present.</p><p><bold>AIMS&METHODS: Aim </bold>To evaluate the success rate of targeted therapy directed by antimicrobial susceptibility testing in patients infected with resistant strains of H pylori.</p><p><bold>Methods</bold></p><p><italic>Design</italic>: Single centre, prospective study. <italic>Patients</italic>: consecutive cases with H pylori infection persistent despite 1 or more treatment attempts in which bacterial culture documented resistance to at least one anti-microbial agent.</p><p><italic>Intervention:</italic> Therapy with either a 10-day levofloxacin-triple (250 mg twice daily) or a 12-day rifabutin-triple (150 mg once daily), in addition to amoxicillin (1 g twice daily) and esomeprazole (40 mg twice daily).</p><p><italic>Outcome:</italic> Eradication success was determined by <sup>13</sup>C-urea breath test 6-8 weeks after therapy. Compliance and tolerance: Compliance and side-effects were determined by using a personal interview at the end of therapy. Rifabutin toxicity was monitored by blood counts.</p><p><bold>RESULTS:</bold> A total of 290 patients were enrolled; 149 were levofloxacin susceptible and 141 had levofloxacin resistance. <italic>H pylori</italic> infection was cured in 128 (86%; 95% CI= 0.79 to 0.90; P< 0, 0001) out of the 149 patients following levofloxacin triple therapy and 129 (91.5%; 95% CI= 0.85 to 0.95; P= 0, 0565) out of the 141 patients with rifabutin triple regimen. In both groups, the cure rate did not significantly differ between patients infected with <italic>H pylori</italic> strains resistant to single or multiple antibiotics. Mild side-effects occurred in 15.5% and 14.9% of patients, respectively, and self-limiting neutropenia was observed in 1 (0.7%) case. Table 1 shows H pylori eradication according to antibiotic resistance.</p><p><bold>Table 1.</bold><italic>H. pylori</italic> eradication rates according to antibiotic resistance.
<table-wrap id="table2-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1"><bold>Antibiotic resistance</bold></th><th rowspan="1" colspan="1"><bold>Levofloxacin- amoxicillin therapy (%; 95% CI) </bold> (N = 149)</th><th rowspan="1" colspan="1"><bold>Rifabutin- amoxicillin therapy (%; 95% CI) </bold> (N = 141)</th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">Levofloxacin + Clarithromycin + Metronidazole</td><td rowspan="1" colspan="1">-</td><td rowspan="1" colspan="1">107/119 (89.9%; 95 % CI= 0.83 TO 0.94)</td></tr><tr><td rowspan="1" colspan="1">Levofloxacin + Clarithromycin</td><td rowspan="1" colspan="1">-</td><td rowspan="1" colspan="1">13/13 (100%; 95% CI = 0,77 TO 1,00)</td></tr><tr><td rowspan="1" colspan="1">Levofloxacin + Metronidazole</td><td rowspan="1" colspan="1">-</td><td rowspan="1" colspan="1">8/9 (88.9% CI=0.56 to 0.98)</td></tr><tr><td rowspan="1" colspan="1">Clarithromycin + Metronidazole</td><td rowspan="1" colspan="1">71/76 (93.4%; CI=0.85 to 0.97)</td><td rowspan="1" colspan="1">-</td></tr><tr><td rowspan="1" colspan="1">Clarithromycin</td><td rowspan="1" colspan="1">54/62 (85.7%; CI=0.74 to 0.92)</td><td rowspan="1" colspan="1">-</td></tr><tr><td rowspan="1" colspan="1">Metronidazole</td><td rowspan="1" colspan="1">10/11 (91%; 95% CI = 0.62 to 0.98)</td><td rowspan="1" colspan="1">-</td></tr></tbody></table></table-wrap></p><p><bold>CONCLUSION:</bold> A culture-based triple therapy with either levofloxacin or low-dose rifabutin is highly effective in curing infection in patient with resistant strains to <italic>H pylori.</italic></p><p><bold>Contact E-mail Address:</bold><email>berardino.vaira@unibo.it</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> culture based therapy, H Pylori</p></sec><sec><title>OP021 EFFICACY AND SAFETY OF PYLERA® AND OMEPRAZOLE GIVEN FOR 10 DAYS IN PATIENTS WHO FAILED PRIOR HELICOBACTER PYLORI TREATMENT WITH PROTON PUMP INHIBITOR, AMOXICILLIN AND CLARITHROMYCIN TRIPLE THERAPY</title><p><bold>J.-C. Delchier</bold><sup>1,*</sup>, P. Malfertheiner<sup>2</sup>, R. Thieroff-Ekerdt<sup>3</sup></p><p><italic><sup>1</sup>gastroenterology, CHU Henri Mondor, Créteil, France, <sup>2</sup>gastroenterology, . Otto-von-Guericke Universität, Magdeburg, Germany, <sup>3</sup>Aptalis Pharma US, Inc, bridgewater, United States</italic></p><p><bold>INTRODUCTION:</bold> Omeprazole, amoxicillin and clarithromycin (OAC) triple therapy remains the standard of care for <italic>Helicobacter pylori</italic> eradication despite increasing clarithromycin resistance (CLA-R) and reduced efficacy. Guidelines recommend bismuth-based quadruple therapy second-line for patients who failed to eradicate <italic>H pylori</italic> with prior treatment. We evaluated efficacy, safety and tolerability of a 10 day(d) course of PYLERA (bismuth subcitrate, metronidazole and tetracycline) plus omeprazole (O) in patients who failed to achieve <italic>H pylori</italic> eradication using OAC.</p><p><bold>AIMS&METHODS:</bold> Patients with <italic>H pylori</italic> who failed eradication using 1 OAC course, with and without additional non-bismuth eradication treatment courses, where courses were completed ≤12 months before screening, were enrolled into an open-label, single-arm study and treated with 10 d of PYLERA + O. Eradication (primary end point) was defined as 1 negative C13 urea breath test performed 28–56 d after treatment.</p><p><bold>RESULTS:</bold> Forty-nine patients received ≥1 dose of PYLERA + O (ITT); 40 (82%) completed 10 d of treatment and were included in the PP analysis. ITT patients had mean (± SD) disease duration of 6.3±3.6 months since the first eradication attempt; 14.3% of ITT and 17.5% of PP patients had history of or active peptic ulcer disease. In both populations, 84% of patients had CLA-R, 42% had metronidazole resistance (MET-R) and 38% had both CLA-R and MET-R. <italic>H pylori</italic> eradication rates exceeded 90% in both the ITT and PP populations (93.2% for ITT and 94.7% for PP population, respectively). One patient discontinued participation in the study due to an adverse event (AE). Thirty-three patients experienced 87 treatment-emergent AEs (TEAEs); the majority (57%) of which were gastrointestinal (dyspepsia, diarrhea, discolored feces) or neurologic (dysgeusia, headache, dizziness) AEs. Transient increases in liver function tests were also observed. The majority of TEAEs were mild and resolved by the end of treatment. Severe TEAEs occurred in 10.2% of patients. No deaths or serious AEs occurred.</p><p><bold>CONCLUSION:</bold> PYLERA + O was safe and highly efficacious after 10 d of treatment for <italic>H pylori</italic> eradication in patients who previously failed to demonstrate eradication after being treated with at least 1 OAC course. The eradication rate observed in this second-line study is similar to those previously observed in first-line <italic>H pylori</italic> eradication studies with PYLERA patients who were not compromised by preexisting MET-R.</p><p><bold>Contact E-mail Address:</bold><email>jean-charles.delchier@hmn.aphp.fr</email></p><p><bold>Disclosure of Interest</bold>: J.-C. Delchier Financial support for research from: Aptalis Pharma, P. Malfertheiner Financial support for research from: Aptalis Pharma, R. Thieroff-Ekerdt Other: employee of Aptalis</p><p><bold>Keywords:</bold> H pylori, PYLERA, quadruple therapy </p></sec><sec><title></title><p><bold>MONDAY, OCTOBER 14, 2013 11:00-12:30</bold></p><p><bold>Endotherapy via the submucosal space – Hall 6</bold></p></sec><sec><title>OP022 PERORAL ENDOSCOPIC MYOTOMY (POEM) COMPARED TO PNEUMATIC DILATATION FOR MANAGEMENT OF ACHALASIA – A RETROSPECTIVE COHORT STUDY</title><p><bold>P. Chiu</bold><sup>1,*</sup>, J. C. Wu<sup>2</sup>, A. Y. Teoh<sup>1</sup>, S. Chan<sup>1</sup>, E. K. Ng<sup>1</sup>, F. K. Chan<sup>2</sup>, J. J. Sung<sup>2</sup>, J. Y. Lau<sup>1</sup></p><p><italic><sup>1</sup>Department of Surgery, <sup>2</sup>Department of Medicine and Therapeutics, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong</italic></p><p><bold>INTRODUCTION:</bold> Endoscopic pneumatic dilatation is a conventional treatment for Achalasia. Peroral endoscopic myotomy emerged as a novel approach to perform myotomy through a submucosal tunnel. This study retrospectively compared the clinical outcomes of pneumatic dilatation against POEM for treatment of Achalasia.</p><p><bold>AIMS&METHODS:</bold> This is a retrospective cohort study comparing the clinical outcomes of patients with Achalasia treated by endoscopic pneumatic dilatation against POEM. From 1998 to 2007, patients who had diagnosis of achalasia received pneumatic dilatation (PD) as primary treatment. All the PDs were performed under intravenous sedation. The size of pneumatic balloon was determined according to the preference of endoscopists. After 2010, patients with Achalasia were treated by POEM under general anesthesia with CO2 insufflation. The method of POEM was described in our previous study [1].</p><p><bold>RESULTS:</bold> From 1998 to 2012, 49 patients with Achalasia were treated with endoscopic pneumatic dilatation while 25 patients received POEM. The mean age of patients was similar between the two groups. All patients presented with symptoms of dysphagia. The operative time for POEM was significantly longer than PD (95.0 vs 21.1 minutes; p < 0.001). The mean hospital stay was significantly longer for POEM (2.28 vs 1.58 days; p = 0.018). Although complication rate was similar between the two groups, 2 patients had perforation after dilatation while no patient sustained leakage from POEM. The PD group had significantly longer follow-up period than POEM. Patients after POEM had significantly lower dysphagia score compared to PD group, whom required a significantly higher re-intervention (32% vs 0%; p = 0.001). There was a significantly higher rate of GERD in the PD group when compared to POEM group.
<table-wrap id="table3-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1"></th><th rowspan="1" colspan="1"><bold>Pneumatic dilatation (49)</bold></th><th rowspan="1" colspan="1"><bold>POEM (25)</bold></th><th rowspan="1" colspan="1"><bold>P value</bold></th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">Mean age (years); gender (M:F)</td><td rowspan="1" colspan="1">50.93±19.11; 32:18</td><td rowspan="1" colspan="1">50.04±15.02; 10:15</td><td rowspan="1" colspan="1">N.S.</td></tr><tr><td rowspan="1" colspan="1">Preoperative LES pressure</td><td rowspan="1" colspan="1">37.93±27.13</td><td rowspan="1" colspan="1">55.65±26.46</td><td rowspan="1" colspan="1">0.027†</td></tr><tr><td rowspan="1" colspan="1">Operative time</td><td rowspan="1" colspan="1">21.10±5.18</td><td rowspan="1" colspan="1">95.00±42.33</td><td rowspan="1" colspan="1">< 0.001†</td></tr><tr><td rowspan="1" colspan="1">Mean Hospital day (days)</td><td rowspan="1" colspan="1">1.58±1.03</td><td rowspan="1" colspan="1">2.28±1.75</td><td rowspan="1" colspan="1">0.018†</td></tr><tr><td rowspan="1" colspan="1">Complication (%)</td><td rowspan="1" colspan="1">4 (8.0%)</td><td rowspan="1" colspan="1">2 (8.0%)</td><td rowspan="1" colspan="1">0.685</td></tr><tr><td rowspan="1" colspan="1">Bleeding</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">0</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">Pneumomediastinum</td><td rowspan="1" colspan="1">0</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">Perforation / leakage</td><td rowspan="1" colspan="1">2</td><td rowspan="1" colspan="1">0</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">Pneumonia</td><td rowspan="1" colspan="1">0</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">Persistent pain</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">0</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">Follow-up (Mean)</td><td rowspan="1" colspan="1">131.6±34.5 months</td><td rowspan="1" colspan="1">20.2±7.5 months</td><td rowspan="1" colspan="1">< 0.001†</td></tr><tr><td rowspan="1" colspan="1">Dysphagia score at 6 months (Mean)</td><td rowspan="1" colspan="1">0.6±0.73</td><td rowspan="1" colspan="1">0</td><td rowspan="1" colspan="1">< 0.001†</td></tr><tr><td rowspan="1" colspan="1">Need of re-intervention</td><td rowspan="1" colspan="1">16 (32%)</td><td rowspan="1" colspan="1">0 (0%)</td><td rowspan="1" colspan="1">0.001†</td></tr><tr><td rowspan="1" colspan="1">GERD after operation</td><td rowspan="1" colspan="1">20 (40%)</td><td rowspan="1" colspan="1">4 (16%)</td><td rowspan="1" colspan="1">0.04†</td></tr></tbody></table></table-wrap></p><p><bold>CONCLUSION:</bold> Compared to pneumatic dilatation, POEM achieved significantly better relief of dysphagia with less need of re-intervention as well as gastroesophageal reflux after treatment. This study is limited by its retrospective nature.</p><p><bold>REFERENCES:</bold></p><p>1. Chiu PW, Wu JC, Teoh AY, et al. Peroral endoscopic myotomy for treatment of achalasia: from bench to bedside. Gastrointest Endosc 2013; 77(1):29-38</p><p><bold>Contact E-mail Address:</bold><email>philipchiu@surgery.cuhk.edu.hk</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Achalasia, Peroral Endoscopic Myotomy (POEM), pneumatic dilatation</p></sec><sec><title>OP023 A CLINICAL COMPARATIVE STUDY OF PERORAL ENDOSCOPIC FULL-THICKNESS AND CIRCULAR MUSCLE MYOTOMY FOR THE TREATMENT OF ACHALASIA</title><p><bold>Q.-L. Li</bold><sup>1</sup>, P.-H. Zhou<sup>1,*</sup>, L.-Q. Yao<sup>1</sup>, W.-F. Chen<sup>1</sup>, M.-D. Xu<sup>1</sup>, Y.-Q. Zhang<sup>1</sup>, J.-W. Hu<sup>1</sup>, M.-Y. Cai<sup>1</sup>, W.-Z. Qin<sup>1</sup></p><p><italic><sup>1</sup>Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China</italic></p><p><bold>INTRODUCTION:</bold> A circular muscle myotomy preserving the longitudinal outer esophageal muscular layer is often recommended during peroral endoscopic myotomy (POEM) for achalasia. However, because the longitudinal muscle fibers of the esophagus are extremely thin and fragile, and completeness of myotomy is the basis for the excellent result of conventional surgical myotomy, this modification needs to be further debated.</p><p><bold>AIMS&METHODS:</bold> Here, we retrospectively analyzed our prospectively maintained POEM database to compare the outcomes of endoscopic full-thickness and circular muscle myotomy. According to the myotomy depth, 103 patients with full-thickness myotomy were assigned to group A, while 131 patients with circular muscle myotomy were assigned to group B. Symptom relief, procedure-related parameters and adverse events, manometry outcomes, and reflux complications were compared between groups.</p><p><bold>RESULTS:</bold> The mean operation times were significantly shorter in group A compared with group B (<italic>P</italic> = 0.02). There was no increase in any procedure-related adverse event after full-thickness myotomy (all <italic>P</italic> < 0.05). During follow-up, treatment success (Eckardt score ≤ 3) persisted for 96.0% (95/99) of cases in group A and for 95.0% (115/121) of cases in group B (<italic>P</italic> = 0.75). There were no statistical significant differences of pre/post-treatment D-value of symptom scores and LES pressures between groups (both <italic>P</italic> > 0.05). The overall clinical reflux complication rates were also similar (21.2% <italic>vs.</italic> 16.5%, <italic>P</italic> = 0.38).</p><p><bold>CONCLUSION:</bold> Short-term symptom relief and manometry outcomes of each method were comparable. Full-thickness myotomy significantly reduced the procedure time but did not increase the procedure-related adverse events or clinical reflux complications.</p><p><bold>Contact E-mail Address:</bold><email>zhou.pinghong@zs-hospital.sh.cn</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Achalasia, Full-thickness myotomy, Peroral endoscopic myotomy</p></sec><sec><title>OP024 SUBMUCOSAL TUNNELING ENDOSCOPIC RESECTION FOR UPPER GASTROINTESTINAL SUBEPITHELIAL TUMORS ORIGINATING FROM THE MUSCULARIS PROPRIA LAYER</title><p><bold>Y. Liping</bold><sup>1,*</sup>, Z. Yu<sup>1</sup>, M. Xin-Li<sup>1</sup>, Z. Lin-hong<sup>1</sup>, Z. Xian-Bin<sup>1</sup>, H. Sai-Qin<sup>1</sup>, C. Ji-Ya<sup>1</sup></p><p><italic><sup>1</sup>Department of Gastroenterology, Taizhou Hospital of Zhejiang Province, Wenzhou Medical College,, Linhai, China</italic></p><p><bold>INTRODUCTION:</bold> Submucosal tunneling endoscopic resection (STER) has emerged as a new technique for resecting upper gastrointestinal SETs. This new endoscopic technique has advantages over ESD in terms of maintaining the normal anatomic structure of digestive tract, reducing the risk of pleural/abdominal infection and promoting wound rapid healing,</p><p><bold>AIMS&METHODS:</bold> STER was performed as follows: (1) Lesions were first located by injection of methylene blue or indigo carmine. A fluid cushion was made after injection of several milliliters of submucosal injection solution 5cm proximal to the SET, and a 2cm longitudinal mucosal incision was made with a hook knife at the gastric or esophageal mucosa as the entry point. (2) A submucosal tunnel to the lesion was created with a hook knife or hybrid knife between the submucosal and muscular layers. Endoscopic resection of the SET was then performed by ESD technique with an insulated-tip knife, hook knife, or hybrid knife. (3) Complete resection of the lesion without interruption of the lesion capsule is important for these patients. In this study, several ml of submucosal injection solution was injected <italic>into the tissue </italic>surrounding the lesion before making a circular excavation around the lesion, which would help differentiate the MP layer from the tumor mass, facilitate excavation of the tumor from the MP layer and avoid the tumor capsule <italic>rupture during the endoscopic resection.</italic> If gastric SETs connect to the underlying MP or serosal layer tightly, the lesion, including its underlying muscularis propria and serosa, was resected with a hook knife, insulated-tip knife or snare. In this situation, a dual-channel gastroscope was used with forceps grasping the tumor into gastric cavity to prevent the tumor falling into the peritoneal. (4) After the lesion was completely resected from esophagus or stomach, it was removed with a snare or forceps. All visible blood vessels of the resection edge were coagulated with hot biopsy forceps or argon plasma coagulation to prevent delayed bleeding. Subsequently, the mucosal incision site was closed with several clips. A 20-gauge needle was used to relieve the pneumoperitoneum during and after the procedure.</p><p><bold>RESULTS:</bold> Successful complete resection by STER was achieved in all 71 cases (success rate: 100%). And all seventy-one tumors were evaluated by histopathology out of which 53 were leiomyoma, 17 were GIST and one was calcifying fibrous tumor.</p><p><bold>CONCLUSION:</bold> In conclusion, STER is a safe, effective and <italic>feasible</italic> procedure for treatment of upper gastrointestinal SETs originating from the MP layer.</p><p><bold>Contact E-mail Address:</bold><email>sunpei@erbechina.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> ESD, Muscularis Propria Layer, STER, Upper Gastrointestinal</p></sec><sec><title>OP025 EARLY DIAGNOSIS AND MANAGEMENT OF ESOPHAGEAL LEAKAGE AFTER PERORAL ENDOSCOPIC MYOTOMY FOR ACHALASIA</title><p><bold>Y.-Q. Zhang</bold><sup>1</sup>, P.-H. Zhou<sup>1,*</sup>, L.-Q. Yao<sup>1</sup>, M.-D. Xu<sup>1</sup>, Q.-L. Li<sup>1</sup>, W.-F. Chen<sup>1</sup>, J.-W. Hu<sup>1</sup>, M.-Y. Cai<sup>1</sup>, W.-Z. Qin<sup>1</sup></p><p><italic><sup>1</sup>Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China</italic></p><p><bold>INTRODUCTION:</bold> Peroral endoscopic myotomy (POEM) has been described as a less invasive surgical myotomy option for treating achalasia. However, like any other surgical procedure, there is the possibility of complications occurring after POEM. Despite its low incidence, esophageal leakage can result in serious conditions, such as pleural infection, pneumonia and segmental atelectasis of the lungs. Delay in diagnosis and treatment can result in a significant increase in morbidity and mortality.</p><p><bold>AIMS&METHODS:</bold> A total of 679 consecutive achalasia patients underwent successful POEM at the Endoscopy Center of Zhongshan Hospital, Fudan University, between August 2010 and April 2013. Patients with postoperative esophageal leakage in the submucosal tunnel were identified from the database, and their medical records were thoroughly investigated.</p><p><bold>RESULTS:</bold> Three patients (0.4%, 3/679) suffered from esophageal leakage after POEM. When leakage is suspected, gastroscopy should be performed as early as possible, because small leakage is difficult to diagnose by esophagography. Esophageal leakage was confirmed by gastroscopy and two cases were sutured by metal clips immediately. Those cases were treated with thoracic drainage. The enteric feeding tube was placed under direct vision, which might contribute to the general nutritional correction from the postsurgical status, and this might contribute to the closure of leakage. Successful closure of leakage was achieved in all cases without the need for surgical interventions.</p><p><bold>CONCLUSION:</bold> Esophageal leakage was a rare and severe complication after POEM. Early diagnosis and treatment can improve the status of patients and shorten the time of recovery. It should be worth mentioning that suture by metal clips is particularly effective for esophageal leakage after POEM.</p><p><bold>Contact E-mail Address:</bold><email>zhou.pinghong@zs-hospital.sh.cn</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> achalasia, esophageal leakage, Peroral endoscopic myotomy</p></sec><sec><title>OP026 TUNNEL METHOD FOR ESOPHAGEAL ESD: COMPARATIVE STUDY WITH THE STANDARD ESD TECHNIQUE.</title><p><bold>V. Lepilliez</bold><sup>1</sup>, M. Pioche<sup>1,2,*</sup>, L. Mais<sup>1</sup>, O. Guillaud<sup>1</sup>, V. Hervieu<sup>3</sup>, J.-C. Saurin<sup>1</sup>, T. Ponchon<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology, Hôpital Edouard Herriot, <sup>2</sup>U1032, INSERM, <sup>3</sup>Pathology, Hôpital Edouard Herriot, Lyon, France</italic></p><p><bold>INTRODUCTION:</bold> Endoscopic Sub-mucosal Dissection (ESD) allows “en bloc” R0 resection for esophageal neoplasms larger than 15 mm but it is a high risk and time consuming method. Tunnel technique consists first to perform an incision at the lower and upper edges of the lesion then to create a tunnel in the sub-mucosal space to join both incisions to finish by lateral incisions. Main advantage of the tunnel is to easily separate mucosa from muscular layer by avoiding rapid disappearance of liquid lifting and by stretching mucosa. We report our experience of esophageal ESD comparing tunnel method versus a standard approach (circumferential incision first).</p><p><bold>AIMS&METHODS:</bold> We reviewed all the consecutive esophageal ESD performed in the unit between January 1, 2010 and January 11, 2013. These patients presented with a superficial esophageal neoplasms, UT1N0 at EUS. The two techniques were compared.</p><p><bold>RESULTS:</bold> Standard ESD was performed in 24 patients and tunnel technique in 11 patients. In the standard group, mean dissected surface was 5.30cm<sup>2</sup> versus 13.25 cm<sup>2</sup> in the group tunnel. Mean speed of dissection was faster for the tunnel group with 16.9 mm<sup>2</sup>/min versus 5.5 mm2/min in the standard group (p < 0.001). Esophageal ESD was en bloc in 100% of cases in the tunnel group versus 91.7 % (2 piece meal resections) in the standard approach. R0 resection was obtained in 81.8 % of the tunnel group versus 62.5% with the standard technique. Complications resolved conservatively: 2 bleedings in the standard group, and one sub cutaneous emphysema in the tunnel group.</p><p><bold>CONCLUSION:</bold> Tunnel method is an interesting option for ESD of superficial esophageal neoplasms. It is faster and more effective than usual technique without higher morbidity.</p><p><bold>Contact E-mail Address:</bold><email>mathieu.pioche@chu-lyon.fr</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> endoscopic submucosal dissection, esophageal cancer, new technique</p></sec><sec><title>OP027 TUBULAR ENDOSCOPIC SUBMUCOSAL DISSECTION (T-ESD) FOR ‘EN BLOC RESECTION’ OF SUPERFICIAL NEOPLASTIC LESIONS OF THE OESOPHAGUS – EXPERIENCE IN 28 PATIENTS</title><p><bold>J. Hochberger</bold><sup>1,*</sup>, E. Kruse<sup>2</sup>, M. Delvaux<sup>1</sup>, J. Huppertz<sup>1</sup>, E. Wedi<sup>1</sup></p><p><italic><sup>1</sup>Hepatogastroenterology, NHC, UNIVERSITY HOSPITAL OF Strasbourg, Strasbourg, France, <sup>2</sup>Hepatogastroenterology, St Bernward Hospital, Hildesheim, Germany</italic></p><p><bold>INTRODUCTION:</bold> ESD, an advanced endoscopic ‘free hand’ resection technique, has initially been developed for the treatment of gastric neoplastic lesions. Experience in the esophagus remains limited so far. We report the initial experience of long tubular ESD for treatment of superficial oesophageal neoplasms.</p><p><bold>AIMS&METHODS:</bold> From November. 2009 to July 2012 all patients referred for treatment of an early oesophageal cancer –squamous cell carcinoma or adenocarcinoma on Barrett– were included in a prospective cohort. Data were obtained for demographics of the patient, technical conditions of the procedure, follow-up and outcome.</p><p><bold>RESULTS:</bold> Twenty-nine ESDs were performed in 28 patients (7 women, 21 men, median age 64 years, range 42-82 years). 18 lesions were Barrett early adenocarcinomas and 11, squamous cell carcinomas. ESD was performed in all patients, starting from the upper limit of the mucosal segment to be resected. In 12 cases, the ESD was not circumferential, allowing the resection of an area of mucosa measured on the formalin-fixed specimen pinned on cork and ranging from 4.1x 2.5 to 16x10 cm. In 17 cases, a circular, tubular (T-ESD) was performed the length of the mucosal segment ranging from 8 to 22 cm. Pathological examination of the resected specimen showed lateral R0 resection in all cases and basal R0 resection in 26 cases (86%). Three patients underwent surgery after ESD (2 pT1b-sm2 with basal R1 and 1 sm2 L1). Surgical specimen showed no tumoral tissue and only one positive lymph node. Median follow-up is 187 days (25-989) without tumour recurrences. Oesophageal stricture developed in 10/13 (77%) patients with circular ESD resection and was managed by bougienage/balloon dilatation. In 4 cases with rapid stricture development a temporary self-expanding covered metal stent was inserted. From August 2011, 16 patients were administred high dose steroid therapy (150-2,5 mg/d//≥8 weeks) and 13out of them (81%) did not develop oesophageal stricture (follow-up 25-324 days).</p><p><bold>CONCLUSION:</bold> Widespread-esophageal ESD and tubular ESD are technically feasible, but experience in western European centers remains limited so far. Mid-term follow-up of the patients shows encouraging results. Secondary strictures can be managed conservatively or with high dose steroid therapy, but are currently the major subject of intense basic research and animal studies.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Barrett’s esophageal cancer, Endoscopic submucocsal resection, Oesophageal carcinoma</p></sec><sec><title></title><p><bold>MONDAY, OCTOBER 14, 2013 11:00-12:30</bold></p><p><bold>Improving colonoscopic practice – Hall 9</bold></p></sec><sec><title>OP028 DO EUROPEAN PANEL ON APPROPRIATENESS OF GASTROINTESTINAL ENDOSCOPY(EPAGE) II GUIDELINES HELP TO SELECT AND PRIORITIZE PATIENTS REFERRED TO COLONOSCOPY?</title><p><bold>S. L. Eskeland</bold><sup>1,*</sup>, E. Dalén<sup>1</sup>, J. Sponheim<sup>2</sup>, E. Lind<sup>2</sup>, C. Brunborg<sup>3</sup>, T. de Lange<sup>2</sup></p><p><italic><sup>1</sup>Department of Medical Research, <sup>2</sup>Department of Medicine, Bærum Hospital, Vestre Viken Hospital Trust, Bærum, <sup>3</sup>3Unit for Biostatistics, Epidemiology and Health Economics, Oslo University Hospital, Oslo, Norway</italic></p><p><bold>INTRODUCTION:</bold> The capacity for colonoscopy is limited; therefore it’s important to prioritize the examinations with the highest diagnostic yield.</p><p><bold>AIMS&METHODS:</bold> We wanted to assess whether appropriate indications according to EPAGE II guidelines affected the diagnostic yield of the examinations in an open-access endoscopy unit. We also wanted to evaluate if other patient- or doctor related factors affected the diagnostic yield. All referrals for colonoscopy during the inclusion period were prospectively assessed, using the EPAGE II guidelines to determine the appropriateness of the colonoscopy and the corresponding diagnostic yield of the examination. The symptoms listed in the referral letters were recorded, as well as the workplace of the referring doctor. The final diagnosis was recorded just after the endoscopy. Patients with an incomplete endoscopic or radiological examination of the colon were excluded from the study.</p><p><bold>RESULTS:</bold> From 26th of January to 6th of October 2004, 306 referrals were included in the study. EPAGE II criteria were applicable in 299 (97.7%) of the referrals. Of these, 246 (82.2%) were considered appropriate, 21 (7.0%) inappropriate and 32 (10.7%) uncertain. The overall diagnostic yield in the cohort was 29.8%. The diagnostic yield increased to 34.1% for the appropriate referrals, and decreased to 9.4% and 9.5% for the uncertain and inappropriate referrals, respectively. The Odds Ratio for finding a significant pathology in the colon with an appropriate indication compared to an inappropriate referral was 4.98(95% CI 1.87- 13.24, p=0.001<sup>1</sup>). The factors influencing the likelihood of having a significant pathological finding are listed in table 1.</p><p>Table 1: Logistic regression of likelihood of having a significant pathology in the colon
<table-wrap id="table4-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th colspan="5" rowspan="1"><hr></hr></th><th colspan="4" rowspan="1"><hr></hr></th></tr><tr><th rowspan="1" colspan="1"></th><th rowspan="1" colspan="1"><bold>Regr. coeff.</bold></th><th rowspan="1" colspan="1"><bold>OR</bold></th><th rowspan="1" colspan="1"><bold>CI (95%)</bold></th><th rowspan="1" colspan="1"><bold>p-value</bold></th><th rowspan="1" colspan="1"><bold>Regr. coeff.</bold></th><th rowspan="1" colspan="1"><bold>OR</bold></th><th rowspan="1" colspan="1"><bold>CI (95%)</bold></th><th rowspan="1" colspan="1"><bold>p-value</bold></th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1"><bold>Age(continuous)</bold></td><td rowspan="1" colspan="1">0.01</td><td rowspan="1" colspan="1">1.01</td><td rowspan="1" colspan="1">1.00-1.03</td><td rowspan="1" colspan="1">0.21<sup>2</sup></td><td rowspan="1" colspan="1">0.003</td><td rowspan="1" colspan="1">1.003</td><td rowspan="1" colspan="1">0.99-1.02</td><td rowspan="1" colspan="1">0.70<sup>2</sup></td></tr><tr><td rowspan="1" colspan="1"><bold>Male sex</bold></td><td rowspan="1" colspan="1">0.62</td><td rowspan="1" colspan="1">1.86</td><td rowspan="1" colspan="1">1.13-3.08</td><td rowspan="1" colspan="1">0.015<sup>2</sup></td><td rowspan="1" colspan="1">0.64</td><td rowspan="1" colspan="1">1.90</td><td rowspan="1" colspan="1">1.14-3.17</td><td rowspan="1" colspan="1">0.014<sup>2</sup></td></tr><tr><td rowspan="1" colspan="1"><bold>EPAGE II appropriateness</bold></td><td rowspan="1" colspan="1">-1.61</td><td rowspan="1" colspan="1">0.20</td><td rowspan="1" colspan="1">0.08-0.52</td><td rowspan="1" colspan="1">0.001<sup>2</sup></td><td rowspan="1" colspan="1">-1.58</td><td rowspan="1" colspan="1">0.21</td><td rowspan="1" colspan="1">0.08-0.55</td><td rowspan="1" colspan="1">0.002<sup>2</sup></td></tr></tbody></table></table-wrap></p><p><sup>1</sup>Chi – square test, <sup>2</sup>Logistic regression</p><p><bold>CONCLUSION:</bold> There was a clear association between a high appropriateness of the indication for colonoscopy according the EPAGE II guidelines and a high diagnostic yield. These guidelines can be useful for both the referring physician and the consultant gastroenterologist when deciding whether or not the patient will benefit from a colonoscopy.</p><p><bold>Contact E-mail Address:</bold><email>seskeland@hotmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> appropriateness, diagnostic yield, EPAGE II, guidelines</p></sec><sec><title>OP029 A MULTI-CENTRE PRAGMATIC STUDY OF AN EDUCATIONAL INTERVENTION TO IMPROVE ADENOMA DETECTION AT COLONOSCOPY</title><p><bold>P. T. Rajasekhar</bold><sup>1,*</sup>, C. J. Rees<sup>2</sup>, M. D. Rutter<sup>1</sup>, B. P. Saunders<sup>3</sup>, M. G. Bramble<sup>4</sup>, P. Hungin<sup>4</sup>, D. W. Wilson<sup>4</sup>, J. E. East<sup>5</sup> and The Quality Improvement in Colonoscopy Study Group</p><p><italic><sup>1</sup>Gastroenterology, <sup>2</sup>Northern Region Endoscopy Group, South Shields, <sup>3</sup>Gastroenterology, St Marks Hospital, London, <sup>4</sup>School of Medicine and Health Sciences, Durham University, Stockton-on-Tees, <sup>5</sup>Gastroenterology, John Radcliffe Hospital, Oxford, United Kingdom</italic></p><p><bold>INTRODUCTION:</bold> High quality colonoscopy prevents colorectal cancers. Low adenoma detection rates (ADR) are linked to subsequent high interval cancer rates. Variability in ADR exists between practitioners. Withdrawal time of > 6 minutes; Buscopan use; position changes; and rectal retroflexion have some evidence to improve lesion detection. Implementation of evidence based 'bundles' of care has shown to be effective in improving outcomes in other healthcare settings<sup>1</sup>.</p><p><bold>AIMS&METHODS:</bold> We aimed to evaluate both the feasibility of implementing a ‘bundle’ comprising the above measures into routine practice and the effect on ADR. Twelve English endoscopy units participated. All nominated a lead endoscopist and nurse. A model combining central training, locally led implementation, feedback and ongoing study team support was used. Colonoscopists’ ADRs were measured for 3 months prior to and for a 9 month period following implementation. Colonoscopists performing ≥ 25 procedures during the period before were ranked according to ADR and quartiles were constructed. Change in Buscopan use was used as a surrogate marker for intervention uptake. A corrected Chi Squared test was used to check for significant change.</p><p><bold>RESULTS:</bold> One hundred and eighteen colonoscopists were included in the global analyses and 68 in analyses of quartiles. The study included 17411 colonoscopies, 4351 and 13060 in the pre and post intervention periods respectively. There was a significant global increase in Buscopan use (15.8% vs. 54.8%, p<0.001), also seen in each quartile, and ADR (16.0% vs. 17.7%, p=0.009), Table 1.</p><p><bold>Table 1.</bold> Summary of change in ADR per quartile.
<table-wrap id="table5-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1"></th><th colspan="2" rowspan="1"><bold>Before</bold></th><th colspan="2" rowspan="1"><bold>After</bold></th><th colspan="2" rowspan="1"></th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1"><bold>Quartile</bold></td><td rowspan="1" colspan="1">N</td><td rowspan="1" colspan="1">ADR (%)</td><td rowspan="1" colspan="1">N</td><td rowspan="1" colspan="1">ADR (%)</td><td rowspan="1" colspan="1">Difference ratio</td><td rowspan="1" colspan="1">p value ADR</td></tr><tr><td rowspan="1" colspan="1"><bold>Upper</bold></td><td rowspan="1" colspan="1">785</td><td rowspan="1" colspan="1">27.4</td><td rowspan="1" colspan="1">2486</td><td rowspan="1" colspan="1">20.7</td><td rowspan="1" colspan="1">0.76</td><td rowspan="1" colspan="1"><0.001</td></tr><tr><td rowspan="1" colspan="1"><bold>Upper Middle</bold></td><td rowspan="1" colspan="1">1116</td><td rowspan="1" colspan="1">17.5</td><td rowspan="1" colspan="1">3097</td><td rowspan="1" colspan="1">19.1</td><td rowspan="1" colspan="1">1.09</td><td rowspan="1" colspan="1">0.24</td></tr><tr><td rowspan="1" colspan="1"><bold>Lower Middle</bold></td><td rowspan="1" colspan="1">785</td><td rowspan="1" colspan="1">13.3</td><td rowspan="1" colspan="1">2484</td><td rowspan="1" colspan="1">18.7</td><td rowspan="1" colspan="1">1.41</td><td rowspan="1" colspan="1"><0.001</td></tr><tr><td rowspan="1" colspan="1"><bold>Lower</bold></td><td rowspan="1" colspan="1">936</td><td rowspan="1" colspan="1">7.3</td><td rowspan="1" colspan="1">2405</td><td rowspan="1" colspan="1">13.9</td><td rowspan="1" colspan="1">1.91</td><td rowspan="1" colspan="1"><0.001</td></tr></tbody></table></table-wrap></p><p>N = number of colonoscopies</p><p><bold>CONCLUSION:</bold> Our evidence based educational intervention resulted in a significant change in behaviour, evidenced by increased Buscopan use. A significant increase in the global ADR occurred, and ADR also improved significantly in the two lower quartiles. A fall was seen in the upper quartile, but the ADR in this group remained above that in the other groups and the global mean of 17.7%. This study demonstrates that simple evidence based educational interventions with support can significantly change practice and ADR, particularly amongst the poorest performers.</p><p><bold>REFERENCES:</bold></p><p>1. Pronovost P et al. An intervention to decrease catheter-related bloodstream infections in the ICU. N Engl J Med 2006;355:2725-32</p><p><bold>Contact E-mail Address:</bold><email>praveen.rajasekhar@nhs.net</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> adenoma detection rate, implementation, Quality of colonoscopy</p></sec><sec><title>OP030 THE IMPACT OF HYOSCINE-N-BUTYLBROMIDE ON ADENOMA DETECTION DURING COLONOSCOPY: A METANALYSIS OF RCTS.</title><p><bold>E. Rondonotti</bold><sup>1,*</sup>, O. Zolk<sup>2</sup>, A. Amato<sup>1</sup>, S. Paggi<sup>1</sup>, A. Baccarin<sup>1</sup>, G. Spinzi<sup>1</sup>, F. Radaelli<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology Unit, Ospedale Valduce, Como, Italy, <sup>2</sup>Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nuremberg , Erlangen, Germany</italic></p><p><bold>INTRODUCTION:</bold> Hyoscine-N-butyl Bromide (HBB) can induce flattening of colonic folds through inhibition of smooth muscles activity, thus improving mucosal visualisation. Whether this effect influences polyp detection is controversial.</p><p><bold>AIMS&METHODS:</bold> Aim: we conducted a meta-analysis to evaluate whether HBB, administered during colonoscopy, improves polyp and adenoma detection.</p><p>Material and Methods:Publications in English (MEDLINE and EMBASE) were searched for RCTs in which, during colonoscopy, patients were randomized to receive HBB or placebo. Outcome measures included: the number of patients with at least one polyp (PDR), the number of patients with at least one adenoma (ADR), the number of patients with at least one advanced adenoma (adv-ADR), the mean number of polyps (PPP) and adenomas (APP) per-patient. Data about safety and tolerability were also extracted.</p><p><bold>RESULTS:</bold> From 510 papers initially retrieved, 5 RCT consisting of 1998 patients (patients receiving HBB: 1006), were included. In all these studies 20 mg of HBB was administered i.v. at time of caecal intubation. Analysis of the pooled data showed that PDR, ADR and adv-ADR do not significantly differ among the two study groups; the odds ratio (OR) with 95% confidence interval (CI) were: OR 1.09; 95% CI: 0.91 – 1.31; OR 1.13, 95% CI: 0.92 – 1.38 and OR: 0.9; 95 % CI: 0.63 – 1.30 respectively). Similar results were also observed as far as PPP and APP are concerned: mean difference: 0.05, 95 % CI: -0.03-0.14 and mean difference: 0.05, 95 % CI: -0.02 – 0.13 respectively. Administration of HBB did not result in a significant increase of drug-related side effects.</p><p><bold>CONCLUSION:</bold> The administration of HBB at time of caecal intubation, although well tolerated, did not improve either polyp or adenoma detection.</p><p><bold>Contact E-mail Address:</bold><email>ema.rondo@libero.it</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> adenoma detection rate, colonoscopy performance, hyoscine N Butylbromide, polyp detection rate</p></sec><sec><title>OP031 CAN REAL-TIME OPTICAL DIAGNOSIS OF ALL COLORECTAL POLYPS IMPROVE THE EFFICIENCY OF COLONOSCOPY PRACTICE? RESULTS FROM THE VETERANS AFFAIRS COLORECTAL LESION IDENTIFICATION AND DIAGNOSIS (VALID -FOR ALL) TRIAL</title><p><bold>T. Kaltenbach</bold><sup>1,*</sup>, A. Rastogi<sup>2</sup>, R. V. Rouse<sup>1</sup>, K. McQuaid<sup>3</sup>, T. Sato<sup>1</sup>, A. Bansal<sup>2</sup>, J. Kosek<sup>1</sup>, R. Soetikno<sup>1</sup></p><p><italic><sup>1</sup>Veterans Affairs Palo Alto, Stanford University, Palo Alto, <sup>2</sup>Veterans Affairs Kansas City, University of Kansas, Kansas City, <sup>3</sup>Veterans Affairs, San Francisco, University of San Francisco, San Francisco, United States</italic></p><p><bold>INTRODUCTION:</bold> Real-time Optical Diagnosis (OD) of all colorectal polyps has the potential to improve the practice of colonoscopy: patients can be informed of the results and surveillance timing at discharge. The criteria for OD of colorectal polyps using the Narrow Band Imaging have been validated <sup>1, 2</sup>. The society guidelines for OD have been established. We hypothesized that the use of close view colonoscope technology can improve the efficiency of practice.</p><p><bold>AIMS&METHODS:</bold> 5 endoscopists made an OD (neoplastic vs non-neoplastic) of the polyp histology using two randomly assigned colonoscopes (close view, CFHQ190 vs standard view, CFH180). They rated the confidence level (high vs low) of each diagnosis using the NBI International Colorectal Endoscopic (NICE) classification. Central, blinded pathology was the reference standard. We compared the feasibility and the diagnostic performance of close and standard view OD; and the agreement with pathology based surveillance intervals.</p><p><bold>RESULTS:</bold> We detected 1309 polyps in 558 subjects in well-balanced study arms; with 76.9% polyp and 60.0% adenoma prevalence. The polyps were predominantly ≤5mm (74.5%); median 4mm, range 1-60mm. The majority was neoplastic (61.9%). Endoscopists were over twice as likely to make an OD with high confidence, using the close (85.9%) as compared to standard view (74.3%), (OR 2.3; 95%CI,1.6-3.2; p=0.003). The high confidence OD had high npv and sensitivity (Table). The median diagnosis time per polyp was 15 seconds using close, and 12 using standard views (p=NS). Correct surveillance recommendations were made in 518 patients, 92.8% of the cohort, as compared with pathology based recommendations.</p><p><bold>Table 1. Diagnostic Operating Characteristics of Optical Diagnosis<sup>a</sup></bold><table-wrap id="table6-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1"><bold>All Polyps, n=1309</bold></th><th rowspan="1" colspan="1"><bold>Close View Optical Diagnosis n=710</bold></th><th rowspan="1" colspan="1"><bold>Standard View Optical Diagnosis n=599</bold></th><th rowspan="1" colspan="1"><bold>P-value Odds Ratio (95% CI)<sup>b,c,d</sup></bold></th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1"><bold>High Confidence Endoscopic Diagnosis</bold></td><td rowspan="1" colspan="1">610 (85.9%)</td><td rowspan="1" colspan="1">445 (74.3%)</td><td rowspan="1" colspan="1">0.003 2.26 (1.61-3.18)</td></tr><tr><td rowspan="1" colspan="1"> Accuracy</td><td rowspan="1" colspan="1">90.2% (87.5-92.4)</td><td rowspan="1" colspan="1">89.2% (86.0-91.9)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"> Sensitivity</td><td rowspan="1" colspan="1">98.8% (97.1-99.6)</td><td rowspan="1" colspan="1">96.5% (93.6-98.3)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"> Negative Predictive Value</td><td rowspan="1" colspan="1">96.8% (92.6-98.9)</td><td rowspan="1" colspan="1">92.5% (86.6-96.3)</td><td rowspan="1" colspan="1"></td></tr></tbody></table></table-wrap></p><p><bold>CONCLUSION:</bold> We observed that real-time OD of all colorectal polyps can be applied in patient care. Endoscopists were twice as likely to make an OD of colorectal polyps with high confidence using colonoscopy with close view, as compared to the conventional standard view. The diagnoses were highly accurate and led to similar surveillance intervals as compared to those made based on pathology.</p><p><bold>REFERENCES:</bold></p><p>1. NCT01288833</p><p><bold>Contact E-mail Address:</bold><email>endoresection@me.com</email></p><p><bold>Disclosure of Interest</bold>: T. Kaltenbach Financial support for research from: Olympus America, Inc, Consultancy for: Olympus America, Inc, A. Rastogi Financial support for research from: Olympus America, Inc, R. Rouse: None Declared, K. McQuaid: None Declared, T. Sato: None Declared, A. Bansal: None Declared, J. Kosek: None Declared, R. Soetikno Financial support for research from: Olympus America, Inc, Consultancy for: Olympus America, Inc</p><p><bold>Keywords:</bold> characteristics and distribution of polyps, colon cancer, narrow band imaging, optical diagnosis, Polyp, randomised controlled trial</p></sec><sec><title>OP032 IMPACT OF UPGRADE FROM WHITE LIGHT TO HIGH DEFINITION ENDOSCOPY. IS IT WORTH THE INVESTMENT?</title><p><bold>E. Waldmann</bold><sup>1,2,*</sup>, M. Britto-Arias<sup>1,2</sup>, I. Gessl<sup>1,2</sup>, G. Heinze<sup>3</sup>, P. Salzl<sup>1,2</sup>, M. Trauner<sup>1</sup>, W. Weiss<sup>2</sup>, A. Ferlitsch<sup>1</sup>, M. Ferlitsch<sup>1,2</sup></p><p><italic><sup>1</sup>Department of Internal Medicine III, Div of Gastroenterology and Hepatology, Medical University of Vienna, <sup>2</sup>Quality Assurance Working Group, Austrian Society of Gastroenterology and Hepatology (OEGGH), <sup>3</sup>Div of Clinical Biometrics, Medical University of Vienna, Vienna, Austria</italic></p><p><bold>INTRODUCTION:</bold> The impact of high resolution (high density, HD) imaging in colonoscopy is discussed controversially.</p><p><bold>AIMS&METHODS:</bold> The aim of this study was to investigate whether the switch to HD function in coloscopes increases the detection rate of premalignant lesions.</p><p>Screening colonoscopy data performed between November 2007 and March 2013 within a nationwide quality assurance program in Austria were included. We compared adenoma detection rate, advanced adenoma detection rate, polyp detection rate, flat polyp detection rate and proximal polyp detection rate of endoscopists who switched from the use of regular white light (low density, LD) to HD endoscopes during our observation period. The observation period was restricted for each investigator to the time range starting one year before the investigator’s upgrade to HD until one year after the upgrade to avoid a bias of participation in a quality improvement program.</p><p><bold>RESULTS:</bold> 6.330 colonoscopies performed by 42 endoscopists were included in the study. The median number of colonoscopies performed per endoscopist was 105 (IQR 54-162), 50 (IQR 28-99, n=3.362) using HD and 54 (IQR 22-102, n=2.968) LD. The HD group included 48.5% women, the LD group 47.5%; mean age was 59.9 (53.3-67.6) vs 60 (54-67.4) years; sedation rate was 88.2% vs 84.2%; cecal intubation rate was 97.7% vs 97%. We found a slightly increased detection rate for adenomas (23.7% vs 20.2%; p=0.0886), advanced adenomas (5.5% vs 4.7%; p=0.479), polyps (41.5% vs 38.8%; p=0.305) and proximal polyps (20.0% vs 18.5%; p=0.469) of endoscopists using HD coloscopes compared to those using LD coloscopes; neither achieved statistical significance. Notably, there was no difference in flat polyp detection rate (5.5% vs 5.5%; p=0.987). Detection rate of adenomas and polyps divided according to size did not reveal significant difference <0.5 cm (ADR 9.9% vs 10.3%; p=0.785, PDR 22.6% vs 23.5%; p=0.673), 0.5-1 cm (ADR 6.8% vs 7.4%; p=0.601, PDR 9.5% vs 10.1%; p=0.673), 1-2 cm (ADR 1.9% vs 2.4%; p=0.503, PDR 2.4% vs 2.6%; p=0.752), >2cm (ADR 0.4% vs 0.7%; p=0.238, PDR 0.6% vs 0.8%; p=0.366).</p><p><bold>CONCLUSION:</bold> The use of HD endoscopes does not increase the quality of colonoscopies in terms of detection rate of premalignant lesions- independent of size of the lesion.</p><p><bold>Contact E-mail Address:</bold><email>elisabeth.waldmann@meduniwien.ac.at</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> adenoma detection rate, high density endoscopy, polyp detection rate, Screening colonoscopy</p></sec><sec><title>OP033 NBI, FICE, ISCAN, AFI OR CONFOCAL ENDOMICROSCOPY FOR DISCARD OPTICAL BIOPSY STRATEGY: A META ANALYSIS OF 97 STUDIES</title><p><bold>L. K. Wanders</bold><sup>1,*</sup>, J. East<sup>2</sup>, S. Uitentuis<sup>1</sup>, M. M. Leeflang<sup>3</sup>, E. Dekker<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology, Academical Medical Center Amsterdam, Amsterdam, Netherlands, <sup>2</sup>Gastroenterology, Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, United Kingdom, <sup>3</sup>Clinical Epidemiology, Academical Medical Center Amsterdam, Amsterdam, Netherlands</italic></p><p><bold>INTRODUCTION:</bold> In the last two decades several new imaging techniques, such as NBI, iSCAN, FICE, AFI and CLE, have been developed in order to improve endoscopic differentiation between neoplastic and non-neoplastic colonic lesions. In 2011 the PIVI (Preservation and Incorporation of Valuable Endoscopic Innovations) was introduced to set a required threshold of a NPV >90% for a technique or device to become appropriate for incorporation into clinical practice. Diagnostic performance has been extensively studied for these techniques; however, an overall overview of the accuracy and precision has never been shown in a meta-analysis.</p><p><bold>AIMS&METHODS:</bold> The aim of this meta-analysis is to determine the sensitivity, specificity and NPV of the differentiation of NBI, iSCAN, FICE, AFI and CLE with histopathology as reference standard. Additional analyses on real-time, polyp size, magnification, high definition and Lucera/Exera were performed if data were available. Medline, Embase, PubMed and Cochrane library were searched. Outcomes were plotted in HSROC-curves with summary point and their 95% confidence region. Quality of the studies was assessed using the QUADAS-2 tool.</p><p><bold>RESULTS:</bold> In total 97 studies were included where sensitivity and specificity were assessed.
<table-wrap id="table7-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1"><bold>Technique</bold></th><th rowspan="1" colspan="1"><bold>Number of studies</bold></th><th rowspan="1" colspan="1"><bold>Sensitivity (95% CI)</bold></th><th rowspan="1" colspan="1"><bold>Specificity (95% CI)</bold></th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1"><bold>NBI</bold></td><td rowspan="1" colspan="1">54</td><td rowspan="1" colspan="1">91.0 (88.6-93.0)</td><td rowspan="1" colspan="1">85.6 (81.3-89.0)</td></tr><tr><td rowspan="1" colspan="1"><bold>iSCAN</bold></td><td rowspan="1" colspan="1">10</td><td rowspan="1" colspan="1">89.3 (83.3-93.3)</td><td rowspan="1" colspan="1">88.2 (80.3-93.2)</td></tr><tr><td rowspan="1" colspan="1"><bold>FICE</bold></td><td rowspan="1" colspan="1">16</td><td rowspan="1" colspan="1">91.8 (87.1-94.9)</td><td rowspan="1" colspan="1">83.5 (77.2-88.3)</td></tr><tr><td rowspan="1" colspan="1"><bold>AFI</bold></td><td rowspan="1" colspan="1">11</td><td rowspan="1" colspan="1">86.7 (79.5-91.6)</td><td rowspan="1" colspan="1">65.9 (50.9 - 78.2)</td></tr><tr><td rowspan="1" colspan="1"><bold>CLE</bold></td><td rowspan="1" colspan="1">12</td><td rowspan="1" colspan="1">92.6 (88.2 - 95.5)</td><td rowspan="1" colspan="1">88.6 (80.3 - 93.7)</td></tr></tbody></table></table-wrap></p><p><bold>CONCLUSION:</bold> Of all advanced imaging techniques NBI is most extensively studied and, when combined with magnification, a NPV of >90% could be reached for the differentiation of diminutive colorectal polyps. Other features did not improve the accuracy. FICE and iSCAN show similar results, but wider confidence intervals. The accuracy of AFI is considerably lower than the other techniques. Although CLE shows a high sensitivity and specificity, due to the highly specialized technique it is not applicable in daily practice.</p><p><bold>REFERENCES:</bold></p><p>1. Rex DK et al. The American Society for Gastrointestinal Endoscopy PIVI (Preservation and Incorporation of Valuable)</p><p><bold>Contact E-mail Address:</bold><email>e.dekker@amc.uva.nl</email></p><p><bold>Disclosure of Interest</bold>: L. Wanders: None Declared, J. East: None Declared, S. Uitentuis: None Declared, M. Leeflang: None Declared, E. Dekker Financial support for research from: Olympus, Other: Equiment on loan Olympus</p><p><bold>Keywords:</bold> COLONIC CANCER, Colonoscopy, Neoplasm</p></sec><sec><title></title><p><bold>MONDAY, OCTOBER 14, 2013 11:00-12:30</bold></p><p><bold>Advances in biliopancreatic imaging – Hall 10</bold></p></sec><sec><title>OP034 EX VIVO MAGNIFYING ENDOSCOPIC OBSERVATION OF NON-NEOPLASTIC BILE DUCT MUCOSA USING NARROW BAND IMAGING</title><p><bold>Y. Ishida</bold><sup>1,*</sup>, Y. Okabe<sup>1</sup>, M. Yasumoto<sup>1,2</sup>, G. Sugiyama<sup>1</sup>, K. Kuraoka<sup>1</sup>, Y. Sasaki<sup>1</sup>, T. Ushijima<sup>1</sup>, R. Kaji<sup>1</sup>, Y. Kitasato<sup>3</sup>, Y. Nakama<sup>3</sup>, H. Horiuchi<sup>3</sup>, H. Kinoshita<sup>3</sup>, O. Tsuruta<sup>1</sup>, M. Sata<sup>1</sup></p><p><italic><sup>1</sup>Division of Gastroenterology, Department of Medicine, <sup>2</sup>Department of Pathology, <sup>3</sup>Department of Surgery, Kurume University School of Medicine, Kurume, Japan</italic></p><p><bold>INTRODUCTION:</bold> The utility of peroral cholangioscopy (POCS) has been reported since a new video POCS was developed. However, endoscopic findings of non-neoplastic bile duct mucosa using POCS with narrow band imaging (NBI) have not yet been established. This is a fundamental study ex vivo to compare magnifying endoscopic findings and histopathological findings.</p><p><bold>AIMS&METHODS:</bold> 39 common bile ducts which were surgically resected were enrolled in this study. These specimens included non-neoplastic bile duct mucosa obtained from 39 patients who underwent pancreatoduodenectomy, bile duct resection, or hepatectomy. We cut each common bile duct open for ex vivo endoscopic observation of its mucosa. We used a magnifying endoscope (FH-260AZI or H-260Z; Olympus Medical Systems, Tokyo, Japan) commonly used for the gastrointestinal tract, and we utilized both conventional white light imaging (WLI) and NBI (CV-260SL processor, CVL-260SL light source; Olympus). After histological diagnosis, the 39 specimens were classified into two categories based on the absence or presence of histological inflammation. Normal to mild inflammatory mucosa was assigned to group A and moderate to severe inflammatory mucosa was to group B. Then we examined the relationship between the magnifying endoscopic findings (using WLI and NBI) and microscopic histopathology.</p><p><bold>RESULTS:</bold> 17 specimens of bile duct mucosa were classified as group A and 22 specimens as group B. In the 16 cases of group A, many oval-shaped, depressed areas and a fine, regular network of microvessels were observed using magnifying endoscopy. In the 22 cases of group B, we could not clearly see these oval-shaped, depressed areas and the network. In eight cases of histologically confirmed severe inflammatory mucosa in group B, the depressed areas and network could not be found and only irregular mucosa and microvessels were observed. Additionally, these bile duct mucosa cases looked like petechial hemorrhaging, scales, or villous structures. In only one case with mild inflammation but with regenerative change, irregular mucosal structure was observed and likely to be mistaken for neoplastic mucosa. In all cases, we could see these findings more clearly when magnifying endoscopy with NBI was used.</p><p><bold>CONCLUSION:</bold> Oval-shaped, depressed areas and a fine, regular network of microvessels are the characteristic features of normal bile duct mucosa. Inflammation obscures these features. NBI can depict mucosal architecture of the bile duct in minute detail.</p><p><bold>Contact E-mail Address:</bold><email>ishida_yuusuke@kurume-u.ac.jp</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Bile duct, cholangioscopy, magnifying endoscopy with narrow-band imaging</p></sec><sec><title>OP035 NEEDLE-BASED CONFOCAL LASER ENDOMICROSCOPY (NCLE) ALLOWS IN VIVO CHARACTERIZATION OF PANCREATIC SEROUS CYSTADENOMAS (SCA)</title><p><bold>B. Napoléon</bold><sup>1,*</sup>, A.-I. Lemaistre<sup>2</sup>, M. Giovannini<sup>3</sup>, F. Caillol<sup>3</sup>, B. Pujol<sup>1</sup>, V. Lepilliez<sup>1</sup>, F. Fumex<sup>1</sup></p><p><italic><sup>1</sup>Hôpital privé Jean Mermoz, <sup>2</sup>Centre Léon Bérard, Lyon, <sup>3</sup>Institut Paoli Calmettes, Marseille, France</italic></p><p><bold>INTRODUCTION:</bold> nCLE enables microscopic observation, <italic>in vivo</italic> and in real-time, during an EUS-FNA procedure. A prospective multicenter french study aims at assessing the yields of nCLE for the diagnosis of pancreatic cysts. As interpretation criteria for SCA have not been defined during a previous study (INSPECT), 2 investigators and 2 pathologists reviewed the 7 first cases, including 5 SCA, and identified a new aspect: the superficial vascular network (SVN). It matches SCA histology.</p><p><bold>AIMS&METHODS:</bold> The aim of this preliminary study is to assess the yields of this criteria for the diagnosis of SCA, as well as the inter (IOA) and intra (ioa) observer agreements.</p><p>Over 6 months, 20 patients were enrolled (lonely pancreatic cyst > 2 cm large, no pancreatic duct communication, no chronic pancreatitis). Following EUS examination, the AQ-Flex 19 miniprobe was introduced in a 19G needle and real-time video sequences of the cyst wall were recorded after puncture. Then intracystic fluid was analyzed. Final diagnosis of SCA (n=9) was based on: - absence of solid mass on EUS, -absence of cytologic criteria suggesting a mucinous lesion +/- SCA cells, -intracystic CEA < 5 ; amylase < 300. The other lesions were considered as mucinous cystadenoma (n=5, proven by surgery), IPMN (n=5), pseudocyst (n=1). After a basic training on 2 patients’ sequences, with and without SVN sign, IOA was evaluated by 6 investigators (4 experts, 2 beginners). They reviewed a set of 18 video sequences (8 SCA and 10 non SCA) in a randomized order. The ioa was evaluated, by one beginner and one expert who reviewed twice the sequences in a different order. For the cases with a discrepancy of interpretation a joint review was done and a final consensus proposed if possible.</p><p><bold>RESULTS:</bold> The ioa was excellent and identical for the beginner and the expert (kappa 0.87). The IOA was good to excellent (kappa 0.69). In 72% of cases the agreement between the 6 observers was complete. A final consensus was obtained in the 28% remaining cases. Compared to the final diagnosis, the accuracy, sensitivity, specificity, PPV and NPV of SVN sign for the diagnosis of SCA were respectively 83%, 62.5%, 100%, 100% and 77%.</p><p><bold>CONCLUSION:</bold> The presence of SVN is a histological particularity of SCA, which can be highlighted by nCLE. The yields of this sign are high with 100% specificity and PPV and a good to excellent intra and interobserver agreement. Its presence could avoid unnecessary surgery. The second phase of the study should enable to prospectively validate the sign and confirm the interest of nCLE for the diagnosis of pancreatic cystic tumors.</p><p><bold>Contact E-mail Address:</bold><email>bertrand.napoleon@dartybox.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> cyst, endomicroscopy, serous, vascular</p></sec><sec><title>OP036 EMID STUDY : FINAL RESULTS OF A PROSPECTIVE BICENTRIC STUDY ASSESSING PROBE-BASED CONFOCAL LASER ENDOMICROSCOPY (PCLE). IMPACT IN THE MANAGEMENT OF BILIARY STRICTURES</title><p><bold>F. Caillol</bold><sup>1,*</sup>, E. bories<sup>1</sup>, F. poizat<sup>2</sup>, C. pesenti<sup>1</sup>, R. dumas<sup>3</sup>, J.-F. demarquay<sup>3</sup>, G. Monges<sup>2</sup>, M. Giovannini<sup>1</sup></p><p><italic><sup>1</sup>endoscopies, <sup>2</sup>pathology, INSTITUT PAOLI CALMETTE, marseille, France, <sup>3</sup>endoscopies, Hopital Grace de Monaco, Monaco, Monaco</italic></p><p><bold>INTRODUCTION:</bold> pCLE is an imaging technology, enabling optical biopsy, or in vivo histology. The definitive results of the EMID study are presented here, comparing optical biopsies with definitive histology.</p><p><bold>AIMS&METHODS:</bold> From July 2007 to May 2012, 61 patients with a biliary stricture without any previous histology were included (mean age 67 years old, 26 women, 33 men). Pre-operating imaging findings were available (MRI or scanner). An endoscopic ultrasound (EUS) had to be conducted before the ERCP procedure. The pCLE imaging was done during the ERCP procedure. The pCLE miniprobe was the CholangioFlex (Cellvizio, Mauna Kea Technologies, France). This probe has a 0.96mm diameter, a 55 microns imaging depth, and a 400-fold magnification. It was introduced into a 8.5F double lumen catheter (Cook Endoscopy, or MTW), positioned in the bile duct on a 0.035 inches guide wire. A 2.5ml injection of fluorescein 10 % was necessary to obtain interpretable images.The pCLE criteria used were the Miami classification criteria (large vessels with double circulation, dark cells aggregates, thick dark bands with irregular branches, epithelium).Results were compared to definitive histology obtained by biopsy or surgery in case of malignant lesions, and by surgery or 1-year follow-up in case of benign lesions.</p><p><bold>RESULTS:</bold> : Six patients were excluded from the study because no definitive histology was available. There were 41 malignant lesions, 14 benign lesions.
<table-wrap id="table8-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1"></th><th rowspan="1" colspan="1">sens</th><th rowspan="1" colspan="1">spec</th><th rowspan="1" colspan="1">PPV</th><th rowspan="1" colspan="1">NPV</th><th rowspan="1" colspan="1">reliability</th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">pCLE</td><td rowspan="1" colspan="1">88%</td><td rowspan="1" colspan="1">79%</td><td rowspan="1" colspan="1">92%</td><td rowspan="1" colspan="1">69%</td><td rowspan="1" colspan="1">85%</td></tr><tr><td rowspan="1" colspan="1">brushing+ biopsies</td><td rowspan="1" colspan="1">76%</td><td rowspan="1" colspan="1">79%</td><td rowspan="1" colspan="1">91%</td><td rowspan="1" colspan="1">52%</td><td rowspan="1" colspan="1">76%*</td></tr><tr><td rowspan="1" colspan="1">pCLE+ brushing+ biopsies</td><td rowspan="1" colspan="1">100%</td><td rowspan="1" colspan="1">71%</td><td rowspan="1" colspan="1">91%</td><td rowspan="1" colspan="1">100%</td><td rowspan="1" colspan="1">93%*</td></tr></tbody></table></table-wrap></p><p>* The diagnostic difference regarding the diagnostic reliability is statistically significant (p=0.03). The biopsies are the tissue samplings obtained by ERCP or EUS.</p><p>19 patients had a biliary stricture without individualized mass on pre-operating imaging findings (6 malignant lesions, 13 benign lesions).</p><p> Sens Spec PPV NPV Reliability pCLE 83 % 77 % 62 % 91 % 79 % brushings+biopsies 50 % 77 % 50 % 77 % 68 % pCLE + brushings + biospies 100 % 69 % 60 % 100% 79 %</p><p><bold>CONCLUSION:</bold> The addition of a pCLE procedure in the diagnostic histological examination of a biliary stricture enables to significantly increase the diagnostic reliability.</p><p><bold>Contact E-mail Address:</bold><email>fcaillol@free.fr</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> biliary strictures, ERCP, pCLE</p></sec><sec><title>OP037 PROSPECTIVE DOUBLE BLINDED COMPARISON OF THE DIAGNOSTIC YIELD OF ENDOSCOPIC ULTRASONOGRAPHY VS SECRETIN ENHANCED CHOLANGIO-MRI IN THE ETIOLOGICAL STUDY OF IDIOPATHIC ACUTE PANCREATITIS.</title><p><bold>J. J. Vila</bold><sup>1,*</sup>, E. Rubio<sup>1</sup>, M. Garaigorta<sup>1</sup>, M. Gómez<sup>1</sup>, M. Basterra<sup>1</sup>, S. Goñi<sup>2</sup>, I. Fernández-Urien<sup>1</sup>, F. J. Jiménez<sup>1</sup></p><p><italic><sup>1</sup>Endoscopy Unit. Gastroenterology Dpt., Complejo Hospitalario de Navarra, Pamplona, <sup>2</sup>Endoscopy Unit. Gastroenterology Dpt., Hospital de Zumárraga, Zumárraga, Spain</italic></p><p><bold>INTRODUCTION:</bold> Double blinded comparison of the diagnostic yield of endoscopic ultrasonography (EUS) and Secretin enhanced Cholangio-MRI (S-CMRI) in patients with idiopathic acute pancreatitis (IAP) has never been published.</p><p><bold>AIMS&METHODS:</bold> We wanted to compare the diagnostic yield of EUS and S-CMRI in the etiological work-up of IAP. Prospective double-blinded study including consecutive patients with IAP diagnosed in june/2009-october/2012. A minimum of 6 months follow up after diagnosis was made (april 2013). IAP was defined: acute pancreatitis bout without etiological findings after anamnesis, laboratory and radiology (2 transabdominal ultrasonography or 1 plus a CT). EUS and S-CMRI were performed >4 weeks after the acute bout. Two radiologists and 2 endosonographers participated in the study and were blinded to the outcome of the other exploration. Chi-square was used to make the statistical analysis.</p><p><bold>RESULTS:</bold> 32 consecutive patients with IAP were proposed to participate. Six patients refused: 4 did not accept EUS and 2 S-CMRI. In the remaining 26, EUS found a possible cause of IAP in 20 (76.9%) and S-CRMI in 9 (34.6%) (p = 0.34). In 7 out of these 9 patients EUS was also positive. The other two patients had a Pancreas Divisum (PD) and an intraductal papillary mucinous tumor (IPMN) not detected with EUS. Both examinations were performed with a median difference of 11 days (2-49). EUS diagnosed 11 cholelithiasis, 1 choledocholithiasis, 2 PD with Santorinicele, 3 chronic pancreatitis and 3 IPMN (1 with malignant citology after FNA). The S-CRMI found 1 choledocholithiasis, 3 PD with Santorinicele, 1 chronic pancreatitis and 4 IPMN. 10 patients with cholelithiasis and two patients with IPMN underwent surgery confirming the diagnosis. Two patients with PD and the patient with choledocolithiasis underwent ERCP confirming the diagnosis. Chronic pancreatitis was confirmed by pancreatic function tests. The other 4 patients refused surgery or ERCP. After a mean follow up of 26.81±13.30 months: 20 patients remain asymptomatic, 2 patients had recurrent abdominal pancreatic type pain and 2 patients had recurrent bouts of pancreatitis. 1 patient was lost from follow up and 1 patient died because of unrelated cause.</p><p><bold>CONCLUSION:</bold> We found no significant differences between the diagnostic yield of EUS and S-CMRI in patients with IAP, although EUS provides superior diagnostic yield due to better detection of cholelithiasis which is the most frequent finding in these patients, and the ability to perform FNA.</p><p><bold>Contact E-mail Address:</bold><email>juanjvila@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Endosonography, Idiopathic Acute Pancreatitis, MRI secretin enhanced</p></sec><sec><title>OP038 SINGLE-OPERATOR CHOLANGIOPANCREATOSCOPY (SOCPS) IN PATIENTS REQUIRING DIAGNOSIS AND THERAPY FOR BILIARY AND PANCREATIC DISEASES: PROSPECTIVE MULTI-CENTER STUDY IN JAPAN</title><p><bold>T. Kurihara</bold><sup>1,*</sup>, T. Itoi<sup>2</sup>, I. Yasuda<sup>3</sup>, T. Tsuyuguchi<sup>4</sup>, H. Isayama<sup>5</sup></p><p><italic><sup>1</sup>Department of Gastroenterology and Hepatology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, <sup>2</sup>Department of Gastroenterology and Hepatology, Tokyo Medical University, 6-7-1 Nishishinjuku Shinjuku-ku Tokyo, <sup>3</sup>First Department of Internal Medicine, Gifu University Hospital, 1-1 Yanagido, Gifu 501-1194, <sup>4</sup>Department of Medicine and Clinical Oncology, Graduate school of Medicine Chiba University, 1-8-1 Inohana, chuo-ku, Chiba, <sup>5</sup>Department of Gastroenterology, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo , Japan</italic></p><p><bold>INTRODUCTION:</bold> The usefulness of single-operator cholangioscopy for biliary diagnosis and treatment was previously reported.</p><p><bold>AIMS&METHODS: Objective: </bold>To assess the utility and safety of single-operator cholangiopancreatoscopy (SOCPS) using Spyglass system in widespread clinical application for biliary and pancreatic diseases.</p><p><bold>Methods: </bold>Design, setting: Prospective case series, twenty-two referral centers in Japan. Patients: One hundred sixty-two patients requiring diagnosis of undetermined biliary and pancreatic lesions or treatment of biliary and pancreatic disease. Interventions: SOCPS examination, SOCPS-directed tissue sampling and stone therapy. Main outcome: Procedural success rate of visualizing target lesions, SOCPS-directed adequate tissue sampling and removal of stone. The sensitivity and specificity of SOCP examination and histological diagnosis of SOCPS-direct biopsies.</p><p><bold>RESULTS: Results</bold>: Diagnosis: The success rate of visualizing target lesions was 95.8% of 119 patients who underwent SOCPS. The overall adequate tissue for histological examination was secured in 76.2% of 105 patients who underwent biopsy under SOCPS (bile duct; 71/90=78.9%, pancreatic duct; 9/15=60.0%). The sensitivity and specificity of SOCPS visual impression of bile duct were 88.1% (59/61) and 80.0% (28/35), respectively. The sensitivity and specificity of SOCPS directed-biopsy for bile duct lesions were 65.1% (41/63) and 89.3% (25/28), respectively. The sensitivity of SOCPS visual impression and directed-biopsy to detect intraductal papillary mucinous neoplasm of main pancreatic duct were 100% (15/15) and 73.3% (9/11), respectively. Stone therapy: Complete biliary and pancreatic stone clearance combined SOCPS-directed stone therapy using EHL or laser lithotripsy achieved in 74.2% (23/31), 28.6% (2/7), respectively. Others: SOCPS using Spyglass system used in cannulation of the cystic duct in two patients and passing across the obstructed self-expandable metallic stent for malignant biliary stricture in two patients. All procedures were successful.The incidence of procedure-related adverse events was 5.6%.</p><p><bold>CONCLUSION:</bold> SOCPS with directed-biopsy and SOCPS directed therapy for biliary or pancreatic disease can be safely performed with high success rate by using Spyglass system.</p><p><bold>Contact E-mail Address:</bold><email>kurihara@tokyo-med.ac.jp</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> cholangioscopy, single operator method</p></sec><sec><title>OP039 A NEWLY DESIGNED PROTOTYPE OF SHORT SBE FOR ERCP IN PATIENTS WITH SURGICALLY ALTERED ANATOMY</title><p><bold>M. Kida</bold><sup>1,*</sup>, H. Yamauchi<sup>1</sup>, K. Okuwaki<sup>1</sup>, S. Miyazawa<sup>1</sup>, T. Iwai<sup>1</sup>, M. Takezawa<sup>1</sup>, H. Kikuchi<sup>1</sup>, M. Watanabe<sup>1</sup>, H. Imaizumi<sup>1</sup>, W. Koizumi<sup>1</sup></p><p><italic><sup>1</sup>Endoscopy & Gastroenterology, Kitasato University Hospital, Sagamihara, Japan</italic></p><p><bold>INTRODUCTION: E</bold>RCP is often difficult to perform in patients with surgically altered anatomy. However, the recent advent of balloon enteroscopy has improved the outcome of ERCP in these patients. Because of the long length of endoscope, we have to use special long devices and can’t use wire-guided devices. Then we have designed newly developed short-type prototype of single balloon enteroscope (SBE) and investigated its usefulness.</p><p><bold>AIMS&METHODS:</bold> From 2009 up to now, we have performed 62 ERCP in 45 patients (R-Y: 37, B- II: 8) with a new prototype of short enteroscope, which is 152 cm in length, 9.2 mm in diameter, and with 3.2 mm working channel. And we historically compared with a standard enteroscope which is used in 26 patients (R-Y: 18, B- II: 8) from 2007 to 2009, 200 cm, 9.2 mm, and with 2.8 mm working channel.</p><p><bold>RESULTS:</bold> Among the all sessions of ERCP, the rate of prototype and standard one of reaching the blind end was 92% (48/52), 84% (16/19) in R-Y, and 90 % (9/10), 100% (9/9) in B-II. The diagnostic success rates were 88%(42/48), 68% (11/16), p=0.09, in R-Y, and 89% (8/9), 89% (8/9) in B- II. The therapeutic success rates were 94% (40/42), 90% (9/10) in R-Y, and 100% (8/8), 100% (8/8) in B-II.</p><p>The mean procedure time were 41 min., 50.6 min. in R-Y, p=0.14, and 36 min., 38.4 min. in B- II. Because of the short length of endoscope, most conventional devices of ERCP could be used. And because the channel diameter was 3.2 mm, we could perform with wire guided devices. Hyperamylasemia and post-ERCP pancreatitis occurred 14.6% (7/48), 18.8% (3/16) and 6.2% (3/48), 12.5% (2/16) in R-Y, and 22.1% (2/9), 11.1% (1/9) and 0% (0/9), 0% (0/9) in B- II. Perforation occurred 3.8% (2/52), 0% (0/18) in R-Y, and 0% (0/9), 0% (0/9) in B- II.</p><p><bold>CONCLUSION:</bold> Short-type SBE is effective for ERCP in patients with surgically altered anatomy and allows most conventional ERCP devices to be used.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> ERCP, single-balloon enteroscopy</p></sec><sec><title></title><p><bold>MONDAY, OCTOBER 14, 2013 11:00-12:30</bold></p><p><bold>Oesophageal cancer: Treatment, prognosis and prognosticators – Hall 8</bold></p></sec><sec><title>OP040 RADIOFREQUENCY ABLATION IN PATIENTS WITH EARLY ESOPHAGEAL NEOPLASIA: A PROSPECTIVE EVALUATION OF 52 CONSECUTIVE CASES</title><p><bold>J. Martinek</bold><sup>1,*</sup>, M. Stefanova<sup>2</sup>, J. Maluskova<sup>3</sup>, J. Krajciova<sup>1</sup>, J. Spicak<sup>1</sup></p><p><italic><sup>1</sup>HEPATO-GASTROENTEROLOGY, INSTITUTE FOR CLINICAL AND EXPERIMENTAL MEDICINE, Praha 4, <sup>2</sup>Internal Medicine, Hospital Na Frantisku, Praha 1, <sup>3</sup>Pathology, INSTITUTE FOR CLINICAL AND EXPERIMENTAL MEDICINE, Praha 4, Czech Republic</italic></p><p><bold>INTRODUCTION:</bold> Radiofrequency ablation (RFA) in combination with endoscopic resection (ER) is method of choice for treatment of early esophageal neoplasia. The aim of this prospective study was to assess the long-term efficacy of RFA.</p><p><bold>Main outcome measurements:</bold> Complete remission defined as an absence of intestinal metaplasia (CR-IM) or neoplasia (CR-neoplasia). A special attention was directed towards a detection of buried glands beneath the neosquamous epithelium.</p><p><bold>AIMS&METHODS:</bold> The aim of this prospective, single center study was to assess the long-term efficacy of RFA. Main outcome measurements were complete remission defined as an absence of intestinal metaplasia (CR-IM) or neoplasia (CR-neoplasia). A special attention was directed towards a detection of buried glands beneath the neosquamous epithelium.</p><p><bold>RESULTS:</bold> The study involved 52 (mean age 62, range 25-86) consecutive patients undergoing endoscopic treatment for esophageal neoplasia in our center during 2009-2013. Fifty patients were diagnosed with Barrett esophagus related neoplasia (BORN), the remaining 2 patients had squamous neoplasia. The median follow up was 24 months (range 0,5-4). In 11 patients (21%), RFA was a single treatment modality while in 41 patients (79%), RFA was combined with endoscopic resection or dissection of a visible lesion (both pre- or post- RFA therapy). The indications for endoscopic treatment were as follows: early adenocarcinoma (EAC): 21 (40%), early squamous carcinoma (ESC): 2 (3%), high grade intraepithelial neoplasia: 19 (36%), low grade intraepithelial neoplasia: 11 (21%).</p><p>A total 99 RFA treatment session was performed (31 with HALO 360, 68 with HALO 90). The total number (median) of treatment sessions per patient (ER + RFA) was 3 (range 3-6) and the total number of RFA sessions per patient was 2 (1-6). In one patient with EAC, RFA with HALO 360 was not successful since even the smallest balloon could not be fully inflated.</p><p>CR-IM and CR-neoplasia were achieved in 69% (95% CI 61-81%) and 91% (95% CI 86-99%), respectively. During the follow-up, there were 3 recurrences of intestinal neoplasia (6%) and no neoplasia recurred. We did not detect buried glands beneath the new squamous epithelium.</p><p>There were no serious complications or adverse events. One patient (2%) developed esophageal stenosis which was managed by esophageal dilatation.</p><p><bold>CONCLUSION:</bold> RFA is effective and safe in treatment of early esophageal neoplasia. Intestinal metaplasia recurs infrequently. In most patients, RFA is combined with endoscopic resection.</p><p><bold>Contact E-mail Address:</bold><email>jan.martinek@volny.cz</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Barrett's neoplasia, radio frequency ablation</p></sec><sec><title>OP041 LONG-TERM OUTCOMES OF ENDOSCOPIC RESECTION FOR SUPERFICIAL PHARYNGEAL SQUAMOUS CELL CARCINOMA INVADING THE SUBEPITHELIAL LAYER</title><p><bold>H. Satake</bold><sup>1,2,*</sup>, T. Yano<sup>1</sup>, K. Minashi<sup>1</sup>, Y. Yoda<sup>1</sup>, T. Kojima<sup>1</sup>, Y. Oono<sup>1</sup>, H. Ikematsu<sup>1</sup>, I. Aoyama<sup>3</sup>, S. Morita<sup>3</sup>, S. Miyamoto<sup>3</sup>, R. Hayashi<sup>4</sup>, K. Kaneko<sup>1</sup>, M. Muto<sup>3</sup></p><p><italic><sup>1</sup>Gastroenterology and GI Oncology, National Cancer Center Hospital East, Kashiwa, <sup>2</sup>Gastroenterology, Kobe City Medical Center General Hospital, Kobe, <sup>3</sup>Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, <sup>4</sup>Head and Neck Surgeon, National Cancer Center Hospital East, Kashiwa, Japan</italic></p><p><bold>INTRODUCTION:</bold> Recently, endoscopic resection (ER) is indicated for superficial pharyngeal squamous cell carcinoma (SPSCC). However, the indication has not been established. Especially, while the SPSCC invading the subepithelial layer would have a risk of lymph node metastasis, the curability of ER for the lesions is unclear.</p><p><bold>AIMS&METHODS:</bold> The aim of this retrospective two-center cohort study is to evaluate the curative potential of ER for the SPSCC invading the subepithelial layer. Selection criteria for this study were as follows: 1) initial ER, 2) histologically proven squamous cell carcinoma (SCC) invading the subepithelial layer, 3) no lymph node nor distant metastasis was not detected by neck/chest/upper abdomen CT before ER, and 4) no prior treatment for head and neck cancer. ER was indicated under general anesthesia.</p><p><bold>RESULTS:</bold> Among the 198 SPSCCs in 176 consecutive patients treated by ER at two tertiary referral centers from June 2002 to July 2010, 50 lesions in 47 patients (male / female: 47 / 0, median age 64 years) were histologically diagnosed as having subepithelial invasion. Median tumor thickness was 1000 (range; 200 to 10000) μm. While six patients developed local recurrence, all of them were cured with organ-preserved intervention: salvage ER, partial resection and chemoradiotherapy. With a median follow-up period of 71 months (range 27-116), one patient had neck lymph node metastasis two months after ER, and was performed a neck lymph node dissection. The 5-year overall survival and cause-specific survival rate were 84.5% (95%CI, 73–96) and 100%, respectively.</p><p><bold>CONCLUSION:</bold> ER could be an alternative, less invasive curative-intent treatment for SPSCC invading the subepithelial layer.</p><p><bold>Contact E-mail Address:</bold><email>takeh1977@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> endoscopic resection, invading the subepithelial layer, Long-term outcomes, superficial pharyngeal squamous cell carcinoma</p></sec><sec><title>OP042 LONG-TERM OUTCOMES OF ENDOSCOPIC SUBMUCOSAL DISSECTION FOR SUPERFICIAL SQUAMOUS CELL CARCINOMAS</title><p><bold>M. Takeuchi</bold><sup>1,*</sup>, M. Kobayashi<sup>2</sup>, S. Hashimoto<sup>2</sup>, K.-I. Mizuno<sup>2</sup>, Y. Aoyagi<sup>1</sup></p><p><italic><sup>1</sup>Department of Gastroenterology, <sup>2</sup>Department of Endoscopy, NIIGATA UNIVERSITY HOSPITAL, Niigata, Japan</italic></p><p><bold>INTRODUCTION:</bold> Endoscopic submucosal dissection (ESD) is currently accepted as the major therapeutic modality for superficial esophageal neoplasms. However, reports about the long-term outcomes of ESD for superficial esophageal squamous cell carcinomas (ESCC) have been limited.</p><p><bold>AIMS&METHODS:</bold> This study aimed to clarify both the advantages and disadvantages of ESD for superficial ESCC based on assessment of long-term outcomes. We analyzed 192 patients with 224 lesions who were treated by ESD from February 2003 to December 2008, and subsequently followed them for more than three years thereafter. Patients with previous esophageal endoscopic resection and either local recurrence after CRT or endoscopic resection were excluded. The patients were categorized into the following groups: group A (n=132), those with a tumor depth of EP/LPM; group B (n=40), those with MM/SM1 carcinoma; and group C (n=20), those with massive submucosal invasive cancer. Local recurrence rates, lymph node or distant metastasis, multiple metachronous ESCC detected over one year after ESD, and the 5-year overall/cause specific survival rates were evaluated.</p><p><bold>RESULTS:</bold> Two patients with vessel infiltration in group B and 9 patients in group C underwent additional treatment comprising CRT or surgery. The local recurrence rate was 0% in all groups during the median follow-up period of 59.5 months (range 6-107 months). Lymph node and distant metastasis did not occur in group A, although lymph node metastasis occurred in one (2.5%) and three (15.0%) patients in groups B and C, respectively. Distant metastasis did not occur in any group. Multiple metachronous carcinomas occurred in 13 (9.8%), three (7.5%) and one (5.0%) of the patients in groups A, B and C, respectively. All metachronous lesions were limited to the muscularis mucosa and were completely removed <italic>en-bloc</italic> by ESD. The 5-year overall/cause specific survival rates were 81.8/100%, 85.0/100% and 70.0/100%, in group A, B and C, respectively. Among 36 patients who died of diseases other than esophageal cancer, 52.8% were due to other organ carcinoma, especially of the head and neck, followed by heart and respiratory disease.</p><p><bold>CONCLUSION:</bold> Long-term follow-up revealed that ESD for superficial ESCC is potentially curative. However, almost all of the patients died of other organ carcinoma, indicating that these patients should be investigated not only for multiple metachronous carcinoma, but also for cancers of other organs.</p><p><bold>Contact E-mail Address:</bold><email>yasuzuka2000@yahoo.co.jp</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> endoscopic submucosal dissection (ESD), esophageal squamous cell carcinoma (ESCC), long-term outcomes</p></sec><sec><title>OP043 ESOPHAGECTOMY FOR ESOPHAGEAL CANCER IN ELDERLY PATIENTS: CLINICAL AND FUNCTIONAL OUTCOME</title><p><bold>M. Scarpa</bold><sup>2,*</sup>, B. Filip<sup>1</sup>, F. Cavallin<sup>2</sup>, M. Cagol<sup>2</sup>, R. Alfieri<sup>2</sup>, C. Castoro<sup>2</sup></p><p><italic><sup>1</sup>Dept of Surgery, University of Medicine of Iasi, Iasi, Romania, <sup>2</sup>Oncological Surgery Unit, Veneto Institute of Oncology (IOV-IRCCS), Padova, Italy</italic></p><p><bold>INTRODUCTION:</bold> Worldwide increased life expectancy is leading to an increased number of elderly patients diagnosed with esophageal cancer who are referred for surgical treatment. Age-related changes in cardiovascular, pulmonary, nervous, hepatorenal and endocrine physiology, associatd to an increased frequency of comorbidities lead to a decreased functional reserve in patients candidate to esophagectomy.</p><p><bold>AIMS&METHODS:</bold> A prospective database of all the patients diagnosed with esophageal cancer evaluated at Veneto Institute of Oncology between January 2008 and December 2012 was collected. A retrospective comparison between patients under and over 70 years in term of patient selection, comorbidities, prognostic scores, postoperative mortality, morbidity, functional outcome and medium term survival was performed. Non parametric statistics was used.</p><p><bold>RESULTS:</bold> A total of 278 consecutive patients were evaluated. Resecability rate was 45 % in patients over 70 years vs. 72.86% for those under 70 (p<0.05). Not operable elderly had higher rate of cardiac comorbidity (92.3% vs. 25.0%, p<0.0001) and had a more frequent III-IV ASA score (95.7% vs. 5.0%, p<0.0001). The overall 90 day mortality was 1.62% (3 cases), two of them under 70 years and one in the second group. There was no difference in term of postoperative complications between the two subgroups of patients (31.7% vs. 45%, p= 0.52). POSSUM score had a relatively equal discriminative ability for patients over 70 years, but was better adapted for patients over 70 years, in terms of calibration. Overall 1-year survival was 94.3% in elderly group and 86.4% in younger group and at 2 years it was, respectively, 63.6% and 61.1% (p=0.63). The frequence of severe symptomatic anastomotic strictures was similar between the two groups of patients (12.5% vs. 13%, p=0.91).</p><p><bold>CONCLUSION:</bold> Esophagectomy could be performed safely in patients over 70 years with the same morbidity, mortality and functional results than in younger patients. The key point to obtain the same postoperative outcomes was the accurate proprativ selection. Further studies are necessary to evaluate quality of life in elderly after esophagectomy.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> elderly patients, esophageal cancer, esophagectomy</p></sec><sec><title>OP044 SURVIVAL OF PATIENTS WITH BARRETT-RELATED ADENOCARCINOMA DETECTED IN A SURVEILLANCE PROGRAM: RESULTS OF A LARGE MULTICENTER PROSPECTIVE COHORT STUDY</title><p><bold>F. Kastelein</bold><sup>1,*</sup>, K. Biermann<sup>1</sup>, E. Steyerberg<sup>1</sup>, L. Looijenga<sup>1</sup>, E. Kuipers<sup>1</sup>, M. Spaander<sup>1</sup>, M. Bruno<sup>1</sup> and the ProBar study group</p><p><italic><sup>1</sup>Erasmus MC, Rotterdam, Netherlands</italic></p><p><bold>INTRODUCTION:</bold> The value of Barrett’s esophagus (BE) surveillance is under discussion given the overall low incidence of neoplastic progression, large screening base, and lack of discriminative tests for risk stratification. One of the key questions in this discussion is whether BE surveillance reduces mortality due to esophageal adenocarcinoma (EAC).</p><p><bold>AIMS&METHODS:</bold> The aim of this study was to evaluate survival of BE patients diagnosed with high-grade dysplasia (HGD) or EAC in a surveillance program. We conducted a multicenter prospective cohort study in 3 academic and 12 regional hospitals throughout the Netherlands. In this study patients were included with BE of at least 2 cm, confirmed by the presence of intestinal metaplasia. Surveillance was performed according to the ACG guidelines and with every endoscopy biopsies were taken according to the Seattle protocol. Biopsies were graded by at least two independent pathologists. Incident cases of HGD and EAC were identified during follow-up.</p><p><bold>RESULTS:</bold> 720 BE patients were included in this study and followed during surveillance for a median duration of 6.6 years (IQR 5.1-7.3). Fifty (7%) patients showed neoplastic progression after a median duration of 3.2 years (IQR 2.0-5.3). Thirty-nine (78%) patients were diagnosed with HGD or carcinoma in situ, 7 (14%) with a T1 tumor, 2 (4%) with a T2 tumor and 2 (4%) with a T3 tumor. The overall incidence rate of HGD and EAC was 1.3 per 100 patient-years (95% CI 0.9-1.7). The incidence rate of invasive EAC was 0.1 per 100 patient-years (95% CI 0.0-0.3). The incidence of neoplastic progression and tumor stage did not significantly change over time. Of all patients with neoplastic progression, 9 (18%) received intensive endoscopic surveillance, 30 (60%) endoscopic treatment, 4 (8%) surgical resection, and 2 (4%) surgical resection with neoadjuvant chemoradiotherapy. Four (8%) patients were only recently diagnosed and did not yet receive treatment. One (2%) patient died before treatment of a cause not related to BE. The 5-year HGD/EAC specific survival was 91% (95% CI 0.81-1.00) and the 5-year overall survival was 78% (95% CI 0.61-0.94).</p><p><bold>CONCLUSION:</bold> BE surveillance enables the detection of HGD or EAC at an early and curable stage when endoscopic treatment is still feasible. The 5-year disease specific survival of all patients with neoplastic progression was 91%, which is the most optimal survival rate that can be achieved in these patients according to AJCC TNM system definitions (stage 0 disease, TisN0M0, 5-year survival > 90%).</p><p><bold>Contact E-mail Address:</bold><email>f.kastelein@erasmusmc.nl</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Barrett’s esophagus, esophageal adenocarcinoma, high grade dysplasia, survival</p></sec><sec><title>OP045 PROGNOSTIC VALUE OF VEGFR-3 AND CXCR4 FOR PALLIATIVE CHEMOTHERAPY IN PATIENTS WITH ADVANCED ESOPHAGOGASTRIC CANCER: TRANSLATIONAL RESEARCH OF A RANDOMIZED PHASE III STUDY OF THE ARBEITSGEMEINSCHAFT INTERNISTISCHE ONKOLOGIE (AIO).</title><p><bold>T. Thomaidis</bold><sup>1,*</sup>, A. Maderer<sup>1</sup>, J. Kany<sup>1</sup>, C. Pauligk<sup>2</sup>, K. Steinmetz<sup>2</sup>, A. Schad<sup>3</sup>, R. Hofheinz<sup>4</sup>, H. Schmalenberg<sup>5</sup>, N. Homann<sup>6</sup>, P. Galle<sup>1</sup>, S.-E. Al- Batran<sup>2</sup>, M. Moehler<sup>1</sup></p><p><italic><sup>1</sup>I. Medical Department, Johannes-Gutenberg University , Mainz, <sup>2</sup>Krankenhaus Nordwest, UCT University Cancer Center, Frankfurt am Main, <sup>3</sup>Institute of Pathology, Johannes-Gutenberg University , Mainz, <sup>4</sup>III. Medical Clinic , University Clinic , Mannheim, <sup>5</sup>Tumor centre, University of Jena, Jena, <sup>6</sup>II. Medical Clinic, Wolfsburg, Germany</italic></p><p><bold>INTRODUCTION:</bold> Standard treatment in advanced esophagogastric cancer is systemic chemotherapy with fluoropyrimidines and platinum derivatives. However, since individual response to these regimes remains uncertain, prognostic markers are needed. The invasion and stem cell markers VEGFR-3 and CXCR4 have been linked with more aggressive esophagogastric cancer types.</p><p><bold>AIMS&METHODS:</bold> Thus, we aimed to assess correlations of VEGFR-3 and/or CXCR4 expression with clinical outcome in a randomized phase-III study of patients with oxaliplatin/leucovorin/5-FU (FLO) versus cisplatin/leucovorin/5-FU (FLP).</p><p>Tumour tissues of 72 patients from the FLO vs FLP phase III AIO trial were examined for VEGFR-3 and CXCR4 expression. The specimens were stained via immunohistochemistry and results were evaluated by two independent pathologists according to the sum of intensity (score:0-3) and extent (score:0-4) of the stained tumour areas. An overall score≥6 was considered as strong positive, whereas score<6 as weak positive. Furthermore, survival analysis was examined for patients receiving FLO vs FLP in correlation to VEGFR-3 and CXCR4 expression.</p><p><bold>RESULTS:</bold> Tumour tissues showed a strong positive expression for VEGFR-3 and CXCR4 in 54% and 36% of the cases, respectively. In the FLO and FLP subgroups, patients with strong expression of VEGFR-3 or CXCR4 on their tumour tissues had better median overall survival (OS) under the treatment of FLP than under FLO, with 21 vs 16 months (p = 0.227) and 28 vs 15 months, (p = 0.05), respectively. Patients with low VEGFR-3 or CXCR4 expression lived longer when FLO was applied, with 22 vs 9 months (p = 0.099) and 20 vs 10 months, (p = 0.073) respectively. A significant benefit under FLO vs FLP treatment was observed for patients with double weak staining for VEGFR-3 and CXCR4 (p < 0.05). Furthermore, VEGFR-3+ or CXCR4+ patients older than 60 years (36/72) profited significantly more in terms of OS under treatment with FLP than patients with weak VEGFR-3 or CXCR4 expression (p = 0.002, p = 0.021 respectively).</p><p><bold>CONCLUSION:</bold> CXCR4+ patients profited in terms of OS from FLP, whereas patients with weak CXCR4 and/or VEGFR-3 expression had a trend to live longer under FLO . VEGFR-3 and CXCR4 might have a predictive value concerning chemotherapy with cisplatin or oxaliplatin containing regimes in advanced esophagogastric cancer.</p><p><bold>Contact E-mail Address:</bold><email>tomagiot@hotmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> advanced esophagogastric cancer, CXCR4, FLO, FLP, VEGFR-3</p></sec><sec><title></title><p><bold>MONDAY, OCTOBER 14, 2013 11:00-12:30</bold></p><p><bold>Hepatocellular carcinoma – Salon 11/12</bold></p></sec><sec><title>OP046 THE MITOGEN-ACTIVATED PROTEIN KINASE ERK5 REGULATES THE DEVELOPMENT AND GROWTH OF HEPATOCELLULAR CARCINOMA</title><p><bold>G. Di Maira</bold><sup>1,*</sup>, E. Rovida<sup>2</sup>, N. Navari<sup>1</sup>, S. Cannito<sup>3</sup>, M. Parola<sup>3</sup>, P. Dello Sbarba<sup>2</sup>, F. Marra<sup>1</sup></p><p><italic><sup>1</sup>Dip. Medicina Sperimentale e Clinica, <sup>2</sup>Dipartimento di Oncologia Sperimentale, University of Florence, Florence, <sup>3</sup>Dipartimento di Medicina e Oncologia Sperimentali, University of Turin, Turin, Italy</italic></p><p><bold>INTRODUCTION:</bold> Current treatment options for hepatocellular carcinoma (HCC) are limited. The interference with signaling pathways deregulated in hepatocarcinogenesis could be considered a promising therapeutic strategy. ERK5 is the least studied member of the MAPK family and has been implicated in several biologic actions relevant for tumor development. Moreover, deregulation of the ERK5 pathway has been shown to be associated with cancer.</p><p><bold>AIMS&METHODS:</bold> Huh-7 and HepG2 were cultured by standard methods. Liver tissue was obtained from HCC and peritumoral areas. ERK5 was silenced by siRNA transfection or with shRNA and lentiviral vectors. The specific ERK5 inhibitor XMD8-92was also used. In vivo development of HCC was evaluated using the Huh-7 xenograft model in athymic nude mice.Aim of this study was to understand the role of ERK5 in HCC in vitro and in vivo.</p><p><bold>RESULTS:</bold> Analysis of ERK5 by IHC in human tissues showed more abundant nuclear localization in patients with HCC or cirrhosis than in normal liver, indicating ERK activation. ERK5 silencing in HCC cells or exposure to XMD8-92 blocked the increase in migration and invasion induced by EGF or serum. Similar results were observed in response to hypoxia. Immunofluorescence experiments demonstrated that ERK5 silencing or inhibition caused cytoskeletal remodeling and rearrangement of focal adhesions, consistent with a reduction in cell motility. In addition, ERK5 activation was necessary for the growth of HCC cells, affecting the G1/S transition. In a mouse model of HCC xenograft, administration of XMD8-92 significantly decreased tumor volume by approximately 40% compared to vehicle, 13 days after starting the treatment. Moreover, in mice injected with Huh-7 cells silenced for ERK5 using a lentiviral shRNA vector, the rate of tumor appearance was significantly lower (4/16 mice, 25%) than in animals inoculated with cells transduced with non targeting shRNA (9/15, 60%). In addition, at the end of the experiment, tumor volume was smaller in the presence of ERK5 silencing.</p><p><bold>CONCLUSION:</bold> The ERK5 pathway plays a critical role in HCC tumor development and growth in vivo. Blocking the ERK5 pathway should be further investigated as a novel approach for the treatment of HCC.</p><p><bold>Contact E-mail Address:</bold><email>giovanni.dimaira@unifi.it</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Cell signaling, HCC</p></sec><sec><title>OP047 THE TEMPORAL DYNAMICS OF THE UNFOLDED PROTEIN RESPONSE AND MULTIDRUG RESISTANCE IN HEPATOCELLULAR CARCINOMA.</title><p><bold>Y.-P. Vandewynckel</bold><sup>1,*</sup>, I. Colle<sup>1</sup>, D. Laukens<sup>1</sup>, B. Lambrecht<sup>2</sup>, C. Vanhove<sup>3</sup>, H. Van Vlierberghe<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology, University of Ghent, <sup>2</sup>Pneumology, Flemish institute of biotechnology (VIB), <sup>3</sup>Infinity lab for small animal imaging, University of Ghent, Ghent, Belgium</italic></p><p><bold>INTRODUCTION:</bold> Hepatocellular carcinoma (HCC) ranks as the fifth most common cancer worldwide. HCC is a chemoresistant tumour. Systemic therapy with cytotoxic drugs yields low response rates. Medications influencing the chemosensitivity profile are therefore needed. The unfolded protein response (UPR) is implicated in the pathophysiology of several diseases including cancer and endoplasmic reticulum (ER) stress could be a cause of the chemoresistance in HCC.</p><p><bold>AIMS&METHODS:</bold> To investigate these phenomena in HCC, we examined the presence and time-dependent alterations of ER stress and multidrug resistance (MDR) in a mouse model of HCC in order to have an <italic>in vivo</italic> method for the evaluation of UPR manipulation strategies as future cancer therapy.</p><p>The<italic> in vivo </italic>study design was a diethylnitrosamine (DEN)-induced mouse model for HCC. Mice (6 groups of n=14) where sacrificed after 20, 25 and 30 weeks of DEN or saline administration. The activation pattern of the UPR and the expression of MDR-related efflux pumps were determined by qRT-PCR, Western blot, ELISA and immunohistochemistry. The histology of the HCC nodules was examined by H/E, Sirius red, F4/80 and reticulin staining. Small animal imaging by dynamic contrast enhanced MRI and choline PET was performed.</p><p><bold>RESULTS:</bold> After 25 weeks of DEN this model showed PET-positive hepatocarcinogenesis occurring in a background of inflammation and fibrosis. The major MDR-related efflux pumps including mdr1, mrp1, mrp4 and brcp were significantly upregulated in the HCC nodules from 25 weeks. The master regulator of the UPR, bip, was significantly induced on 25 and even more on 30 weeks. Downstream targets of the perk branch (phosphorylated eif2a part: atf4, chop, gadd34 and nrf2 part: gclc, gsta1 and -2) were significantly upregulated after 25 weeks and continued to rise until 30 weeks. Unexpectedly, we could not show an increase in xbp1 splicing, spliced xbp1 targets or ire1a phosphorylation in the HCC nodules compared to the normal liver tissue. Only after 30 weeks the atf6 pathway and the downstream targets showed significant induction.</p><p><bold>CONCLUSION:</bold> Here, we provide the first evidence of the presence and the time-dependent alterations of MDR-related efflux pumps and a specific activation pattern of the UPR in the HCC nodules of a DEN-induced mouse model. Consequently, this model can be used to manipulate the fine-tuning of the UPR in hepatocarcinogenesis and related MDR development.</p><p><bold>REFERENCES:</bold></p><p>1. V. C. B. H. working group; B. steering committee. Van Vlierberghe H, Borbath I, Delwaide J, Henrion J, Michielsen P, “BASL guidelines for the surveillance, diagnosis and treatment of hepatocellular carcinoma.,” <italic>Acta Gastroenterol Belg</italic>, vol. 67, no. 1, pp. 14–25, 2004.</p><p>2. T. Uehara, G. R. Ainslie, K. Kutanzi, I. P. Pogribny, L. Muskhelishvili, T. Izawa, J. Yamate, O. Kosyk, S. Shymonyak, B. U. Bradford, G. A. Boorman, R. Bataller, and I. Rusyn, “Molecular mechanisms of fibrosis-associated promotion of liver carcinogenesis.,” <italic>Toxicological sciences: an official journal of the Society of Toxicology</italic>, vol. 132, no. 1, pp. 53–63, Mar. 2013.</p><p>3. F. Heindryckx, K. Mertens, N. Charette, B. Vandeghinste, C. Casteleyn, C. Van Steenkiste, D. Slaets, L. Libbrecht, S. Staelens, P. Starkel, A. Geerts, I. Colle, and H. Van Vlierberghe, “Kinetics of angiogenic changes in a new mouse model for hepatocellular carcinoma,” <italic>Molecular Cancer</italic>, vol. 9, no. 1, p. 219, 2010.</p><p>4. A. Chakrabarti, A. W. Chen, and J. D. Varner, “A review of the mammalian unfolded protein response.,” <italic>Biotechnology and bioengineering</italic>, vol. 108, no. 12, pp. 2777–93, Dec. 2011.</p><p>5. A. Stolz and D. H. Wolf, “Endoplasmic reticulum associated protein degradation: a chaperone assisted journey to hell.,” <italic>Biochimica et biophysica acta</italic>, vol. 1803, no. 6, pp. 694–705, Jun. 2010.</p><p>6. L. Tagliavacca, A. Caretti, P. Bianciardi, and M. Samaja, “In vivo up-regulation of the unfolded protein response after hypoxia.,” <italic>Biochimica et biophysica acta</italic>, Mar. 2012.</p><p>7. H.-R. Park, A. Tomida, S. Sato, Y. Tsukumo, J. Yun, T. Yamori, Y. Hayakawa, T. Tsuruo, and K. Shin-ya, “Effect on tumor cells of blocking survival response to glucose deprivation.,” <italic>Journal of the National Cancer Institute</italic>, vol. 96, no. 17, pp. 1300–10, Sep. 2004.</p><p>8. R. C. Austin, “The unfolded protein response in health and disease.,” <italic>Antioxidants & redox signaling</italic>, vol. 11, no. 9, pp. 2279–87, Sep. 2009.</p><p>9. H. Kraskiewicz and U. Fitzgerald, “InterfERing with endoplasmic reticulum stress.,” <italic>Trends in pharmacological sciences</italic>, vol. 33, no. 2, pp. 53–63, Feb. 2012.</p><p>10. D. Ron and P. Walter, “Signal integration in the endoplasmic reticulum unfolded protein response.,” <italic>Nature reviews. Molecular cell biology</italic>, vol. 8, no. 7, pp. 519–29, Jul. 2007.</p><p>11. J. H. Lin, H. Li, D. Yasumura, H. R. Cohen, C. Zhang, B. Panning, K. M. Shokat, M. M. Lavail, and P. Walter, “IRE1 signaling affects cell fate during the unfolded protein response.,” <italic>Science (New York, N.Y.)</italic>, vol. 318, no. 5852, pp. 944–9, Nov. 2007.</p><p>12. E. Bobrovnikova-Marjon, C. Grigoriadou, D. Pytel, F. Zhang, J. Ye, C. Koumenis, D. Cavener, and J. A. Diehl, “PERK promotes cancer cell proliferation and tumor growth by limiting oxidative DNA damage.,” <italic>Oncogene</italic>, vol. 29, no. 27, pp. 3881–95, Jul. 2010.</p><p>13. J. Wu, D. T. Rutkowski, M. Dubois, J. Swathirajan, T. Saunders, J. Wang, B. Song, G. D.-Y. Yau, and R. J. Kaufman, “ATF6alpha optimizes long-term endoplasmic reticulum function to protect cells from chronic stress.,” <italic>Developmental cell</italic>, vol. 13, no. 3, pp. 351–64, Sep. 2007.</p><p>14. K. Mori, “Signalling pathways in the unfolded protein response: development from yeast to mammals.,” <italic>Journal of biochemistry</italic>, vol. 146, no. 6, pp. 743–50, Dec. 2009.</p><p>15. C. Hetz, F. Martinon, D. Rodriguez, and L. H. Glimcher, “The unfolded protein response: integrating stress signals through the stress sensor IRE1α.,” <italic>Physiological reviews</italic>, vol. 91, no. 4, pp. 1219–43, Oct. 2011.</p><p>16. B. F. Teske, S. A. Wek, P. Bunpo, J. K. Cundiff, J. N. McClintick, T. G. Anthony, and R. C. Wek, “The eIF2 kinase PERK and the integrated stress response facilitate activation of ATF6 during endoplasmic reticulum stress.,” <italic>Molecular biology of the cell</italic>, vol. 22, no. 22, pp. 4390–405, Nov. 2011.</p><p>17. G. Jing, J. J. Wang, and S. X. Zhang, “ER stress and apoptosis: a new mechanism for retinal cell death.,” <italic>Experimental diabetes research</italic>, vol. 2012, p. 589589, Jan. 2012.</p><p>18. R. V Rao, A. Peel, A. Logvinova, G. del Rio, E. Hermel, T. Yokota, P. C. Goldsmith, L. M. Ellerby, H. M. Ellerby, and D. E. Bredesen, “Coupling endoplasmic reticulum stress to the cell death program: role of the ER chaperone GRP78.,” <italic>FEBS letters</italic>, vol. 514, no. 2–3, pp. 122–8, Mar. 2002.</p><p>19. E. Szegezdi, S. E. Logue, A. M. Gorman, and A. Samali, “Mediators of endoplasmic reticulum stress-induced apoptosis.,” <italic>EMBO reports</italic>, vol. 7, no. 9, pp. 880–5, Sep. 2006.</p><p>20. A. S. Lee, “GRP78 induction in cancer: therapeutic and prognostic implications.,” <italic>Cancer research</italic>, vol. 67, no. 8, pp. 3496–9, Apr. 2007.</p><p>21. F. Y. Al-Rawashdeh, P. Scriven, I. C. Cameron, P. V Vergani, and L. Wyld, “Unfolded protein response activation contributes to chemoresistance in hepatocellular carcinoma.,” <italic>European journal of gastroenterology & hepatology</italic>, vol. 22, no. 9, pp. 1099–105, Sep. 2010.</p><p>22. M. Shuda, “Activation of the ATF6, XBP1 and grp78 genes in human hepatocellular carcinoma: a possible involvement of the ER stress pathway in hepatocarcinogenesis,” <italic>Journal of Hepatology</italic>, vol. 38, no. 5, pp. 605–614, May 2003.</p><p>23. M. Arai, N. Kondoh, N. Imazeki, A. Hada, K. Hatsuse, F. Kimura, O. Matsubara, K. Mori, T. Wakatsuki, and M. Yamamoto, “Transformation-associated gene regulation by ATF6alpha during hepatocarcinogenesis.,” <italic>FEBS letters</italic>, vol. 580, no. 1, pp. 184–90, Jan. 2006.</p><p>24. F. Borel, R. Han, A. Visser, H. Petry, S. J. H. van Deventer, P. L. M. Jansen, and P. Konstantinova, “Adenosine triphosphate-binding cassette transporter genes up-regulation in untreated hepatocellular carcinoma is mediated by cellular microRNAs.,” <italic>Hepatology (Baltimore, Md.)</italic>, vol. 55, no. 3, pp. 821–32, Mar. 2012.</p><p>25. M. Liu, D. Li, R. Aneja, H. C. Joshi, S. Xie, C. Zhang, and J. Zhou, “PO(2)-dependent differential regulation of multidrug resistance 1 gene expression by the c-Jun NH2-terminal kinase pathway.,” <italic>The Journal of biological chemistry</italic>, vol. 282, no. 24, pp. 17581–6, Jun. 2007.</p><p>26. G. Li, X. Chen, Q. Wang, Z. Xu, W. Zhang, and L. Ye, “The roles of four multi-drug resistance proteins in hepatocellular carcinoma multidrug resistance.,” <italic>Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban</italic>, vol. 27, no. 2, pp. 173–5, Apr. 2007.</p><p>27. Z. Sun, Z. Zhao, G. Li, S. Dong, Z. Huang, L. Ye, H. Liang, J. Qu, X. Ai, W. Zhang, and X. Chen, “Relevance of two genes in the multidrug resistance of hepatocellular carcinoma: in vivo and clinical studies.,” <italic>Tumori</italic>, vol. 96, no. 1, pp. 90–6, 2010.</p><p>28. M. A. Moustafa, D. Ogino, M. Nishimura, N. Ueda, S. Naito, M. Furukawa, T. Uchida, I. Ikai, H. Sawada, and M. Fukumoto, “Comparative analysis of ATP-binding cassette (ABC) transporter gene expression levels in peripheral blood leukocytes and in liver with hepatocellular carcinoma.,” <italic>Cancer science</italic>, vol. 95, no. 6, pp. 530–6, Jul. 2004.</p><p>29. C. H. Sukowati, N. Rosso, D. Pascut, B. Anfuso, G. Torre, P. Francalanci, L. S. Crocè, and C. Tiribelli, “Gene and functional up-regulation of the BCRP/ABCG2 transporter in hepatocellular carcinoma.,” <italic>BMC gastroenterology</italic>, vol. 12, p. 160, Jan. 2012.</p><p>30. K. Hoffmann, L. Shibo, Z. Xiao, T. Longerich, M. W. Büchler, and P. Schemmer, “Correlation of gene expression of ATP-binding cassette protein and tyrosine kinase signaling pathway in patients with hepatocellular carcinoma.,” <italic>Anticancer research</italic>, vol. 31, no. 11, pp. 3883–90, Nov. 2011.</p><p>31. P. V Korita, T. Wakai, Y. Shirai, Y. Matsuda, J. Sakata, M. Takamura, M. Yano, A. Sanpei, Y. Aoyagi, K. Hatakeyama, and Y. Ajioka, “Multidrug resistance-associated protein 2 determines the efficacy of cisplatin in patients with hepatocellular carcinoma.,” <italic>Oncology reports</italic>, vol. 23, no. 4, pp. 965–72, Apr. 2010.</p><p>32. P. Grudé, F. Conti, D. Mennecier, A. Louvel, D. Houssin, B. Weill, and Y. Calmus, “MDR1 gene expression in hepatocellular carcinoma and the peritumoral liver of patients with and without cirrhosis.,” <italic>Cancer letters</italic>, vol. 186, no. 1, pp. 107–13, Dec. 2002.</p><p>33. K. Effendi, T. Mori, M. Komuta, Y. Masugi, W. Du, and M. Sakamoto, “Bmi-1 gene is upregulated in early-stage hepatocellular carcinoma and correlates with ATP-binding cassette transporter B1 expression.,” <italic>Cancer science</italic>, vol. 101, no. 3, pp. 666–72, Mar. 2010.</p><p>34. Grude P., Conti F., Mennecier D., Louvel A., Houssin D., Weill B., and Calmus Y., “MDR1 gene expression in hepatocellular carcinoma and the peritumoral liver of patients with and without cirrhosis,” <italic>Cancer Letters</italic>, vol. 186, no. 1, p. 7.</p><p>35. E. Mizukoshi, M. Honda, K. Arai, T. Yamashita, Y. Nakamoto, and S. Kaneko, “Expression of multidrug resistance-associated protein 3 and cytotoxic T cell responses in patients with hepatocellular carcinoma.,” <italic>Journal of hepatology</italic>, vol. 49, no. 6, pp. 946–54, Dec. 2008.</p><p>36. S. Vander Borght, M. Komuta, L. Libbrecht, A. Katoonizadeh, R. Aerts, S. Dymarkowski, C. Verslype, F. Nevens, and T. Roskams, “Expression of multidrug resistance-associated protein 1 in hepatocellular carcinoma is associated with a more aggressive tumour phenotype and may reflect a progenitor cell origin.,” <italic>Liver international: official journal of the International Association for the Study of the Liver</italic>, vol. 28, no. 10, pp. 1370–80, Dec. 2008.</p><p>37. Z.-S. Chen and A. K. Tiwari, “Multidrug resistance proteins (MRPs/ABCCs) in cancer chemotherapy and genetic diseases.,” <italic>The FEBS journal</italic>, vol. 278, no. 18, pp. 3226–45, Sep. 2011.</p><p>38. Y. Xu, H. Yu, H. Qin, J. Kang, C. Yu, J. Zhong, J. Su, H. Li, and L. Sun, “Inhibition of autophagy enhances cisplatin cytotoxicity through endoplasmic reticulum stress in human cervical cancer cells.,” <italic>Cancer letters</italic>, vol. 314, no. 2, pp. 232–43, Jan. 2012.</p><p>39. M. J. Mann and L. M. Hendershot, “UPR activation alters chemosensitivity of tumor cells,” <italic>Cancer Biology & Therapy</italic>, vol. 5, no. 7, pp. 736–740, Jul. 2006.</p><p>40. Y. Liang, T. Zheng, R. Song, J. Wang, D. Yin, L. Wang, H. Liu, L. Tian, X. Fang, X. Meng, H. Jiang, J. Liu, and L. Liu, “Hypoxia-mediated sorafenib resistance can be overcome by EF24 through VHL-dependent HIF-1α inhibition in Hepatocellular Carcinoma.,” <italic>Hepatology (Baltimore, Md.)</italic>, Jan. 2013.</p><p>41. W. E. Naugler, T. Sakurai, S. Kim, S. Maeda, K. Kim, A. M. Elsharkawy, and M. Karin, “Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production.,” <italic>Science (New York, N.Y.)</italic>, vol. 317, no. 5834, pp. 121–4, Jul. 2007.</p><p>42. C. Szpirer and J. Szpirer, “A mouse hepatoma cell line which secretes several serum proteins including albumin and alpha-foetoprotein.,” <italic>Differentiation; research in biological diversity</italic>, vol. 4, no. 2, pp. 85–91, Oct. 1975.</p><p>43. K. Zhang, S. Wang, J. Malhotra, J. R. Hassler, S. H. Back, G. Wang, L. Chang, W. Xu, H. Miao, R. Leonardi, Y. E. Chen, S. Jackowski, and R. J. Kaufman, “The unfolded protein response transducer IRE1α prevents ER stress-induced hepatic steatosis.,” <italic>The EMBO journal</italic>, vol. 30, no. 7, pp. 1357–75, Apr. 2011.</p><p>44. Y. Yamamoto, Y. Nishiyama, R. Kameyama, K. Okano, H. Kashiwagi, A. Deguchi, M. Kaji, and M. Ohkawa, “Detection of hepatocellular carcinoma using 11C-choline PET: comparison with 18F-FDG PET.,” <italic>Journal of nuclear medicine: official publication, Society of Nuclear Medicine</italic>, vol. 49, no. 8, pp. 1245–8, Aug. 2008.</p><p>45. S.-O. Lim, S.-G. Park, J.-H. Yoo, Y.-M. Park, H.-J. Kim, K.-T. Jang, J.-W. Cho, B.-C. Yoo, G.-H. Jung, and C.-K. Park, “Expression of heat shock proteins (HSP27, HSP60, HSP70, HSP90, GRP78, GRP94) in hepatitis B virus-related hepatocellular carcinomas and dysplastic nodules.,” <italic>World journal of gastroenterology: WJG</italic>, vol. 11, no. 14, pp. 2072–9, Apr. 2005.</p><p>46. J. M. Luk, C.-T. Lam, A. F. M. Siu, B. Y. Lam, I. O. L. Ng, M.-Y. Hu, C.-M. Che, and S.-T. Fan, “Proteomic profiling of hepatocellular carcinoma in Chinese cohort reveals heat-shock proteins (Hsp27, Hsp70, GRP78) up-regulation and their associated prognostic values.,” <italic>Proteomics</italic>, vol. 6, no. 3, pp. 1049–57, Feb. 2006.</p><p>47. J. M. Matos, F. A. Witzmann, O. W. Cummings, and C. M. Schmidt, “A pilot study of proteomic profiles of human hepatocellular carcinoma in the United States.,” <italic>The Journal of surgical research</italic>, vol. 155, no. 2, pp. 237–43, Aug. 2009.</p><p>48. D. Dong, M. Ni, J. Li, S. Xiong, W. Ye, J. J. Virrey, C. Mao, R. Ye, M. Wang, L. Pen, L. Dubeau, S. Groshen, F. M. Hofman, and A. S. Lee, “Critical role of the stress chaperone GRP78/BiP in tumor proliferation, survival, and tumor angiogenesis in transgene-induced mammary tumor development.,” <italic>Cancer research</italic>, vol. 68, no. 2, pp. 498–505, Jan. 2008.</p><p>49. Z. Li and Z. Li, “Glucose regulated protein 78: A critical link between tumor microenvironment and cancer hallmarks.,” <italic>Biochimica et biophysica acta</italic>, Mar. 2012.</p><p>50. H. Yoshida, T. Matsui, A. Yamamoto, T. Okada, and K. Mori, “XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor.,” <italic>Cell</italic>, vol. 107, no. 7, pp. 881–91, Dec. 2001.</p><p>51. H. Yoshida, M. Oku, M. Suzuki, and K. Mori, “pXBP1(U) encoded in XBP1 pre-mRNA negatively regulates unfolded protein response activator pXBP1(S) in mammalian ER stress response.,” <italic>The Journal of cell biology</italic>, vol. 172, no. 4, pp. 565–75, Feb. 2006.</p><p>52. Y. Qi, X. Chen, C. Chan, D. Li, C. Yuan, F. Yu, M. C. Lin, D. T. Yew, H.-F. Kung, and L. Lai, “Two-dimensional differential gel electrophoresis/analysis of diethylnitrosamine induced rat hepatocellular carcinoma.,” <italic>International journal of cancer. Journal international du cancer</italic>, vol. 122, no. 12, pp. 2682–8, Jun. 2008.</p><p>53. M. Valko, C. J. Rhodes, J. Moncol, M. Izakovic, and M. Mazur, “Free radicals, metals and antioxidants in oxidative stress-induced cancer.,” <italic>Chemico-biological interactions</italic>, vol. 160, no. 1, pp. 1–40, Mar. 2006.</p><p>54. A. Jauhiainen, C. Thomsen, L. Strömbom, P. Grundevik, C. Andersson, A. Danielsson, M. K. Andersson, O. Nerman, L. Rörkvist, A. Ståhlberg, and P. Aman, “Distinct Cytoplasmic and Nuclear Functions of the Stress Induced Protein DDIT3/CHOP/GADD153.,” <italic>PloS one</italic>, vol. 7, no. 4, p. e33208, Jan. 2012.</p><p>55. S. J. Marciniak, C. Y. Yun, S. Oyadomari, I. Novoa, Y. Zhang, R. Jungreis, K. Nagata, H. P. Harding, and D. Ron, “CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum.,” <italic>Genes & development</italic>, vol. 18, no. 24, pp. 3066–77, Dec. 2004.</p><p>56. H. Nishitoh, “CHOP is a multifunctional transcription factor in the ER stress response.,” <italic>Journal of biochemistry</italic>, vol. 151, no. 3, pp. 217–9, Mar. 2012.</p><p>57. H. Zinszner, M. Kuroda, X. Wang, N. Batchvarova, R. T. Lightfoot, H. Remotti, J. L. Stevens, and D. Ron, “CHOP is implicated in programmed cell death in response to impaired function of the endoplasmic reticulum.,” <italic>Genes & development</italic>, vol. 12, no. 7, pp. 982–95, Apr. 1998.</p><p>58. M. C. Hollander, S. Poola-Kella, and A. J. Fornace, “Gadd34 functional domains involved in growth suppression and apoptosis.,” <italic>Oncogene</italic>, vol. 22, no. 25, pp. 3827–32, Jun. 2003.</p><p>59. I. Saeki, S. Terai, K. Fujisawa, T. Takami, N. Yamamoto, T. Matsumoto, Y. Hirose, Y. Murata, T. Yamasaki, and I. Sakaida, “Bortezomib induces tumor-specific cell death and growth inhibition in hepatocellular carcinoma and improves liver fibrosis.,” <italic>Journal of gastroenterology</italic>, Sep. 2012.</p><p><bold>Contact E-mail Address:</bold><email>yvespaul.vandewynckel@Ugent.be</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> animal study, chemoresistance, endoplasmic reticulum stress, Hepatocelluar carcinoma, small animal imaging</p></sec><sec><title>OP048 CHEMOTHERAPY-INDUCED APOPTOTIC HEPATOMA CELLS STIMULATE COMPENSATORY PROLIFERATION</title><p><bold>M. Osawa</bold><sup>1,*</sup>, Y. Matsuda<sup>2</sup>, S. Fujimaki<sup>2</sup>, T. Wakai<sup>3</sup>, M. Kubota<sup>1</sup></p><p><italic><sup>1</sup>Division of Pediatric Surgery, Niigata University Graduate School of Medical and Dental Sciences, <sup>2</sup>Department of Medical Technology, Niigata University Graduate School of Health Sciences, <sup>3</sup>Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan</italic></p><p><bold>INTRODUCTION:</bold> Accumulating evidence suggests that dying apoptotic cells are involved in various types of extracellular stimuli. We addressed whether chemotherapy-induced dying hepatoma cells affect the growth of intact living tumour cells, leading to a paradoxical response to chemotherapy.</p><p><bold>AIMS&METHODS:</bold> HepG2 and PLC/PRF/5 cells were incubated with doxorubicin (DOX), 5-fluorouracil (5FU) and cisplatin (CDDP) for 24 hours. After culture media were refreshed, cells were maintained for 24 hours and served as donor cultures. The conditioned media of donor cells was transferred to recipient hepatoma cell cultures, which were harvested 2-48 hours later. Cell growth and apoptosis were analysed by trypan blue and MTT assay; western blotting was used to analyse cell growth-related signalling. In a xenograft tumour model, nude mice were inoculated with HepG2 (4 × 10<sup>6</sup> cells) with or without cisplatin-sensitized dying HepG2 (4 × 10<sup>6</sup> cells). Tumour growth rates were followed for 40 days.</p><p><bold>RESULTS:</bold> In chemotherapy-treated donor cells, cell viabilities were decreased by 2-8%. When these cells were maintained for more than 10 days, the numbers of living donor cells remained unchanged and p21/Cip1 was significantly increased (4-8 fold), suggesting that they were in a senescent state. Cell numbers of the recipient HepG2 cells increased by 1.4-, 1.6- and 2.1-fold (all <italic>P</italic> < 0.05) by exposure to media from DOX-, 5FU-, and CDDP-treated donor cells, respectively. In recipient PLC/PRF/5 cells, cell numbers increased by 2.1-, 1.4- and 2.8-fold (all <italic>P</italic> < 0.05) by exposure to media of DOX-, 5FU-, and CDDP-treated donors, respectively. In recipient cells cultured in media from CDDP-sensitized cells, levels of phosphorylated CDK2, MAP kinases, STAT3, NFkB and p65 significantly increased. In animal models, tumours were invisible in mice inoculated with CDDP-induced dying cells. Mean tumour size was 450 mm<sup>3</sup> in mice administered with living HepG2 cells, but 782 mm<sup>3</sup> in mice administered the mixture of living and dying cells (<italic>P</italic> < 0.05).</p><p><bold>CONCLUSION:</bold> Chemotherapy-induced dying hepatoma cells stimulate compensatory proliferation of living tumour cells. Compensatory proliferation might be a useful target for treating hepatocellular carcinoma.</p><p><bold>Contact E-mail Address:</bold><email>yasunobu@med.niigata-u.ac.jp</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> compensatory proliferation, drug resistance, hepatocellular carcinoma</p></sec><sec><title>OP049 HIGH UBIQUITOUS MITOCHONDRIAL CREATINE KINASE EXPRESSION IN HEPATOCELLULAR CARCINOMA DENOTES A POOR PROGNOSIS WITH HIGHLY-MALIGNANT POTENTIAL.</title><p><bold>H. Ikeda</bold><sup>1,*</sup>, K. Enooku<sup>1</sup>, B. Uranbileg<sup>1</sup>, H. Yoshida<sup>1</sup>, K. Moriya<sup>1</sup>, K. Koike<sup>1</sup>, Y. Yatomi<sup>1</sup></p><p><italic><sup>1</sup>The University of Tokyo, Tokyo, Japan</italic></p><p><bold>INTRODUCTION:</bold> We previously reported the increase in serum mitochondrial creatine kinase (MtCK) activity in patients with hepatocellular carcinoma (HCC), which was mostly due to the increase in ubiquitous MtCK (uMtCK) among two MtCK isoenzymes, and the high uMtCK mRNA expression in HCC cell lines.</p><p><bold>AIMS&METHODS:</bold> We explored the mechanism(s) and the significance of high uMtCK expression in HCC. Consecutive 105 HCC patients, who underwent radiofrequency ablation with curative intent, were enrolled to analyze their prognosis.</p><p><bold>RESULTS:</bold> In hepatitis C virus core gene transgenic mice, known to develop mitochondrial injury and subsequently HCC in the liver, uMtCK mRNA expression was increased in HCC tissues but not in liver tissues with mitochondrial injury alone or non-tumorous tissues of the livers bearing HCC. Transient overexpression of ankyrin repeat and suppressor of cytokine signaling box protein 9 (ASB9) reduced uMtCK protein levels in HCC cells. Then, the reduction of uMtCK expression by siRNA led to increased cell death, and reduced proliferation, migration and invasion in HCC cell lines. Finally, the patients with serum MtCK activity >19.4 U/L prior to the treatment had significantly shorter survival time than those with serum MtCK activity ≤19.4 U/L, where higher serum MtCK activity was retained as an independent risk for HCC-related death on multivariate analysis.</p><p><bold>CONCLUSION:</bold> High uMtCK expression in HCC may be caused by hepatocarcinogenesis <italic>per se</italic> but not by mitochondrial injury, where ASB9 could be one of the regulators of uMtCK protein levels, and associated with highly-malignant potential to suggest a poor prognosis.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> ankyrin repeat and suppressor of cytokine signaling box protein 9, ubiquitous mitochondrial creatine kinase</p></sec><sec><title>OP050 AUTOCRINE VEGF SIGNALING DIRECTLY SUPPORTS CELL PROLIFERATION IN HEPATOCELLULAR CARCINOMA</title><p><bold>S. Peng</bold><sup>1,*</sup>, M. Chen<sup>1</sup></p><p><italic><sup>1</sup>Division of Gastroenterology and Hepatology, The First Affiliated Hospital of Sun-Yat Sen University, Guangzhou, China</italic></p><p><bold>INTRODUCTION:</bold> Vascular endothelial growth factor (VEGF), well recognized as a potent inducer of angiogenesis, recently has been shown to exert direct pro-proliferative and pro-survival effects on cancer cells. In hepatocellular carcinoma (HCC), angiogenesis has been shown to be a significant phenotype associated with the process of tumor development. In addition, increased expression of VEGF receptors are also found in HCC tumor cells as independent prognostic factors, suggesting that autocrine VEGF signaling loop exists in an angiogenesis-independent fashion. However, the roles of autocrine VEGF signaling in HCC remain unknown.</p><p><bold>AIMS&METHODS:</bold> Immunohistochemistry (IHC) and Western blotting (WB) were used to characterize the expression of VEGF and VEGFR1, VEGFR2, and activated VEGFR1 (pVEGFR1) and VEGFR2 (pVEGFR2) in normal liver, peritumor, tumor and metastasized tumor tissues from HCC patients (N=32), Using HCC cell line HepG2, 7703 and Huh7, we measured baseline protein levels of VEGF and its receptors and studied roles of VEGF and its receptors on cell proliferation.</p><p><bold>RESULTS:</bold> By IHC and WB, VEGF was found located in cytoplasm with gradual increase from liver, peritumor, to tumor tissue. The activated VEGF receptors (pVEGFR1 and pVEGFR2) were mainly located on cell membrane and cytoplasm in normal liver and peritumor tissues; while in tumor and metastasized tissues, the pVEGFR1 and pVEGFR2 were mainly in nuclei with a significantly higher expression level (p=0.023). Multivariate analysis identified that the high expression of VEGF(OR = 3.919, 95%CI 1.33–11.53; P = 0.013) in HCC patients was associated with tumor diameter larger than 3cm. Treatment with human recombinant VEGF (rhVEGF) significantly increased cell proliferation in HepG2 (+13.4%) and 7703(+17.4%), and Huh7 (+14.5%) (P<0.05), while treatment with neutralization antibody against VEGF significantly decreased cell proliferation (-12.4%. -13.5%, and -11.5% for HepG2, Huh7, and 7703 respectively) (P<0.05). Treatment with VEGFR-1 and VEGFR-2 neutralization antibody VEGFR1, and VEGFR2 not only significantly decreased cell proliferation but also reduced baseline VEGF secretion in HepG2, 7703 and Huh7 cells.</p><p><bold>CONCLUSION:</bold> In HCC, VEGF promotes cell proliferation and regenerates self-sustainable growth signals (by causing novel VEGF synthesis and secretion) through interaction with VEGFR1 and VEGFR2 on cancer cells. The findings of autocrine VEGF signaling support additional molecular mechanism of the VEGF/R-targeting agents for use in chemotherapeutic treatment.</p><p><bold>Contact E-mail Address:</bold><email>pengsui2002@sina.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> hepatocellular carcinoma, Proliferation, vascular endothelial growth factor receptor</p></sec><sec><title>OP051 VALPROIC ACID CONFERS RESISTANCE TO SORAFENIB IN MICE WITH HEPATOCELLULAR CARCINOMA</title><p><bold>Y. Matsuda</bold><sup>1,*</sup>, M. Osawa<sup>2</sup>, S. Fujimaki<sup>1</sup>, T. Wakai<sup>3</sup>, M. Kubota<sup>2</sup>, M. Takamura<sup>4</sup>, S. Yamagiwa<sup>4</sup>, Y. Aoyagi<sup>4</sup></p><p><italic><sup>1</sup>Department of Medical Technology, Niigata University Graduate School of Health Sciences, <sup>2</sup>Division of Pediatric Surgery, <sup>3</sup>Division of Digestive and General Surgery, <sup>4</sup>Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan</italic></p><p><bold>INTRODUCTION:</bold> Sorafenib, a multi-kinase inhibitor, rarely causes tumour regression in patients with hepatocellular carcinoma (HCC). We addressed whether cytokine-mediated signalling is involved in this drug resistance, and investigated whether combination treatment might defer this mechanism and enhance the efficacy of sorafenib.</p><p><bold>AIMS&METHODS:</bold> HepG2 and Hepa1-6 cells were incubated with EGF, HGF and TGF-β for 48 hours, and were treated with sorafenib (7.5 micro-M) in combination with clinically available agents, including celecoxib, fluvastatin, candesartan, chloroquine or valproic acid, for 48 hours. Kinetics of cell growth and apoptosis was analysed by MTT assay. Western blotting was used to examine sorafenib-targeted signalling. An orthotopic tumour model was set up by intrahepatic injection of Hepa1-6 cells into mice with or without carbon tetrachloride-induced chronic liver injury. Based on the results of in vitro experiments, mice were administered sorafenib (30 mg/Kg/day) with valproic acid (0.4% in drinking water) for 4 weeks.</p><p><bold>RESULTS:</bold> In cultured cells, sorafenib decreased levels of phosphorylated MAP kinases and Akt, resulting in decreased cell growth. In TGF-β-pretreated cells, however, the effect of sorafenib on cell growth was inhibited by 60-70% (<italic>P</italic> < 0.05) and the levels of phosphorylated MAP kinases and Akt were restored. When TGF-β-treated cells were exposed to sorafenib plus valproic acid, phospho-MAP kinases and Akt were significantly decreased and apoptotic cell numbers were increased to 6-8-fold of those treated with sorafenib alone (<italic>P</italic> < 0.01). In the mouse model, mean TGF-β serum concentrations were increased compared to normal mice (75 ng/mL vs. 210 ng/mL; <italic>P</italic> < 0.05). Sorafenib treatment decreased mean tumour size (<italic>P</italic> < 0.05), but this effect was marginal in mice with chronic liver injury. Sorafenib plus valproic acid resulted in significantly decreased tumour size in mice with liver injury (<italic>P</italic> < 0.01).</p><p><bold>CONCLUSION:</bold> TGF-β might play a role in acquired resistance to sorafenib in some types of hepatoma cells. Combination treatment with valproic acid might improve the efficacy of sorafenib in HCC patients with underlying liver diseases.</p><p><bold>Contact E-mail Address:</bold><email>yasunobu@med.niigata-u.ac.jp</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> drug resistance, hepatocellular carcinoma, sorafenib</p></sec><sec><title></title><p><bold>MONDAY, OCTOBER 14, 2013 14:00-15:30</bold></p><p><bold>Getting more out of anti-TNF therapy in IBD – Hall 2</bold></p></sec><sec><title>OP052 STRATEGIC TIMING OF ANTI-TNF THERAPY IN POSTOPERATIVE CROHN’S DISEASE: COMPARISON OF ROUTINE USE IMMEDIATELY POSTOPERATIVELY WITH SELECTIVE USE AFTER DEMONSTRATED RECURRENCE AT 6 MONTH ENDOSCOPY. RESULTS FROM POCER</title><p><bold>P. De Cruz</bold><sup>1,*</sup>, M. Kamm<sup>1</sup>, A. Hamilton<sup>1</sup>, K. Ritchie<sup>1</sup>, S. Krejany<sup>1</sup>, A. Gorelik<sup>1</sup>, D. Liew<sup>1</sup>, L. Prideaux<sup>1</sup>, I. Lawrance<sup>1</sup>, J. Andrews<sup>1</sup>, P. Bampton<sup>1</sup>, M. Sparrow<sup>1</sup>, T. Florin<sup>1</sup>, P. Gibson<sup>1</sup>, H. Debinski<sup>1</sup>, R. Gearry<sup>1</sup>, F. Macrae<sup>1</sup>, R. Leong<sup>1</sup>, I. Kronborg<sup>1</sup>, G. Radford-Smith<sup>1</sup>, W. Selby<sup>1</sup>, M. Johnston<sup>1</sup>, R. Woods<sup>1</sup>, R. Elliott<sup>1</sup>, S. Bell<sup>1</sup>, S. Brown<sup>1</sup>, W. Connell<sup>1</sup>, P. Desmond<sup>1</sup></p><p><italic><sup>1</sup>St Vincent's Hospital and University of Melbourne, Melbourne, Australia</italic></p><p><bold>INTRODUCTION:</bold> Recent data suggest that anti-TNF therapy prevents postoperative recurrence of Crohn’s disease. Routine postoperative use is costly and may lead to overtreatment; an alternative may be selective use for early endoscopic recurrence. These strategies have been compared with mucosal healing as the goal in this “treat to target” study.</p><p><bold>AIMS&METHODS:</bold> In the Post Operative Crohn’s Endoscopic Recurrence, “POCER” study, after resection patients were stratified for risk of recurrence as high (smoker, perforating disease, ≥2nd operation) or low risk. All patients received 3 months metronidazole 400mg bd. High risk patients also received daily azathioprine 2mg/kg or 6 mercaptopurine 1.5mg/kg, or adalimumab 40mg fortnightly if thiopurine intolerant. Patients were randomised to endoscopy at 6 months or no endoscopy; endoscopic remission defined as Rutgeerts score i0 or i1 & recurrence as ≥i2. For endoscopic recurrence at 6 months high risk patients on thiopurine stepped up to adalimumab 40mg fortnightly, & high risk thiopurine-intolerant patients stepped up to weekly adalimumab. All patients were colonoscoped at 18 months: the primary endpoint endoscopic recurrence. In this intent-to-treat sub-analysis we compared the 18 month outcomes of high risk patients in the endoscopy arm on immediate postoperative adalimumab to those initially on thiopurine who stepped-up to combined adalimumab + thiopurine for recurrence at 6 months.</p><p><bold>RESULTS:</bold> Endoscopic recurrence at 18 months occurred in 12/28 (43%) patients on adalimumab immediately postoperatively compared to 19/32 (59%) patients initially on thiopurine who stepped up to adalimumab + thiopurine at 6 months; P=0.20. Complete mucosal normality (i0) occurred in 9/28 (32%) v 7/32 (22%); P=0.37. Severe disease (i3 & i4) occurred in 3/28 (11%) v 3/32 (9%); P=NS.</p><p><bold>CONCLUSION:</bold> Recurrence did not differ significantly between immediate postoperative adalimumab & step-up adalimumab at 6 months for endoscopic recurrence, although the former tended to be more effective. There was minimal difference in rates of severe disease recurrence between the two strategies. Step-up with anti-TNF therapy based on endoscopic findings is a viable postoperative strategy in patients at high risk of recurrence.</p><p><bold>Contact E-mail Address:</bold><email>Peter.DECRUZ@svhm.org.au</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Crohn`s disease, Inflammatory bowel disease (IBD), Postoperative recurrence</p></sec><sec><title>OP053 IMPACT OF CONCOMITANT IMMUNOMODULATOR TREATMENT ON EFFICACY AND SAFETY OF ANTI-TNF THERAPY IN CROHN’S DISEASE: A META-ANALYSIS OF PLACEBO CONTROLLED TRIALS WITH INDIVIDUAL PATIENT-LEVEL DATA</title><p><bold>J. Jones</bold><sup>1</sup>, G. Kaplan<sup>2</sup>, L. Peyrin-Biroulet<sup>3,*</sup>, L. Baidoo<sup>4</sup>, S. Devlin<sup>2</sup>, G. Melmed<sup>5</sup>, D. Tanyingoh<sup>2</sup>, L. Raffals<sup>6</sup>, P. Irving<sup>7</sup>, P. Kozuch<sup>8</sup>, M. Sparrow<sup>9</sup>, F. Velayos<sup>10</sup>, B. Bressler<sup>11</sup>, A. Cheifetz<sup>12</sup>, J.-F. Colombel<sup>13</sup>, C. Siegel<sup>14</sup></p><p><italic><sup>1</sup>Hepato Gastro-enterology, University of Saskatchewan, Saskatoon, <sup>2</sup>Hepato Gastro-enterology, University Hospital of Calgary, Calgary, Canada, <sup>3</sup>Hepato Gastro-enterology, University Hospital of Nancy, Vandoeuvre-lès-Nancy, France, <sup>4</sup>Hepato Gastro-enterology, University of Pittsburgh, Pittsburgh, <sup>5</sup>Hepato Gastro-enterology, Cedars-Sinai Medical Center, Los Angeles, <sup>6</sup>Hepato Gastro-enterology, Mayo Clinic, Rochester, United States, <sup>7</sup>Hepato Gastro-enterology, Guy's and St. Thomas' Hospitals, London, United Kingdom, <sup>8</sup>Hepato Gastro-enterology, Jefferson University, Philadelphia, United States, <sup>9</sup>Hepato Gastro-enterology, Alfred Hospital, Melbourne, Australia, <sup>10</sup>Hepato Gastro-enterology, University of California, San Francisco, United States, <sup>11</sup>Hepato Gastro-enterology, University of British Columbia, Vancouver, Canada, <sup>12</sup>Hepato Gastroenterology, Beth Israel Deaconess Medical Center, Boston, <sup>13</sup>Hepato Gastro enterology, Icahn Medical School at Mount Sinai, New York, <sup>14</sup>Hepato Gastro enterology, Dartmouth-Hitchcock Medical Center, Lebanon, United States</italic></p><p><bold>INTRODUCTION:</bold> Whether patients with Crohn’s disease (CD) starting anti-TNF therapy should continue concomitant immunomodulator treatment is debated. We conducted a systematic review and meta-analysis of randomized controlled trials (RCT) of anti-TNF agents to compare the efficacy and safety of concomitant immunomodulator therapy versus anti-TNF monotherapy.</p><p><bold>AIMS&METHODS:</bold> A systematic review of Embase, Medline and Web of Science (1980-2008) was conducted to identify RCTs of anti-TNF therapies in CD. The primary endpoints were clinical response (weeks 4-14 and 24-30), clinical remission (weeks 24-30), fistula closure (partial or complete), infusion/injection site reactions, and significant adverse events defined as serious infections, malignancy or death.</p><p><bold>RESULTS:</bold> Eleven RCTs were identified. Overall, combination therapy was no more efficacious than monotherapy for 6 month remission (OR 1.06; 95% CI 0.83-1.35), induction or maintenance of response (OR 1.06; 95% CI 0.81 – 1.40 and OR 1.46; 95% CI 0.70- 3.05), and partial or complete fistula closure (OR 1.26; 95% CI 0.84-1.88 and OR 1.1; 95% CI 0.68 – 1.79). In subgroup analyses, combination therapy was more efficacious than monotherapy for 6 month remission in those treated with infliximab (OR 1.79; 95% CI 1.06-3.01), but not adalimumab (OR 0.88; 95% CI: 0.58-1.35) or certolizumab (OR 0.93; 95% CI 0.65-1.34:). Combination therapy was not associated with serious adverse events in comparison to monotherapy (OR 1.11; 95% CI:0.56-2.20) across all anti-TNF treated agents. In subgroup analysis, combination therapy with infliximab was associated with fewer infusion reactions (OR 0.43; 0.19-0.97). Publication bias was not observed.</p><p><bold>CONCLUSION:</bold> When initiating infliximab, the continued use of an immunomodulator is associated with greater clinical remission rates, and fewer infusion reactions. Continued immunomodulator use did not influence the efficacy or safety of adalimumab and certolizumab.</p><p><bold>Disclosure of Interest</bold>: J. Jones: None Declared, G. Kaplan: None Declared, L. Peyrin-Biroulet Lecture fee(s) from: MSD and Abbvie, Consultancy for: MSD and Abbvie, L. Baidoo: None Declared, S. Devlin: None Declared, G. Melmed: None Declared, D. Tanyingoh: None Declared, L. Raffals: None Declared, P. Irving: None Declared, P. Kozuch: None Declared, M. Sparrow: None Declared, F. Velayos: None Declared, B. Bressler: None Declared, A. Cheifetz: None Declared, J.-F. Colombel: None Declared, C. Siegel: None Declared</p><p><bold>Keywords:</bold> Anti-TNF, Crohn's disease, Immunomodulator, Meta-analysis</p></sec><sec><title>OP054 EFFICACY OF ADALIMUMAB FOR TREATMENT OF PERIANAL FISTULA IN CHILDREN WITH MODERATELY TO SEVERELY ACTIVE CROHN’S DISEASE: RESULTS FROM IMAGINE 1</title><p><bold>F. Ruemmele</bold><sup>1,*</sup>, J. Rosh<sup>2</sup>, R. Colletti<sup>3</sup>, W. Faubion<sup>4</sup>, J. Markowitz<sup>5</sup>, S. Eichner<sup>6</sup>, Y. Wang<sup>6</sup>, A. Lazar<sup>7</sup>, R. Thakkar<sup>6</sup>, J. Hyams<sup>8</sup></p><p><italic><sup>1</sup>Universite Sorbonne Paris-Cite Hospital Necker-Enfants Malades, Paris, France, <sup>2</sup>Goryeb Children's Hospital/Atlantic Health, Morristown, <sup>3</sup>University of Vermont, Burlington, <sup>4</sup>Mayo Clinic, Rochester, <sup>5</sup>Cohen Children's Medical Center of NY, New Hyde Park, <sup>6</sup>AbbVie, N Chicago, United States, <sup>7</sup>AbbVie, Ludwigshafen, Germany, <sup>8</sup>Connecticut Children's Medical Center, Hartford, United States</italic></p><p><bold>INTRODUCTION:</bold> Objective: To evaluate adalimumab (ADA) efficacy on fistula closure and improvement in paediatric patients (pts) with moderately to severely active Crohn’s disease (CD) enrolled in the randomised clinical trial IMAGINE 1.</p><p><bold>AIMS&METHODS:</bold> In IMAGINE 1<sup>1</sup>, pts aged 6-17 years with Baseline (BL) PCDAI >30 and CD resistant or intolerant to conventional therapy received open-label induction of ADA at wks 0/2 according to body weight (≥40kg, 160/80mg; <40kg, 80/40mg). At wk 4, pts were randomised to double-blind higher-dose (HD) ADA (≥40kg, 40mg every other week [eow]; <40kg, 20mg eow) or lower-dose (LD) ADA (≥40kg, 20mg eow; <40kg, 10mg eow). Pts experiencing disease-flare or non-response could move to blinded weekly dosing after wk 12. Fistula closure (closure of all BL draining fistulae for at least 2 consecutive visits) and fistula improvement (decrease ≥50% from BL in the number of draining fistulae for at least 2 consecutive visits) were measured in pts that had at least 1 draining fistula at screening and at wk 0. Non-responder imputation (NRI) was used for missing data.</p><p><bold>RESULTS:</bold> 19% (36/188) of pts had at least 1 draining fistula at BL. A greater proportion of pts receiving HD than LD ADA achieved fistula closure from wks 12-52, although no statistically significant differences were observed between treatment groups (Table). Similar results were seen for fistula improvement. Rates of fistula closure and improvement were stable over time in HD ADA-treated pts (NRI). Detailed safety data for LD and HD ADA have been reported previously<sup>1</sup>. No new safety signals were detected and no significant differences were observed between LD and HD ADA<sup>1</sup>.</p><p>Table. Proportion of ADA-treated pts with fistula closure or improvement
<table-wrap id="table9-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1"></th><th colspan="4" rowspan="1"><hr></hr>Fistula Closure</th><th colspan="4" rowspan="1"><hr></hr>Fistula Improvement</th></tr><tr><th rowspan="1" colspan="1"></th><th colspan="2" rowspan="1"><hr></hr>ADA LD 20/10mg</th><th colspan="2" rowspan="1"><hr></hr>ADA HD 40/20mg</th><th colspan="2" rowspan="1"><hr></hr>ADA LD 20/10mg</th><th colspan="2" rowspan="1"><hr></hr>ADA HD 40/20mg</th></tr><tr><th rowspan="1" colspan="1"></th><th rowspan="1" colspan="1">NRI</th><th rowspan="1" colspan="1">OC</th><th rowspan="1" colspan="1">NRI</th><th rowspan="1" colspan="1">OC</th><th rowspan="1" colspan="1">NRI</th><th rowspan="1" colspan="1">OC</th><th rowspan="1" colspan="1">NRI</th><th rowspan="1" colspan="1">OC</th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">Wk 12, n/N (%)</td><td rowspan="1" colspan="1">9/21 (42.9)</td><td rowspan="1" colspan="1">9/19 (47.4)</td><td rowspan="1" colspan="1">7/15 (46.7)</td><td rowspan="1" colspan="1">7/13 (53.8)</td><td rowspan="1" colspan="1">12/21 (57.1)</td><td rowspan="1" colspan="1">12/19 (63.2)</td><td rowspan="1" colspan="1">7/15 (46.7)</td><td rowspan="1" colspan="1">7/13 (53.8)</td></tr><tr><td rowspan="1" colspan="1">Wk 26, n/N (%)</td><td rowspan="1" colspan="1">8/21 (38.1)</td><td rowspan="1" colspan="1">8/18 (44.4)</td><td rowspan="1" colspan="1">7/15 (46.7)</td><td rowspan="1" colspan="1">7/11 (63.6)</td><td rowspan="1" colspan="1">8/21 (38.1)</td><td rowspan="1" colspan="1">8/18 (44.4)</td><td rowspan="1" colspan="1">8/15 (53.3)</td><td rowspan="1" colspan="1">8/11 (72.7)</td></tr><tr><td rowspan="1" colspan="1">Wk 52, n/N (%)</td><td rowspan="1" colspan="1">5/21 (23.8)</td><td rowspan="1" colspan="1">5/15 (33.3)</td><td rowspan="1" colspan="1">6/15 (40.0)</td><td rowspan="1" colspan="1">6/11 (54.5)</td><td rowspan="1" colspan="1">6/21 (28.6)</td><td rowspan="1" colspan="1">6/15 (40.0)</td><td rowspan="1" colspan="1">6/15 (40.0)</td><td rowspan="1" colspan="1">6/11 (54.5)</td></tr></tbody></table></table-wrap></p><p>OC: observed case; All p values >0.05 for LD vs HD ADA (Logistic regression)</p><p><bold>CONCLUSION:</bold> Fistula improvement and closure were seen in children with moderately to severely active CD treated with ADA. Pts in both dosing groups achieved these benefits.</p><p><bold>REFERENCES:</bold></p><p>1. Hyams, et al. 2012. Gastroenterology; 143:365.</p><p><bold>Disclosure of Interest</bold>: F. Ruemmele Lecture fee(s) from: Shering-Plough, Nestlé, MeadJohnson, Ferring, MSD, Johnson & Johnson, Centocor, Other: Board membership: SAC:DEVELOP (Johnson & Johnson), invited to MSD France, Nestlé Nutrition Institute, invited to Nestlé Health Science, invited to Danane, invited to MeadJohnson, Biocodex, J. Rosh Financial support for research from: AstraZeneca, AbbVie, Janssen, UCB, Lecture fee(s) from: Abbott Nutrition, Prometheus, Consultancy for: AbbVie, Janssen, Soligenex, Other: Board membership: GI Health Foundation, R. Colletti Financial support for research from: Janssen , Consultancy for: Janssen OrthoBiotech, W. Faubion Financial support for research from: AbbVie, Shire Development Inc, Consultancy for: Genentech, Connecticut Children’s Medical Center - Safety officer on subcontracted award through NIH for clinical trial, Other: Board membership: Shire Development, Inc - Pediatric UC Advisory Board, Janssen Services LLC- DEVELOP Registry Scientific Advisory Committee, UCB Biosciences Advisory Board, J. Markowitz Consultancy for: AbbVie, Janssen OrthoBiotech, UCB , S. Eichner Shareholder of: AbbVie, Other: AbbVie employee, Y. Wang Shareholder of: AbbVie, Other: AbbVie employee, A. Lazar Shareholder of: AbbVie, Other: AbbVie employee, R. Thakkar Shareholder of: AbbVie, Other: AbbVie employee, J. Hyams Lecture fee(s) from: Janssen Orthobiotech, Consultancy for: Janssen Orthobiotech, AbbVie, Other: Expert testimony: Janssen Orthobiotech; Payment for development of educational presentations: Janssen Orthobiotech</p><p><bold>Keywords:</bold> adalimumab, Crohn's disease, fistula</p></sec><sec><title>OP055 ADALIMUMAB IS MORE EFFECTIVE THAN AZATHIOPRINE AND MESALAMINE AT PREVENTING POSTOPERATIVE RECURRENCE OF CROHN’S DISEASE – A RANDOMIZED TRIAL</title><p><bold>E. Savarino</bold><sup>1,*</sup>, G. Bodini<sup>2</sup>, P. Dulbecco<sup>2</sup>, V. Savarino<sup>2</sup></p><p><italic><sup>1</sup>Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, <sup>2</sup>Department of Internal Medicine, University of Genoa, Genoa, Italy</italic></p><p><bold>INTRODUCTION:</bold> Postsurgical recurrence of Crohn’s disease (CD) is very frequent and to date only Infliximab has been shown to be useful at preventing it. The efficacy of Adalimumab (ADA) is poorly known.</p><p><bold>AIMS&METHODS:</bold> We evaluated whether the administration of ADA after resective intestinal surgery reduces postoperative CD recurrence.</p><p>We randomly assigned 51 patients with CD who had undergone ileocolonic resection to receive after 2 weeks from surgery ADA at the dose of 160/80/40 mg eow (n=16; 8F/8M), azathioprine (AZA) at 2mg/kg day<sup>-1</sup> (n=17; 8F/9M) or mesalamine (MESA) at 3g/day (n=18; 10F/8M) and they were followed up for 2 years. Patients underwent endoscopy and magnetic resonance imaging at 12 and 24 months, physical examination and blood tests every 2 months. The primary end point was the proportion of patients with endoscopic and clinical recurrence based on Rutgeerts score (endoscopic remission was defined by a score of i0 or i1 and recurrence by a score of i2, i3, or i4) and clinical recurrence grading scale (clinical recurrence was defined as a score of 2 or greater on a scale where 1 indicates absent, 2 mild, 3 moderate and 4 severe symptoms), respectively. Secondary end point was the assessment of quality of life by means of a previously validated questionnaire [inflammatory bowel disease questionnaire, IBD-Q; range 32 (=very poor) – 224 (=perfect)].</p><p><bold>RESULTS:</bold> Baseline characteristics of the 3 groups were similar in terms of mean age (45 vs. 49 vs. 46, p=0.671), active smokers (9 vs. 4 vs. 6, p=0.138), mean CD duration (8.4y vs. 7.9y vs. 6.9y, p=0.637), phenotype (B2 or B3, p=0.922), prior surgical resection and IFX use (p=0.785 and p=0.136, respectively), mean CDAI (268 vs. 248 vs. 266, p=0.74), mean CRP (0.6 vs. 0.7 vs. 0.6, p=0.812), mean ESR (54 vs. 46 vs. 48, p=0.165) and mean IBD-Q (71 vs. 75 vs. 68, p=0.798). The rate of endoscopic recurrence was significantly lower in ADA [1/16 (6.3%)] compared with AZA [11/17 (64.7%); OR=0.036 (95%CI 0.004-0.347)] and MESA groups [15/18 (83.3%); OR=0.013 (95%CI 0.001-0.143)]. There was a significant lower proportion of patients in clinical recurrence in ADA group [2/16 (12.5%] compared with the AZA [11/17 (64.7); OR=0.078 (95%CI 0.013-0.464)] and MESA ones [9/18 (50%); [OR=0.143 (95%CI 0.025-0.819)]. The quality of life was higher in ADA (202) than AZA [90 OR=0.028 (95%CI 0.004-0.196)] and MESA groups 98 [OR=0.015 (95%CI 0.002-0.134)].</p><p><bold>CONCLUSION:</bold> The administration of ADA after intestinal resective surgery was greatly effective at preventing endoscopic and clinical recurrence of CD. Further larger studies are necessary to confirm the therapeutic advantage and to show the costs of this biologic therapy.</p><p><bold>Contact E-mail Address:</bold><email>edoardosavarino@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> adalimumab, IBD, Postoperative recurrence</p></sec><sec><title>OP056 LONG-TERM EFFECTIVENESS OF ADALIMUMAB IN CROHN’S DISEASE: OBSERVATIONAL DATA FROM THE PYRAMID REGISTRY</title><p><bold>E. V. Loftus</bold><sup>1,*</sup>, G. D'Haens<sup>2</sup>, W. Reinisch<sup>3</sup>, J. Satsangi<sup>4</sup>, R. Panaccione<sup>5</sup>, R. Thakkar<sup>6</sup>, S. Eichner<sup>6</sup>, M. Castillo<sup>6</sup>, N. Kan-Dobrosky<sup>7</sup>, M. Skup<sup>6</sup>, P. Mulani<sup>6</sup>, J. Chao<sup>6</sup></p><p><italic><sup>1</sup>Mayo Clinic, Rochester, United States, <sup>2</sup>Imelda GI Clinical Research Center, Bonheiden, Belgium, <sup>3</sup>Medical University of Vienna, Vienna, Austria, <sup>4</sup>Western General Hospital, Edinburgh, United Kingdom, <sup>5</sup>University of Calgary, Calgary, Canada, <sup>6</sup>AbbVie Inc., North Chicago, United States, <sup>7</sup>AbbVie, Deutschland GmbH & Co. KG, Ludwigshafen, Germany</italic></p><p><bold>INTRODUCTION:</bold> Adalimumab (ADA), an anti-tumor necrosis factor agent, is approved for the treatment of moderately to severely active Crohn’s disease (CD).</p><p><bold>AIMS&METHODS:</bold> We assessed long-term effectiveness of ADA in patients enrolled in an observational study initiated in 2007, PYRAMID. ADA was prescribed according to local product labels, and patients were followed for 6 years. Effectiveness measures assessed include Physician’s Global Assessment (PGA; composite of Harvey-Bradshaw Index and a rectal bleeding score), Short Inflammatory Bowel Disease Questionnaire (SIBDQ), and 4 components of the Work Productivity and Activity Impairment Questionnaire (WPAI): absenteeism, presenteeism, total work productivity impairment (TWPI), and total activity impairment (TAI). These effectiveness analyses are interim in nature, and results are summarized with descriptive statistics for patients who were naïve to adalimumab therapy at the time of study enrollment.</p><p><bold>RESULTS:</bold> As of 1 December 2012, 5061 patients have been enrolled. 41% (2095/5061) of patients were ADA-naïve at the time of enrollment. Mean age of ADA-naive patients was 37 years, mean CD duration was 10 years, 58% were women, and 96% were white. Mean scores for PGA improved from baseline to years 1, 2, 3, and 4 for new ADA users. Clinically meaningful improvements in mean scores for SIBDQ and WPAI (absenteeism, presenteeism, TWPI, and TAI) were maintained over 4 years (<bold>table</bold>).</p><p><bold>Efficacy Measures for ADA-naïve Patients</bold><table-wrap id="table10-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="2" colspan="1">Measure</th><th rowspan="2" colspan="1">Baseline, mean (SD)</th><th colspan="4" rowspan="1"><hr></hr>Change From Baseline, mean (SD)</th></tr><tr><th rowspan="1" colspan="1">1 year</th><th rowspan="1" colspan="1">2 years</th><th rowspan="1" colspan="1">3 years</th><th rowspan="1" colspan="1">4 years</th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">PGA</td><td rowspan="1" colspan="1">8.1 (5.6) N=2007</td><td rowspan="1" colspan="1">-3.7 (5.4) N=1341</td><td rowspan="1" colspan="1">-3.7 (5.5) N=1116</td><td rowspan="1" colspan="1">-4.2 (5.1) N=922</td><td rowspan="1" colspan="1">-4.8 (5.1) N=275</td></tr><tr><td rowspan="1" colspan="1">SIBDQ</td><td rowspan="1" colspan="1">40.6 (12.7) N=1455</td><td rowspan="1" colspan="1">11.5 (13.1) N=723</td><td rowspan="1" colspan="1">10.8 (14.2) N=526</td><td rowspan="1" colspan="1">11.5 (13.6) N=399</td><td rowspan="1" colspan="1">13.7 (13.7) N=142</td></tr><tr><td rowspan="1" colspan="1">Absenteeism</td><td rowspan="1" colspan="1">21.9 (33.3) N=825</td><td rowspan="1" colspan="1">-11.5 (34.5) N=331</td><td rowspan="1" colspan="1">-10.9 (32.8) N=228</td><td rowspan="1" colspan="1">-15.2 (33.1) N=167</td><td rowspan="1" colspan="1">-12.2 (36.0) N=64</td></tr><tr><td rowspan="1" colspan="1">Presenteeism</td><td rowspan="1" colspan="1">41.4 (29.9) N=855</td><td rowspan="1" colspan="1">-19.2 (32.2) N=354</td><td rowspan="1" colspan="1">-20.3 (35.1) N=258</td><td rowspan="1" colspan="1">-21.8 (31.8) N=183</td><td rowspan="1" colspan="1">-23.0 (38.4) N=61</td></tr><tr><td rowspan="1" colspan="1">TWPI</td><td rowspan="1" colspan="1">50.1 (33.3) N=823</td><td rowspan="1" colspan="1">-23.4 (34.9) N=327</td><td rowspan="1" colspan="1">-23.7 (38.9) N=225</td><td rowspan="1" colspan="1">-26.8 (34.4) N=163</td><td rowspan="1" colspan="1">-23.6 (38.6) N=63</td></tr><tr><td rowspan="1" colspan="1">TAI</td><td rowspan="1" colspan="1">50.6 (30.1) N=1419</td><td rowspan="1" colspan="1">-22.8 (31.8) N=698</td><td rowspan="1" colspan="1">-23.4 (34.2) N=513</td><td rowspan="1" colspan="1">-22.9 (32.1) N=377</td><td rowspan="1" colspan="1">-26.1 (34.9) N=132</td></tr></tbody></table></table-wrap></p><p><bold>CONCLUSION:</bold> In this worldwide, observational study of ADA use in routine clinical practice, clinically meaningful improvements in disease activity, work productivity, and activity impairment were seen in patients with CD 1 year after initiation of ADA therapy. These improvements were maintained over a 4-year assessment period.</p><p><bold>Disclosure of Interest</bold>: E. Loftus Financial support for research from: AbbVie, Amgen, Braintree, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Janssen Biotech, Millenium-Takeda, Pfizer, Santarus, Shire, UCB, Consultancy for: AbbVie, Cubist, Elan, Eisai, Given, Hospira, Ironwood, Janssen Biotech, UCB, G. D'Haens Consultancy for: AbbVie, Other: Study Investigator, CME events/Educational grants: AbbVie, W. Reinisch Lecture fee(s) from: Ferring, Consultancy for: AbbVie, Aesca, Centocor, Genentech, Novartis, Schering-Plough, UCB, J. Satsangi: None Declared, R. Panaccione Financial support for research from: AbbVie, Bristol-Myers Squibb, Centocor, Elan, Ferring, Janssen, Millennium, Schering-Plough, Proctor & Gamble, Lecture fee(s) from: AbbVie, AstraZeneca, Centocor, Elan, Janssen, Prometheus, Schering-Plough, Shire, Warner Chilcott, Consultancy for: AbbVie, Amgen, Aptalis, AstraZeneca, Baxter, Bristol-Myers Squibb, Centocor, Eisai, Elan, Ferring, GlaxoSmithKline, Jansen, Merck, Pfizer, Schering-Plough, Shire, UCB, Warner Chilcott, Other: Advisory board: AbbVie, Amgen, Aptalis, AstraZeneca, Baxter, Bristol-Myers Squibb, Centocor, Eisai, Ferring, Elan, GlaxoSmithKline, Janssen, Merck, Pfi zer, Schering-Plough, Shire, UCB, Warner Chilcott, R. Thakkar Shareholder of: AbbVie, Other: Employee: AbbVie, S. Eichner Shareholder of: AbbVie, Other: Employee: AbbVie, M. Castillo Shareholder of: AbbVie, Other: Employee: AbbVie, N. Kan-Dobrosky Shareholder of: AbbVie, Other: Employee: AbbVie, M. Skup Shareholder of: AbbVie, Other: Employee: AbbVie, P. Mulani Shareholder of: AbbVie, Other: Employee: AbbVie, J. Chao Shareholder of: AbbVie, Other: Employee: AbbVie</p><p><bold>Keywords:</bold> adalimumab, Crohn’s disease, disease activity, observational study , work productivity</p></sec><sec><title>OP057 OPTIMISING POST-OPERATIVE CROHN’S DISEASE MANAGEMENT: BEST DRUG THERAPY ALONE VERSUS ENDOSCOPIC MONITORING WITH TREATMENT STEP-UP. THE POCER STUDY</title><p><bold>P. De Cruz</bold><sup>1,*</sup>, M. Kamm<sup>1</sup>, A. Hamilton<sup>1</sup>, K. Ritchie<sup>1</sup>, S. Krejany<sup>1</sup>, A. Gorelik<sup>1</sup>, D. Liew<sup>1</sup>, L. Prideaux<sup>1</sup>, I. Lawrance<sup>1</sup>, J. Andrews<sup>1</sup>, P. Bampton<sup>1</sup>, M. Sparrow<sup>1</sup>, T. Florin<sup>1</sup>, P. Gibson<sup>1</sup>, H. Debinski<sup>1</sup>, R. Gearry<sup>1</sup>, F. Macrae<sup>1</sup>, R. Leong<sup>1</sup>, I. Kronborg<sup>1</sup>, G. Radford-Smith<sup>1</sup>, W. Selby<sup>1</sup>, M. Johnston<sup>1</sup>, R. Woods<sup>1</sup>, R. Elliott<sup>1</sup>, S. Bell<sup>1</sup>, S. Brown<sup>1</sup>, W. Connell<sup>1</sup>, P. Desmond<sup>1</sup></p><p><italic><sup>1</sup>St Vincent's Hospital and University of Melbourne, Melbourne, Australia</italic></p><p><bold>INTRODUCTION:</bold> Disease recurs in the majority of patients with Crohn’s disease requiring intestinal resection. Given the absence of strategy to prevent recurrence we investigated whether endoscopic monitoring and treatment step-up for early recurrence is superior to optimal drug therapy alone commenced immediately after surgery. Endoscopic mucosal healing has been shown previously to be predictive of subsequent clinical remission, and was therefore the goal in this “treat to target” study.</p><p><bold>AIMS&METHODS:</bold> In this Post Operative Crohn’s Endoscopic Recurrence, “POCER” study, following intestinal resection patients were stratified for risk of recurrence as high risk (smoker, perforating disease, ≥2nd operation) or low risk. All patients received 3 months metronidazole 400mg bd. High risk patients also received daily azathioprine 2mg/kg or 6 mercaptopurine 1.5mg/kg. High risk patients intolerant of thiopurine received adalimumab induction then 40mg fortnightly. Patients were randomised 2:1 to colonoscopy at 6 months (“active care”) or no colonoscopy (“standard care”). Endoscopic remission was defined as Rutgeerts score i0 or i1 and recurrence as ≥i2. For endoscopic recurrence at 6 months low risk patients stepped up to thiopurine, high risk patients on thiopurine stepped up to adalimumab 40mg fortnightly, and high risk thiopurine-intolerant patients stepped up to weekly adalimumab. All patients were colonoscoped at 18 months, with the primary end-point endoscopic recurrence at 18 months.</p><p><bold>RESULTS:</bold> 174 patients (83% high risk) were enrolled. Of the 122 active care patients 45 (37%) underwent treatment step-up. At 18 months endoscopic recurrence was observed in 60 / 122 (49%) active care patients versus 35 / 52 (67%) standard care (P=0.028). Complete mucosal normality (i0) was observed in 22% v 8% (P=0.029); severe disease (i3 and i4) occurred in 12% v 15% (P=0.466) respectively.</p><p><bold>CONCLUSION:</bold> Treating according to risk of recurrence, with 6 month colonoscopy and treatment step-up for recurrence, is significantly superior to optimal drug therapy alone, in preventing postoperative recurrence of Crohn’s disease. Selective potent immune suppression, adjusted if needed based on colonoscopy, rather than its use in all high risk patients, leads to effective disease control in a majority of patients.</p><p><bold>Contact E-mail Address:</bold><email>Peter.DECRUZ@svhm.org.au</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Crohn`s disease, Inflammatory bowel disease (IBD), Postoperative recurrence</p></sec><sec><title></title><p><bold>MONDAY, OCTOBER 14, 2013 14:00-15:30</bold></p><p><bold>Management of GI bleeding: A case based discussion – Hall 3</bold></p></sec><sec><title>OP057-LB1 ENDOSCOPIC TREATMENT OF ACUTE VARICEAL HEMORRHAGE USING HEMOSTATIC POWDER TC-325: A PROSPECTIVE PILOT STUDY</title><p><bold>M. Ibrahim</bold><sup>1,2,*</sup>, A. El-Mikkawy<sup>1</sup>, I. Mostafa<sup>1</sup>, J. Devière<sup>2</sup></p><p><italic><sup>1</sup>Department of Gastroenterology and Hepatology, Theodor Bilharz Research Institute, Cairo, Egypt, <sup>2</sup>Gastroenterology & Hepato-Pancreatology, ERASME HOSPITAL UNIVERSITÉ LIBRE DE BRUXELLES, Brussels, Belgium</italic></p><p><bold>INTRODUCTION:</bold> Current standard of care of acute variceal bleeding combines hemodynamic stabilization, antibiotic prophylaxis, pharmacological agents and endoscopic treatment. The latter may be challenging in emergency. An hemostatic powder has recently been introduced for management of non variceal upper GI bleeding and was shown effective in preliminary studies for managing peptic ulcer bleeding, cancer related bleeding or temporizing uncontrollable bleeding in severe situations.</p><p><bold>AIMS & METHODS:</bold> A bi-centric prospective trial to assess the effectiveness of a pre-established delivery protocol of a hemostatic powder to control acute variceal bleeding (AVB) originating from the esophagus or the gastroesophageal (GE) junction. Fourteen consecutive patients with known liver cirrhosis and suspected acute variceal bleeding originating from the esophagus up to the GE junction consented to be included in the study. The ethical committees of Erasme University Hospital and Theodor Bilharz Research Institute approved the protocol.</p><p><bold>RESULTS:</bold> Fourteen patients with cirrhosis (13 post hepatitis C and 1 alcoholic) and suspected first episode of AVB were consented. Five were excluded (3 patients without acute bleeding and 2 patients with bleeding originating from duodenal varices) and 9 had confirmed AVB originating from the esophagus or the GE junction. Endoscopy was performed under sedation without endotracheal intubation. Bleeding stopped during the endoscopy performed with application of 21 g of hemostatic powder from the cardia up to 15 cm above the GE junction. No rebleeding was observed in all patients within 24 hours. No mortality was observed at 15 days follow-up.</p><p><bold>CONCLUSION:</bold> Hemospray appears to be safe in controlling, at least temporally, AVB in this series of patients. Nevertheless, further studies, preferably randomized controlled trials are required to determine its role and effectiveness in acute variceal bleeding and its potential impact on patients outcome.</p><p><bold>Contact E-mail Address:</bold><email>mostafa.ibrahim@me.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> hemospray, Variceal bleeding</p></sec><sec><title>OP058 PREDICTIVE FACTOR OF EARLY AND DELAYED BLEEDING AFTER ENDOSCOPIC SUBMUCOSAL DISSECTION FOR EARLY GASTRIC NEOPLASM</title><p><bold>H. J. Kim</bold><sup>1,*</sup>, H. Lee<sup>1,2</sup>, H. J. Park<sup>1</sup>, J. K. Kim<sup>1</sup>, J. C. Park<sup>1,2</sup>, S. K. Shin<sup>1,2</sup>, S. K. Lee<sup>1,2</sup>, Y. C. Lee<sup>1,2</sup></p><p><italic><sup>1</sup>Department of Internal Medicine, Yonsei University College of Medicine, <sup>2</sup>Institute of Gastroenterology, Yonsei University college of Medicine, Seoul, Korea, Republic Of</italic></p><p><bold>INTRODUCTION:</bold> Postoperative bleeding is a major complication of endoscopic submucosal dissection(ESD). Although there have been several reports regarding complications, especially bleeding, of ESD for gastric neoplasm, little is known about the difference of early and delayed bleeding risk.</p><p><bold>AIMS&METHODS:</bold> The aim of this study is to determine the incidence rate of early (defined as bleeding occurring within 48 hours after the procedure) and delayed (defined as bleeding occurring on or after 48 hours after the procedure) postoperative bleeding and analyze clinical factors after ESD in case of gastric neoplasm. We retrospectively investigated 3759 lesions from 3384 consecutive patients undergoing ESD for gastric neoplasm between January 2007 and December 2012. Clinicopathological factors of postoperative bleeding were analyzed.</p><p><bold>RESULTS:</bold> Total postoperative bleedings were evident in 156 lesions from 146 patients. Early postoperative bleeding occurred in 111 lesions from 103 patients and delayed postoperative bleeding occurred in 45 lesions from 43 patients.</p><p>The mean age of patients was 64.6 years and male/female ratio was 3.9:1.The mean size of the lesions was 16.4mm. There was tendency for the location of lesions to be in the lower third of the stomach, there was significant difference in locations. Emergency surgery was required in 2 of 111 lesions (1.8%) with early bleeding, embolization was required in 3 of 111 lesions (2.7%) with early bleeding , whereas embolization was required in 1 of 45 lesions (2.2%) with delayed bleeding. The others underwent either endoscopic hemostasis or endoscopic confirming.</p><p> Univariate analysis showed that smoking(P=0.013), endoscopic lesion size(P=0.043), tumor location in the upper third of the stomach (P=0.034), clipping of hemostasis during procedure (P=0.021) were significantly associated with difference between early and delayed postoperative bleeding.</p><p> Multivariate analysis showed that tumor location in the upper third of the stomach (OR 17.673, 95% CI 1.973 to 158.293, P=0.010) and the endoscopic lesion size (OR 0.941, 95% CI 0.885 to 0.999, P=0.047) were the factors that were statistically significantly associated with difference between early and delayed postoperative bleeding.</p><p><bold>CONCLUSION:</bold> The size of endoscopic lesion was a significant risk factor for early postoperative bleeding. The tumor location in the upper third of the stomach was an important predictive factor for delayed postoperative bleeding. These findings suggest the patients with high risk of early or delayed postoperative bleeding need strict follow-up.</p><p><bold>REFERENCES:</bold></p><p>1. Kazuhisa Okada. Risk factors for delayed bleeding after endoscopic submucosal dissection for gastric neoplasm. Surg Endosc (2011) 25:98–107</p><p>2. MUNETAKA NAKAMURA. Risk factors for delayed bleeding from endoscopic submucosal dissection of gastric neoplasms. Scandi navian Jou rnal of Gast roenterol ogy. 2012; 47: 1108 – 1114</p><p><bold>Contact E-mail Address:</bold><email>hj0390041@yuhs.ac</email>,
<email>LEEHYUK@yuhs.ac</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> bleeding, early gastric neoplasm, endoscopic submucosal dissection</p></sec><sec><title></title><p><bold>MONDAY, OCTOBER 14, 2013 14:00-15:30</bold></p><p><bold>IBD: Extraintestinal manifestations and complications – Hall Prague</bold></p></sec><sec><title>OP059 IMMUNOLOGICAL PROFILE IN CROHN’S DISEASE PATIENTS WITH SKIN LESIONS INDUCED BY ANTI-TNF-ALFA THERAPY</title><p><bold>M. Włodarczyk</bold><sup>1,*</sup>, A. Sobolewska<sup>1</sup>, M. Wiśniewska-Jarosińska<sup>1</sup></p><p><italic><sup>1</sup>Departemnt of Gastroenterology, Medical Univeristy of Lodz, Łódź, Poland</italic></p><p><bold>INTRODUCTION:</bold><italic>Anti </italic>tumour necrosis factor <italic>α </italic>(anti-<italic>TNF-α</italic>) biological agents are used in the treatment of <italic>Crohn's disease (CD) with a good clinical response, but they are also related to</italic> various side effects, including skin lesions. Inhibition of CD immune pathway associated with the excessive secretion of TNF-α and interferon γ (IFN-γ) by CD4+ Th1 lymphocytes, results in immunological changes leading to an activation of Th-17 lymphocytes dependent on interleukin-23 (IL-23). Excessive levels of interleukin-17A (IL-17A) secreted by activated Th-17 lymphocytes may induce inflammatory pathways in dermis.</p><p><bold>AIMS&METHODS:</bold> The study aimed at evaluating the frequency and variety of skin lesions in patients with CD induced by anti-TNF-α agents and to investigate the impact of IL-17A, IL-23 and IFN-γ levels on their development. 30 adult patients (11 women and 19 men; mean age±SD 32.0±8.6 years) with CD during anti-TNF-α therapy were enrolled to the study. The control group consisted of 12 healthy subjects. Diagnostic questionnaire was carried out and in each patient careful skin examination was performed. In all the study participants blood tests were performed and serum levels of IL-17A, IL-23 and IFN-γ were measured using an ELISA technique.</p><p><bold>RESULTS:</bold> Skin lesions occurred in 18 of patients (60%) with CD during anti-TNF-α therapy. Skin lesions in patients with CD occurred on the average 11.03±10.09 months after the beginning of therapy, which is at the end of 52-week treatment cycle. The studied patients presented with the following skin lesions: furunculosis (33.3%), psoriasiform lesions (22.2%), erythema (22.2%), excessive skin dryness (22.2%), eczema (16.7%), acne (16.7%) and ulcers (11.1%). Analysis of cytokine levels showed a statistically significant increase in serum levels of IL-17A, IL-23 and IFN-γ in CD patients on anti-TNF-α biological therapy compared to the controls. The levels of IL-17A and IL-23 in patients with skin lesions were significantly higher compared to these without changes (IL-17A: 39.01±7.03 pg/ml vs. 25.71±4.90 pg/ml, p<.001; IL-23: 408.78±94.13 pg/ml vs. 312.15±76.24 pg/ml, p=.005). The results of the study showed the statistically significant positive correlation between IL-17 and IL-23 serum levels(r=0.482, p=0.007).</p><p><bold>CONCLUSION:</bold> In patients with CD treated with anti-TNF-α agents, the concentrations of IL-17A, IL-23 and IFN-γ are higher compared to the controls. There is also a significant correlation between IL-17A and IL-23 with the presence of cutaneous lesions in CD patients treated with anti-TNF-α agents. The measurement of serum levels of these cytokines may be used as predictors of skin lesions during biological treatment, however this hypothesis should be confirmed in further studies.</p><p><bold>Contact E-mail Address:</bold><email>dr.mwlodarczyk@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> ANTI-TNF-ALPHA THERAPY, CROHN´S DISEASE, INTERFERON GAMMA, INTERLEUKIN-17A, INTERLEUKIN-23, SKIN LESIONS</p></sec><sec><title>OP060 STEROID PULSE THERAPY IS FAVOURABLE THAN THE CONVENTIONAL ONE IN PREVENTING THE INCREASE OF BODY FAT PERCENTAGE IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE RECEIVING SHORT COURSE OF CORTICOSTEROID THERAPY</title><p><bold>K. Farkas</bold><sup>1,*</sup>, Z. Valkusz<sup>1</sup>, Z. Szepes<sup>1</sup>, F. Nagy<sup>1</sup>, M. Szücs<sup>2</sup>, A. Bálint<sup>1</sup>, R. Bor<sup>1</sup>, E. Csajbok<sup>1</sup>, T. Wittmann<sup>1</sup>, T. Molnár<sup>1</sup></p><p><italic><sup>1</sup>First Department of Medicine, <sup>2</sup>Department of Medical Physics and Informatics, University of Szeged, Szeged, Hungary</italic></p><p><bold>INTRODUCTION:</bold> The effect of a 12-weeks course of corticosteroids on the metabolic processes and bone formation has not been well studied.</p><p><bold>AIMS&METHODS:</bold> The aim of this pilot study was to evaluate the changes in bone and lipid metabolism as well as the body fat percentage in IBD patients treated with steroids for 12 weeks and to compare two types of oral tapering of methylprednisolone. Nineteen patients with IBD received iv. methylprednisolone of 1 mg/kg for 5 days due to an acute exacerbation of the disease tapered by 4 mg per week. Patients were prospectively randomized in two groups. In “conventional” group (I) steroids were given daily. In “pulse” group (II) weekly dose of steroids were given on special days of the week. Finally, both groups received the same methylprednisolone dose. The body mass index were measured before and after the corticosteroid therapy. Blood samples were collected to assess different laboratory parameters, serum cortisol, serum osteocalcin and serum crosslaps values. Total body composition was performed at the beginning and at the end of the steroid therapy to determine the fat and fat-free component of the body.</p><p><bold>RESULTS:</bold> Serum cholesterol and bilirubin level significantly increased, whereas serum cortisol and thrombocyte level significantly decreased after steroid therapy in both groups. Serum osteocalcin was higher in both groups after vs. before steroid therapy and also higher in Group II vs. Group I after the therapy. Serum crosslaps levels did not show any difference after the steroid therapy in the groups. Body fat percentage significantly increased at the end of the steroid therapy in Group I patients. Less side-effect occurred in Group II vs. Group I.</p><p><bold>CONCLUSION:</bold> Our results suggest that even a 12-weeks course systemic steroid therapy may negatively affect bone metabolism. Steroid pulse therapy seems to be favourable than the conventional taper of steroids in preventing the increase of body fat percentage and in the development of steroid specific side-effects.</p><p><bold>Contact E-mail Address:</bold><email>farkas.klaudia@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> bone metabolism, corticosteroids, inflammatory bowel disease</p></sec><sec><title>OP061 CANCER IN ELDERLY-ONSET INFLAMMATORY BOWEL DISEASE: A POPULATION-BASED STUDY</title><p><bold>H. Cheddani</bold><sup>1,*</sup>, L. Dauchet<sup>2</sup>, C. Charpentier<sup>1</sup>, M. Fumery<sup>3</sup>, J. Salleron<sup>4</sup>, A.-M. Bouvier<sup>5</sup>, J.-L. Dupas<sup>3</sup>, F. Vasseur<sup>4</sup>, E. Lerebours<sup>1</sup>, E. Laberenne<sup>6</sup>, L. Peyrin-Biroulet<sup>7</sup>, J.-F. Colombel<sup>8</sup>, G. Savoye<sup>1</sup>, C. Gower-Rousseau<sup>2</sup> and EPIMAD Group</p><p><italic><sup>1</sup>Gastroenterology, UNIVERSITY AND HOSPITAL Rouen , Rouen, <sup>2</sup>Epidemiology, UNIVERSITY AND HOSPITAL LILLE , Lille, <sup>3</sup>Gastroenterology, University and Hospital Amiens, Amiens, <sup>4</sup>Biostatistics EA2694, UNIVERSITY AND HOSPITAL LILLE , Lille, <sup>5</sup>Registre Bourguignon des Cancers Digestifs , INSERM U 866 - Registre Associé InVS-INCa , Dijon, <sup>6</sup>Gastroenterology, General Hospital Seclin, Seclin, <sup>7</sup>Gastroenterology, University Hospital Nancy Inserm U954, Nancy, France, <sup>8</sup>Henry Janowicz Divsion of Gastroenterology, Mount Sinai Hospital, New-York, United States</italic></p><p><bold>INTRODUCTION:</bold> The ageing of the population makes elderly-onset inflammatory bowel diseases (IBD) a rising problem. Risk of cancer is unknown in this population.</p><p><bold>AIMS&METHODS:</bold> We studied this risk in a population-based cohort of patients with IBD. <bold>Patients and methods</bold>: In a French population-based cohort, we identified 841 IBD patients >60 years of age at diagnosis from 1988 to 2006, including 367 Crohn’s disease (CD) and 472 ulcerative colitis (UC)<sup>1</sup>. We compared incidence of cancer among patients with IBD with that observed in the French Network of population-based Cancer Registries (FRANCIM). Only cancers occurring after IBD diagnosis were taken into account. Confidence interval (CI) was estimated assuming a Poisson specific law for rare events. Results were expressed using the standardized ratios of incidence (SIR) and their CI 95%.</p><p><bold>RESULTS:</bold> After a median follow-up of 6 years [2-11], 103 (12.3%) patients with IBD including 42 CD and 61 UC developed a cancer corresponding to a SIR of 1.00 [0.83-1.21]. Eleven patients (1.3%) developed at least 2 cancers.There was no increased risk of colorectal cancer in IBD (SIR=1.06 [0.65-1.72], CD (SIR=1.15 [0.54-2.40] and UC (SIR=0.99 [0.52-1.91]. An increased risk of malignant lymphoproliferative disorders was found in IBD (SIR=2.71 [1.41-5.20] and in UC (SIR=3.05 [1.37-6.79]) but not in CD (SIR=2.21 [0.71-6.86]). An increased risk of extraintestinal tumors was observed only for the liver in CD (SIR=3.25 [1.04-4.07]). Immunomodulator exposure (n=26) was not associated with an increased risk of cancer (SIR=0.75 [0.43-1.29]) nor with any specific risk including malignant lymphoproliferative disorders (SIR=1.89 [0.26-13.44]). Only 2 patients of this cohort received biotherapy.</p><p><bold>CONCLUSION:</bold> There is no increased risk for developing intestinal cancer among patients with elderly-onset IBD in this population-based cohort. There is an increased risk of developing malignant lymphoproliferative disorders in UC and an increased risk for developing liver cancer in CD. These data reinforce the peculiarity of elderly-onset IBD as compared with younger age at onset IBD<sup>1</sup>.</p><p><bold>REFERENCES:</bold><italic><sup>1</sup> Charpentier C et al. Gut 2013</italic></p><p><bold>Contact E-mail Address:</bold><email>corinne.gower@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Cancer risk, Elderly, population-based</p></sec><sec><title>OP062 DIFFERENT EFFECT OF ANTI-TNF ALPHA DRUGS ON SMALL BOWEL MACROSCOPIC INFLAMMATION IN PATIENTS WITH ANKYLOSING SPONDYLITIS</title><p><bold>M. Rimba</bold><sup>1,*</sup>, M. Marinescu<sup>1</sup>, S. Caraiola<sup>2</sup>, C. G. Badea<sup>2</sup>, R. A. Ionescu<sup>2</sup>, A. Nicolau<sup>2</sup>, G. Ticu<sup>3</sup>, M. Pârvu<sup>4</sup>, T. A. Voiosu<sup>1</sup>, A. Voiosu<sup>5</sup>, M. R. Voiosu<sup>5</sup>, C. R. Băicu<sup>2</sup></p><p><italic><sup>1</sup>Gastroenterology Department, Colentina Clinical Hospital, <sup>2</sup>Internal Medicine Department, Colentina Clinical Hospital, CAROL DAVILA UNIVERSITY OF MEDICINE AND PHARMACY, <sup>3</sup>Internal Medicine Department, <sup>4</sup>Rheumatology Department, <sup>5</sup>Gastroenterology Department, Colentina Clinical Hospital, Bucharest, Romania</italic></p><p><bold>INTRODUCTION:</bold> The similarities in intestinal inflammatory involvement between patients with ankylosing spondylitis (AS) and inflammatory bowel disease (IBD) gave rise to the hypothesis that, similarly to their effect in IBD, biologic anti-TNF alpha drugs can also lower the intestinal inflammation in AS patients.</p><p><bold>AIMS&METHODS:</bold> Between January 2008 and April 2013, 38 consecutive AS patients on stable doses of anti-rheumatic medication and 23 controls were prospectively enrolled and submitted to a small bowel videocapsule endoscopy (VCE) examination. After reading each VCE recording, the capsule endoscopy scoring index for small bowel mucosal inflammatory change (Lewis score) was computed for the bowel as a whole, as well as separately for its proximal, mid and distal tertiles.</p><p><bold>RESULTS:</bold> 33 patients (86.8%) had evidence of small bowel mucosal inflammation (Lewis score > 135), statistically significant in comparison with the control group (mean of Lewis scores of 580.9 <italic>vs.</italic> 81.0, p<0.01). 16 patients (42.1%) received anti-TNF alpha biologic therapy at the time of the VCE examination, and these patients had significantly lower Lewis scores in comparison with the other AS patients (306.3 <italic>vs.</italic> 790.1, p=0.015). The Lewis scores were much lower in the Adalimumab/Infliximab group than in the Etanercept group for the bowel as a whole (262.4 <italic>vs.</italic> 379.6, p=0.069) and its distal tertile (61.7 <italic>vs.</italic> 272.5, p=0.060), but not for its proximal (227.2 <italic>vs.</italic> 257.3, p=0.22) and mid tertiles (128.9 <italic>vs.</italic> 137.5, p=0.82). In fact, the marked reduction in intestinal inflammation for the distal intestinal tertile in the Adalimumab/Infliximab group reached the intestinal inflammatory level of the control group (mean of Lewis scores of 61.7 and 46.7, respectively).</p><p><bold>CONCLUSION:</bold> These results bring into question the possible role of an early intervention with anti-TNF alpha drugs in patients with AS and ileal inflammation, condition that predicts an aggressive course of their rheumatologic disease. Compared to the other anti-TNF alpha agents available, and similarly with IBD, Etanercept seems to be different in its therapeutic action on the intestinal inflammation in AS.</p><p>Acknowledgement: supported by PNII–IDEI, ID_323/2007; registered on ClinicalTrials.gov with No. NCT00768950.</p><p><bold>Contact E-mail Address:</bold><email>mrimbas@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> ankylosing spondylitis, anti TNF therapy, etanercept, Lewis Score, small bowel inflammatory involvement, video capsule</p></sec><sec><title>OP063 COMBINED IMMUNOSUPPRESSION, CORTICOIDS AND MENOPAUSE HAVE SIGNIFICANT INFLUENCE OF BONE MINERAL DENSITY OF IBD PATIENTS. A PROSPECTIVE STUDY.</title><p><bold>T. Hlavaty</bold><sup>1,*</sup>, A. Krajcovicova<sup>1</sup>, Z. Killinger<sup>2</sup>, E. Miznerova<sup>1</sup>, J. Toth<sup>1</sup>, D. Cierny<sup>2</sup>, T. Koller<sup>1</sup>, J. Letkovsky<sup>1</sup>, Z. Zelinkova<sup>1</sup>, M. Huorka<sup>1</sup>, J. Payer<sup>2</sup></p><p><italic><sup>1</sup>Dept. Gastroenterology and Hepatology, <sup>2</sup>Osteocenter, University hospital Bratislava, Bratislava, Slovakia</italic></p><p><bold>INTRODUCTION:</bold> There is a high prevalence of osteoporosis and osteopenia among patients with inflammatory bowel diseases (IBD). The effect of recommended vitamin D (VD) and calcium (Ca) supplementation in IBD patients is not precisely known. Furthermore there is lack of clinical data on the impact of corticosteroid (CS) and immunosuppressive therapy (IS) on the bone mineral density (BMD).</p><p><bold>AIMS&METHODS:</bold> The aim was to analyse the effect of VD/Ca, CS and IS therapy on the BMD of IBD patients. The cohort consisted of 52 IBD patients. In every patient demographic, clinical characteristics and medication were recorded at baseline and on every follow-up visit. Patients with low BMD at baseline were supplemented with 800 IU VD and 1000 mg Ca bid. The BMD was determined by dual-energy X-ray absorptiometry (DXA) at the lumbar spine and total femur at baseline and then every 1-2 years at follow-up. We calculated the average change in BMDL per year (ΔBMDL/yr) and analysed the impact of clinical factors, medication and VD/Ca supplementation. ΔBMDL was compared with least significant change (LSC<0.03) to determine significant improvement or worsening.</p><p><bold>RESULTS:</bold> The median follow-up was 2.9 years. The average BMDL at baseline was 0.964±0.113 g/cm2. The average BMDL at the last follow-up visit was 0.985±0.133 g/cm2. The average ΔBMDL/yr was 0,010 g/cm2/year (in average +1,0%). We observed significant improvement in BMDL (ΔBMDL>LSC) in 26/52 (50%) of patients, no change in 17/52 (32.7%) and worsening in 9/52 (17.3%).</p><p>On multivariate analysis the ΔBMDL/yr was positively influenced by combined IS and antiTNFa therapy (COMBO) and negatively by CS and menopause. ΔBMDL/yr in men was 0.014±0.005 g/cm2/yr, in premenopausal women 0.016±0.006 g/cm2/yr and in postmenopausal women -0.012±0.009 g/cm2/yr; p=0,01. Among patients with no IS the ΔBMDL/yr was -0.001±0.010 g/cm2/yr, patients with AZA -0.001±0.013 g/cm2/yr, patients with antiTNFα 0.003±0.006 g/cm2/yr and among patients with COMBO 0.027±0.004 g/cm2/yr; p<0.05 COMBO vs any other subgroup. ΔBMDL/yr among patients treated with CS was -0.031±0.012 g/cm2/yr versus CD free patients 0.013±0.004 g/cm2/yr; p<0.001.</p><p>There was no effect of VD/Ca supplementation on BMDL, neither on the serum VD levels.</p><p><bold>CONCLUSION:</bold> In our prospective study the bone mineral density of IBD patients was positively influenced by combined immunosuppressive/antiTNF therapy and negatively by corticosteroids and menopause. Vitamin D and calcium supplementation in standard dosing had no effect.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> corticosteroids, Crohn’s disease, Immunosuppression, menopause, osteoporosis, ulcerative colitis</p></sec><sec><title>OP064 DEPRESSION IS ASSOCIATED WITH A WORSE CLINICAL COURSE IN INFLAMMATORY BOWEL DISEASE</title><p><bold>M. Barreiro-de Acosta</bold><sup>1,2,*</sup>, M. Iglesias-Rey<sup>2</sup>, R. Ferreiro-Iglesias<sup>1,2</sup>, A. Lorenzo-González<sup>1</sup>, J. E. Dominguez-Muñoz<sup>1,2</sup></p><p><italic><sup>1</sup>Gastroenterology, University Hospital of Santiago de Compostela, <sup>2</sup>Foundation for Research in Digestive Diseases, Santiago de Compostela, Spain</italic></p><p><bold>INTRODUCTION:</bold> Anxiety and depression are highly prevalent in IBD patients, but their role of anxiety in the clinical course of the disease is unknown. We hypothesised that anxiety and depression are predictors of a worse clinical course in IBD</p><p><bold>AIMS&METHODS:</bold> The aim of the study was to evaluate the influence of anxiety and depression symptoms in emergency visits and hospitalisations in IBD patients.</p><p><bold>Methods: </bold>A prospective observational cohort study was designed. The cohort consisted of consecutive patients with IBD (Crohn´s disease (CD) and ulcerative colitis (UC)) who attended our monographic IBD Unit. In order to identify anxiety or depression, a psychological evaluation was performed at baseline in all of them by the Hospital Anxiety and Depression scale (HAD). In order to assess the clinical course of IBD, all emergency visits and hospitalisations related with IBD over a follow-up period of 18 months were recorded. Results are shown as RR and 95%CI and analysed by Poisson Regression.</p><p><bold>RESULTS:</bold> 716 patients were included (343 male, mean age 44.50 years, ages ranging from 18 to 86 years), 297 (41.8%) patients with CD and 413 (58.2%) with UC. At baseline evaluation, anxiety and depression symptoms were present in 75 (10.5%) and 144 (20.1%) patients respectively. The mean of emergency visits was 1.05 (SD: 1.68, range 0-14) and for hospitalizations it was 0.35 (SD: 0.94, range 0-9). After a follow up of 18 months, depression at baseline was a risk factor for more emergency visits (RR: 1.38, CI95%: 1.14-1.65; p=0.001) but not anxiety (RR: 1.11, CI95%: 0.87-1.41; p=0.395). Regarding hospitalizations in the next 18 months, after controlling by relevant sociodemographic and clinical variables, anxiety and depression (RR: 1.18, CI95%: 0.75-1.83, p=0.472; RR: 0.70, CI95%: 0.75-1.83, p=0.059) were not risk factors for an increased number of them.</p><p><bold>CONCLUSION:</bold> An important number of IBD patients present anxiety or depressive symptoms. Depression seems to be a risk factor for more emergency visits in the following months. Therefore, these patients would probably benefit from psychological support.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> depression, inflamatory bowel disease</p></sec><sec><title></title><p><bold>MONDAY, OCTOBER 14, 2013 14:00-15:30</bold></p><p><bold>Improving survival in colon cancer: Lessons learned from rectal cancer – Hall Oslo</bold></p></sec><sec><title>OP065 SAFETY AND CURABILITY OF ENDOSCOPIC SUBMUCOSAL DISSECTION FOR COLORECTAL TUMORS COMPARING WITH ENDOSCOPIC MUCOSAL RESECTION (EMR) AND PIECEMEAL EMR</title><p><bold>Y. Tamegai</bold><sup>1,*</sup>, T. Kishihara<sup>1</sup>, A. Chino<sup>1</sup>, S. Suzuki<sup>1</sup>, T. Suganuma<sup>1</sup>, M. Igarashi<sup>1</sup></p><p><italic><sup>1</sup>Endoscopy Division, Cancer Institute Hospital, Tokyo, Japan</italic></p><p><bold>INTRODUCTION:</bold> The progress of the endoscopic resection technique such as endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) has led to changes in therapeutic strategies for early colorectal cancers. ESD technique is a very useful endoscopic procedure, making it possible to perform en bloc resection of colorectal tumors regardless of lesion size. In this study, we evaluated the safety and curability between these endoscopic treatments.</p><p><bold>AIMS&METHODS:</bold> ESD was performed for 565 cases of tumor in 551 patients (male: female = 329:222; mean age, 66.2years). In same periods, we experienced 3,920 EMR cases and 352 cases with piecemeal EMR. We compared the incidence of perforation and residual/local recurrence between ESD, EMR, and piecemeal EMR.</p><p><bold>RESULTS:</bold> The incidence of perforation was 0.15% with EMR, 0.57% with EPMR, and 0.18% with ESD. This result revealed that ESD has become a very safe procedure similar to the EMR technique. The incidence of residual/local recurrence was 0.6% with EMR, 7.1% with piecemeal EMR, and 0% with ESD. Thus, although there is no significant difference in the incidence of perforation between these endoscopic procedures, the rate of residual/local recurrence after EPMR was significantly higher than afterEMR and ESD. The possibility to completing ESD for colorectal tumor sometime depends on the existence of fibrosis in submucosal layer rather than the size and location. Among 565 ESD cases, 135 cases were accompanied by SM fibrosis. Among 135 cases with SM fibrosis, of which 39 cases were considered related to cancer invasion and 96 cases were unrelated. En bloc resection rate of the tumor without fibrosis was 96.7% (416/430), and the tumor was accompanied with fibrosis in 83.7% (113/135). We experienced only one case of perforation (0.18%), which was accompanied with fibrosis. From the view point of safety and curability, use of the ESD procedure is thought to be limited for this group at high risk of perforation and recurrence. For the above mentioned reasons, we have developed safe resection procedure using laparoscopic and endoscopic cooperative surgery (LECS) in order to perform en bloc resection of tumors for which is difficult to complete ESD due to firm fibrosis in submucosal layer.</p><p><bold>CONCLUSION:</bold> It is important to establish the limitations of EMR and ESD in the therapeutic strategy for treating early colorectal cancer. We have established safe ESD technique and its applied LECS procedure in order to complete safe and curative en bloc resection for tumors accompanied with firm fibrosis in submucosal layer.</p><p><bold>Contact E-mail Address:</bold><email>yoshiro.tamegai@jfcr.or.jp</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> colorectal cancer, EMR, ESD complications</p></sec><sec><title>OP066 LONG-TERM RESULTS OF ESD FOR LARGE INTESTINE TUMOR</title><p><bold>S. Katsuki</bold><sup>1,*</sup>, T. F. Fujita<sup>2</sup>, K. Takanashi<sup>1</sup>, E. W. Waga<sup>1</sup>, K. Kitaoka<sup>1</sup>, Y. Komatsu<sup>1</sup>, H. Ohota<sup>3</sup>, Y. S. Sato<sup>4</sup></p><p><italic><sup>1</sup>Center of Gastroenterology, <sup>2</sup>OTARU EKISAIKAI HOSPITAL, Otaru, <sup>3</sup>Gastroenterology, Sapporo Orthopedics and cardiovascular Hospital, <sup>4</sup>Fourth Department of internal Medicine, Sapporo Medical University School of medicine, Sapporo, Japan</italic></p><p><bold>INTRODUCTION:</bold> Large intestine ESD is considered to be a difficult treatment due to the thinness of colon wall, its flexural structure and enterobacterial existence.</p><p>Therefore large intestine ESD has not yet become a common treatment.</p><p>At our hospital, we have performed large intestine ESD treatments</p><p>positively since 2003.</p><p><bold>AIMS&METHODS:</bold> From the results of large intestine ESD performed at our hospital, we evaluate the usefulness of ESD for large intestine tumor.</p><p>A retrospective study was carried out.</p><p>696 lesions on which were performed ESD during this past ten years (from April, 2003 to March, 2013) at our hospital were the objects. We divided the ten years into two 5-year periods.</p><p>We defined the first five years as IP (initial period of introduction), and the latter five years as SP (stable period).</p><p>And we divided the size of the tumor into 3 groups: group A (less than 2cm), group B (2cm or more to less than 5cm) and group C (5cm or more).</p><p>We examined the treatment time, the completing rate, the negative rate of cut end (lateral and vertical), and the perforation rate.</p><p>Furthermore, we examined 235 cases, for which more than four years had passed since the ESD treatment.</p><p><bold>RESULTS:</bold> The average treatment time (minutes) of group A,B,C in IP were 24.1±11.1, 51.3±18.2, 81.6±31.9, respectively and those in SP were 21.9±12.4 ,43.1±18.1 , 59.2±34.4</p><p>The negative rates of lateral cut end in IP were 87.9%, 81.1%, 65.6%, and those in SP were 100%, 96.3%, 97.1%. The negative rates of vertical cut end in IP were 100%, 92.6%, 89.0%, and those in SP were 100%, 99.1%, 100%.</p><p>The completing rates in IP were 95.4%, 88.4%, 90.6%, and those in SP were 100%, 99.1%, 100%. The perforation rates in IP were 0%, 4.2%, 10.9%, those in SP were 0%, 0.9%, 0.6%.</p><p>Among 293 cases, for which over four years had passed since the ESD treatment, in 235 cases, which were able to receive endoscopic follow-up, any local recurrences were not detected.</p><p><bold>CONCLUSION:</bold> In IP as a tumor grew bigger, there is a tendency that the completing rate and the negative rate of cut end decreased more, and a perforation rate increased more, but on the other hand, in SP, regardless of the size of the lesion, stable results were obtained. Skilled technique enables safe large intestine ESD treatment.</p><p><bold>Contact E-mail Address:</bold><email>sinichi-katuki@otaru-ekisaikai.jp</email></p><p><bold>Disclosure of Interest</bold>: S. Katsuki : No conflict of interest to declare, T. F. Fujita : No conflict of interest to declare, K. Takanashi : No conflict of interest to declare, E. W. Waga : No conflict of interest to declare, K. Kitaoka : No conflict of interest to declare, Y. Komatsu : No conflict of interest to declare, H. Ohota : No conflict of interest to declare, Y. S. Sato : No conflict of interest to declare</p><p><bold>Keywords:</bold> colon cancer, ESD (endoscopic submucosal dossection)</p></sec><sec><title></title><p><bold>MONDAY, OCTOBER 14, 2013 14:00-15:30</bold></p><p><bold>Colorectal sensory and motor dysfunction in constipation: Lessons for the management of adult and paediatric patients – Roof Garden</bold></p></sec><sec><title>OP067 CHRONIC CONSTIPATION: ROME III CRITERIA AND WHAT PATIENTS THINK. ARE WE TALKING THE SAME LANGUAGE?</title><p><bold>D. Gambaccini</bold><sup>1,*</sup>, C. Racale<sup>1</sup>, S. Salvadori<sup>2</sup>, P. Alduini<sup>3</sup>, G. Bassotti<sup>4</sup>, E. Battaglia<sup>5</sup>, R. Bocchini<sup>6</sup>, A. Bove<sup>7</sup>, F. Pucciani<sup>8</sup>, M. Bellini<sup>1</sup></p><p><italic><sup>1</sup>Gastrointestinal Unit, Cisanello University Hospital Pisa, <sup>2</sup>CNR, Institute of Clinical Physiology, Pisa, <sup>3</sup>Digestive Endoscopy Unit, Massa Hospital, Massa, <sup>4</sup>Gastroenterology and Hepatology Section, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, <sup>5</sup>Gastroenterology and Endoscopy Unit, Cardinal Massaja Hospital, Asti, <sup>6</sup>Gastroenterology and Endoscopy Unit, Malatesta Novello Hospital, Cesena, <sup>7</sup>Department of Gastroenterology, AORN A. Cardarelli, Gastroenterology and Endoscopy Unit, Naples, <sup>8</sup>Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy</italic></p><p><bold>INTRODUCTION:</bold> Chronic constipation is usually diagnosed using Rome III Criteria, but in clinical practice many physicians do not use these criteria and many patients consider themselves constipated while not showing symptoms consistent with these criteria. They also often require help from their physicians reporting a so called “self perceived constipation” (SPC). On the other hand some people could meet the Rome criteria for constipation while considering themselves perfectly “normal”.</p><p><bold>AIMS&METHODS:</bold> To evaluate the correlation between SPC, functional constipation (FC) and irritable bowel syndrome with constipation (IBS-C) diagnosed according Rome III criteria.</p><p>934 patients referred for gastroenterological visit and 980 carers were asked if they considered themselves constipated. Afterward they were invited to record anonymously symptoms in order to verify if they could be diagnosed as FC or IBS-C or SPC. Subjects with known or suspected severe organic diseases potentially causing constipation or assuming potentially constipating drugs were excluded.</p><p><bold>RESULTS:</bold> Data from 1914 subjects (patients and carers) were obtained (38.2% M; 61.8% F; mean age 50.6 ± SD 15.8). Among these 661/1914 (34.5%) subjects considered themselves to be constipated and 1253 (65.5%) not to be constipated (p<0.001). Among the “constipated“ group 485/661 (73.3%) were patients and 176/661 (26.7%) carers (p<0.001); Rome III criteria for FC and IBS-C were satisfied in 545/661 (82.5%) and in 282/661 (42.7%), respectively (p<0.001). In 1253 subjects that not considered themselves to be constipated, diagnosis of FC and IBS-c according to Rome III criteria were feasible in 208 (16.6%) and 76 (6%) subjects, respectively (p<0.001). As a whole criteria for FC and IBS-C were satisfied in 753/1914 subjects (39.3%) and 358/1914 (18.7%) subjects, respectively (p<0.001). Among 753 subjects diagnosed as FC 513 (68.1%) were patients and 240 (31.9%) carers; among 358 subjects diagnosed as IBS-C 273 (76.3%) were patients and 85 (23.7%) carers (p:0.007).</p><p><bold>CONCLUSION:</bold> People and gastroenterologists have often a different perception about what is constipation. FC, IBS-C and SCP are not easily separable conditions in clinical practice<bold>. </bold>Patients tend often to define “constipation” the combination of different symptoms that are not usually included in Rome III criteria for the diagnosis of constipation. Moreover in many cases patients define “constipation” what their doctors call “IBS-C”. Is it time for a revision of Rome Criteria for constipation?</p><p><bold>Contact E-mail Address:</bold><email>dario.gambaccini@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> constipation, Irritable bowel syndrome, Rome III criteria</p></sec><sec><title>OP068 EFFICACY OF A CARBON DIOXIDE-RELEASING SUPPOSITORY (EDUCTYL®) IN DYSCHEZIA: A DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED CLINICAL TRIAL</title><p><bold>A.-L. Tarrerias</bold><sup>1,*</sup>, L. Abramowitz<sup>2</sup>, P. Coulom<sup>3</sup>, C. Merlette<sup>4</sup>, G. Staumont<sup>3</sup>, V. Berger<sup>5</sup>, B. Savarieau<sup>6</sup>, M. Marty<sup>5</sup></p><p><italic><sup>1</sup>Service de chirurugie générale et digestive, Hôpital Foch, SURESNES, <sup>2</sup>Cabinet de gastro-entérologie, PARIS, <sup>3</sup>Centre des maladies de l'appareil digestif, Clinique St Jean Languedoc, TOULOUSE, <sup>4</sup>Cabinet Médical, FRESNES, <sup>5</sup>Département études cliniques, Nukleus, PARIS, <sup>6</sup>Service d’hépato-gastroentérologie, Hôpital Intercommunal, CRETEIL, France</italic></p><p><bold>INTRODUCTION:</bold> Dyschezia, a frequent defecatory disorder, has a detrimental impact on quality of life. Strong evidence on which to base the treatment is still lacking. Biofeedback retraining is a well-established technique and is considered as the only treatment of defecatory disorders of proven efficacy, but poses several logistical challenges that limit its use. Eductyl<sup>®</sup>, a carbon dioxide-releasing suppository, stimulates rectal mechanoreceptors and triggers defecation by release of gas (around 100 mL) in the rectum. This study was designed to assess the efficacy and safety of the carbon dioxide-releasing suppository.</p><p><bold>AIMS&METHODS:</bold> EDUCDYS was a randomized, double-blind, placebo-controlled study. Patients (18-75 years) were eligible if they had dyschezia defined according to modified Rome III criteria. Patients were randomly allocated a once-a-day suppository (carbon dioxide-releasing suppository or placebo) to be used in the morning at the time of scheduled defecation for 21 days. The primary endpoint was the change from D0 to D21 in intensity of discomfort related to dyschezia self-assessed by the patient on a VAS rated from 0 to 100. The primary endpoint was analyzed in the full analysis set population using a model of analysis of covariance.</p><p><bold>RESULTS:</bold> 323 patients were randomized (166 intervention group and 157 placebo group). A greater reduction from baseline to D21 in discomfort VAS score was observed in the intervention group (-34.5; SEM: 1.8) than in the placebo group (- 26.2; SEM: 1.9). The difference -8.2 [95% CI -12.9; - 3.6] was statistically significant (p<0.0005). Similar trends were observed in analyses in the intent-to-treat and per-protocol populations. All secondary efficacy parameters demonstrated superiority of the carbon dioxide-releasing suppository: percentage of 50% responders at D21 (p=0.002), changes between baseline and D21 for the four subscales and the overall scale of the Constipation-related Quality of Life questionnaire (p=0.001) and of the Bowel Functional Index scores (p=0.003).</p><p><bold>CONCLUSION:</bold> These are the first results to indicate the efficacy of a pharmacological treatment (carbon dioxide-releasing suppository) based on a well-designed randomized, controlled trial in patients with dyschezia.</p><p>ClinicalTrial.gov, number NCT01243723</p><p><bold>Disclosure of Interest</bold>: A.-L. Tarrerias Financial support for research from: Techni Pharma Laboratory, L. Abramowitz Financial support for research from: Techni Pharma Laboratory, P. Coulom Financial support for research from: Techni Pharma Laboratory, C. Merlette Financial support for research from: Techni Pharma Laboratory, G. Staumont Financial support for research from: Techni Pharma Laboratory, V. Berger Financial support for research from: Techni Pharma Laboratory, B. Savarieau Financial support for research from: Techni Pharma Laboratory, M. Marty Financial support for research from: Techni Pharma Laboratory</p><p><bold>Keywords:</bold> clinical trial, dioxide-releasing suppository, dyschezia, quality of life</p></sec><sec><title></title><p><bold>MONDAY, OCTOBER 14, 2013 14:00-15:30</bold></p><p><bold>Coeliac disease: From the tip of the iceberg to deep water – Hall Helsinki</bold></p></sec><sec><title>OP069 THE YOUNG COELIACS OF THE PREVENTCD STUDY - A PROSPECTIVE COHORT AT HIGH-RISK FOR COELIAC DISEASE</title><p><bold>S. L. Vriezinga</bold><sup>1,*</sup>, R. Auricchio<sup>2</sup>, E. Bravi<sup>3</sup>, G. Castillejo<sup>4</sup>, A. Chmielewska<sup>5</sup>, P. Crespo<sup>6</sup>, J. Gyimesi<sup>7</sup>, C. Hartman<sup>8</sup>, S. Kolaček<sup>9</sup>, S. Koletzko<sup>10</sup>, I. Korponay-Szabo<sup>7</sup>, E. Martinez-Ojinaga<sup>11</sup>, A. Močić Pavić<sup>9</sup>, E. Mummert<sup>12</sup>, I. Polanco<sup>11</sup>, H. Putter<sup>13</sup>, C. Ribes-Koninckx<sup>6</sup>, J. Romanos<sup>14</sup>, R. Shamir<sup>8</sup>, H. Szajewska<sup>5</sup>, K. Werkstetter<sup>10</sup>, C. Wijmenga<sup>14</sup>, R. Troncone<sup>2</sup>, M. L. Mearin<sup>1</sup> and the PreventCD working group</p><p><italic><sup>1</sup>Pediatrics, Leiden University Medical Center, Leiden, Netherlands, <sup>2</sup>Pediatrics, University Federico II, Naples, <sup>3</sup>Eurospital SpA, Trieste, Italy, <sup>4</sup>Pediatrics, Hospital Universitari Sant Joan, Reus, Spain, <sup>5</sup>Pediatrics, Medical University of Warsaw, Warsaw, Poland, <sup>6</sup>Pediatrics, La Fe University Hospital, Valencia, Spain, <sup>7</sup>Coeliac Disease Center, Heim Pál Children's Hospital, Budapest, Hungary, <sup>8</sup>Schneider Children’s Medical Center, Sackler faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel, <sup>9</sup>University Children's Hospital Zagreb, Zagreb, Croatia, <sup>10</sup>Hauner Children's Hospital, University of Munich, Munich, Germany, <sup>11</sup>Pediatrics, La Paz University Hospital, Madrid, Spain, <sup>12</sup>Phadia GmbH/ThermoFisher, Freiburg, Germany, <sup>13</sup>Medical Statistics, Leiden University Medical Center, Leiden, <sup>14</sup>Genetics, University Medical Center Groningen, Groningen, Netherlands</italic></p><p><bold>INTRODUCTION:</bold> The EU-PreventCD project (<ext-link ext-link-type="uri" xlink:href="www.preventcd.com">www.preventcd.com</ext-link>) is a prospective double-blind intervention study investigating the effect of early gluten introduction on development of coeliac disease (CD) in high risk children. The analysis is still blinded as to the effect of the intervention.</p><p><bold>AIMS&METHODS:</bold> The aim of this study is to characterize the development of CD in the prospective cohort of PreventCD at the age of 3y. From 2007-2010, 1324 infants with a 1<sup>st</sup> degree relative with CD were recruited in 8 countries shortly after birth. 814 children, HLA-DQ2+ and/or DQ8+, have been followed clinically and serologically until the age of 3y. Small bowel biopsies (SBBs) were performed based on symptoms suggestive of CD, and/or anti-tissuetransglutaminase antibodies (TG2A) or anti-gliadin antibodies (AGA).</p><p><bold>RESULTS:</bold> Mean age 4.3y; 48.5% girls; 89% of the children were DQ2+ (16% homozygous); 52% were breastfed ≥ 6 months. Seventy-four SBBs were performed in 68 children. CD was confirmed by SBBs in 53 children and in another 3 without SBBs (new ESPGHAN criteria). The cumulative incidence (CI) of CD at 3y was 5.2%. The mean age at diagnosis was 2.7y, with 64% being diagnosed under 3y. All 56 children with CD had elevated TG2A, 82% had elevated AGA, and 64% had symptoms. CD was not significantly associated with pregnancy duration, birth weight, duration of breastfeeding, or number/type of relatives with CD. CD developed more frequently in girls (CI 7.2% v.s. 3.3%; p=0.03). HLA genotypes were highly related to the CI of CD (p<0.0001, see table).
<table-wrap id="table11-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1"><bold>HLA genotypes</bold></th><th rowspan="1" colspan="1"><bold>Frequency (%)</bold></th><th rowspan="1" colspan="1"><bold>CI at 3y (%)</bold></th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">DR3-DQ2/DR3-DQ2</td><td rowspan="1" colspan="1">4.9</td><td rowspan="1" colspan="1">25.3</td></tr><tr><td rowspan="1" colspan="1">DR3-DQ2/DR7-DQ2</td><td rowspan="1" colspan="1">7.9</td><td rowspan="1" colspan="1">14.3</td></tr><tr><td rowspan="1" colspan="1">DR3-DQ2/DR5-DQ7</td><td rowspan="1" colspan="1">11.2</td><td rowspan="1" colspan="1">6.9</td></tr><tr><td rowspan="1" colspan="1">DR7-DQ2/DR7-DQ2</td><td rowspan="1" colspan="1">3.2</td><td rowspan="1" colspan="1">4.5</td></tr><tr><td rowspan="1" colspan="1">DR3-DQ2/DQX</td><td rowspan="1" colspan="1">31.6</td><td rowspan="1" colspan="1">3.5</td></tr><tr><td rowspan="1" colspan="1">DR7-DQ2/DR5-DQ7</td><td rowspan="1" colspan="1">8.6</td><td rowspan="1" colspan="1">3.5</td></tr><tr><td rowspan="1" colspan="1">DR7-DQ2/DQX</td><td rowspan="1" colspan="1">12.3</td><td rowspan="1" colspan="1">2.4</td></tr><tr><td rowspan="1" colspan="1">DR3-DQ2/DR4-DQ8</td><td rowspan="1" colspan="1">6.0</td><td rowspan="1" colspan="1">2.4</td></tr><tr><td rowspan="1" colspan="1">Other</td><td rowspan="1" colspan="1">14.4</td><td rowspan="1" colspan="1">0</td></tr></tbody></table></table-wrap></p><p><bold>CONCLUSION:</bold> These preliminary results show that genetically susceptible children from high-risk families develop CD at a very young age and that this is significantly associated with homozygosity for DQ2. Even in very young children, presence of TG2A is a powerful predictor of CD.</p><p><bold>Contact E-mail Address:</bold><email>s.l.vriezinga@lumc.nl</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> children, Coeliac disease, Prospective Studies </p></sec><sec><title>OP070 LARGE VARIATIONS IN INCIDENCE AND PREVALENCE OF CLINICALLY DIAGNOSED COELIAC DISEASE IN THE UK</title><p><bold>J. West</bold><sup>1</sup>, K. Fleming<sup>1</sup>, L. Tata<sup>1</sup>, T. Card<sup>1</sup>, C. J. Crooks<sup>1,*</sup></p><p><italic><sup>1</sup>Epidemiology and Public Health, UNIVERSITY OF NOTTINGHAM, Nottingham, United Kingdom</italic></p><p><bold>INTRODUCTION:</bold> Worldwide, few studies have quantified the incidence and prevalence of coeliac disease (CD) and dermatitis herpetiformis (DH) across time, all age groups and the whole population of a nation. Understanding the epidemiology of the occurrence of these diseases in such a manner is crucial for hypothesising about causes and quantifying the burden of disease.</p><p><bold>AIMS&METHODS:</bold> Patients with coeliac disease or Dermatitis herpetiformis were identified in the Clinical Practice Research Datalink between 1990 and 2011 using Read codes we have previously published. Incidence rates and prevalence were calculated by age group, sex, year and region of residence.</p><p>Incidence rate ratios adjusted for age, sex and region (IRR) were calculated with Poisson regression.</p><p><bold>RESULTS:</bold> 9087 incident cases of coeliac disease and 809 incident cases of Dermatitis herpetiformis were identified from the CPRD. Between 1990 and 2011 the incidence rate of coeliac disease increased from 5.2/100,000 (95% CI, 3.8-6.8) to 19.1/100,000 (17.8-20.5) (IRR 3.6, 95% CI 2.7-4.8). The highest incidence of coeliac disease was seen in Northern Ireland (absolute incidence 22.3 per 100,000 person years) and the lowest in the London region (absolute incidence 10 per 100,000 person years). The incidence of dermatitis herpetiformis decreased over the same time period from 1.8/100,000 to 0.8/100,000 (average annual IRR 0.96, 95% CI 0.94-0.97). There were large regional variations in prevalence for CD but not DH (selected regions shown in table).
<table-wrap id="table12-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1"></th><th rowspan="1" colspan="1">Coeliac Disease (n)</th><th rowspan="1" colspan="1">Prevalence %</th><th rowspan="1" colspan="1">95% CI</th><th rowspan="1" colspan="1">Dermatitis Herpetiformis (n)</th><th rowspan="1" colspan="1">Prevalence %</th><th rowspan="1" colspan="1">95% CI</th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">North East</td><td rowspan="1" colspan="1">171</td><td rowspan="1" colspan="1">0.22</td><td rowspan="1" colspan="1">[0.18,0.25]</td><td rowspan="1" colspan="1">22</td><td rowspan="1" colspan="1">0.03</td><td rowspan="1" colspan="1">[0.02,0.04]</td></tr><tr><td rowspan="1" colspan="1">East Midlands</td><td rowspan="1" colspan="1">226</td><td rowspan="1" colspan="1">0.28</td><td rowspan="1" colspan="1">[0.24,0.32]</td><td rowspan="1" colspan="1">23</td><td rowspan="1" colspan="1">0.03</td><td rowspan="1" colspan="1">[0.02,0.04]</td></tr><tr><td rowspan="1" colspan="1">West Midlands</td><td rowspan="1" colspan="1">944</td><td rowspan="1" colspan="1">0.25</td><td rowspan="1" colspan="1">[0.23,0.27]</td><td rowspan="1" colspan="1">91</td><td rowspan="1" colspan="1">0.02</td><td rowspan="1" colspan="1">[0.02,0.03]</td></tr><tr><td rowspan="1" colspan="1">East of England</td><td rowspan="1" colspan="1">819</td><td rowspan="1" colspan="1">0.23</td><td rowspan="1" colspan="1">[0.22,0.25]</td><td rowspan="1" colspan="1">86</td><td rowspan="1" colspan="1">0.02</td><td rowspan="1" colspan="1">[0.02,0.03]</td></tr><tr><td rowspan="1" colspan="1">South West</td><td rowspan="1" colspan="1">1072</td><td rowspan="1" colspan="1">0.28</td><td rowspan="1" colspan="1">[0.26,0.30]</td><td rowspan="1" colspan="1">106</td><td rowspan="1" colspan="1">0.03</td><td rowspan="1" colspan="1">[0.02,0.03]</td></tr><tr><td rowspan="1" colspan="1">London</td><td rowspan="1" colspan="1">905</td><td rowspan="1" colspan="1">0.16</td><td rowspan="1" colspan="1">[0.15,0.17]</td><td rowspan="1" colspan="1">87</td><td rowspan="1" colspan="1">0.02</td><td rowspan="1" colspan="1">[0.01,0.02]</td></tr><tr><td rowspan="1" colspan="1">Northern Ireland</td><td rowspan="1" colspan="1">592</td><td rowspan="1" colspan="1">0.39</td><td rowspan="1" colspan="1">[0.36,0.42]</td><td rowspan="1" colspan="1">67</td><td rowspan="1" colspan="1">0.04</td><td rowspan="1" colspan="1">[0.03,0.06]</td></tr><tr><td rowspan="1" colspan="1">Scotland</td><td rowspan="1" colspan="1">1203</td><td rowspan="1" colspan="1">0.27</td><td rowspan="1" colspan="1">[0.26,0.29]</td><td rowspan="1" colspan="1">166</td><td rowspan="1" colspan="1">0.04</td><td rowspan="1" colspan="1">[0.03,0.04]</td></tr><tr><td rowspan="1" colspan="1">Wales</td><td rowspan="1" colspan="1">970</td><td rowspan="1" colspan="1">0.22</td><td rowspan="1" colspan="1">[0.21,0.24]</td><td rowspan="1" colspan="1">114</td><td rowspan="1" colspan="1">0.03</td><td rowspan="1" colspan="1">[0.02,0.03]</td></tr></tbody></table></table-wrap></p><p><bold>CONCLUSION:</bold> We found that across a 21 year period there was a 4-fold increase in the incidence of CD in the UK with large regional variations in prevalence. This contrasted starkly with a 4% year on year decrease in the incidence of DH with minimal regional variations in prevalence. This contrast could reflect differences in diagnosis between CD (serological diagnosis and case finding) and DH (symptomatic presentation). Our reported prevalence of CD and DH remains lower than the known seroprevalence of undetected CD in the UK (1%)<sup>1</sup>. As the latter does not vary by region, inequalities in access and implementation of diagnostic pathways may still exist to explain the variations in clinical disease that we observed.</p><p><bold>REFERENCES:</bold></p><p>1. Gut 2003;52:960-965</p><p><bold>Contact E-mail Address:</bold><email>colin.crooks@nottingham.ac.uk</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Coeliac disease, Dermatitis herpetiformis, incidence, prevalence</p></sec><sec><title>OP071 ESPGHAN 2012 COELIAC DISEASE DIAGNOSTIC CRITERIA VALIDATION: A RETROSPECTIVE SPANISH MULTICENTRIC STUDY</title><p><bold>E. Donat</bold><sup>1,*</sup>, J. M. Ramos<sup>2</sup>, F. Sanchez-Valverde<sup>3</sup>, A. Moreno<sup>4</sup>, M. Martinez<sup>5</sup>, R. Leis<sup>6</sup>, L. Peña<sup>7</sup>, G. Castillejo<sup>8</sup>, S. Fernandez<sup>9</sup>, Z. Garcia<sup>10</sup>, L. Ortigosa<sup>11</sup>, E. Balmaseda<sup>12</sup>, J. M. Marugán<sup>13</sup>, F. J. Eizaguirre<sup>14</sup>, H. Lorenzo<sup>15</sup>, J. Barrio<sup>16</sup>, C. Ribes-Koninckx<sup>1</sup> SEGHNP (Spanish Society of Pediatric Gastroenterology, Hepatology and Nutrition)</p><p><italic><sup>1</sup>Gastroenterology Unit, Hospital La Fe, Valencia, <sup>2</sup>Gastroenterology Unit, Complejo Hospitalario Universitario de Vigo, Vigo, <sup>3</sup>Gastroenterology Unit, Hospital Virgen del Camino, Pamplona, <sup>4</sup>Gastroenterology Unit, Hospital Teresa Herrrera, A coruña, <sup>5</sup>Gastroenterology Unit, Hospital Universitario Niño Jesus, Madrid, <sup>6</sup>Gastroenterology Unit, Hospital Clínico Universitario de Santiago, santiago Compostela, <sup>7</sup>Gastroenterology Unit, Hospital General de Las Palmas de Gran Canaria, Gran Canaria, <sup>8</sup>Gastroenterology Unit, Hospital Universitari de Sant Joan de Reus, Reus, <sup>9</sup>Gastroenterology Unit, H.severo Ochoa, Madrid, <sup>10</sup>Gastroenterology Unit, Hospital de Txagorritxu, Vitoria, <sup>11</sup>Gastroenterology Unit, Hospital Universitario Ntra Sra de Candelaria , Tenerife, <sup>12</sup>Gastroenterology Unit, Hospital General de Albacete, Albacete, <sup>13</sup>Gastroenterology Unit, Hospital Clínico Universitario de Valladolid, Valladolid, <sup>14</sup>Gastroenterology Unit, Hospital de Donostia, Donostia, <sup>15</sup>Gastroenterology Unit, Hospital Universitario de Basurto , Basurto, <sup>16</sup>Gastroenterology Unit, Hospital Universitario de Fuenlabrada , Madrid, Spain</italic></p><p><bold>INTRODUCTION:</bold> The main objective is to determine whether in certain circumstances a diagnosis of celiac disease (CD) can be safely established without performing a small bowel biopsy (SBB), as proposed in the new ESPGHAN guidelines 2012 for the diagnosis of CD which establishes that the SBB could be avoided in HLA DQ2/DQ8 symptomatic patients with positive endomysial antibodies (EMA) and anti-transglutaminase antibodies (TTG) whenever the title is 10 times the upper limit of normal (TTG> 10xULN). Besides challenge is not longer recommended to be mandatory in all cases with a SBB performed before the age of 2 at the time of diagnosis.</p><p><bold>AIMS&METHODS:</bold> Histological, serologic, clinical and genetic data were retrospectively collected in paediatric patients with a SBB performed between the years 2000 to 2009 and a minimum follow-up period of 2 years. Same data were collected from all children who underwent a gluten challenge.</p><p><bold>RESULTS:</bold> 33 centres and 12 regions were involved, 16 of them contributing with more than 60 cases each. 2647 patients were included, with 440 (16.7%) children under 2 years at the 1<sup>st</sup> SBB.In 95.9% of the cases (2537 patients) a CD diagnosis was firmly established, the remaining patients (4.1 %) are non CD or unclear cases.In 845 patient’s data for TTG, EMA and HLA were available, 729 of them being symptomatic. 383 out of these were HLA DQ2/DQ8 positive, had positive EMA and TTG> 10xULN, and thus in these latter a SBB could have been avoided applying the ESPGHAN 2012 recommendations i.e 52.5%.Four patients also positive for HLA, EMA and with TTG > 10xULN had a Marsh 1 lesion but they were asymptomatic. Gluten challenge was carried out in 71 patients younger than 2 at the 1<sup>st</sup> SBB; all but 8 did relapse: in 5 no serological data were available at diagnosis or the histological findings were not conclusive, thus CD diagnosis was doubtful. 3 are still on follow-up.</p><p><bold>CONCLUSION:</bold> Application of the new CD diagnosis 2012 ESPGHAN criteria in our population would have avoided a SBB in a 50% of the cases, without the risk of overdiagnosis (100% specificity) as in asymptomatic patients, regardless of serology, SBB is still mandatory.</p><p><bold>Contact E-mail Address:</bold><email>esterdonat@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> celiac disease, epidemilogic, new criteria</p></sec><sec><title>OP072 THE POPULATION PREVALENCE OF SELF-REPORTED GLUTEN SENSITIVITY AND REFERRAL CHARACTERISTICS TO SECONDARY CARE</title><p><bold>I. Aziz</bold><sup>1,*</sup>, N. R. Lewis<sup>1</sup>, M. Hadjivassiliou<sup>2</sup>, S. N. Winfield<sup>1</sup>, N. Rugg<sup>1</sup>, A. Kelsall<sup>1</sup>, L. Newrick<sup>1</sup>, D. S. Sanders<sup>1</sup></p><p><italic><sup>1</sup>Department of Gastroenterology, <sup>2</sup>Neurology, Sheffield Teaching Hospitals, Sheffield, United Kingdom</italic></p><p><bold>INTRODUCTION:</bold> Reports suggest gluten sensitivity (GS) exists in the absence of coeliac disease (CD). This clinical entity has been termed non-coeliac gluten sensitivity (NCGS). We aimed to determine the population prevalence of self-reported GS and referral characteristics to secondary care.</p><p><bold>AIMS&METHODS:</bold> A United Kingdom population survey screened for GS and related symptoms. Diagnostic outcomes were also analyzed in patients referred to secondary care with GS. CD diagnosis entailed a positive celiac serology (endomysial and/or tissue transglutaminase antibodies) plus Marsh 1-3 on duodenal biopsies. NCGS diagnosis was based on exclusion of CD.</p><p><bold>RESULTS:</bold> 1002 adults in the population (female 55%, mean-age 39yrs). The self-reported prevalence for GS was 13% (female 79% [p<0.0001], mean-age 39yrs). Subjects with GS had an increased prevalence of fulfilling the ROME III criteria for irritable bowel syndrome (IBS), in comparison to those without GS (20% vs. 3.89%, OR 6.23, p<0.0001).</p><p>In secondary care 160 GS patients (female 84%, mean-age 39yrs) were investigated, in whom 10% had CD and 90% NCGS. All CD patients were HLA DQ2 or DQ8 positive compared to 46% of NCGS cases (p<0.0001). Nutritional deficiencies (p<0.011), autoimmune disorders (22.3% vs. 10.6%, p=0.003) and a lower mean body mass index (23.7 vs. 25.5, p=0.005) were significantly associated with CD compared to NCGS. There was no difference in family history of CD between the groups (CD 7.4% vs. NCGS 12.8%, p=0.058).</p><p><bold>CONCLUSION:</bold> GS is commonly self-reported with symptoms suggesting an association with IBS. The majority of patients have NCGS, an entity which demonstrates clinical and immunologic difference to CD.</p><p><bold>REFERENCES:</bold></p><p>1. Carroccio A, Mansueto P, Iacono G, et al. Non-celiac wheat sensitivity diagnosed by double-blind placebo-controlled challenge: exploring a new clinical entity. <italic>Am J Gastroenterol</italic> 2012;<bold>107</bold>(12):1898-906</p><p>2. Biesiekierski JR, Newnham ED, Irving PM, et al. Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double-blind randomized placebo-controlled trial. <italic>Am J Gastroenterol</italic> 2011;<bold>106</bold>(3):508-14</p><p>3. Volta U, De Giorgio R. New understanding of gluten sensitivity. <italic>Nat Rev Gastroenterol Hepatol</italic> 2012;<bold>9</bold>(5):295-9.</p><p>4. Aziz I, Hadjivassiliou M, Sanders DS. Does gluten sensitivity in the absence of coeliac disease exist? <italic>BMJ</italic> 2012;<bold>345</bold>:e7907.</p><p>5. Sapone A, Bai JC, Ciacci C, et al. Spectrum of gluten-related disorders: consensus on new nomenclature and classification. <italic>BMC Med</italic> 2012;<bold>10</bold>:13</p><p><bold>Contact E-mail Address:</bold><email>imran.aziz@sth.nhs.uk</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Coeliac disease, Irritable bowel syndrome, Non-coeliac gluten sensitivity</p></sec><sec><title>OP073 DOES IGA TISSUE TRANSGLUTAMINASE ANTIBODY LEVELS CORRELATE WITH HISTOLOGICAL FINDINGS OF COELIAC DISEASE (CD)?</title><p><bold>M. Kurien</bold><sup>1,*</sup>, A. Johnston<sup>1</sup>, A. Avgerinos<sup>1</sup>, D. S. Sanders<sup>1</sup></p><p><italic><sup>1</sup>Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield, United Kingdom</italic></p><p><bold>INTRODUCTION:</bold> The current gold standard diagnostic test for CD is oesophogastroduodenoscopy (OGD) and duodenal biopsies, aiming to demonstrate the presence of villous atrophy. Given the low sensitivity of endoscopic markers and the patchy distribution of CD within the small bowel, a duodenal bulb biopsy is currently recommended. However, recent studies have raised questions about the need for biopsies in CD, particularly within the paedatric literature, with high anti-tissue transglutaminase antibody (TTG) levels believed to be sufficient. The hypothesis being that high TTG levels correlate closely with definitive CD histology (Marsh 3a-c) giving a high positive predicative value (PPV). This study evaluates TTG levels and histology (inclusive of a bulb biopsy) in adult patients suspected of having CD, with the aim of defining a cut off value for TTG when biopsy may be unnecessary.</p><p><bold>AIMS&METHODS:</bold> Between Nov 2008 and July 2012, 523 adult patients (>16 years) with suspected coeliac disease were prospectively recruited into a study evaluating bulb biopsies in a university hospital. All patients had a minimum of 5 duodenal biopsies taken whilst on a gluten containing diet, with at least one being a bulb biopsy. Furthermore, all patients were tested for IgA TTG, Endomysial Antibody (EMA) and total IgA immunoglobulin at the time of their endoscopy. This study retrospectively reviews the correlation between TTG levels (Aesku Diagnostics, Wendelsheim, Germany) and histological outcomes in these patients, with CD being defined as villous atrophy (Marsh 3a-3c) and a clinical and serological response to a gluten free diet.</p><p><bold>RESULTS:</bold> Of the 523 adult patients (median age 51 years, range 16-91) recruited, 212 (41%) had positive TTG serology (>15 U/ml). EMA positivity was identified in 31% of the cohort (163/523) with CD diagnosed in 32% (169/523). The PPV for diagnosing CD for differing TTG levels are demonstrated in Table 1. No cut off level was associated with a PPV of 100%, with the highest PPV value of 97.1% seen when the TTG level was set at 300U/ml (20 x upper normal limit).
<table-wrap id="table13-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="2" colspan="1">TTG cut off U/ml</th><th rowspan="2" colspan="1">x ULN</th><th colspan="2" rowspan="1"><hr></hr>Number of Patients</th><th rowspan="2" colspan="1">PPV (%)</th></tr><tr><th rowspan="1" colspan="1">Coeliac disease</th><th rowspan="1" colspan="1">Not Coeliac Disease</th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">>15</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">152</td><td rowspan="1" colspan="1">60</td><td rowspan="1" colspan="1">71.7</td></tr><tr><td rowspan="1" colspan="1">>30</td><td rowspan="1" colspan="1">2</td><td rowspan="1" colspan="1">146</td><td rowspan="1" colspan="1">34</td><td rowspan="1" colspan="1">81.1</td></tr><tr><td rowspan="1" colspan="1">>75</td><td rowspan="1" colspan="1">5</td><td rowspan="1" colspan="1">132</td><td rowspan="1" colspan="1">12</td><td rowspan="1" colspan="1">91.7</td></tr><tr><td rowspan="1" colspan="1">>105</td><td rowspan="1" colspan="1">7</td><td rowspan="1" colspan="1">128</td><td rowspan="1" colspan="1">9</td><td rowspan="1" colspan="1">93.4</td></tr><tr><td rowspan="1" colspan="1">>150</td><td rowspan="1" colspan="1">10</td><td rowspan="1" colspan="1">117</td><td rowspan="1" colspan="1">7</td><td rowspan="1" colspan="1">94.4</td></tr><tr><td rowspan="1" colspan="1">>225</td><td rowspan="1" colspan="1">15</td><td rowspan="1" colspan="1">105</td><td rowspan="1" colspan="1">5</td><td rowspan="1" colspan="1">95.5</td></tr><tr><td rowspan="1" colspan="1">>300</td><td rowspan="1" colspan="1">20</td><td rowspan="1" colspan="1">99</td><td rowspan="1" colspan="1">3</td><td rowspan="1" colspan="1">97.1</td></tr><tr><td colspan="5" rowspan="1">TTG; anti-tissue transglutaminase antibody; UNL; Upper Normal Limit; PPV; Positive Predicitve Value</td></tr></tbody></table></table-wrap></p><p><bold>CONCLUSION:</bold> Contrary to ESPHGAN guidelines our findings would not support a biopsy avoidance strategy in those with high TTG levels, with patient potentially being wrongly diagnosed. We advocate that duodenal biopsies including a bulb biopsy remain the gold standard diagnostic test in those with suspected CD.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Coeliac disease, Serology</p></sec><sec><title>OP074 TO INVESTIGATE OR NOT: ‘IRONING OUT THE EVIDENCE’.</title><p><bold>J. L. Hulley</bold><sup>1,*</sup>, J. Pickard<sup>1</sup>, J. Robertson<sup>1</sup>, M. Gunn<sup>1</sup></p><p><italic><sup>1</sup>Department of Gastroenterology, Royal Victoria Infirmary, Newcastle-upon-Tyne, United Kingdom</italic></p><p><bold>INTRODUCTION:</bold> Investigation of patients who have an isolated iron deficiency in the absence of anaemia is of disputed value. The British Society of Gastroenterologists (BSG) recommends that this group of patients are investigated based on symptoms or family history.<sup>1 </sup>We reviewed patients referred to our nurse-led iron deficiency anaemia (IDA) service over a 16 month period to look at outcomes in patients with an isolated iron deficiency.</p><p><bold>AIMS&METHODS:</bold> Data was collected retrospectively over a 16 month period on all patients referred to the nurse-led IDA service at the Royal Victoria Infirmary, Newcastle-upon-Tyne. Patients were defined as having an iron deficiency with a ferritin less than 40, but normal haemoglobin (Hb) (Hb >11.0 g/dl in females; Hb >12.0 g/dl in males). The following outcomes were examined: total number of patients investigated, including reasons for not investigating; the presence of symptoms and/or family history; detection of significant malignant and significant benign pathology including coeliac disease.</p><p><bold>RESULTS:</bold> Between January 2012 and April 2013, 458 patients were referred to the IDA service; 114 were found to have an isolated iron deficiency. Gender distribution: 32 males and 82 females, 14 of whom were menstruating females. Across both genders the mean age was 62.5 years and mean ferritin was 14. Eight patients went straight-to-test and the remaining 106 were seen in clinic by a nurse specialist.</p><p>Of the 114 patients: 82 (72%) underwent GI investigations: 56/82 (68%) patients were investigated due to GI symptoms and/or significant family history; 26/82(32%) patients were investigated due to patient choice. The commonest reason for non-investigations was patient choice, but other reasons such as menstruation, recent GI investigations or patients failure to attend were also noted.</p><p>Abnormal and significant pathology was detected in 28/82 patients (34%): 3 malignancies (1 ampulla, 1 colorectal and 1 ovarian), 3 coeliac disease, and 22 other significant benign pathology (peptic ulcer disease, oesophagitis, multiple gastric erosions, moderate-severe duodenitis).</p><p><bold>CONCLUSION:</bold> Investigation of isolated iron deficiency in the absence of anaemia based on a symptom or significant family history approach in our cohort of patients demonstrates a significant yield of pathology (34% of patients). This supports current recommendations from the latest BSG guidelines.</p><p><bold>REFERENCES:</bold></p><p>1. Goddard A, James M, McIntyre A, Scott B, Gut 2011;60:1309e1316. doi:10.1136/gut.2010.228874</p><p>2. In order to make a comprehensive patient assessment and allow patients to make informed decisions about their healthcare they should first be seen in a gastroenterology outpatient clinic. We recommend referral to an IDA outpatient service in all patients with iron deficiency in the absence of anaemia or menstrual cause for iron deficiency.</p><p><bold>Contact E-mail Address:</bold><email>melanie.gunn@nuth.nhs.uk</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Anaemia, iron deficiency</p></sec><sec><title></title><p><bold>MONDAY, OCTOBER 14, 2013 14:00-15:30</bold></p><p><bold>Prevention and early detection of upper GI cancer – Hall 7</bold></p></sec><sec><title>OP075 A COMPARISON OF LONG-TERM OUTCOMES BETWEEN ENDOSCOPIC RESECTION AND SURGERY FOR DIFFERENTIATED EARLY GASTRIC CANCER</title><p><bold>Y.-I. Kim</bold><sup>1,*</sup>, J. H. Lee<sup>1</sup>, C. G. Kim<sup>1</sup>, S.-J. Cho<sup>1</sup>, J. Y. Lee<sup>1</sup>, K. W. Ryu<sup>1</sup>, B.-H. Nam<sup>2</sup>, M.-C. Kook<sup>1</sup>, Y.-W. Kim<sup>1</sup>, I. J. Choi<sup>1</sup></p><p><italic><sup>1</sup>Center for Gastric Cancer, <sup>2</sup>Center for Clinical Trials, National Cancer Center, Goyang, Korea, Republic Of</italic></p><p><bold>INTRODUCTION:</bold> Endoscopic resection (ER) has been recommended for early gastric cancer (EGC) confined to mucosa meeting the criteria for no risk of lymph node metastasis.</p><p><bold>AIMS&METHODS:</bold> In this study, we compared the long-term outcomes of EGC patients who underwent ER with those underwent surgery. We retrospectively reviewed data of gastric cancer patients who underwent ER or surgery for EGC confined to mucosal layer, less than 2 cm in size, with well or moderately differentiated histology between 2002 and 2007. Long-term outcomes including development of metachronous gastric cancer and overall survival (OS) were compared between ER and surgery.</p><p><bold>RESULTS:</bold> Among 375 patients enrolled, 261 underwent ER (ER group) and 114 underwent surgery (Surgery group). ER group had smaller tumor size (mean, 1.2 cm vs. 1.5 cm; <italic>P</italic><0.001) and showed less moderately differentiated histology (23.4% vs. 34.2%; <italic>P</italic>=0.029) than Surgery group. The rate of complications after treatment was lower in ER group than in Surgery group (2.7% vs. 7.9%; <italic>P</italic>=0.028). During a median follow-up of 76.4 months, metachronous gastric cancer occurred more frequently in ER group (6.1%, 16/261) than in Surgery group (0.9%, 1/114) (<italic>P</italic>=0.024). However, most of metachronous cancers (93.8%, 15/16) in ER group were curatively treated by repeated ER. The 5-year OS rates were 95.7% in ER group and 93.6% in Surgery group. A multivariate Cox-proportional hazard regression analysis showed that patients underwent ER showed no significant differences in OS, in compared with those underwent surgery (adjusted hazard ratio, 0.76; 95% confidence interval, 0.32 to 1.84; <italic>P</italic>=0.543).</p><p><bold>CONCLUSION:</bold> OS of ER for mucosal EGC, which were of differentiated type and less than 2 cm in size, were comparable to those of surgery.</p><p><bold>Contact E-mail Address:</bold><email>cij1224@ncc.re.kr</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Early gastric cancer, Endoscopic resection, Surgery</p></sec><sec><title>OP076 RISK STRATIFICATION USING OLGIM SYSTEM AND MODIFIED VRIES RISK SCORE IN A HIGH RISK POPULATION</title><p><bold>A. C. Caetano</bold><sup>1</sup>, S. Rua<sup>2</sup>, B. Gonçalves<sup>1,*</sup>, A. Ferreira<sup>1</sup>, J. B. Soares<sup>1</sup>, R. Gonçalves<sup>1</sup>, C. Rolanda<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology Department, <sup>2</sup>Braga Hospital, Braga, Portugal</italic></p><p><bold>INTRODUCTION:</bold> A cascade of premalignant gastric lesions such as atrophic gastritis (AG), intestinal metaplasia (IM) and dysplasia precedes intestinal-type adenocarcinoma. Other risk factors seem to be related with an increased risk of progression to gastric cancer (GC). It is consensual the need to identify subgroups of patients with higher risk of progression to GC. The Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) was recently proposed with this purpose.</p><p><bold>AIMS&METHODS:</bold> Aims: To determine if GC risk stratification by OLGIM system can be applied in a high risk population and if its association with other factors can influence the selection and follow-up of patients with AG and IM. Methods: A prospective study included 84 patients with premalignant gastric lesions/conditions. An upper GI endoscopy was performed and extensive biopsy samples were obtained for OLGIM staging. Endoscopy surveillance indication and demographic data were collected. A modified Vries risk score was created by using family history of GC, alcohol use and III-IV OLGIM stages.</p><p><bold>RESULTS:</bold> From 84 patients (34♀/50♂, median age 59±12 years), 36 were classified as III-IV OLGIM stages and 48 patients were classified as 0-II OLGIM stages. An association between the III-IV OLGIM stages and the occurrence of dysplasia was not found (p = 0,14) as well as between a high modified Vries risk score and dysplasia (p = 0,26). In a multivariate analysis, high-risk OLGIM stages (III-IV) were associated with male sex (p=0,02).</p><p><bold>CONCLUSION:</bold> This population, known to benefit from long-lasting attentive endoscopic surveillance, should not rely only in OLGIM system to stratify future risk of GC. Other factors can have major influence in this area of high GC prevalence. Moreover, the proposed risk score (that incorporated OLGIM classification) can not at this time be recommended. These provocative results demand further efforts to improve the reproducibility of any staging criteria.</p><p><bold>REFERENCES:</bold></p><p>1. Dinis-Ribeiro M, Areia M, Vries A, <italic>et al</italic>. Guidelines for the Management of Precancerous Conditions and Lesions in the Stomach (MAPS). An European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter Study Group (EHSG), European Society of Pathology (ESP) and Sociedade Portuguesa de Endoscopia Digestiva (SPED) Guideline. Endoscopy (2012); 44: 74–94.</p><p>2. Rugge M, Fassan M, Pizzi M, <italic>et al</italic>. Operative link for gastritis assessment vs operative link on intestinal metaplasia assessment. World J Gastroenterol. (2011); 17(41): 4596-601.</p><p>3. Vries A, Haringsma J, Vries R, <italic>et al</italic>. The use of clinical, histological and serological parameters to predict the intragastric extent of intestinal metaplasia: a recommendation for routine practice. Gastrointestinal Endoscopy (2009); 70: 18-25.</p><p>4. Dixon M, Genta R, Yardley J, Correa P. Classification and grading of gastritis. The updated Sydney system. International Workshop on the Histopathology of Gastritis, Houston 1994. American Journal of Surgical Pathology (1996); 20: 1161-81.</p><p><bold>Contact E-mail Address:</bold><email>anaceliacaetanocs@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> OLGIM system, premalignant gastric lesions/conditions </p></sec><sec><title>OP077 GASTRIC CANCER PREVENTION BY 5-AZA-2’DEOXYCYTIDINE IS ASSOCIATED WITH REACTIVATION OF GROWTH/DIFFERENTIATION FACTOR 1</title><p><bold>A. S. L. Cheng</bold><sup>1,*</sup>, W. Yang<sup>1</sup>, M. S. M. Li<sup>1</sup>, H. Wang<sup>2</sup>, A. W. Chan<sup>3</sup>, W. Kang<sup>3</sup>, E. K. W. Ng<sup>1</sup>, K. F. To<sup>1</sup>, J. Yu<sup>1</sup>, F. K. L. Chan<sup>1</sup>, J. J. Y. Sung<sup>1</sup></p><p><italic><sup>1</sup>Institute of Digestive Disease, <sup>2</sup>The Jockey Club School of Public Health and Primary Care, <sup>3</sup>Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, Hong Kong</italic></p><p><bold>INTRODUCTION:</bold> Gastric cancer is the fourth most common malignancy worldwide. The limited benefit of <italic>H. pylori</italic> eradication and nutritional intervention in risk reduction underlies the urgent need for new targets for gastric cancer prevention. Epigenetic alterations are fundamental hallmarks of cancer genomes.</p><p><bold>AIMS&METHODS:</bold> Since aberrant DNA methylation occurs early in <italic>H. pylori</italic>-induced gastric carcinogenesis<sup>1</sup>, we investigated whether 5-aza-2'-deoxycytidine (5’Aza-dC, 0.5 mg/kg), a FDA-approved potent and specific demethylating agent, reduces gastric cancer burden in a chemical-induced model, of which 7-week-old C57BL6 mice were received alternate week of N-methyl-N-nitrosourea (MNU, 240 p.p.m.) in drinking water for 10 weeks. We further identified the key hypermethylated genes in gastric cancer development by Methylated-DNA capture-microarray using 3 normal mucosa, 4 intestinal metaplasias (IMs), 4 pairs of tumors/adjacent tissues and 3 5’Aza-dC-treated normal mucosa, followed by validation in 36 pairs of human gastric cancer samples and 8 cell lines.</p><p><bold>RESULTS:</bold> After 52 weeks of MNU exposure, gastric cancer and IM were developed in 8 and 8 out of 19 mice, respectively. Biweekly i.p. injection of 5’Aza-dC for 24 weeks significantly reduced cancer incidence (42.1 to 11.1%, <italic>p </italic>< 0.05). Microarray analysis uncovered 12 significant and recurrent hypermethylated genes in gastric tumors but not in normal or 5’Aza-dC-treated mucosa. Quantitative RT-PCR analysis showed that only <italic>growth/differentiation factor 1 </italic>(<italic>Gdf1</italic>), but not the other 11 genes, had significantly lower mRNA expression in gastric tumors compared to both tumor-adjacent and normal tissues (<italic>p </italic>< 0.05). Moreover, 5’Aza-dC treatment reactivated <italic>Gdf1 </italic>expression to normal level. In human, <italic>GDF1 </italic>expression was found to be significantly down-regulated in gastric tumors compared to tumor-adjacent tissues (<italic>p </italic>< 0.005). Compared with normal human mucosa, 7/8 gastric cancer cell lines exhibited <italic>GDF1 </italic>silencing, which could be reactivated by genome demethylation. Treatment with recombinant GDF1 significantly inhibited gastric cancer cell proliferation.</p><p><bold>CONCLUSION:</bold> Epigenetic repression of GDF1, a ligand for the TGF-β signaling pathway, may render selective growth advantage to gastric epithelial cells. Our findings suggest a causal relationship between DNA methylation and gastric carcinogenesis and lend support to demethylating drug trial for gastric cancer prevention. *This study was supported by RFCID (08070172) and CUHK Direct Grant.</p><p><bold>REFERENCES:</bold></p><p>1. Cheng AS, et al. Gastroenterology 2013;144:122-33.e9.</p><p><bold>Contact E-mail Address:</bold><email>alfredcheng@cuhk.edu.hk</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> DNA methylation, Gastric cancer</p></sec><sec><title>OP078 ASSESSMENT OF GASTRIC PHENOTYPE USING MAGNIFYING NARROW-BAND IMAGING FOR DIFFERENTIATION OF GASTRIC CARCINOMA FROM ADENOMA BY LESS-EXPERIENCED ENDOSCOPISTS</title><p><bold>M. Kobayashi</bold><sup>1,*</sup>, K.-I. Mizuno<sup>1</sup>, M. Takeuchi<sup>2</sup>, S. Hashimoto<sup>1</sup>, Y. Ajioka<sup>3</sup>, Y. Aoyagi<sup>2</sup></p><p><italic><sup>1</sup>Department of Endoscopy, Niigata University Medical and Dental Hospital, <sup>2</sup>Division of Gastroenterology, <sup>3</sup>Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan</italic></p><p><bold>INTRODUCTION:</bold> Conventional white-light endoscopy and forceps biopsy are insufficient for a definitive diagnosis and therapeutic planning in patients with gastric adenoma. Immunohistochemical studies have reported an obvious phenotypic difference between adenomas and carcinomas. We previously described narrow-band imaging with magnifying endoscopy (NBI-ME) allows visualization of the papillary and pit appearances of the surface structures, which correlate with gastric and intestinal phenotypes, respectively<sup>1</sup>.</p><p><bold>AIMS&METHODS:</bold> The aim of the present study was to investigate the utility of NBI-ME for phenotypic assessment and discrimination of carcinomas from adenomas, especially by less-experienced endoscopists (LEEs). As previously reported, NBI-ME findings were classified into A, B and AB types, which reveal papillary, tubular pits and groove microstructures, respectively. B type was sub-classified according to the presence of clear (B-ca) or faint (B-ad) mesh-form microvessels. To validate the A-B classification retrospectively, 137 patients (155 lesions), who were diagnosed pre-therapeutically with adenoma or borderline by biopsy, were enrolled. Mucin phenotype was analyzed immunohistochemically in the first 60 lesions. To prospectively evaluate diagnostic improvement of 10 LEEs, NBI-ME image catalogs from 30 adenomas and 30 size-matched carcinomas were displayed randomly. All of LEEs were trainees whose training periods in gastrointestinal endoscopy were less than 2 years. Before and after a training lecture describing the proposed differentiation by NBI-ME, LEEs indicated their diagnoses as either adenoma or carcinoma.</p><p><bold>RESULTS:</bold> NBI-ME characterized lesions as A, AB, or B-ca in 122 (98%) of 125 carcinomas, and as B-ad in 27 (90%) of 30 adenomas, as determined histologically after endoscopic submucosal dissection. B-ad correlated to histological adenoma (sensitivity 90%, specificity 98%, accuracy 96%). Mucin phenotypes were gastric or gastrointestinal in A and AB type carcinomas (31/37, 84%), and were intestinal in all 10 adenomas. In the prospective study by LEEs, overall diagnostic accuracy did not improve after the training lecture. However, in A and AB type lesions, the diagnostic accuracy was 86%, which significantly (<italic>P </italic>< 0.05) improved, and inter-observer agreements (Fleiss κ values) were graded as substantial.</p><p><bold>CONCLUSION:</bold> The proposed A-B classification under NBI-ME can distinguish gastric or gastrointestinal-type carcinomas with acceptable accuracy even by LEEs, allowing stricter selection for endoscopic treatment.</p><p><bold>REFERENCES:</bold></p><p>1. Kobayashi M, et al. Mucin phenotype and narrow-band imaging with magnifying endoscopy for differentiated-type mucosal gastric cancer. J Gastroenterol 2011; 46: 1064-70</p><p><bold>Contact E-mail Address:</bold><email>masakoba@med.niigata-u.ac.jp</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> gastric adenoma, less-experienced endoscopist, mucin phenotype, narrow-band imaging</p></sec><sec><title>OP079 ACCURACY OF A SCORING SYSTEM FOR THE DIFFERENTIAL DIAGNOSIS OF COMMON GASTRIC SUBEPITHELIAL TUMORS BASED ON ENDOSCOPIC ULTRASONOGRAPHY</title><p><bold>S. J. Hong</bold><sup>1,*</sup>, S. W. Seo<sup>1</sup>, J. P. Han<sup>1</sup>, M. H. Choi<sup>1</sup>, J.-Y. Song<sup>1</sup>, H. K. Kim<sup>2</sup>, T. H. Lee<sup>1</sup>, B. M. Ko<sup>1</sup>, J. Y. Cho<sup>1</sup>, J. S. Lee<sup>1</sup>, M. S. Lee<sup>1</sup></p><p><italic><sup>1</sup>Internal medicine, <sup>2</sup>Pathology, Soonchunhyang University College of Medicine, Bucheon, Korea, Republic Of</italic></p><p><bold>INTRODUCTION:</bold> Gastric subepithelial tumor (SET) is difficult to diagnose using routine endoscopic examination with conventional biopsies. Simple methods of predicting a tissue diagnosis for gastric SETs have not been introduced. We validate a new scoring system for differential diagnosis of major gastric SETs before acquiring tissue.</p><p><bold>AIMS&METHODS:</bold> To evaluate simple scoring system predicting the histology of common gastric SETs, four variables on EUS (tumor location, originating layer, echogenicity, and shape) were included. A database of 226 patients treated by endoscopic resection or surgery for gastric SETs was used to validate the new scoring system.</p><p><bold>RESULTS:</bold> Among the 226 gastric SETs, 69 (30.5%) were gastrointestinal stromal tumors (GISTs), 68 (30.1%) were ectopic pancreases, and 35 (15.5%) were leiomyomas. Many of the GISTs were located in the fundus and body (79.7%), whereas the majority of leiomyomas were found in the cardia (80%). Most ectopic pancreases were found in the antrum (88.2%). GISTs were mainly irregular and round in shape, ectopic pancreases and lipomas were oval, and leiomyomas were irregularly shaped on EUS. The sensitivity and specificity values for the scoring system were 75.8% and 85.4% for GISTs, 84.6% and 73.1% for ectopic pancreas, and 75.9% and 99.5% for leiomyomas, respectively.</p><p><bold>CONCLUSION:</bold> The new scoring system was simple and relatively useful for predicting common gastric SET histology without acquiring tissue.</p><p><bold>Contact E-mail Address:</bold><email>drhsj@dreamwiz.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> diagnosis, gastric subepithelial tumor, histology, scoring system</p></sec><sec><title>OP080 LOW-GRADE DYSPLASIA IN BARRETT’S OESOPHAGUS HAS A HIGH RISK OF PROGRESSION WHEN CONFIRMED BY A PANEL OF EXPERT PATHOLOGISTS</title><p><bold>L. C. Duits</bold><sup>1,*</sup>, K. N. Phoa<sup>1</sup>, W. L. Curvers<sup>1</sup>, F. J. Ten Kate<sup>1</sup>, G. A. Meijer<sup>2</sup>, C. A. Seldenrijk<sup>3</sup>, G. J. Offerhaus<sup>1</sup>, M. Visser<sup>1</sup>, S. L. Meijer<sup>1</sup>, K. K. Krishnadath<sup>1</sup>, R. C. Mallant-Hent<sup>1,4</sup>, J. J. Bergman<sup>1</sup></p><p><italic><sup>1</sup>Academic Medical Centre, Amsterdam, <sup>2</sup>VU University Medical Centre, Amsterdam, <sup>3</sup>St. Antonius Hospital, Nieuwegein, <sup>4</sup>Flevoziekenhuis, Almere, Netherlands</italic></p><p><bold>INTRODUCTION:</bold> The natural history of low-grade dysplasia (LGD) in Barrett’s oesophagus (BO) is uncertain. Reported progression rates to high-grade dysplasia (HGD) or oesophageal adenocarcinoma (OAC) range from 0.6% to 13.4% per yr. This uncertainty may be explained by reliability of the baseline LGD diagnosis and/or differences in quality of endoscopic follow-up (FU).</p><p><bold>AIMS&METHODS:</bold> We aim to study the natural history of LGD confirmed by a panel of expert pathologists organised in our regional Barrett’s Advisory Committee (BAC) to which all Dutch centres have free access. All BO cases referred to the BAC for pathology revision of LGD diagnosed at community hospitals between 2000 and 2011 were included. Slides were evaluated by two or three pathologists with extensive experience in BO neoplasia. In case of discordance a consensus diagnosis was reached in a dedicated consensus meeting. All FU endoscopy and pathology reports were retrieved from referring hospitals. The expert panel diagnosis was compared to histological outcome during endoscopic FU. Primary endpoint was development of any neoplastic progression (HGD/OAC).</p><p><bold>RESULTS:</bold> 467 LGD patients (76% male; mean 62 yrs ±11.8) underwent pathology revision. 70% was downstaged to non-dysplastic BO (NDBO) or indefinite for dysplasia. In 28% the initial LGD diagnosis was confirmed, 9 patients (2%) were upstaged to HGD. 61 patients were excluded from endoscopic FU due to baseline HGD (n=9), participation in a randomised ablation study (n=17), comorbidity (n=17) or declined informed consent (n=13). Of the remaining 411 patients, 5 (1%) were lost to FU. 406 patients were analysed for outcome during endoscopic FU (median 51 months FU (IQR 25-90)). Based on the community LGD diagnosis, the incidence rate for HGD/OAC during FU was 2.6% per pt yr. In patients with confirmed LGD the incidence rate for HGD/OAC during FU was 10.1% per pt yr, compared to 0.9% per pt yr for patients with a consensus diagnosis of NDBO.</p><p><bold>CONCLUSION:</bold> This is the largest cohort of LGD patients undergoing expert pathology revision described to date. The results indicate that confirmed LGD in BO has a markedly increased risk of malignant progression. However, the vast majority of patients with a community LGD diagnosis will be downstaged after expert revision and have a low risk of progression, similar to reported progression rates for NDBO. Therefore, all BO patients with LGD should undergo expert revision of the histological diagnosis.</p><p><bold>Contact E-mail Address:</bold><email>l.c.duits@amc.uva.nl</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Barrett's esophagus, Low-grade dysplasia, Neoplastic progression</p></sec><sec><title></title><p><bold>MONDAY, OCTOBER 14, 2013 14:00-15:30</bold></p><p><bold>Endoscopy towards, into and through the stomach – Hall 6</bold></p></sec><sec><title>OP081 RANDOMIZED STUDY COMPARING PERORAL ENDOSCOPIC MYOTOMY,BOTULINUM TOXIN INJECTION AND BALLOON DILATION FOR ACHALASIA</title><p><bold>E. Linghu</bold><sup>1,*</sup>, H. Li<sup>1</sup></p><p><italic><sup>1</sup>Department of Gastroenterology and Hepatology, the Chinese PLA General Hospital, Beijing, China</italic></p><p><bold>INTRODUCTION:</bold> Endoscopic treatments for achalasia include peroral endoscopic myotomy (POEM),botulinum toxin injection (BTI) and balloon dilation (BD),yet no randomized studies have compared POEM with the other two treatments.This randomized study was aimed to compare the efficacy and safety of the three treatments.</p><p><bold>AIMS&METHODS:</bold> Forty-five patients were averagely randomized into three treatment groups,namely 15 patients in POEM,15 in BTI and 15 in BD.Outcomes at 1 year after treatment were documented and compared among the groups.The primary outcome was symptom remission,and the secondary outcome was complication, lower esophageal sphincter pressure (LESP) and maximum esophageal width by barium swallow. Symptom remission was defined as a reduction in the Eckardt score to no more than 3.This study was registered online at the Chinese Clinical Trial Registry (Registration number:ChiCTR-TRC-12002204).During POEM,only the inner circular muscle was incised.During the procedure of BTI,a total of 100 units of botulinum toxin was injected into muscularis propria at the level of lower esophageal sphincter (LES) at one time by injecting 25 units of toxin into each of the four quadrants of the LES.BD was performed as a single-procedure in the patients with a Rigiflex pneumatic dilation balloon of 30 mm in diameter with its maximum pressure up to 12 PSI,which was maintained for 60 seconds after gradually reaching maximum pressure during dilation under direct endoscopic vision.</p><p><bold>RESULTS:</bold> Endoscopic treatments were successfully performed in all of the 45 patients,and 93.3% of patients were successfully followed up at 1 year after treatment.Symptom remission rate was 100% in POEM group,5.4% in BTI group and 64.3% in BD group,and the difference was statistically significant between every two groups.Complication rate was 20.0% in POEM group,0% in BTI group and 6.7% in BD group with no statistical difference found between the three groups. LESP,maximum width of esophagus were similar both before and 3 months after treatment among the three groups.</p><p><bold>CONCLUSION:</bold> Symptom remission of POEM was higher than BTI and BD at 1-year after treatment,and complications were similar among the 3 groups.</p><p><bold>Contact E-mail Address:</bold><email>linghuenqiang@vip.sina.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> balloon dilation, botulinum toxin injection, peroral endoscopic myotomy, randomized controlled trial </p></sec><sec><title>OP082 RISK FACTORS FOR HISTOLOGICAL POSITIVE HORIZONTAL TUMOR MARGIN AFTER EN BLOC ENDOSCOPIC SUBMUCOSAL DISSECTION FOR EARLY GASTRIC CANCER AND ITS MANAGEMENT</title><p><bold>N. Numata</bold><sup>1,*</sup>, S. Oka<sup>1</sup>, S. Tanaka<sup>1</sup>, K. Kagemoto<sup>2</sup>, Y. Sanomura<sup>1</sup>, S. Yoshida<sup>1</sup>, K. Arihiro<sup>3</sup>, F. Shimamoto<sup>4</sup>, K. Chayama<sup>2</sup></p><p><italic><sup>1</sup>Department of Endoscopy, <sup>2</sup>Department of Gastroenterology and Metabolism, <sup>3</sup>Department of Pathology, Hiroshima University Hospital, <sup>4</sup>Faculty of Human Culture and Science, Prefectural University of Hiroshima, Hiroshima-shi, Japan</italic></p><p><bold>INTRODUCTION:</bold> Because there is no consensus regarding the management of hitological positive horizontal tumor margin (HM+) after en bloc endoscopic submucosal dissection (ESD) for early gastric cancer (EGC), the aim of this study is to determine the risk factors for HM+ after en bloc ESD for EGC and assess its management.</p><p><bold>AIMS&METHODS:</bold> We examined 890 consecutive patients with 1053 intramucosal EGCs resected by en bloc ESD at Hiroshima University Hospital between April 2005 and June 2011. HM+ rate, local recurrence rate, characteristics of local recurrent tumor, risk factors for HM+ and outcomes of treatment for local recurrent tumor were evaluated. The curative criteria after ESD are to satisfy well- or moderately differentiated adenocarcinoma, ≤ 2 cm in diameter, no ulceration, absence of vessel invasion. HM+ was defined as a directly positive tumor margin or the presence of cancerous cells on either end of the section of all sections cut into 2mm thick.</p><p><bold>RESULTS:</bold> HM+ rate was 2.4% (25/1053). The local recurrent rate was 0.3% (3/1053), and all local recurrent lesions were intramucosal caners. These local recurrent lesion developed in 12% (3/25) of patients with HM+. Univariate analysis showed the tumor location (upper-third of the stomach), an ESD specimen within the curative criteria and the presence of severe fibrosis were the risk factors for HM+. Multivariate analysis with logistic regression showed the tumor location (upper-third of the stomach) and the lesion out of the curative criteria were the independent risk factors for HM+. The direct tumor margin was positive at least 2 section in 2 recurrent cases. Another case with local recurrence showed no direct positive tumor margin. All local recurrent lesions were resected curatively by additional ESD.</p><p><bold>CONCLUSION:</bold> The risk factors for HM+ after en bloc ESD for EGC are the location in the upper-third of the stomach, or the lesion out of the curative criteria. Local recurrent lesions could be cured by additional ESD.</p><p><bold>Contact E-mail Address:</bold><email>nnumata@hiroshima-u.ac.jp</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> early gastric cancer, endoscopic submucosal dissection (ESD), horizontal margin</p></sec><sec><title>OP083 ENDOSCOPIC SUBMUCOSAL DISSECTION (ESD) IN EARLY GASTRIC CANCER (EGC) – RESECTION BEYOND THE „GUIDELINE CRITERIA” IN EUROPE</title><p><bold>A. Probst</bold><sup>1,*</sup>, M. Anthuber<sup>2</sup>, B. Maerkl<sup>3</sup>, H. Messmann<sup>1</sup></p><p><italic><sup>1</sup>Department of Gastroenterology, <sup>2</sup>Department of Visceral Surgery, <sup>3</sup>Institute of Pathology, Klinikum Augsburg, Augsburg, Germany</italic></p><p><bold>INTRODUCTION:</bold> ESD is the treatment of choice in endoscopic resection of early gastric cancer. In Japan "expanded resection criteria" have been defined after introduction of ESD and with Gotoda´s data on the risk for lymph node metastasis in EGC (Soetikno et al, JCO2005 – Gotoda et al, Gastric Cancer 2000). The German guideline allows endocopic resection for small, well diferentiated lesions without submucosal invasion ("guideline criteria"). For lesions beyond these criteria surgery is recommended. However only very few follow-up data are available from Europe after resection of "expanded criteria" lesions.</p><p><bold>AIMS&METHODS:</bold> From 05/2005 to 04/2013 ESD was performed in 120 EGC´s.</p><p><bold>RESULTS:</bold> In 114 cases ESD was technically possible (94%). In 6 cases ESD had to be stopped (non-lifting n=5, one perforation). Only 20 of 114 resections were peformed within the "guideline criteria" (17.5%) while 94 lesions fulfiled the "expanded criteria" (82.5%). "Expanded criteria" known prior to resection were lesions diameter in 77/94 lesions (81.9%) and ulceration in 9 lesions (7.9%). "Expanded criteria" which were seen only after resection were G3 histology in 16/94 (17%), sm infiltration in 16/94 (17%) and L1 histology in 5/94 (5%). In G3 lesions, L1 lesions, sm infiltration or R1 resection at the basal margin surgery was recommended. En bloc resection rate was 89.5% (102/114). In 10.5% (12/114) resection had to be performed piecemeal. R0 resection rate was 76.3% (87/114) for all lesions. For "guideline criteria" en bloc resection rate was 100% (20/20) and R0 resection rate was 95% (19/20). For "expanded criteria" en bloc resection rate was 87.2 % (82/94) and R0 resection rate was 72,3 % (68/94). 6 recurrences so far (5 after piecemeal resection, 1 after en bloc resection). When lesions were classified "expanded" only because of their size >20mm and histology showed no other risk criteria (G1/2, L0, V0, R0, no sm infiltration) no recurrence or metastasis was seen so far (mean follow-up 20 months).</p><p><bold>CONCLUSION:</bold> ESD in EGC´s shows high en bloc resection rates and R0 resection rates. The "expanded resection criteria" include heterogenous lesions (diameter, grading, sm infiltration). In Europe the majority of lesions fulfill the “expanded criteria” due to the lesions diameter >20mm. Endoscopic resection seems to be an adequate treatment for this subgroup also in Europe when other risk factors are excluded. Further European data and especially longer follow-up data are needed to answer this question.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Early gastric cancer, ESD (endoscopic submucosal dossection) </p></sec><sec><title>OP084 CLINICAL OUTCOMES OF ENDOSCOPIC SUBMUCOSAL DISSECTION FOR UNDIFFERENTIATED-TYPE OR SUBMUCOSAL INVASIVE EARLY GASTRIC CANCER</title><p><bold>H. Kim</bold><sup>1,*</sup>, B. Bang<sup>1</sup>, K. Kwon<sup>1</sup>, Y. Shin<sup>1</sup></p><p><italic><sup>1</sup>gastroenterology, Inha University Hospital, Incheon, Korea, Republic Of</italic></p><p><bold>INTRODUCTION:</bold> Endoscopic submucosal dissection (ESD) has become an important curative option for early gastric cancer (EGC). However, the usefulness of ESD for undifferentiated EGC (UD-EGC) or submucosal invasive EGC (SM-EGC) still remains controversial because of the lack of long-term follow-up data. The aim of this study was to evaluate long-term clinical outcome of ESD for UD-EGC, SM-EGC.</p><p><bold>AIMS&METHODS:</bold> From January 2006 to December 2011, 22 lesions in 22 patients with undifferentiated EGC (11 poorly differentiated adenocarcinoma, 11 signet ring cell carcinoma) and 32 lesions in 32 patients with submucosal invasive cancer were treated by ESD. En bloc resection rate, complete resection rate (CR), recurrence rate were assessed.</p><p><bold>RESULTS:</bold> The en bloc resection and CR rate in UD-EGC were 86.3% (19/22) and 77.2% (17/22), respectively. 22 lesions (12 mucosal lesions and 10 submucosal lesions) in UD-EGC were resected by ESD. Local recurrence rate were 8.3% (1/12) and 10% (1/10). Of 2 case recurred, 1 case was underwent surgery and the other case was lost follow-up. Median follow-up period in UD-EGC was 32 months (range 6-72 months). The en bloc resection rate in SM-EGC was 78.1% (25/32). Local recurrence rate was 6.3% (2/32). 1 of 2 cases was underwent gastrectomy. The lesion had lymphatic invasion. Median follow-up period in SM-EGC was 19 months (range 6-48 months). Only one patient was expired by the other disease, there was no mortality related to EGC during follow-up.</p><p><bold>CONCLUSION:</bold> ESD may be feasible to treatment for carefully selected patients of undifferentiated EGC and submucosal invasive EGC.</p><p><bold>Contact E-mail Address:</bold><email>kimhg@inha.ac.kr</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> endoscopic submucosal dissection (ESD), outcome, submucosal invasive adenocarcinoma, undifferentiated adenocarcinoma</p></sec><sec><title>OP085 TECHNICAL RESULTS OF ENDOSCOPIC SUBMUCOSAL DISSECTION FOR EARLY GASTRIC CANCER WITH SCARRING</title><p><bold>S. Nonaka</bold><sup>1,*</sup>, I. Oda<sup>1</sup>, S. Abe<sup>1</sup>, H. Suzuki<sup>1</sup>, S. Yoshinaga<sup>1</sup>, T. Nakajima<sup>1</sup>, Y. Saito<sup>1</sup></p><p><italic><sup>1</sup>Endoscopy Division, NATIONAL CANCER CENTER HOSPITAL, Tokyo, Japan</italic></p><p><bold>INTRODUCTION:</bold> There are many reports on endoscopic submucosal dissection (ESD) of early gastric cancer (EGC) although increased technical difficulty involved in performing ESDs on EGCs with scarring due to previous ulceration (UL+) has not been addressed previously.</p><p><bold>AIMS&METHODS:</bold> The aim of this study was to analyze the clinical outcomes of ESDs for EGC with scarring and to evaluate the causes for non-curative ESDs. We retrospectively assessed technical results of ESDs performed on EGC patients with solitary lesions diagnosed as intramucosal differentiated adenocarcinoma <3cm in size with scarring (UL+ Group) and EGC patients with solitary lesions diagnosed as intramucosal cancer <2cm without ulceration (UL- Group) before treatment from January 2000 to February 2012 at our institution. EGCs in the remnant stomach after gastrectomy and reconstructed gastric tube following esophagectomy were excluded as well as local recurrence of previous endoscopic resection.</p><p><bold>RESULTS:</bold> Study subjects included 602 UL+ Group patients (505 males/97 females) with a mean age of 65.2 years; and 2,033 UL- Group patients (1,573 males/460 females) with a mean age of 65.4 years. Lesion locations (upper/middle/lower) in the UL+ and UL- groups were 107/319/176 and 349/769/915, respectively, with median lesion sizes of 18mm and 10mm (ranges, 3-30 and 3-20), respectively. Technical results for the UL+/UL- groups were median procedure times of 80/60 minutes (range, 15-680/5-480) (<italic>p</italic><0.0001); en-bloc resections of 98.8%/99.7% (595/2,027) (<italic>p</italic><0.003); en-bloc resections with histologically tumor-free margins of 86.7%/95.8% (522/1,947) (<italic>p</italic><0.0001); curative resections of 68.6%/87.3% (413/1,774) (<italic>p</italic><0.0001); perforations of 3.2%/1.7% (19/35) (<italic>p</italic><0.03); and delayed bleeding of 5.3%/3.3% (32/67) (<italic>p</italic><0.03). Significant factors for en-bloc resections with positive/inconclusive tumor margins in the UL+/UL- groups included incidental incision made inside lesion during ESD procedures of 5.1%/0.4% (31/9) (<italic>p</italic><0.0001); inconclusive tumor margins resulting from burning effect, 2.0%/0.5% (12/11) (<italic>p</italic><0.0008); and tumor-positive vertical margins due to submucosal deep invasion, 2.7%/1.2% (16/24) (<italic>p</italic><0.01).</p><p><bold>CONCLUSION:</bold> Technical results for the UL+ Group were significantly lower for en-bloc resections with histologically tumor-free margins and significantly higher for perforations and incidental incision made inside lesion during ESD procedures compared to the UL- Group. Such outcomes were thought to have been caused by difficulty in identifying appropriate dissection lines during ESDs due to severe submucosal layer fibrosis resulting from previous ulceration. Cases of ESD for EGC with scarring should be performed by experienced endoscopists.</p><p><bold>Contact E-mail Address:</bold><email>snonaka@ncc.go.jp</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Early gastric cancer, endoscopic submucosal dissection, ulceration</p></sec><sec><title>OP086 TRANS-ESOPHAGO-CARDIAL-GASTRIC TUNNELING ACCESS FOR NOTES: A NEW PERITONEAL ACCESS TECHNIQUE</title><p><bold>B. Liu</bold><sup>1,*</sup>, J. Song<sup>1</sup>, L. Kong<sup>1</sup></p><p><italic><sup>1</sup>Department of Gastroenterology and Hepatology, THE SECOND HOSPITAL OF HARBIN MEDICAL UNIVERSITY, Harbin, China</italic></p><p><bold>INTRODUCTION:</bold> Peritoneal access techniques are among the most important concerns in the clinical application of natural orifice transluminal endoscopy surgery (NOTES). However, an optimal peritoneal access technique remains unknown.</p><p><bold>AIMS&METHODS:</bold> Aim of this study was to develop a new trans-esophago-cardial-gastric tunneling (TECGT) peritoneal access and evaluate the feasibility of the approach to peritoneal cavity in NOTES. Animal survival study was conducted with 10 Beagle dogs<bold>: </bold>(1) longitudinal mucosal incision on esophageal right wall approximately 5 cm proximal to the esophagogastric junction (EGJ); (2) creation of submucosal tunnel advancing into stomach for 3-5 cm distal to the EGJ; (3) the seromuscular layer incision at the end of the tunnel for establishing TECGT peritoneal access; (4) endoscopic closure of esophageal mucosal entry after intraperitoneal exploration. Main outcome measurements included the rate of successful TECGT peritoneal access, the time to entering peritoneal cavity, complications during and after the procedure, clinical observation, follow-up endoscopy and necropsy.</p><p><bold>RESULTS:</bold> The peritoneal cavity was successfully entered without complications in all 10 dogs. The mean time to entering peritoneal cavity was 33.8 min (range 22-48 min). Esophageal mucosal entry was easily closed by endoclips. All dogs recovered well and gained weight. Follow-up endoscopy showed healing of esophageal mucosal entry in 9 dogs and mucosal tearing in one dog (but submucosa healing well without fistula formation). Necropsy confirmed complete closure of gastric serosal exit without any intraperitoneal problems.</p><p><bold>CONCLUSION:</bold> The TECGT peritoneal access is feasible technically and safe for NOTES procedures.</p><p><bold>Contact E-mail Address:</bold><email>13704510648@126.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> natural orifice transluminal endoscopy surgery, submucosal endoscopy, transluminal technique</p></sec><sec><title></title><p><bold>MONDAY, OCTOBER 14, 2013 14:00-15:30</bold></p><p><bold>Today's science; tomorrow's medicine: Genetics of functional disorders – Hall 9</bold></p></sec><sec><title>OP087 IDENTIFICATION OF NOVEL MOLECULAR DEFECTS IN CHRONIC INTESTINAL PSEUDO-OBSTRUCTION (CIPO)</title><p><bold>E. Bonora</bold><sup>1,*</sup>, F. Bianco<sup>1</sup>, L. Cordeddu<sup>2</sup>, M. D'Amato<sup>2</sup>, M. Bamshad<sup>3</sup>, V. Stanghellini<sup>1</sup>, G. Lindberg<sup>2</sup>, Z. Mungan<sup>4</sup>, K. Cefle<sup>4</sup>, T. Ozcelik<sup>5</sup>, S. Palanduz<sup>4</sup>, S. Ozturk<sup>4</sup>, A. Gedikbasi<sup>6</sup>, R. Cogliandro<sup>1</sup>, E. Boschetti<sup>1</sup>, C. Graziano<sup>1</sup>, M. Seri<sup>1</sup>, G. Romeo<sup>1</sup>, R. De Giorgio<sup>1</sup></p><p><italic><sup>1</sup>University of Bologna, Bologna, Italy, <sup>2</sup>Karolinska Institutet, Stockholm, Sweden, <sup>3</sup>University of Washington, Seattle, United States, <sup>4</sup>University of Istanbul, Istanbul, <sup>5</sup>Bilkent University, Bilkent-Ankara, <sup>6</sup>Bakirkoy Sadi Konuk Hospital, Istanbul, Turkey</italic></p><p><bold>INTRODUCTION:</bold> CIPO is characterized by a severe impairment of gut motility mimicking a mechanical sub-occlusion in the absence of occluding causes. Although most patients are sporadic, some CIPO cases show a familial cluster with a likely genetic origin.</p><p><bold>AIMS&METHODS:</bold> The aims were to: establish the gene(s) involved in a previously studied Turkish family with syndromic CIPO; test whether the genetic abnormalities found in that family may have implications in sporadic CIPO. Methods used: whole exome sequencing (WES) analysis; western blot on sera; immunofluorescence staining on gut biopsies;electromobility shift assay (EMSA) on Caco-2 cells.</p><p><bold>RESULTS:</bold> In the consanguineous Turkish family where we mapped a linkage interval on chr8q<sup>1</sup>, WES analysis revealed a novel homozygous mutation, c.1864 G>A, p.622 Ala>Thr in <italic>RAD21</italic>. RAD21 belongs to the cohesin complex regulating cell replication and gene expression. The reported change cosegregated with the disease status and was not detected in 1000 Turkish control chromosomes. PolyPhen-2 predicted it as probably damaging (HumDiv score: 0.999), since it resides in a conserved position. <italic>RAD21</italic> screening in 12 Swedish and 24 Italian well-characterized sporadic CIPO patients did not show coding mutations. However, we established a relationship between RAD21 and sporadic CIPO based on our data on APOB expression. APOB mRNA and protein levels were increased in CIPO patients vs. controls. In silico analysis of human <italic>APOB</italic> promoter identified three RAD21-putative binding sites. EMSA with anti-RAD21 antibodies showed that RAD21 binds to these regions. A significant increase in APOB and RAD21 immunoreactive cells was also detected in the <italic>lamina propria</italic> of gut biopsies of CIPO patients vs. controls.</p><p><bold>CONCLUSION:</bold> We identified a novel mutation of <italic>RAD21</italic> in a familial syndromic form of CIPO and an altered expression of RAD21 and APOB in sporadic CIPO. These previously uncharacterized pathways contribute to clarify CIPO and bear clinical implications for diagnosis and prognosis of this disabling syndrome.</p><p><bold>REFERENCES:</bold></p><p>1. Degl'Incerti et al Eur J Hum Genet 2007</p><p><bold>Contact E-mail Address:</bold><email>elena.bonora6@unibo.it</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> APOB, chronic intestinal pseudo-obstruction, RAD21, whole exome sequencing</p></sec><sec><title>OP088 FAMILIAL ACHALASIA ASSOCIATED OR NOT TO ALLGROVE SYNDROME: ABOUT 18 FAMILIES</title><p><bold>A. Tebaibia</bold><sup>1,*</sup>, M. A. Boudjella<sup>1</sup>, F. Benmediouni<sup>1</sup>, M. Lahcene<sup>1</sup>, N. Oumnia<sup>1</sup></p><p><italic><sup>1</sup>inernal medecine department, kouba hospital, Algiers, Algeria</italic></p><p><bold>INTRODUCTION:</bold> familial Achalasia is a very rare condition. Very few studies are available and tackle usually isolated cases. Aim: to evaluate the prevalence of familial achalasia and study its clinical profile in a large series.</p><p><bold>AIMS&METHODS:</bold> over a period of 20 years (1990-2010) 817 patients with achalasia (425 were females and 392 males, mean age 38.3 ± 18.7 years; extremes: 3 months-86 years) referred to our centre (the only centre in our country). All patients underwent a standardized symptoms questionnaire, a barium esophagogram, an upper endoscopy and an oesophageal manometry. Achalasia was diagnosed according to manometric criteria. Familial achalasia: isolated (called classical achalasia) or associated to Allgrove syndrome was systematically checked in both parents and siblings.</p><p><bold>RESULTS:</bold> 18 families with 41(5%) patients were identified (mean age: 16 ±8 .2 years, extremes: 4- 37). In 14 families, 2 members were affected in each of them, in three others, 3 members per family and for the remaining 4 members. All achalasia were observed in siblings transversal, parent/child vertical association was unfound. Achalasia was isolated (classic achalasia: group A) in 3 families (n: 7, F: 4, M: 3; mean age:), it was associated to Allgrove syndrome (group B) in 15 families (n: 34, F: 20, M: 14; mean age: 16.8+/-8) . 3A syndrome (alacrima, achalasia, adrenal insufficiency) was observed in 67%, 2 A syndrome (alacrima, achalasia) in 23.6% and 4 A syndrome (alacrima, achalasia, adrenal insufficiency, autonomic neuropathy) in 8.8%. Consanguineous parents were found in 89% of patients, and death at a young age in the siblings, probably by adrenal insufficiency, was recorded in 27% of cases. Alacrima was constant and present at birth in all cases of Allgrove syndrome. Achalasia was present before the age of 5 years in 75% of cases. There was no difference between the two groups for age, age at onset, sex and the presence of the cardinal signs of achalasia.</p><p><bold>CONCLUSION:</bold> Familial achalasia is almost exclusively infantile. It is rarely isolated; most often fall under Allgrove syndrome. It reaches only siblings. Alacrima is the earliest sign that should lead to the diagnosis of the Allgrove syndrome. Prognosis is related to the acute adrenal insufficiency.</p><p><bold>Contact E-mail Address:</bold><email>tebaibia@hotmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Achalasia, Alacrima, Allgrove'syndrome</p></sec><sec><title>OP089 IMPAIRED MIRNA REGULATION MAY LEAD TO ALTERED 5-HT4 RECEPTOR LEVELS IN IBS-D PATIENTS</title><p><bold>C. Wohlfarth</bold><sup>1,*</sup>, J.-D. Härtle<sup>1</sup>, P. P. Becker<sup>1</sup>, S. Pöhner<sup>1</sup>, L. A. Houghton<sup>2,3</sup>, H. Mönnikes<sup>4</sup>, E. A. Mayer<sup>5</sup>, G. S. Sayuk<sup>6</sup>, G. Boeckxstaens<sup>7</sup>, M. M. Wouters<sup>7</sup>, M. D'Amato<sup>8</sup>, F. Lasitschka<sup>9</sup>, G. A. Rappold<sup>1</sup>, B. Niesler<sup>1</sup> and GENIEUR - Pan-European interdisciplinary network to identify genetic factors</p><p><italic><sup>1</sup>Department of Human Molecular Genetics, Institute of Human Genetics, Heidelberg, Germany, <sup>2</sup>University of Manchester, Manchester, United Kingdom, <sup>3</sup>Mayo Clinic, Jacksonville, United States, <sup>4</sup>Martin-Luther Krankenhaus, Berlin-Grunewald, Germany, <sup>5</sup>Center for Neurobiology of Stress, Division of Digestive Diseases, University of California, Los Angeles, <sup>6</sup>Washington University School of Medicine, St. Louis, United States, <sup>7</sup>TARGID, University Hospital Leuven, Leuven, Belgium, <sup>8</sup>Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden, <sup>9</sup>Institute of Pathology, University of Heidelberg, Heidelberg, Germany</italic></p><p><bold>INTRODUCTION:</bold> Irritable bowel syndrome (IBS) is a complex gastrointestinal (GI) disorder in which disturbed motility is thought to play a role. 5-HT<sub>4</sub> receptors regulate motor function and are targeted therapeutically in the treatments of IBS with constipation (IBS-C) and functional constipation. We hypothesize that disturbed 5-HT<sub>4</sub> receptor regulation or functional defects in the 5-HT<sub>4</sub> receptor gene (<italic>HTR4</italic>) may be involved in the motor dysfunction seen in these patients.</p><p><bold>AIMS&METHODS:</bold> As 3’ untranslated regions (3’UTRs) are a major site of posttranscriptional regulation, we screened different <italic>HTR4</italic> isoforms in an IBS pilot cohort for variants in their 3’UTRs. Associated polymorphisms were followed up in larger case-control cohorts and their functional relevance investigated in reporter gene assays.</p><p><bold>RESULTS:</bold> In the pilot study cohort, we identified the rare SNP (rs201253747) <italic>HTR4b</italic> c.*61T>C to be exclusively present in IBS with diarrhoea (IBS-D) patients (2/98 in IBS-D, 0/100 in IBS-C and 0/92 in controls). In a subsequent replication study, we confirmed the polymorphism as significantly increased in IBS-D patients compared with healthy controls (p=0.033; OR=3.09; 2185 healthy controls, 613 IBS-C and 829 IBS-D patients were tested in total).The SNP locates in a putative miR-16 family binding site. We show that <italic>HTR4</italic> is specifically downregulated by this miRNA family via multiple target sites. Furthermore we describe a novel isoform of <italic>HTR4b</italic> with an alternatively spliced 3’UTR. This isoform escapes miR-16 regulation in reporter assays when the <italic>HTR4b</italic> c.*61C allele is present, suggesting an increase of 5-HT<sub>4</sub> receptor expression in <italic>HTR4b</italic> c.*61C carriers.</p><p><bold>CONCLUSION:</bold> In conclusion, we have shown for the first time that <italic>HTR4</italic> is susceptible to miRNA regulation and that the c.*61T>C polymorphism impairs the regulation of <italic>HTR4</italic> via the miR-16 family. Thus we postulate that people carrying this SNP may have a higher 5-HT<sub>4</sub> receptor activity and therefore higher risk of developing IBS-D.</p><p><bold>Contact E-mail Address:</bold><email>Beate.Niesler@med.uni-heidelberg.de</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> 5-HT4 receptor, IBS, miRNAs, motility</p></sec><sec><title>OP090 A META-ANALYSIS OF IMMUNOGENETIC ASSOCIATION STUDIES IN IRRITABLE BOWEL SYNDROME</title><p><bold>B. Czogalla</bold><sup>1,*</sup>, S. Schmitteckert<sup>1</sup>, L. A. Houghton<sup>2,3</sup>, G. S. Sayuk<sup>4</sup>, A. Olivo-Diaz<sup>5</sup>, M. D ´Amato<sup>6</sup>, M. Camilleri<sup>7</sup>, R. Spiller<sup>8</sup>, M. M. Wouters<sup>9</sup>, G. Boeckxstaens<sup>9</sup>, G. A. Rappold<sup>1</sup>, J. Lorenzo Bermejo<sup>10</sup>, B. Niesler<sup>1</sup> GENIEUR - Pan-European interdisciplinary network to identify genetic factors contributing to IBS etiopathogenesis</p><p><italic><sup>1</sup>Department of Human Molecular Genetics, Institute of Human Genetics, Heidelberg , Germany, <sup>2</sup>University of Manchester, Manchester, United Kingdom, <sup>3</sup>Mayo Clinic, Jacksonville, <sup>4</sup>Washington University School of Medicine, St. Louis, United States, <sup>5</sup>Hospital General "Dr. Manuel Gea Gonzalez", Mexico City, Mexico, <sup>6</sup>Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden, <sup>7</sup>Mayo Clinic, Rochester, United States, <sup>8</sup>NIHR Biomedical Research Unit , Nottingham Digestive Diseases Centre, Nottingham, United Kingdom, <sup>9</sup>TARGID, University Hospital Leuven, Leuven, Belgium, <sup>10</sup>Institute of Medical Biometry and Informatics, University Hospital Heidelberg, Heidelberg, Germany</italic></p><p><bold>INTRODUCTION:</bold> There is much controversial discussion on the role of immunological and inflammatory factors in the pathoaetiology of Irritable Bowel Syndrome (IBS). Moreover, it remains unclear how immune-response disturbances relate to its pathophysiology. Although family and twin studies suggest an inherited IBS component, genetic studies are still in their infancy. Only a few case-control cohorts exist together with a small number of association studies of single nucleotide polymorphisms (SNP) in selected candidate genes. These have reported various SNPs in cytokine genes to associate with IBS risk, and to influence expression levels of mediator cytokines.</p><p><bold>AIMS&METHODS:</bold> In order to validate previous data, we conducted a replication study on 16 SNPs in <italic>IL1R1, IL4, IL6, IL8, IL10, IL23R, TNF</italic> and <italic>TNFSF15</italic> which have been found to be associated with IBS risk. We genotyped two case-control cohorts of Caucasian origin: one from the UK (205 patients and 92 healthy volunteers) and one from the USA (198 patients and 96 healthy volunteers). Subsequently, a meta-analysis including 11 earlier studies of Caucasian people was performed to examine the relationship between inherited immunological diversity and IBS risk. Our study included 3020 patients (480 IBS- M, 825 IBS- C, 1063 IBS- D) and 3048 healthy volunteers.</p><p><bold>RESULTS:</bold> No previously reported SNP association was replicated in our study cohort, but the association with the susceptibility SNP rs4263839 in the <italic>TNFSF15</italic> gene was confirmed in the meta-analysis. An association with IBS overall was reflected in a summary OR of 1.19 (95% CI 1.08-1.31, four studies), and with IBS-C in a combined OR of 1.24 (95% CI 1.08-1.42).</p><p><bold>CONCLUSION:</bold> Our findings emphasize the difficulty in investigating the role of inherited genetic variants in heterogenous conditions like IBS. This might be related to a large heterogeneity among recruiting centres, perhaps based on their major management focus and prevented in the future by better characterization of patients and controls according to harmonized rules.</p><p><bold>Contact E-mail Address:</bold><email>Beate.Niesler@med.uni-heidelberg.de</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> cytokine polymorphisms, IBS, immune system, meta-analysis </p></sec><sec><title>OP091 GENOTYPIC HETEROGENEITY AND CLINICAL FEATURES IN ALLGROVE SYNDROME: ABOUT 78 CASES</title><p><bold>A. Tebaibia</bold><sup>1,*</sup>, M. A. Boudjella<sup>1</sup>, M. Lahcene<sup>1</sup>, F. Benmediouni<sup>1</sup>, N. Oumnia<sup>1</sup></p><p><italic><sup>1</sup>internal medicine department, kouba hospital, Algiers, Algeria</italic></p><p><bold>INTRODUCTION:</bold> Allgrove syndrome is a rare autosomal recessive disorder characterized by alacrima, achalasia, adrenal insufficiency and autonomic/neurological abnormalities. Rarely reported in adult patients, it is usually present during the first decade of life. Recent studies have identified mutations in the AAAS, a candidate gene on chromosome 12q13 (16 exons).</p><p><bold>AIMS&METHODS:</bold> to describe clinical finding and genotypic analysis. over a period of 20 years (1992-2012), 78 consecutive patients (Females: 41, Males: 37; mean age: 16.55 ± 10.68 (6 months - 41 years), were enrolled in this study. They were 47 (60%) children and 31 (40%) adult. All patients underwent a standardized symptoms questionnaire, a complete clinical check up, an ophthalmologic check up with a Schirmer test, an adrenal hormone balance, an esophageal barium swallow, an upper endoscopy and an esophageal manometry. Achalasia was diagnosed according to manomertric criteria. In 23 families (30 patients: F: 16, M: 14) and their unaffected parents underwent a genetic study (RFLP analysis): checking for ESV9 and IVS14 mutation.</p><p><bold>RESULTS:</bold> 55 patients (71%) were consanguineous. The syndrome was familial (siblings) in 35 cases (16 families). All patients had alacrima at birth, they all developed achalasia later (100%). Whereas, adrenal insufficiency was found in 42 cases (52%) and autonomic dysautonomia/ neurological abnormalities (thenar and hypothenar muscle atrophy, reduced force of abduction and adduction of fingers, mental retardation, optic atrophy, ataxia, …) in 18 cases (23%) . It was a 3A syndrome (achalasia, alacrima, Addison) in 46 cases and a 4A syndrome in seven cases. The syndrome was incomplete or called syndrome 2A (alacrima, achalasia) in the other cases. In familial 3A (08 families), 17 cases of probable Allgrove syndrome who had at least alacrima were identified, they died probably after an acute adrenal insufficiency. Genetic analysis was performed in 30 patients and revealed that:<bold> - </bold>10 patients (33%) have the EVS9 mutation of AAAS gene: mutation of the exon 9 AAAS (chromosome 12) è likely, to be confirmed by sequencing. - 20 patients (67%) carry the IVS14 + 1G> A mutation of AAAS gene: mutation of the intron 14 of the AAAS gene (chromosome 12) è confirmed by RFLP and sequencing.</p><p><bold>CONCLUSION:</bold> Allgrove syndrome is a rare genetic condition. It is more frequent in children than in adults. Every alacrima of children or teenagers should trigger suspicion for Allgrove syndrome. Achalasia is the most frequent disorder seen after alacrima. The mutation IVS14 + 1G> A in intron 14 of the AAAS gene (chromosome 12) seems to be the most common.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Achalasia, Addison, Allgrove</p></sec><sec><title>OP092 ASSOCIATION OF POLYMORPHISMS IN 5-HT2A AND 5-HT2C RECEPTORS GENES WITH DEPRESSIVE AND ANXIETY DISORDERS IN PATIENTS WITH IRRITABLE BOWEL SYNDROME</title><p><bold>A. Mulak</bold><sup>1,*</sup>, E. Waszczuk<sup>1</sup>, J. A. Beszlej<sup>2</sup>, M. Szechinski<sup>2</sup>, D. Frydecka<sup>2</sup>, M. Szewczuk-Boguslawska<sup>2</sup>, M. Grzesiak<sup>2</sup></p><p><italic><sup>1</sup>Department of Gastroenterology and Hepatology, <sup>2</sup>Department of Psychiatry, WROCLAW MEDICAL UNIVERSITY, Wroclaw, Poland</italic></p><p><bold>INTRODUCTION:</bold> Serotonin (5-HT) plays a crucial role both in the pathophysiology of irritable bowel syndrome (IBS) and mental disorders. Serotonin-related genetic polymorphisms have been suggested to be associated with a high prevalence of anxiety and depressive disorders in patients with IBS.</p><p><bold>AIMS&METHODS:</bold> To investigate the association of the 1438 G/A and 102 T/C polymorphisms in 5-HT2A and 23 G/C polymorphism in 5-HT2C receptors genes with depressive and anxiety disorders in IBS patients. Ninety five IBS patients selected according to the Rome II criteria (mean age 49; 81 F, 14 M) participated in the study. The lifetime prevalence of depressive and anxiety disorders in IBS patients was assessed by the Munich version of the Composite International Diagnostic Interview (CIDI). Single nucleotide polymorphisms were detected by minisequencing method. The chi-squared test was used to evaluate the accordance of the observed genotype frequency distribution with the Hardy-Weinberg equilibrium. For frequencies less than 5 Yates' correction was applied.</p><p><bold>RESULTS:</bold> Depressive and anxiety disorders were diagnosed in 54 participants (57%). The IBS patients were divided into 4 subgroups: with no mental disorders (n=41, 43%), with depressive disorders only (n=20, 21%), with anxiety disorders only (n=25, 26%), and with coexisting anxiety-depressive disorders (n=9, 10%). In comparison to IBS patients without any mental disorder, IBS patients with depressive disorders were characterized by a lower frequency of the 1438 A allele in 5-HT2A receptor gene (OR=0.38, 95% IC=0.17-0.83, p=0.024). The frequency of the 1438 A/A genotype was also lower in IBS patients with depressive disorders, but it did not reach statistical significance (chi(2)=5.7, p=0.058). No significant association of the 102 T/C polymorphism in 5-HT2A receptor gene with depressive and anxiety disorders in IBS patients was revealed. Interestingly, the presence of comorbid anxiety disorders in IBS was associated with a lower frequency of the G allele in 23 G/C polymorphism of 5-HT2C receptor gene (OR=2.80, 95% IC=1.13-6.92, p=0.04), as well as with a lower frequency of the 23 G/G genotype (chi(2)=6.1, p=0.048) in comparison with IBS patients with no mental disorders.</p><p><bold>CONCLUSION:</bold> Our results provide further evidence for the involvement of 5-HT2A receptor in the pathophysiology of depressive disorders in IBS. The new findings in this study indicate also that the polymorphism of 23 G/C in 5-HT2C receptor gene may be associated with the susceptibility to anxiety disorders in IBS patients. Supported by KBN No2 P05B07230</p><p><bold>Contact E-mail Address:</bold><email>agata.mulak@wp.pl</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> anxiety, depression, genetic polymorphisms, IBS, serotonin </p></sec><sec><title>OP093 MICRO-INFLAMMATION AND OVEREXPRESSION OF CACNA1H ION CHANNEL IN THE COLONIC MUCOSA OF PATIENTS WITH IRRITABLE BOWEL SYNDROME: A CASE-CONTROL STUDY.</title><p><bold>J. Scanzi</bold><sup>1,2,*</sup>, E. Muller<sup>2</sup>, F. Carvalho<sup>2</sup>, A. Accarie<sup>2</sup>, D. Ardid<sup>2</sup>, M. Dapoigny<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology department, CHU Estaing Clermont-Ferrand, <sup>2</sup>UMR 1107 INSERM Neurodol, Université d'Auvergne, Clermont-Ferrand, France</italic></p><p><bold>INTRODUCTION:</bold> Visceral hypersensitivity (VH) is a key point in the pathophysiology of irritable bowel syndrome (IBS). Recent investigations suggest that impairment of the intestinal epithelial barrier could lead to persistent low-grade mucosal inflammation and to VH. Preclinical studies indicate that VH involves sensitization of the colonic primary afferent fibers, via an overexpression of ion channels that increase neuronal excitability, including the voltage-gated calcium channel CACNA1H. In a rodent model mimicking IBS, the genetic or pharmacological blockade of CACNA1H channels prevents the development of colonic hypersensitivity.</p><p><bold>AIMS&METHODS:</bold> The aim of the study was to assess the expression of CACNA1H channels and the proinflammatory state in the colonic mucosa of symptomatic IBS patients (cases) and healthy subjects (controls). Each enrolled patient was referred for colonoscopy, for IBS symptoms or colonic cancer screening. Colonic biopsies were systematically performed, with histological analysis to rule out inflammatory or microscopic colitis. Transcriptional and protein expression levels of CACNA1H channels were studied respectively by real-time polymerase chain reaction (RT-PCR) and immunohistochemical detection. The density of intra-mucosal mast cells and their proximity to the nerve fibers was also carried out by co-immunohistochemical detection.</p><p><bold>RESULTS:</bold> Twenty-nine patients were included, forming two groups of 13 cases and 16 controls, matched for sex and age (mean age=54). In all cases, the colonoscopy was normal. Analysis by quantitative RT-PCR of CACNA1H mRNA shows a significant overexpression of these channels in the IBS group compared to the control group (<italic>p=0.034</italic>). The immunofluorescence study of the CACNA1H channel tissue distribution in the colonic mucosa shows that this channel is particularly expressed in colonic nerve fibers. This is consistent with the involvement of CACNA1H in the hyperexcitability of colonic nociceptive neurons causing VH. This overexpression of the CACNA1Hchannelin IBS patients is associated with a significant increase in the density of intra-mucosal mast cells (<italic>p=0.007</italic>).</p><p><bold>CONCLUSION:</bold> This study confirms the involvement of the CACNA1H ion channel in IBS, which may has a role in the neuronal excitability involved in VH. It opens new therapeutic perspectives through antagonist molecules specifically targeting these CACNA1H channels. This study also confirms the presence of a low-grade inflammatory state in this disease, with an increased density of intra-mucosal mast cells in IBS patients.</p><p><bold>Contact E-mail Address:</bold><email>jscanzi@chu-clermontferrand.fr</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> ion channels, Irritable bowel syndrome, micro-inflammation, visceral hypersensitivity</p></sec><sec><title></title><p><bold>MONDAY, OCTOBER 14, 2013 14:00-15:30</bold></p><p><bold>Multimodal therapies in biliopancreatic diseases – Hall 10</bold></p></sec><sec><title>OP094 EXTRA-ANATOMICAL ENDOSCOPIC-RADIOLOGICAL RECONSTRUCTION OF IATROGENIC COMPLETE TRANSSECTION OF HEPATICS OR COMMON BILE DUCT</title><p><bold>G. Donatelli</bold><sup>1,*</sup>, B. M. Vergeau<sup>1</sup>, S. Derhy<sup>1</sup>, J. Dumont<sup>1</sup>, T. Tuszynski<sup>1</sup>, P. Dhumane<sup>2</sup>, B. Meduri<sup>1</sup></p><p><italic><sup>1</sup>Unité d'Endoscopie Thérapeutique, Hôpital Privé des Peupliers, Paris, France, <sup>2</sup>General Surgery, Lilavati Hospital, Mumbai, India</italic></p><p><bold>INTRODUCTION:</bold> Iatrogenic transsection of Bile Duct (BD) is a troublesome complication of open or laparoscopic hepatic-biliary surgery. Difficulty in promptly recognizing and technically demanding surgery makes the primary repair a difficult option. However surgery proposed (hepatico-jejunostomy or end-to-end choledocal anastomosis) carries high morbidity and mortality.</p><p><bold>AIMS&METHODS:</bold> We report our experience of Extra-Anatomical Endoscopic-Radiological reconstruction (EAERr) of iatrogenic injured BD. Since 1/2008 an EAERr of BD was attempted in 19 symptomatic patients (10 F), with median age of 57 (31-89) years, having iatrogenic complete transsection of hepatics or common bile duct diagnosed by impossibility to pass a guide wire in the intra-hepatics bile ducts during endoscopic retrograde cholangiography. Follow endoscopic sphincterotomy a dormia basket was passed through the choledocal stump in the sub-hepatic space for catching a percutaneously inserted thin long transhepatic guide wire. Then it was pulled out through the scope in order to reestablish the biliary continuity. Over guide wire a biliary dilation was performed, followed by deployment of a long plastic 10 Fr stent. The stents were changed every three months, for maximum 24, till a good caliber of BD gets reconstructed over the stents as confirmed by cholangiographic picture. The stents were then removed and the case was followed up clinical evaluation and biochemical parameters.</p><p><bold>RESULTS:</bold> In 18/19 (94.7%) patients, EAERr of BD was possible, in 4 pts it was injured during open hepatectomy, and in the other 15 during cholecystectomy. In 1 patient (5.26%) EAERr failed because of aberrant anatomy and the patient was subsequently operated. The median time duration between surgery and EAERr was of 43 (6 – 180) days. 5 pts (26.31%) needed a double EAERr (right and left), to obtain complete drainage of all liver segments. At Avril 2013 one patient is lost to follow up, 2 (11.7%) pts are still under treatment, 14 (82.35%) patients are declared cured and 1 was addressed to surgery seen the inability to achieve a good caliber of reconstructed duct. The median time of stents in place, was of 14 months (8-24) and at a median follow up of 13 months (4-47) they are clinically well and have normal liver test. The median number of stents delivered was of 8 (3-22) and a median of 9 (6-14) endoscopy sessions was necessary per patient.</p><p><bold>CONCLUSION:</bold> EAERr, of iatrogenic complete transsection of BD, seems to be a valid mini-invasive alternative to re-established continuity of transsected duct with no mortality and low morbidity related, despite multiple endoscopic sessions.</p><p><bold>Contact E-mail Address:</bold><email>donatelligianfranco@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> BILE DUCT TRANSSECTION, BILIARY RENDEZ VOUS, BILIARY STENTING, ERCP, EXTRA ANATOMICAL RECONSTRUCTION, IATROGENIC BILE DUCT LESION</p></sec><sec><title>OP095 PREOPERATIVE BILIARY DRAINAGE FOR HILAR CHOLANGIOCARCINOMA: ENDOSCOPIC OR PERCUTANEOUS DRAINAGE.</title><p><bold>J. K. Wiggers</bold><sup>1,*</sup>, E. Rauws<sup>2</sup>, J. Lameris<sup>3</sup>, O. Busch<sup>1</sup>, D. J. Gouma<sup>1</sup>, T. van Gulik<sup>1</sup></p><p><italic><sup>1</sup>Surgery, <sup>2</sup>Gastroenterology, <sup>3</sup>Radiology, Academic Medical Centre, Amsterdam, Netherlands</italic></p><p><bold>INTRODUCTION:</bold> Most patients undergoing preoperative biliary drainage for hilar cholangiocarcinoma (HCCA) have previously been treated with endoscopic biliary drainage (EBD) on referral, while percutaneous transhepatic biliary drainage (PTBD) is used to treat recurrent cholangitis or overcome technical difficulties.</p><p><bold>AIMS&METHODS:</bold> The aim of this study was to analyze a single-centre cohort of 171 patients that underwent EBD and/or PTBD before explorative laparotomy for HCCA between 2001 - 2013. The study’s primary endpoint was therapeutic failure of EBD, defined as the need for secondary PTBD to achieve adequate preoperative biliary drainage. The secondary study endpoint was post-PTBD cholangitis<italic>.</italic></p><p><bold>RESULTS:</bold> There were 155 patients initially treated with EBD, among whom there were 98 patients with therapeutic success after EBD (63%), and 57 patients (37%) that needed secondary PTBD. Indications for secondary PTBD were technical failure of the EBD procedure in 9 patients (6%), stent dysfunction with or without cholangitis in 29 (29%), and inadequate drainage of the future remnant liver in 19 (12%). Multivariate analysis indicated that factors associated with EBD failure include bilirubin level (p=0.003, OR 1.16), hospital of initial procedure (academic versus regional hospital; p=0.02, OR 2.95), and tumor extension. Patients with Bimsuth-Corlette type IV tumors (63%, p<0.001, OR 37.6) and patients with type III tumors (39%, p=0.002, OR 11.9) more often required secondary PTBD treatment than patients with type I/II tumors (7%). A total of 73 patients had undergone PTBD, either as primary treatment (16 patients) or as secondary treatment after previous EBD (57 patients). Among these patients, 26 patients (36%) developed a post-PTBD cholangitis. Univariate analysis indicated that the pre-PTBD bilirubin level (p=0.04), and previous EBD treatment (p=0.03) were associated with post-PTBD cholangitis.</p><p><bold>CONCLUSION:</bold> Patients with Bismuth-Corlette type III and type IV tumors are often not adequately treated with EBD as preoperative biliary drainage for HCCA. Preferably, all patients with complex biliary tumors should undergo biliary drainage in high volume centres, but especially patients at high risk for failure of EBD treatment would benefit from direct referral and PTBD as treatment of first choice, as failed EBD treatment is associated with cholangitis after PTBD.</p><p><bold>Contact E-mail Address:</bold><email>j.k.wiggers@amc.nl</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Biliary drainage, endoscopic complications, percutaneous</p></sec><sec><title>OP096 A MULTICENTER STUDY ON EUS- GUIDED EXPANDABLE BILIARY METAL STENT PLACEMENT: CHOICE OF ACCESS ROUTE, DIRECTION OF STENT INSERTION, AND DRAINAGE ROUTE</title><p><bold>V. Dhir</bold><sup>1</sup>, E. L. Artifon<sup>2</sup>, K. Gupta<sup>3</sup>, J. J. Vila<sup>4,*</sup>, M. Frazao<sup>2</sup>, A. Maydeo<sup>1</sup></p><p><italic><sup>1</sup>Endoscopy Unit. Gastroenterology Dpt., Baldota Institute of Digestive Science. Global Hospital., Mumbai, India, <sup>2</sup>Endoscopy Unit. Gastroenterology Dpt., Universtiy of Sao Paulo., Sao Paulo, Brazil, <sup>3</sup>Endoscopy Unit. Gastroenterology Dpt., Cedars-Sinai Medical Centre., Los Angeles, United States, <sup>4</sup>Endoscopy Unit. Gastroenterology Dpt., Complejo Hospitalario de Navarra, Pamplona, Spain</italic></p><p><bold>INTRODUCTION:</bold> EUS-guided biliary drainage (EUS-BD) has emerged as an acceptable alternative when ERCP fails. However there is no consensus over the preferred access route (trans-hepatic or extra-hepatic), direction of stent insertion (antegrade or retrograde) or drainage route (trans-luminal or trans-papillary).</p><p><bold>AIMS&METHODS:</bold> We designed a multicentre retrospective study to compare success and complication rate in patients undergoing EUS-BD via different access routes, direction of stent insertion, and drainage routes. Patients who underwent EUS-BD for malignant obstructive jaundice were included. Data from 4 centres was included. Details were recorded of the access route, direction of stent insertion (antegrade: direction from liver to bile duct and viceversa), and drainage route (transluminal: choledocho-duodenostomy or hepatico-gastrostomy; transpapillary: antegrade and retrograde (rendezvous) transpapillary stenting procedures. Comparisons were done using Chi square test, Student T test, and stepwise logistic regression.</p><p><bold>RESULTS:</bold> 68 patients (34 males) were analyzed. Median age of the cohort was 66 years (34-95 years). Fifty five patients (81%) had a distal block. Sixty four patients (94%) had previously failed ERCP. EUS-BD was successful in 65 patients (95.6%). Complications were seen in 14 patients (20.6%, cholangitis 5, bile leak 4, perforations 2, pneumobilia 2, and bleed 1) and mortality in 3 patients (4.4%, cholangitis 2, perforation 1). The results of various techniques are summarized in the table. Logistic regression analysis showed trans-hepatic access to be the only independent risk factor for complications (p=0.031, t=2.2).
<table-wrap id="table14-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1"></th><th rowspan="1" colspan="1">Technique(n)</th><th rowspan="1" colspan="1">Success(%)</th><th rowspan="1" colspan="1">P value</th><th rowspan="1" colspan="1">Complications (%)</th><th rowspan="1" colspan="1">P value</th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">Access route</td><td rowspan="1" colspan="1">Transhepatic(36)</td><td rowspan="1" colspan="1">34 (94.4)</td><td rowspan="1" colspan="1">0.345</td><td rowspan="1" colspan="1">11 (30.5)</td><td rowspan="1" colspan="1">0.030</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">Extrahepatic(32)</td><td rowspan="1" colspan="1">31 (96.8)</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">3 (9.3)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">Stent Direction</td><td rowspan="1" colspan="1">Antegrade (25)</td><td rowspan="1" colspan="1">23 (92)</td><td rowspan="1" colspan="1">0.303</td><td rowspan="1" colspan="1">8 (32)</td><td rowspan="1" colspan="1">0.073</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">Retrograde (43)</td><td rowspan="1" colspan="1">42 (97.6)</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">6 (13.9)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">Exit route</td><td rowspan="1" colspan="1">Transluminal(32)</td><td rowspan="1" colspan="1">30 (93.7)</td><td rowspan="1" colspan="1">0.455</td><td rowspan="1" colspan="1">6 (20)</td><td rowspan="1" colspan="1">0.480</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">Transpapillary(36)</td><td rowspan="1" colspan="1">35 (97.2)</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">8 (22.8)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">Direct or rendezvous</td><td rowspan="1" colspan="1">Direct (48)</td><td rowspan="1" colspan="1">45 (93.7)</td><td rowspan="1" colspan="1">0.345</td><td rowspan="1" colspan="1">11 (22.9)</td><td rowspan="1" colspan="1">0.352</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">Rendezvous (20)</td><td rowspan="1" colspan="1">20 (100)</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">3 (15)</td><td rowspan="1" colspan="1"></td></tr></tbody></table></table-wrap></p><p><bold>CONCLUSION:</bold> EUS-BD can be performed with high success rate regardless of the choice of access route, stent direction or drainage route. The complications appear to be higher in patients following trans-hepatic access, antegrade stent insertion, and in those with proximal block. Extra-hepatic route should be preferred for EUS-guided direct and rendezvous stent placements. Patients with proximal blocks need careful evaluation before EUS-BD.</p><p><bold>Contact E-mail Address:</bold><email>juanjvila@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Biliary Drainage, ercp, Stent, Therapeutic endosonography </p></sec><sec><title>OP097 ENDOSCOPIC ULTRASOUND GUIDED HEPATOGASTROSTOMY : LARGE RETROSPECTIVE STUDY</title><p><bold>E. Bories</bold><sup>1,*</sup>, F. caillol<sup>1</sup>, C. pesenti<sup>1</sup>, M. giovannini<sup>2</sup></p><p><italic><sup>1</sup>ENDOSCOPY, <sup>2</sup>INSTITUT PAOLI CALMETTES, MARSEILLE, France</italic></p><p><bold>INTRODUCTION:</bold> EUS-guided biliary drainage was purposed as an alternative of percutaneous transhepatic cholangiography in case of endoscopic retrograde cholangiopancreatography (ERCP) failure. Several EUS-guided procedures were published: rendezvous technique, transgastric anterograde transpapillary stenting, choledocoduodenal anastomosis and EUS-guided bilio-gastric anastomosis or hepaticogastrostomy (HG).</p><p><bold>AIMS&METHODS:</bold> Ninety two EUS-guided biliary procedures were performed from June 2000 to february 2013 in our institution. Among these procedures, 74 HG were found. After exclusion of patients included in a randomized prospective study, 61 patients were included in this monocentric retrospective study. Aims of this study was to analyse feasibility and outcome of transgastric EUS-guided biliary procedures.</p><p><bold>RESULTS:</bold> During the study period, 61 patients (female=32; mean age=65yrs, range 38-93) were treated by HG. This technique was chosen due to impossibility to reach the papilla, ERCP failure or to achieve left biliary ducts drainage respectively in 33%, 16% and 51%. Biliary stricture was malignant in 85%.</p><p>Sixty-five procedures were attempted. Technical success rate was 94%. Morbidity rate was 33% including pneumoperitoneum (n=5), bile leakage (n=7), haemorrhage (n=1) and sepsis (n=5). Stent migration rate was 11%. All complications were treated medically with favourable outcome in all cases except one death.</p><p>During the study, several type of stents was used: plastic stents (n=12), covered or uncovered SEMS (n=11), covered and uncovered SEMS (n=26) or a half covered SEMS (P4=16). Morbidity rate was respectively 25%, 63%, 34% and 19%.</p><p><bold>CONCLUSION:</bold> EUS guided therapeutic biliary procedures are feasible with high technical success rate. Procedure related complications after biliary drainage were elevated, but acceptable for these selected difficult cases. Use of half covered SEMS seems to reduce morbidity rate.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> EUS guided biliary drainage, Hepaticogastrostomy (HG)</p></sec><sec><title>OP098 RESULTS OF PROGRAMMED EUS-GUIDED NECROSECTOMY IN PATIENTS WITH INFECTED WALLED-OFF PANCREATIC NECROSIS AFTER SEVERE ACUTE PANCREATITIS</title><p>J. C. Ardengh<sup>1</sup>, T. Baron<sup>2</sup>, E. Taglieri<sup>1</sup>, <bold>O. Micelli-Neto</bold><sup>1,*</sup>, E. T. Orsini<sup>1</sup>, G. Motta<sup>1</sup>, R. Kemp<sup>1</sup>, J. S. dos Santos<sup>1</sup></p><p><italic><sup>1</sup>Surgery and Anatomy of HCFMRP-USP, Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto - Universidade de São Paulo, Ribeirão Preto, Brazil, <sup>2</sup>Gastroenterology, Mayo Clinic, Rochester, United States</italic></p><p><bold>INTRODUCTION:</bold> Acute severe pancreatitis may progress to the development of walled-off pancreatic necrosis (WOPN) characterized by a mixture of solid and liquid components. Infected WOPN often leads to severe clinical deterioration necessitating open debridement or endoscopic necrosectomy. Programmed EUS-guided necrosectomy allows creation of multiple transluminal gateways to improve transmural removal of necrosis.</p><p><bold>AIMS&METHODS:</bold> The aim of this study is evaluate the efficacy of a EUS-guided necrosectomy. Patients with severe acute pancreatitis complicated by infected WOPN were treated by programmed EUS-guided necrosectomy every 7 days. One or more sites of transmural entry via EUS designated as EUS-N 1, 2 or 3 were performed. Direct necrosectomy was performed and after debridement and irrigation plastic pigtail stents were placed.</p><p><bold>RESULTS:</bold> 17 patients with infected WOPN were treated by programmed EUS-N. The average sessions per patient was 2.5 (1-6). Successful resolution of WOPN was achieved in15/17 (88.2%) patients. Plastic pigtail stents were placed in 12 and self-expandable metallic stents (SEMS) in 3 and in 2 patients no stents were placed. Three patients experienced bleeding (entry side (2), inside cavity (1)) and worsening of infection (33.3%) after EUS-N, all of which were successfully treated endoscopically by another session of EUS-N. The mortality rate was (11.7%). One patient underwent surgery (5.8%) and one patient died due to poor medical conditions. The mean duration of hospital stay was 19 days (5-48 d).</p><p><bold>CONCLUSION:</bold> Programmed EUS-N is an effective option for the treatment of infected WOPN because it eliminates the need for surgery and can be performed in the absence of a visible bulging. Prospective studies are needed to confirm these preliminary and promising results.</p><p><bold>REFERENCES:</bold></p><p>1. van Brunschot S, van Santvoort HC, Gooszen HG, Fockens P. [Endoscopic versus surgical treatment of infected necrotising pancreatitis: the TENSION study]. Nederlands tijdschrift voor geneeskunde. 2012;156(4):A4329.</p><p>2. van Santvoort HC, Besselink MG, Bakker OJ, Vleggaar FP, Timmer R, Weusten BL, et al. Endoscopic necrosectomy in necrotising pancreatitis: indication is the key. Gut. 2010 Nov;59(11):1587.</p><p><bold>Contact E-mail Address:</bold><email>jcelso@uol.com.br</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Acute necrotising, Debridement, Drainage, Endosonography, Pancreatitis, Treatment response</p></sec><sec><title>OP099 EUS-GUIDED DRAINAGE OF PANCREATIC PSEUDOCYSTS (PP) UTILIZING A NOVEL ANCHORING, COVERED SELF-EXPANDING METAL STENT (ACSEMS): RESULTS FROM A PROSPECTIVE, MULTI-CENTER STUDY</title><p><bold>R. J. Shah</bold><sup>1</sup>, J. N. Shah<sup>2</sup>, I. Waxman<sup>3</sup>, T. E. Kowalski<sup>4</sup>, A. Sanchez-Yague<sup>5</sup>, J. Nieto<sup>6</sup>, B. C. Brauer<sup>1</sup>, M. Gaidhane<sup>7</sup>, M. Kahaleh<sup>7,*</sup></p><p><italic><sup>1</sup>Gastroenterology & Hepatology, University of Colorado Anschutz Medical Campus, Aurora, <sup>2</sup>Gastroenterology & Hepatology, California Pacific Medical Center (CPMC), San Francisco, <sup>3</sup>Gastroenterology & Hepatology, University of Chicago Medical Center (UCMC), Chicago, <sup>4</sup>Gastroenterology & Hepatology, Thomas Jefferson University, Philadelphia, United States, <sup>5</sup>Gastroenterology & Hepatology, Hospital Costa del Sol, Marbella, Spain, <sup>6</sup>Gastroenterology & Hepatology, Borland-Groover Clinic (BGC), Jacksonville, <sup>7</sup>Gastroenterology & Hepatology, Weill Cornell Medical College, New York, United States</italic></p><p><bold>INTRODUCTION:</bold> Placement of double pigtail plastic stents, with limited lumen size, for endoscopic pancreatic pseudocyst (PP) drainage requires repeat wire access of the cystenterostomy after initial stent deployment. Conventional covered self-expanding metal stents (CSEMS) are larger in diameter and permit single-step insertion but have a stent migration risk. The AXIOS (XLUMENA, Inc) stent (ACSEMS), a fully-covered Nitinol stent, has a dual-flange design allowing an anchoring effect to maintain a cystenterostomy tract. Our objective was to evaluate the safety & efficacy of ACSEMS for PP drainage.</p><p><bold>AIMS&METHODS:</bold> 7 centers (6 US, 1 EU) included patients with symptomatic PP requiring drainage that was ≥ 6 cm with ≥ 70% fluid content. Cystenterostomy creation technique and AXIOS stent diameter (10 or 15 mm) was per endoscopist preference. Safety outcomes: access site-related bleeding, infection, perforation, tissue injury, and stent migration. Efficacy endpoints: successful insertion and removal of ACSEMS, PP resolution defined as ≥ 50% reduction in size, and lumen patency.</p><p><bold>RESULTS:</bold> From Oct ‘11 to June ‘12, 33 patients (18M; age 53 ± 14 yrs) were enrolled with 28 (85%) having underlying pancreatitis. Mean PP size was 9 ± 3.3 cm. ACSEMS was successfully placed via EUS guidance in 30/33 (91%) patients, with remaining 3 receiving double pigtail stents. Stent was implanted for 30 days n=20) or 60 days (n=9). Procedure time was 64 ± 38 minutes. PP resolution was achieved in 31/33 (94%); and 28/30 (93%) receiving ACSEMS with 93% lumen patency at stent removal. In ACSEMS subjects, PP size decreased significantly (6.7 cm, p<0.0001) from baseline (10 ± 4 cm) to 30 days post-stent placement (3.4 ± 3.9 cm). For 10 subjects, the PP size was 1.9 ± 1.6 cm at 60 days. 10 subjects underwent direct endoscopic necrotic debridement through the indwelling ACSEMS to achieve PP resolution in 9/10 subjects. Complications included abdominal pain (3), left shoulder/back pain (1), spontaneous stent migration (1), and access-site infection and stent dislodgement (1).</p><p><bold>CONCLUSION:</bold> ACSEMS was successfully placed in 91% of subjects. PP resolution of 93% is comparable to plastic pigtail stent data with the distinct advantage of single-step stent deployment and the ability to perform endoscopic necrosectomy through the stent. Optimizing the delivery system and improved operator experience will increase technical success.</p><p><bold>Contact E-mail Address:</bold><email>mkahaleh@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: R. Shah Financial support for research from: Xlumena Inc., J. Shah Financial support for research from: Xlumena Inc., I. Waxman Financial support for research from: Xlumena Inc., T. Kowalski Financial support for research from: Xlumena Inc., A. Sanchez-Yague Financial support for research from: Xlumena Inc., J. Nieto Financial support for research from: Xlumena Inc., B. Brauer Financial support for research from: Xlumena Inc., M. Gaidhane: None Declared, M. Kahaleh Financial support for research from: Xlumena Inc., Consultancy for: Xlumena Inc.</p><p><bold>Keywords:</bold> Chronic Pancreatitis, EUS, Pancreatic Pseudocyst, Stent</p></sec><sec><title></title><p><bold>MONDAY, OCTOBER 14, 2013 14:00-15:30</bold></p><p><bold>Basic Science Workshop 1: The metagenomic approach to GI disease – Hall 8</bold></p></sec><sec><title>OP100 WESTERN DIET MODIFIES GUT HOMEOSTASIS, LEADING TO EXACERBATION OF DSS-INDUCED COLITIS</title><p><bold>A. Agus</bold><sup>1,*</sup>, J. Denizot<sup>1</sup>, J. Thevenot<sup>1</sup>, E. Billard<sup>1</sup>, S. Denis<sup>1</sup>, A. Darfeuille-Michaud<sup>1</sup>, N. Barnich<sup>1</sup></p><p><italic><sup>1</sup>M2iSH, U1071, Université d'Auvergne, Clermont-Ferrand, France</italic></p><p><bold>INTRODUCTION:</bold> Western diet is a risk factor for Inflammatory Bowel Disease (IBD). Such diet induces changes in gut microbiota composition, alters host homeostasis and favors Crohn’s disease-associated Adherent-Invasive <italic>Escherichia coli</italic> (AIEC) gut colonization in genetically predisposed mouse model. Here, we evaluated the effects of a High-Fat/High-Sugar (HF/HS) diet in C57BL/6 mice on gut micro-inflammation, selection of <italic>E. coli</italic> population, concentration of short-chain fatty acids (SCFA) and mouse sensitivity to DSS-induced colitis.</p><p><bold>AIMS&METHODS:</bold> C57BL/6 mice were fed a conventional or a HF/HS diet for a 18 week-period. Fecal lipocalin 2 (Lcn-2) was measured by ELISA to detect low-grade inflammation during the course of treatment. <italic>E. coli</italic> populations associated to colonic and ileal mucosa were quantified by plating onto Drigalsky agar plate. Concentrations of short-chain fatty acids were measured by gas chromatography in fecal samples. Colitis was induced using 1% of DSS treatment in drinking water for 10 days and the severity of colitis was assessed by disease activity index (DAI) measurement, histological score, cytokine production and myeoloperoxidase (MPO) activity.</p><p><bold>RESULTS:</bold> HF/HS diet increased Lcn-2 level in stools from 5 weeks until 18 weeks of treatment, showing that HF/HS diet creates a specific inflammatory environment in the gut. The size and composition of mesenteric lymph nodes and Peyer’s patches were modified by HF/HS diet. Abnormal proportions of <italic>E. coli</italic> bacteria were recovered from colonic and ileal mucosa of mice under HF/HS diet, compared to mice under conventional diet SCFA concentrations (acetate, propionate, butyrate) were significantly decreased in fecal samples from mice under HF/HS diet compared to mice fed a conventional diet. Thus, HF/HS diet led to dysbiosis with an increase of pro-inflammatory bacteria and a decrease in protective SCFA-producing bacteria. In addition, HF/HS diet led to an exacerbation of gut inflammation following DSS-induced colitis, with increased DAI, histological score and MPO activity.</p><p><bold>CONCLUSION:</bold> Western diet modifies gut microbiota composition and induces gut micro-inflammation. The particular micro-environment created by HF/HS diet leads to decreased SCFA concentrations, favors <italic>E. coli</italic> bacteria associated to mucosa, and increases sensitivity to colitis. These results support the multifactorial etiology of IBD and highlight the importance of diet in IBD pathogenesis.</p><p><bold>Contact E-mail Address:</bold><email>allison.agus1@udamail.fr</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> DSS-induced colitis, dysbiosis, high-fat/high-sugar diet, intestinal inflammation, short-chain fatty acids</p></sec><sec><title>OP101 CHARACTERIZATION OF THE GASTRIC MICROBIOTA IN PATIENTS WITH CHRONIC GASTRITIS AND GASTRIC CARCINOMA</title><p><bold>R.M. Ferreira</bold><sup>1,*</sup>, J. L. Costa<sup>1</sup>, C. Figueiredo<sup>1,2</sup>, J. C. Machado<sup>1,2</sup></p><p><italic><sup>1</sup>IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, <sup>2</sup>Dept. Pathology and Oncology, Faculty of Medicine of the University of Porto, Porto, Portugal</italic></p><p><bold>INTRODUCTION:</bold> Gastric carcinoma is the second cause of cancer death worldwide. The majority of gastric carcinoma cases are related to <italic>Helicobacter pylori </italic>infection. This infection induces chronic inflammation that, depending on the strain virulence, host susceptibility factors, and other environmental factors, increases the risk of progression towards carcinoma. During gastric carcinogenesis other bacteria may grow in the stomach as a result of the profound changes in gastric physiology induced by<italic> H. pylori</italic>. The new bacterial growth that competes for the gastric niche may have the potential to enhance inflammation, contributing to gastric carcinogenesis.</p><p><bold>AIMS&METHODS:</bold> The aim of this study is to characterize the gastric microbiota present in individuals with chronic gastritis and gastric carcinoma. To date we have analysed data from ten chronic gastritis and seven gastric carcinoma patients. The next generation sequencing platform Ion PGM was used to sequence part of the bacterial 16S rRNA gene. This gene contains highly variable regions that provide discriminatory power for the characterization of microbiota. The data resulting from mass parallel sequencing was analysed in Qiime pipeline. Clustering of samples was evaluated by Principal Coordinate Analysis (PCoA).</p><p><bold>RESULTS:</bold> So far we have obtained 1,715,309 high quality sequences representing on average 90,279 reads per individual, which were converted in 17,971 operational taxonomic units. A complex and diverse gastric microbiota was identified, which varied considerably between individuals. The majority of the gastric microbiota could be distributed in five main <italic>phyla</italic>, <italic>Proteobacteria</italic>, <italic>Firmicutes</italic>, <italic>Actinobacteria</italic>, <italic>Bacteroidetes</italic>, and <italic>Fusobacteria</italic>. In patients with chronic gastritis and with gastric carcinoma the most representative <italic>phylum</italic> was the <italic>Proteobacteria</italic> with 69.5% and 84.2% reads, respectively. The remaining four <italic>phyla</italic> were always less represented in patients with gastric carcinoma than in patients with chronic gastritis. Interestingly, the abundance of <italic>Helicobacter sp.</italic> was significantly lower in patients with gastric carcinoma (15.8%) than in patients with chronic gastritis (63.9%). Analysis of the diversity between groups of individuals by PCoA, revealed clustering based on the type of disease, meaning that distinct profiles of microbiota distinguish the two patient groups.</p><p><bold>CONCLUSION:</bold> Apart from the complex and diverse gastric microbiota found within individuals, we were able to identify gastric microbiota profiles that distinguish between patients with chronic gastritis and gastric carcinoma. The microbiota profiles identified may have an important role in <italic>H. pylori</italic>-associated gastric carcinogenesis.</p><p><bold>REFERENCES:</bold></p><p>1. Lancet. 2005 Oct 1;366(9492):1210-22.</p><p>2. Arch Intern Med. 2011 Jul 25;171(14):1294-6</p><p>3. <ext-link ext-link-type="uri" xlink:href="http://www.danielbaumgart.de">http://www.danielbaumgart.de</ext-link></p><p><bold>Contact E-mail Address:</bold><email>josem@ipatimup.pt</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Gastric adenocarcinoma, microbiota</p></sec><sec><title>OP102 ESCALATING INCIDENCE OF IBD IN THE EAST AND WEST – IS THE MICROBIOTA THE KEY? IMPACT OF ETHNICITY, GEOGRAPHY, AND DISEASE ON THE MICROBIOTA. THE ENIGMA STUDY.</title><p><bold>L. Prideaux</bold><sup>1,*</sup>, S. Kang<sup>2</sup>, J. Wagner<sup>3</sup>, M. Buckley<sup>2</sup>, J. E. Mahar<sup>3</sup>, P. De Cruz<sup>1</sup>, Z. Wen<sup>4</sup>, L. Chen<sup>5</sup>, B. Xia<sup>5</sup>, D. R. van Langenberg<sup>6</sup>, T. Lockett<sup>2</sup>, S. C. Ng<sup>7</sup>, J. J. Sung<sup>7</sup>, P. Desmond<sup>1</sup>, C. McSweeney<sup>2</sup>, M. Morrison<sup>2</sup>, C. D. Kirkwood<sup>3</sup>, M. A. Kamm<sup>1</sup></p><p><italic><sup>1</sup>Department of Gastroenterology, St Vincent's Hospital, and The University of Melbourne, <sup>2</sup>Commonwealth Scientific and Industrial Research Organisation (CSIRO), Australia, <sup>3</sup>Enteric Virus Group, Murdoch Childrens Research Institute, Parkville, Australia, <sup>4</sup>West China Hospital, Sichuan University, Chengdu, <sup>5</sup>Zhongnan Hospital, Wuhan University School of Medicine, Wuhan, China, <sup>6</sup>Department of Gastroenterology, Box Hill Hospital, Melbourne, Australia, <sup>7</sup>Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Li Ka Shing Institute of Health Sciences, Hong Kong, Hong Kong</italic></p><p><bold>INTRODUCTION:</bold> The gut microbiota is central to health and plays a central pathophysiological role in inflammatory bowel disease (IBD). Differences in microbiota related to geography and ethnicity may hold the key to recent changes in incidence of inflammatory bowel disease. We therefore studied healthy subjects, IBD patients and healthy IBD relatives in the East (Hong Kong) and West (Australia), and surveyed their dietary history.</p><p><bold>AIMS&METHODS:</bold> In this Eastern Inflammatory Bowel Disease Gut Microbiota (“ENIGMA”) study gut mucosal microbiota (ileum, caecum and/or rectum biopsies) was analysed in 190 samples from 87 Caucasian and Chinese subjects, from Australia and Hong Kong, comprising: 22 Crohn’s disease (CD) patients, 30 ulcerative colitis (UC) patients, 29 healthy controls, and 6 healthy relatives of CD patients. Bacterial 16S rRNA microarray and 454 pyrosequencing were performed.</p><p><bold>RESULTS:</bold> The microbiota was diverse in health, regardless of ethnicity or geography [Operational Taxonomic Unit number and Shannon diversity index]. Ethnicity (p=0.017) and geography (p=0.015), however, did significantly affect microbial composition. CD resulted in substantially reduced bacterial diversity, regardless of ethnicity or geography, and was the strongest determinant of composition (p=0.0001). In UC, diversity was significantly reduced in Chinese subjects only (p<0.0004), suggesting that ethnicity is a determinant of bacterial diversity, while composition was determined by disease (p=0.002) and ethnicity (p=0.003). Specific phylotypes were different between health and disease. Chinese IBD patients more often than healthy Chinese tended to have had a Western diet in childhood, in the East and West.</p><p><bold>CONCLUSION:</bold> The healthy microbiota is diverse but composition is affected by geographical and ethnic factors. The microbiota is substantially altered in IBD, but ethnicity may also play an important role. This may be key to the changing epidemiology in developing countries, and emigrants to the West. Diet may be one of the important factors underlying these differences.</p><p>Supported by the Broad Foundation.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> ethnicity, inflammatory bowel disease, microbiota</p></sec><sec><title>OP103 DECIPHERING MICROBIOTA-DRIVEN CELL SIGNALING MODULATION IN THE HUMAN GUT USING A FUNCTIONAL METAGENOMIC APPROACH</title><p><bold>M. Nepelska</bold><sup>1</sup>, S. Guglietta<sup>2</sup>, N. Lapaque<sup>1</sup>, D. Brunelli<sup>2</sup>, A. Jamet<sup>1</sup>, T. de Wouters<sup>1</sup>, O. Berteau<sup>1</sup>, A. Benjdia<sup>1</sup>, A. Cultrone<sup>1</sup>, M. Rhimi<sup>1</sup>, F. Ledue<sup>1</sup>, F. Dumetz<sup>1,3</sup>, S. D. Ehrlich<sup>3</sup>, E. Maguin<sup>1</sup>, J. Doré<sup>1</sup>, M. Rescigno<sup>4</sup>, H. M. Blottière<sup>1,3,*</sup></p><p><italic><sup>1</sup>UMR 1319 Micalis, INRA, Jouy en Josas, France, <sup>2</sup>European Institute of Oncology, Milan, Italy, <sup>3</sup>US 1367 MetaGenoPolis, INRA, Jouy en Josas, <sup>4</sup>European Institute of Oncology, Milan, France</italic></p><p><bold>INTRODUCTION:</bold> The intestinal microbiota is a complex community, which exerts functions often associated with beneficial effects for its host, including contribution to mucosal homeostasis and maturation of the immune system. The microbiota complexity associated to the inability to culture the vast majority of these microbes lead to the development of new and powerful approaches namely metagenomics.</p><p><bold>AIMS&METHODS:</bold> To study the interactions between intestinal epithelial cells (IECs) and commensal bacteria, a high throughput cell-based functional metagenomic approach was established (Lakhdari <italic>et al.</italic>, PLoS one, 2010).</p><p>Stably transfected human IECs bearing the luciferase reporter gene under the control of promoter of key genes or binding element of key signaling pathways (NF-κB, PPARγ, AP1) were obtained and used to screen metagenomic libraries bearing large DNA fragments (∼40 kb) derived from human fecal microbiota. To do so, a high throughput screening (HTS) platform was established.</p><p><bold>RESULTS:</bold> HTS led to the identification of bioactive metagenomic clones modulating key pathways in IEC. Sequencing, annotation and transposon mutagenesis allowed the identification of putative genes implicated. For one stimulatory clones derived from a <italic>Bacteroides</italic>-related strain, we identified 2 loci involved in the NF-κB stimulatory effect. Another clone, derived from a Firmicutes, was selected for its stimulation of NF-κB, AP1 and TSLP reporter systems. It also stimulated IL-8 expression and secretion. Biochemical characterization indicated that a small heat resistant compound was secreted and transposon mutagenesis in an ABC transporter system abolished this effect. In a co-culture system, this clone indirectly activated dendritic cells through IEC stimulation and further modulated T cell activity. Furthermore, in a new ex-vivo set up of human organ culture (Tsilingiri <italic>et al</italic>. Gut, 2012), it protected the intestinal mucosa from the destructive effect of a <italic>Salmonella</italic> strain. Finally, this clone displayed a protective effect in a preventive set up DSS colitis model.</p><p><bold>CONCLUSION:</bold> Our Functional Metagenomic approach allowed the identification of new bacterial genes involved in the cross-talk with gut epithelium.</p><p><bold>REFERENCES:</bold></p><p>1. Lakhdari O, Cultrone A, Tap J, Gloux K, Bernard F, Ehrlich SD, Lefèvre F, Doré J, Blottière HM. Functional metagenomics: a high throughput screening method to decipher microbiota-driven NF-κB modulation in the human gut. PLoS One. 2010; 5: e13092.</p><p>2. Tsilingiri K, Barbosa T, Penna G, Caprioli F, Sonzogni A, Viale G, Rescigno M.Probiotic and postbiotic activity in health and disease: comparison on a novel polarised ex-vivo organ culture model. Gut. 2012; 61:1007-15.</p><p><bold>Contact E-mail Address:</bold><email>herve.blottiere@jouy.inra.fr</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> inflamatory pathways, metagenomic, microbial findings, Microbiota, NF-kappaB</p></sec><sec><title></title><p><bold>MONDAY, OCTOBER 14, 2013 14:00-15:30</bold></p><p><bold>Aids to improving endoscopic practice – Salon 11/12</bold></p></sec><sec><title>OP104 TABLET COMPUTER BASED MULTIMEDIA ENHANCED MEDICAL TRAINING IMPROVES PERFORMANCE IN BOARD EXAMS COMPARED WITH TRADITIONAL MEDICAL EDUCATION – RESULTS FROM A PROSPECTIVE, RANDOMIZED, CONTROLLED TRIAL</title><p><bold>I. Wende</bold><sup>1</sup>, D. C. Baumgart<sup>1,*</sup></p><p><italic><sup>1</sup>Department of Medicine, Division of Gastroenterology and Hepatology, Charité Medical Center - Medical School of the Humboldt-University of Berlin, Berlin, Germany</italic></p><p><bold>INTRODUCTION:</bold> Traditional teaching concepts in medical education do not take full advantage of information technology, despite the fact that modern gastroenterology and endoscopy are packed with digital media resources. Although the use of mobile communication devices by health care professionals has dramatically increased, scientific data on their impact on endoscopy education and training is very limited.</p><p><bold>AIMS&METHODS:</bold> Eighty participants were recruited, phenotyped and randomized to either the tablet or controls groups, respectively. The test group could take advantage of their tablet computer based resources (i.e. eBooks, eJournals, digital animations and videos, access to online course management system (Moodle), educational software programs and podcasts from leading medical publishers including the AGA Institute, ASGE and ACP), while the control group had access to all conventional resources (i.e. library, books, journals) for the entire duration their four month rotation. Their performance was statistically analyzed and compared by administration of random generator selected, thematically equally distributed questions from the Gastrointestinal Endoscopy Self-Assessment Program GESAP® (n=200) at the beginning and the end of their rotation. The potential impact of confounding variables on test scores and correlation between self-rated and objectively assessed knowledge was investigated.</p><p><bold>RESULTS:</bold> Data of 55 participants (female n= 35; tablet n=24, controls, n=31, median age 28 years) were evaluable. At the beginning and the end oft hier rotation the following median GESAP® scores were recorded: tablet group (38.10 vs. 52.25) control group (38.1020 vs. 35.64). The Wilcoxon signed rank test demonstrated a highly significant score difference median (positive delta) for the tablet (Δ 12.85; p = 0.0001, CI 95%) but not the control group (Δ -1.13; p = 0.146, CI 95%).</p><p><bold>CONCLUSION:</bold> Tablet based multimedia enhanced training is a promising concept for gastroenterology trainming programs.</p><p>Lancet. 2005 Oct 1;366(9492):1210-22</p><p>Arch Intern Med. 2011 Jul 25;171(14):1294-6</p><p><ext-link ext-link-type="uri" xlink:href="http://www.danielbaumgart.de">http://www.danielbaumgart.de</ext-link></p><p><bold>Contact E-mail Address:</bold><email>daniel.baumgart@charite.de</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> computer, education, endoscopy, exam, tablet, training</p></sec><sec><title>OP105 OPTIMIZATION OF UPPER GASTROINTESTINAL ENDOSCOPY: VALUE OF REAL-TIME GASTRIC JUICE ANALYSIS</title><p><bold>A. Ummarino</bold><sup>1</sup>, F. A. Tucci<sup>1</sup>, G. Pezzicoli<sup>1,*</sup>, D. Parigino<sup>1</sup>, A. P. Di Virgilio<sup>1</sup>, P. Tucci<sup>2</sup>, M. Rugge<sup>3</sup>, A. Tucci<sup>1,4</sup>, A. Andriulli<sup>4</sup></p><p><italic><sup>1</sup>Etromapmacs Pole, Biomedical Sciences School, Lesina (FG), <sup>2</sup>Electronics, Computer Engineering and Systems, University of Bologna, Bologna, <sup>3</sup>Pathology, University of Padova, Padova , <sup>4</sup>Division of Gastroenterology, Casa Sollievo Sofferenza Hospital, IRCCS, San Giovanni R. (FG), Italy</italic></p><p><bold>INTRODUCTION:</bold> Conventional EGDS cannot identify microscopic lesions.</p><p><bold>AIMS&METHODS:</bold> Aim of this study was to determine the diagnostic contribution of a novel and automated method for real-time gastric juice analysis during EGDS.</p><p>Endoscopy, histology and real-time gastric juice analysis (pH, ammonium) were performed in 216 patients. We assessed the following diagnostic strategies: EGDS alone (strategy 1), EGDS with two antral biopsies [hematoxylin-eosin (H-E) staining] in hypochlorhydric patients (strategy 2) or all patients (strategy 3), EGDS with two antral and two fundic biopsies (H-E staining) in hypochlorhydric patients (strategy 4) or all patients (strategy 5) and EGDS with two antral and two fundic biopsies (H-E and immunohistochemical staining) in hypochlorhydric patients (strategy 6). We determined how many of the pathological conditions identified by the complete histological evaluation would have been detected by each strategy.</p><p><bold>RESULTS:</bold> In total, 220 pathological conditions were identified. Hypochlorhydria was strongly correlated (r = 0.67; p < 0.01) with histological lesions (85% lesions were detected in hypochlorhydric patients) and high ammonium levels, with <italic>Helicobacter pylori</italic> infection (r = 0.69; p < 0.01). Strategy 1 (EGDS alone) identified 5% conditions, while strategies 3 and 5 (biopsies in all patients) detected 68.6% and 83.2% conditions, respectively. Strategies 2, 4 and 6 (based on gastric juice analysis) yielded detection rates (61.4%, 75.5% and 90.9%, respectively) similar to or better than those of strategies 3 and 5.
<table-wrap id="table15-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1">Pathological conditions</th><th rowspan="1" colspan="1">Strategy 1</th><th rowspan="1" colspan="1">Strategy 2</th><th rowspan="1" colspan="1">Strategy 3</th><th rowspan="1" colspan="1">Strategy 4</th><th rowspan="1" colspan="1">Strategy 5</th><th rowspan="1" colspan="1">Strategy 6</th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">Antral glandular atrophy</td><td rowspan="1" colspan="1">4/19 21.1%</td><td rowspan="1" colspan="1">11/19 57.9%</td><td rowspan="1" colspan="1">19/19 100%</td><td rowspan="1" colspan="1">11/19 57.9%</td><td rowspan="1" colspan="1">19/19 100%</td><td rowspan="1" colspan="1">11/19 57.9%</td></tr><tr><td rowspan="1" colspan="1">Oxyntic glandular atrophy</td><td rowspan="1" colspan="1">4/25 16%</td><td rowspan="1" colspan="1">4/25 16%</td><td rowspan="1" colspan="1">4/25 16%</td><td rowspan="1" colspan="1">24/25 96%</td><td rowspan="1" colspan="1">25/25 100%</td><td rowspan="1" colspan="1">24/25 96%</td></tr><tr><td rowspan="1" colspan="1">Antral intestinal metaplasia</td><td rowspan="1" colspan="1">0/20 0%</td><td rowspan="1" colspan="1">15/20 75%</td><td rowspan="1" colspan="1">20/20 100%</td><td rowspan="1" colspan="1">15/20 75%</td><td rowspan="1" colspan="1">20/20 100%</td><td rowspan="1" colspan="1">15/20 75%</td></tr><tr><td rowspan="1" colspan="1">Oxyntic intestinal metaplasia</td><td rowspan="1" colspan="1">0/9 0%</td><td rowspan="1" colspan="1">0/9 0%</td><td rowspan="1" colspan="1">0/9 0%</td><td rowspan="1" colspan="1">9/9 100%</td><td rowspan="1" colspan="1">9/9 100%</td><td rowspan="1" colspan="1">9/9 100%</td></tr><tr><td rowspan="1" colspan="1">Other</td><td rowspan="1" colspan="1">3/3 100%</td><td rowspan="1" colspan="1">3/3 100%</td><td rowspan="1" colspan="1">3/3 100%</td><td rowspan="1" colspan="1">3/3 100%</td><td rowspan="1" colspan="1">3/3 100%</td><td rowspan="1" colspan="1">3/3 100%</td></tr><tr><td rowspan="1" colspan="1">Antral G cell hyperplasia</td><td rowspan="1" colspan="1">0/17 0%</td><td rowspan="1" colspan="1">0/17 0%</td><td rowspan="1" colspan="1">0/17 0%</td><td rowspan="1" colspan="1">0/17 0%</td><td rowspan="1" colspan="1">0/17 0%</td><td rowspan="1" colspan="1">15/17 88.2%</td></tr><tr><td rowspan="1" colspan="1">ECL cell hyperplasia</td><td rowspan="1" colspan="1">0/20 0%</td><td rowspan="1" colspan="1">0/20 0%</td><td rowspan="1" colspan="1">0/20 0%</td><td rowspan="1" colspan="1">0/20 0%</td><td rowspan="1" colspan="1">0/20 0%</td><td rowspan="1" colspan="1">19/20 95%</td></tr><tr><td rowspan="1" colspan="1">Helicobacter pylori colonization</td><td rowspan="1" colspan="1">0/107 0%</td><td rowspan="1" colspan="1">102/107 95.3%</td><td rowspan="1" colspan="1">105/107 98.1%</td><td rowspan="1" colspan="1">104/107 97.2%</td><td rowspan="1" colspan="1">107/107 100%</td><td rowspan="1" colspan="1">104/107 97.2%</td></tr><tr><td rowspan="1" colspan="1"><bold>Total pathological conditions</bold></td><td rowspan="1" colspan="1">11/220 5%</td><td rowspan="1" colspan="1">135/220 61.4% °</td><td rowspan="1" colspan="1">151/220 68.6% °</td><td rowspan="1" colspan="1">166/220 75.5% §</td><td rowspan="1" colspan="1">183/220 83.2% #</td><td rowspan="1" colspan="1">200/220 90.9% *</td></tr></tbody></table></table-wrap></p><p><bold>CONCLUSION:</bold> Real-time gastric juice analysis provided information about the presence of gastric lesions in an otherwise “normal” stomach at EGDS. It improved the diagnostic yield and optimized resource utilization without any additional effort by the endoscopist.</p><p><bold>Contact E-mail Address:</bold><email>atucci@scienzebiomediche.it</email></p><p><bold>Disclosure of Interest</bold>: A. Ummarino: None Declared, F. A. Tucci: None Declared, G. Pezzicoli: None Declared, D. Parigino: None Declared, A. P. Di Virgilio: None Declared, P. Tucci: None Declared, M. Rugge: None Declared, A. Tucci Other: He is the inventor and patent owner of the Endofaster 21-42, A. Andriulli: None Declared</p><p><bold>Keywords:</bold> Atrophic gastritis, Endocrine cells hyperplasia, Gastric juice, Helicobacter pylori, Hypochlorhydria, pH-monitoring</p></sec><sec><title>OP106 DEVELOPMENT OF A PORCINE MODEL OF EARLY CHRONIC PANCREATITIS FOR EUS EXAMINATION: A PILOT STUDY.</title><p><bold>A. Irisawa</bold><sup>1,*</sup>, T. Ikeda<sup>2</sup>, T. Takagi<sup>2</sup>, G. Shibukawa<sup>1</sup>, R. Suzuki<sup>2</sup>, H. Ohira<sup>2</sup></p><p><italic><sup>1</sup>Gastroenterology, Fukushima Medical University Aizu Medical Center, Aizuwakamatsu, <sup>2</sup>Gastroenterology and Rheumatology, Fukushima Medical University School of Medicine, Fukushima, Japan</italic></p><p><bold>INTRODUCTION:</bold> Endoscopic ultrasonography (EUS) is a well-established and less-invasive modality for chronic pancreatitis (CP) diagnosis. In2009, the Japan Pancreas Society proposed the new diagnostic criteria for early CP. In this criteria, the characteristic imaging for early CP were set as the following EUS features; lobularity, hyperechoic foci without shadowing, stranding, cysts, dilated side branches, and hyperechoic ductal margin. Although several researchers have investigated whether EUS features of definite CP are correlated with histology, it is difficult to assess in early CP due to the difficulty in obtaining pancreatic tissue of early CP for histology in humans.</p><p><bold>AIMS&METHODS:</bold> The aim of this study is to develop an animal model of early CP for evaluation of the correlation between EUS and histology. Five miniature pigs weight 20kg were used in this study (1 in normal control, 4 in treatment for early CP). For developing an animal model of early CP, a guide wire was passed into the pancreatic duct and a 5-Fr pancreatic stent was introduced over the wire into the pancreatic duct at laparotomy, according to previous report (1). The end of the stent, which protruded the duodenum, was sutured onto the inner wall of the duodenum. The observation period was set at 28 days. EUS examination (GF-UCT260 and GF-UE260, Olympus Medical Systems Corp., Tokyo, Japan) was performed under anesthesia to image the whole pancreas through the gastric wall before and 28 days after the placement of a pancreatic stent, and then followed by euthanasia. The pancreatic sections were taken from the location where was visualized by EUS, and histologically evaluated.</p><p><bold>RESULTS:</bold> The histopathological examination suggests that the pancreatic duct stent insertion caused pancreatic disorders, as mild to severe acinar atrophy, slight cellular infiltration, and slight fibrosis. At baseline EUS, the pancreas appeared homogeneous with only a few hyperechoic foci and strands, and there were no lobularity in the parenchyma. At 28 days poststenting, EUS images showed the following changes: hyperechoic foci and strands, lobularity, hyperechoic ductal margin, and inhomogeneous parenchymal echo. A normal control had no remarkable changes in EUS findings before and after stenting.</p><p><bold>CONCLUSION:</bold> Our experimental results have indicated that the porcine model of early CP developed by the placement of the pancreatic stent is useful for studying the correlation between EUS and histology.</p><p><bold>REFERENCES:</bold></p><p>1. Bhhutani et al. Endoscopy. 2009;41:352-6.</p><p><bold>Contact E-mail Address:</bold><email>irisawa@fmu.ac.jp</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> early chronic pancreatitis, EUS, porcine model</p></sec><sec><title>OP107 PREDICTIVE FACTORS FOR PAIN RELIEF AFTER ENDOSCOPIC ULTRASOUND-GUIDED UPPER PLEXUS NEUROLYSIS</title><p><bold>H. Sakamoto</bold><sup>1,*</sup>, M. Kitano<sup>1</sup>, M. Kudo<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterolgy and Hepatology, Kinki University Faculty of Medicine, osakasayama, Japan</italic></p><p><bold>INTRODUCTION:</bold> Endoscopic ultrasound-guided Celiac plexus neurolysis(EUS-CPN)<sup>1)</sup>is an established treatment for upper abdominal cancer pain. Recently, two alternative techniques, EUS-guided celiac ganglia neurolysis(CGN)<sup> 2)</sup>and EUS-guided broad plexus neurolysis(BPN)<sup>3)</sup> for abdominal pain management have been reported. However, these procedures are not always efficacious. We determined the predictive factors for response to these EUS upper abdominal neurolysis.</p><p><bold>AIMS&METHODS:</bold> In a retrospective analysis of prospective database, a EUS database tracking patients and complications at Kinki University hospital, data for consecutive 134 patients (CPN 54, BPN 33, CGN 5,CPN+CGN 11,BPN+CGN 31) between April 2003 and March 2013. To evaluate the neurolytic spread, contrast was mixed with the neurolytic agent and post-procedure computed tomography scanning was performed and neurolytic spread area were divided into six areas. Pain intensity was measured according to a standardized visual 11-pointed continuous analog scale (VAS). If the VAS scores dropped by more than 3 points after the procedures, this was judged to reflect good pain relief. The efficacy in pain relief was evaluated based on the pain score at day 7 after procedure.</p><p><bold>RESULTS:</bold> RESULTS: Pain relief was obtained in 108 patients (81%). Narcotic using dose (≦60mg/day), tumor size (≦30mm), and neurolytic spread area (≦3 areas) were significant factors for a negative response to EUS-upper abdominal neurolysis.</p><p><bold>CONCLUSION:</bold> This study revealed Narcotic using dose, tumor size, and neurolytic spread area were predict factors for pain relief after EUS-upper abdominal neurolysis. The results suggest upper abdominal neurolysis for the management to cancer pain should be considered earlier in the disease.</p><p><bold>REFERENCES:</bold></p><p>1. Sakamoto H, Kitano M, Kudo M, et al.Endoscopic ultrasounded neurolysis in pancreatic cancer. Pancreatology 2011;2:52-8.</p><p>2. Levy MJ, Topazian MD, Wiersema MJ, et al.Initial evaluation of the efficacy and safety of endoscopic ultrasound-guided direct Ganglia neurolysis and block. Am J Gastroenterol 2008;103:98-103.</p><p>3. Sakamoto H, Kitano M, Kudo M, et al. EUS guided plexus neurolysis over the superior mesenteric artery using a 25 gauge needle. Am J Gastroenterol 2010;105:2599-606.</p><p><bold>Contact E-mail Address:</bold><email>hirokizzzz88@yahoo.co.jp</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> EUS., EUS-CPN, Pancreatic Cancer</p></sec><sec><title>OP108 LOOKING FOR AN IDEAL INDICATOR OF QUALITY OF COLONOSCOPY - THE HISTOLOGICALLY COMPLETE POLYPECTOMY RATE (HCPR) IS EASY AND PRECISE</title><p><bold>M. Benes</bold><sup>1,*</sup>, P. Drastich<sup>1</sup>, P. Stirand<sup>1</sup>, T. Hucl<sup>1</sup>, P. Wohl<sup>1</sup>, J. Spicak<sup>1</sup></p><p><italic><sup>1</sup>Hepatology and Gastroenterology, Institute of Clinical and Experimental Medicine, Prague, Czech Republic</italic></p><p><bold>INTRODUCTION:</bold> Caecum intubation rate (CR) and adenoma detection rate (ADR) are historically the most commonly used indicators of quality of colonoscopy. More complex and precise criteria such as histologtically complete endoscopic mucosal resection rate (HCEMR) have been used nowadays. However, HCEMR is no applicable to most colonoscopies where polyps are removed by polypectomy.</p><p><bold>AIMS&METHODS:</bold> The aim of our study was to evaluate and compare various indicators of quality of colonoscopy in a retrospective analysis of all colonoscopies performed in one center between 2009 and 2012. All colonoscopies were performed by 6 experts, each of them performing at least 250 colonoscopies/year and more than 1000 colonoscopies in their carrier. The data were statistically evaluated using correlation tests (Spearman’s coefficient).</p><p><bold>RESULTS:</bold> Altogether, we evaluated 3852 consecutive colonoscopies The mean caecum intubation rate (CR) was 97% (range 93% - 98%), the mean terminal ileum intubation rate was 90% (range 87% - 93%), the mean adenoma detection rate (ADR) was 33% (range 21% - 42%), the mean colorectal cancer detection rate was 4% (range 3% - 5%), the rate of flat lesion detection was 8% (range 5% - 11%). In total 342 EMR were carried out in 325 patients. The percentage of histologically complete EMR (complete removal of lesion with histologically proven margin free of neoplasia, HCEMR) of significant polyps and flat lesions was 42% (21%>63%). The mean percentage of complications after EMR was 2% (range 1% - 3%). In total 1351 polypecomies of significant polyps (greater than 1cm) were carried out. The mean histologically complete polypectomy rate (HCPR) of significant polyps was 51% (range 32% - 69%). The HCPR significantly correlated with ADR, CR and HCEMR.</p><p><bold>CONCLUSION:</bold> Histologically complete polypectomy rate (HCPR) appears to be completely comparable with histologically complete EMR rate (HCEMR) and could an ideal indicator of quality of colonoscopy.</p><p><bold>Contact E-mail Address:</bold><email>mabx@ikem.cz</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> colon cancer, Quality of colonoscopy, Screening colonoscopy </p></sec><sec><title>OP109 USEFULNESS OF THE NEW EQUIPMENT “CONTINUOUS SUCTION MOUTHPIECE” DURING PERCUTANEOUS ENDOSCOPIC GASTROSTOMY</title><p><bold>T. Maekita</bold><sup>1,*</sup>, J. Kato<sup>1</sup>, Y. Nakatani<sup>2</sup>, S. Enomoto<sup>1</sup>, T. Nakaya<sup>2</sup>, Y. Maeda<sup>1</sup>, K. Moribata<sup>1</sup>, Y. Muraki<sup>1</sup>, H. Deguchi<sup>1</sup> T. Niwa I <sup>1</sup>, Inoue<sup>1</sup>, M. Iguchi<sup>1</sup>, H. Tamai<sup>1</sup>, M. Ichinose<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology, School of Medicine, Wakayama Medical University, <sup>2</sup>Internal Medicine, Nakaya Hospital, Wakayama City , Japan</italic></p><p><bold>INTRODUCTION:</bold> Percutaneous endoscopic gastrostomy (PEG) is important as a route for administering enteral nutrition. Salivary flow is often difficult to control during PEG, and therefore, there appears to be considerable risk of aspiration, because PEG is performed in elderly patients with dysphagia at the supine position. However, no mouthpiece has been designed for the purpose of prevention of aspiration.</p><p><bold>AIMS&METHODS:</bold> We made a new continuous suction mouthpiece (CSM) to prevent aspiration and evaluated the usefulness of the equipment in PEG. This is a single center, prospective, randomized, controlled study. The CSM was developed with the following procedures. After cutting the junction part of a suction tube, the tube was bent double, and each part was connected with two movable short bands. The three parts divided by the short bands were made into:a changeable loop intraoral part with 6 holes for suction; a binding loop part to fit any mouthpieces; and an extraoral part to connect the suction unit continuously performed at low pressure. Seventy-two patients who underwent or exchanged PEG were assigned to each of the groups: the group using the CSM and the group using the conventional mouthpiece. Aspiration during and after the procedure, and extent of salivary flow, frequency of saliva suction and number of choking episodes during the procedure were evaluated and compared with two groups. The extent of salivary flow was defined from grade 1; "no flow out of the mouth", to grade 4, "flow extending to the hair or clothing". When a rumbling sound was heard, an assistant suctioned using the suction catheter. Choking episodes were counted each time they occurred during the procedure.</p><p><bold>RESULTS:</bold> There were no significant differences between the two groups in gender, age, procedure type, duration of procedure, depth of sedation, and indication for PEG. Aspiration and other significant adverse events were not observed in either group. The grade of salivary flow was significantly lower (<italic>P</italic> < 0.001) in patients with the CSM than in patients with the conventional mouthpiece. Suctions and choking episodes were significantly less frequent (<italic>P</italic> = 0.013 and <italic>P</italic> = 0.015) in patients with the CSM than in patients with the conventional mouthpiece.</p><p><bold>CONCLUSION:</bold> We developed a new equipment “CSM“. The CSM could reduce the extent of salivary flow, frequency of suctions and choking episodes in PEG-related procedures. This equipment is also expected to reduce complications in other types of endoscopic procedures.</p><p><bold>Contact E-mail Address:</bold><email>maekita@wakayama-med.ac.jp</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> aspiration, mouthpiece, percutaneous endoscopic gastrostomy</p></sec><sec><title></title><p><bold>MONDAY, OCTOBER 14, 2013 15:45-17:15</bold></p><p><bold>Clinical challenges in the anorectal region – Hall 3</bold></p></sec><sec><title>OP110 THE INFLUENCE OF SOMATISATION AND HEALTH LOCUS OF CONTROL IN PATIENTS UNDERGOING SACRAL NERVE STIMULATION FOR FAECAL INCONTINENCE</title><p><bold>A. Alam</bold><sup>1,*</sup>, M. Abdel-Halim<sup>2</sup>, R. Cohen<sup>3</sup>, A. Emmanuel<sup>1</sup>, S. Chapman<sup>4</sup>, R. Horne<sup>4</sup></p><p><italic><sup>1</sup>Gastroenterology, University College London, <sup>2</sup>Gastroenterology, <sup>3</sup>General Surgery, University College London Hospital, <sup>4</sup>Centre of Behavioural Medicine, University College London, London, United Kingdom</italic></p><p><bold>INTRODUCTION:</bold> Faecal incontinence is a disabling condition affecting between 2.2-25.5% of the population. Failing conservative treatment, including maximum medical management and bio-feedback, neuro-modulation in the form of sacral nerve stimulation (SNS) is now a well established treatment option for these patients. Although SNS is effective it is not successful in all patients. It is not clear whether a patient’s psychological status has any influence on the outcome with sacral nerve stimulation. We used the multi-dimensional health locus of control to assess whether patient’s health beliefs influence patient outcome following treatment with SNS for faecal incontinence. We also used the 15 point patient health questionnaire (PHQ-15) to assess whether somatisation in patients undergoing SNS for faecal incontinence had an influence on their outcome.</p><p><bold>AIMS&METHODS:</bold> A total of 34 patients were suitable for SNS following investigations and having failed conservative treatment. One patient who was offered SNS declined surgery and was thus not included in the study. Failure at any stage of treatment was defined as less than 50% improvement in the wexner score from baseline</p><p><bold>RESULTS:</bold> There was a significant negative correlation between the somatisation score and the improvement in wexner score following temporary SNS implant and at 12 months following permanent SNS implant (correlation coefficient -0.40 p=0.02 & -0.56 p=0.006).There was also a significant positive correlation between the chance health locus of control and the improvement in wexner score following temporary SNS implant and at 12 months following the permanent implant (correlation coefficient 0.42 p=0.01 & 0.43 p=0.04). Regression analysis confirmed the negative relation between somatisation and outcome at the temporary SNS (β -0.395 p=0.042) and 12 month (β -0.698 p=0.015) following permanent SNS stages and showed a negative relation of the internal health locus of control and outcome following temporary SNS (β -0.400 p=0.018).</p><p><bold>CONCLUSION:</bold> A higher somatisation score has a negative influence on patient outcome following sacral nerve stimulation for faecal incontinence. Having a higher chance health locus of control appears to have a positive influence on patient outcome with sacral nerve stimulation following the temporary and permanent SNS implant with a surprising negative impact of internal locus of control at the temporary SNS stage. The approach to managing these patients should therefore be a multidisciplinary one</p><p><bold>REFERENCES:</bold></p><p>1. Norton C, Whitehead WE, Bliss DZ, Harari D, Lang J. Management of fecal incontinence in adults. Neurourol Urodyn 2010;29(1):199-206.</p><p><bold>Contact E-mail Address:</bold><email>ahsan_alam1@yahoo.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> fecal incontinence, psychological comorbidity, Sacral nerve stimulation</p></sec><sec><title>OP111 LEVATOR ANI TENDERNESS IN PATIENTS WITH DYSSYNERGIC DEFECATION</title><p><bold>G. Chiarioni</bold><sup>1,2,*</sup>, S. Heymen<sup>2</sup>, S. M. Kim<sup>2</sup>, I. Vantini<sup>3</sup>, W. E. Whitehead<sup>2</sup></p><p><italic><sup>1</sup>Gastroenterology, Azienda Ospedaliera Universitaria Integrata di Verona, Verona, Italy, <sup>2</sup>UNC Center for Functional GI & Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States, <sup>3</sup>Division of Gastroenterology, University of Verona, Verona, Italy</italic></p><p><bold>INTRODUCTION:</bold> Recently we reported the surprising finding that patients with levator ani syndrome share many pathophysiologic features with dyssynergic defecation (DD): Among 94 patients with a primary complaint of chronic proctalgia who had tenderness on digital rectal exam, 86%% exhibited paradoxical contraction of pelvic floor muscle when straining to defecate and 87% could not evacuate a 50-ml water-filled balloon. Moreover, improvement in these parameters was associated with reductions in rectal pain.</p><p><bold>AIMS&METHODS:</bold> To further explore the hypothesis of shared pathophysiology by determining whether patients with DD report tenderness when traction is applied to the levator ani muscles. <bold>Methods</bold>: 242 patients with chronic constipation referred to an ambulatory GI practice in Verona, Italy, were evaluated by physical examination including palpation of the levator muscles by standard protocol, questionnaire, balloon evacuation test (BET), and (if they failed to respond to fiber treatment) by anorectal manometry (ARM). Patients were diagnosed DD if they failed to relax anal canal pressures and anal EMG on ARM and also failed to evacuate a 50-ml water filled balloon within 2 minutes. The last 148 of 242 referrals had a second physical exam by an independent physician to assess reliability of tenderness assessment.</p><p><bold>RESULTS:</bold> Three subjects were excluded for technical reasons and 41 due to a positive response to fiber supplements, leaving 198 for analysis. Average age was 45 years and 94% were female. Constipation type was DD in 44.4%, normal transit (NT) in 28%, slow transit (ST) in 11%, and outlet obstruction in 14.1%; 5 had dyssynergia on manometry but normal BET. Tenderness on digital rectal exam was reported by 87/198 patients (43.9%). 71.2% of DD reported tenderness compared to 23.4% of patients with other types of constipation (p<.001). 73.6% of patients reporting tenderness also reported that they had pain with 25% or more of their defecations vs. 15.3% for those without tenderness (p<.001) . Patients reporting tenderness were also younger (41.8 vs. 47.6 years, p=.007). Two independent physician examiners agreed on the assessment of tenderness in 93.5% of cases.</p><p><bold>CONCLUSION:</bold> These data provide further support that the pathophysiology of DD is similar to that of levator ani syndrome because 71.2% of patients with DD report tenderness on palpation of the levator ani muscles and 73.6% of those with tenderness during digital rectal exam report pain during defecation. Assessment of levator ani tenderness is reliable (93.5% agreement). [Supported in part by R01 DK31369]</p><p><bold>REFERENCES:</bold></p><p>1. Chiarioni G, Nardo A, Vantini I, et al. Biofeedback is superior to electrogalvanic stimulation and massage for treatment of levator ani syndrome. Gastroenterology. 2010;138(4):1321-1329</p><p><bold>Contact E-mail Address:</bold><email>chiarioni@tin.it</email></p><p><bold>Disclosure of Interest</bold>: G. Chiarioni : No COI to be declared, S. Heymen : No COI to be declared, S. Kim : No COI to be declared, I. Vantini : No COI to be declared, W. Whitehead : No COI to be declared</p><p><bold>Keywords:</bold> chronic proctalgia, constipation, dyschezia</p></sec><sec><title></title><p><bold>MONDAY, OCTOBER 14, 2013 15:45-17:15</bold></p><p><bold>Long-term outcomes in IBD – Hall Prague</bold></p></sec><sec><title>OP112 FACTORS ASSOCIATED WITH DURABLE RESPONSE TO INFLIXIMAB 5 YEARS AND BEYOND: A MULTI CENTER INTERNATIONAL COHORT</title><p><bold>P. Juillerat</bold><sup>1,2,*</sup> H. Sokol V <sup>3</sup>, Yajnik<sup>2</sup>, F. Froehlich<sup>4</sup>, L. Beaugerie<sup>3</sup>, J. Cosnes<sup>3</sup>, B. Burnand<sup>5</sup>, A. Macpherson<sup>1</sup>, J. R. Korzenik<sup>2</sup></p><p><italic><sup>1</sup>University Clinic for Visceral Surgery and Medicine, Gastroenterology, Bern University Hospital, Bern, Switzerland, <sup>2</sup>Medicine / GI Unit, Massachusetts General Hospital, Boston, United States, <sup>3</sup>Gastroenterology, Saint Antoine Hospital, Paris, France, <sup>4</sup>Gastroenterology, Basle University Hospital, Basle, <sup>5</sup>Institute of Social & Preventive Medicine, Lausanne University Hospital, Lausanne, Switzerland</italic></p><p><bold>INTRODUCTION:</bold> Infliximab (IFX) have been used for about a decade worldwide, but initially not as maintenance regimen for Crohn’s disease. Therefore, little is known about the clinical characteristics of the patients who become long term treated.</p><p><bold>AIMS&METHODS:</bold> To perform a descriptive analysis of Crohn’s disease (CD) patients who received infliximab longterm in 3 different countries and to develop prognostic factors for successful long term use of IFX (LTUI).</p><p><bold>RESULTS:</bold> We collected data on 348 CD patients (57% female), of whom 111 were identified as LTUI. In the comparison group were 138 CD patients (27 primary non responders (PNR), 39 los of response (LOR) and 72 adverse events (AE)) included. Among LTUI, disease extension was 14% ileum, 30% colon, 56% ileocolonic. Additional locations were 6 % upper GI and 52% perianal. Penetrating disease behavior associated with perianal lesions (Montreal classification B3+P) was significantly higher in the LTUI (34% vs 22 %; p=0.04). Higher levels of education were observed in LTUI. Among the PNR and AE groups, the prevalence of active smokers was 15% in twice as frequent as among LTUI (p=0.04) and more people were older than 40 years (p=0.02). Thirty-five percent of LTUI required dose escalation to 10 mg/kg (vs 20% in comparison groups, p=0.1). Concomitant thiopurines were administered in a numerically but not statistically significant higher proportion in LTUI (30% vs 20%, p=0.2) whereas comparison groups included more patients with previous thiopurines AE (31% vs 20%, p=0.5).
<table-wrap id="table16-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1"></th><th rowspan="1" colspan="1"><bold>LTUI (N=250)</bold></th><th rowspan="1" colspan="1"><bold>PNR/LOR/AE (N=290)</bold></th><th rowspan="1" colspan="1"><bold>p value </bold></th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">Gender (female) </td><td rowspan="1" colspan="1">55% </td><td rowspan="1" colspan="1">58% </td><td rowspan="1" colspan="1"> 0.5</td></tr><tr><td rowspan="1" colspan="1">Age (yrs +/-SD) </td><td rowspan="1" colspan="1">41.5 (+/-13) </td><td rowspan="1" colspan="1">44 (+/- 14) </td><td rowspan="1" colspan="1"> 0.05</td></tr><tr><td rowspan="1" colspan="1">Location (Montreal) L1 / L2 / L3 / L4</td><td rowspan="1" colspan="1">16% / 35% / 42% / 7% </td><td rowspan="1" colspan="1">26% / 21% / 45% / 8% </td><td rowspan="1" colspan="1">0.01 </td></tr><tr><td rowspan="1" colspan="1">Behavior (Montreal) B1 / B2 / B3 B1+P / B2+P / B3+P </td><td rowspan="1" colspan="1">20% / 17% / 10% 5% / 3% / 46% </td><td rowspan="1" colspan="1">22% / 26% / 16% 5% / 4% / 29% </td><td rowspan="1" colspan="1">0.001 </td></tr><tr><td rowspan="1" colspan="1">Perianal disease</td><td rowspan="1" colspan="1">54% </td><td rowspan="1" colspan="1">37% </td><td rowspan="1" colspan="1"><0.001 </td></tr><tr><td rowspan="1" colspan="1">IFX duration (mo +/-SD) </td><td rowspan="1" colspan="1">77.2 (+/- 27) </td><td rowspan="1" colspan="1">8 (+/- 12) </td><td rowspan="1" colspan="1"><0.001 </td></tr><tr><td rowspan="1" colspan="1">Age start IFX (yrs +/-SD) </td><td rowspan="1" colspan="1">33.1 (+/- 13) </td><td rowspan="1" colspan="1">38.2 (+/- 14) </td><td rowspan="1" colspan="1"><0.001 </td></tr><tr><td rowspan="1" colspan="1">Dose escalation rate </td><td rowspan="1" colspan="1">31% </td><td rowspan="1" colspan="1">20% </td><td rowspan="1" colspan="1">0.09 </td></tr><tr><td rowspan="1" colspan="1">Surg. resections</td><td rowspan="1" colspan="1">48%</td><td rowspan="1" colspan="1">60%</td><td rowspan="1" colspan="1">0.03</td></tr></tbody></table></table-wrap></p><p><bold>CONCLUSION:</bold> A shorter duration of disease at time of first infusion and concomitant immunosuppressants seems to be good prognostic factors of long term success of IFX therapy. Age and smoking are associated with PNR and increased adverse events. These results need to be interpreted cautiously due to potential confounding by indication. Hence, patients with a high level of education, perianal and penetrating disease have higher rates of long term infliximab use.</p><p><bold>Contact E-mail Address:</bold><email>pascal.juillerat@insel.ch</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> ANTI-TNF-ALPHA THERAPY, Clinical Epidemiology, Crohn’s disease, Inflammatory bowel disease (IBD), infliximab, treatment </p></sec><sec><title>OP113 OCCURRENCE OF STRICTURING AND PENETRATING COMPLICATIONS IS DIMINISHED IN CROHN’S DISEASE PATIENTS TREATED BY IMMUNOMODULATORY AND/OR ANTI-TNF THERAPY WITHIN THE FIRST TWO YEARS OF DISEASE DURATION WHEN CORRECTED FOR DIAGNOSTIC DELAY</title><p><bold>E. Safroneeva</bold><sup>1,*</sup>, S. Vavricka<sup>2</sup>, N. Fournier<sup>3</sup>, G. Rogler<sup>2</sup>, A. Straumann<sup>4</sup>, A. Schoepfer<sup>5</sup> Swiss Inflammatory Bowel Disease Cohort Study Group</p><p><italic><sup>1</sup>Institute of Social and Preventive Medicine, University of Bern, Bern, <sup>2</sup>Gastroenterology and Hepatology, University Hospital Zurich, Zurich, <sup>3</sup>Institute of Social and Preventive Medicine, University of Lausanne / CHUV, Lausanne, <sup>4</sup>Gastroenterology and Hepatology, University Hospital Basel, Basel, <sup>5</sup>Gastroenterology and Hepatology, University Hospital Lausanne / CHUV , Lausanne, Switzerland</italic></p><p><bold>INTRODUCTION:</bold> Treatment with immunomodulatory (IM) and/or anti-TNF therapy within the first two years of Crohn’s disease diagnosis may be associated with better clinical response and remission rates when compared to treatment later in the disease course. However, a true disease duration, which is comprised of the diagnostic delay period (time from the onset of first symptoms to diagnosis) and a period following the establishment of diagnosis, has never been examined.</p><p><bold>AIMS&METHODS:</bold> We aimed to assess if treatment with IM and/or anti-TNF therapy within the first two years of CD symptom onset (diagnostic delay is taken into account, “early therapy”) is associated with the diminished risk in developing complications when compared to initiating these therapies > 2 years after CD onset (“late therapy”).</p><p>Data for CD patients of the Swiss IBD Cohort were analyzed. Immunomodulators were defined as azathioprin, 6-mercaptopurine, or methotrexate, whereas anti-TNF therapy included use of infliximab, adalimumab, or certolizumab pegol. The following outcomes/interventions were assessed using logistic regression modelling: stenosis, internal fistulas, perianal fistulas, intestinal surgery, and perianal surgery.</p><p><bold>RESULTS:</bold> A group of 181 CD patients on “early therapy” (49.5% females) was compared to a group of 269 CD patients on “late therapy” (46.1% females). Regression modeling evaluating age at diagnosis, gender, disease duration, and therapy initiation time revealed that “early therapy” was negatively associated with stricture formation (OR 0.431, 95% CI 0.251-0.739, p=0.002) and development of perianal fistulas (OR 0.490, 95% CI 0.256-0.935, p=0.031). The overall disease duration was positively correlated with stricture formation (OR 1.037, 95% CI 10.14-1.060, p=0.001) and risk of undergoing intestinal surgery (OR 1.091, 95% CI 1.061-1.121, p<0.001).</p><p><bold>CONCLUSION:</bold> Treatment with IM and/or anti-TNF therapy during the first two years of CD onset is associated with a reduced risk for development of bowel stenosis and perianal fistulas. The disease duration, adjusted for diagnostic delay, is positively correlated with the increased risk of developing bowel stenoses and undergoing intestinal surgery. Future studies evaluating the relationship between treatment efficacy and disease duration should consider assessing a true disease duration that takes into account the length of diagnostic delay.</p><p><bold>Contact E-mail Address:</bold><email>alain.schoepfer@chuv.ch</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> ANTI-TNF-ALPHA THERAPY, Crohn's disease, early treatment, immunomodulators, surgery</p></sec><sec><title>OP114 UNCHANGED SURGERY RATES IN AN EAST-WEST EUROPEAN INCEPTION COHORT DESPITE DIFFERENCES IN USE OF BIOLOGICALS - AN ECCO-EPICOM STUDY</title><p><bold>J. Burisch</bold><sup>1,*</sup>, S. Odes<sup>2</sup>, I. Vind<sup>3</sup>, O. Shonová<sup>4</sup>, R. Salupere<sup>5</sup>, P. Munkholm<sup>1</sup> ECCO-EpiCom</p><p><italic><sup>1</sup>Herlev University Hospital, Copenhagen, Denmark, <sup>2</sup>Soroka Medical Center and Ben Gurion University of the Negev, Beer Sheva, Israel, <sup>3</sup>Bispebjerg Hospital, Copenhagen, Denmark, <sup>4</sup>Hospital České Budějovice, České Budějovice, Czech Republic, <sup>5</sup>Tartu University Hospital, Tartu, Estonia</italic></p><p><bold>INTRODUCTION:</bold> The EpiCom-cohort is a European prospective population-based cohort of unselected, uniformly diagnosed patients with inflammatory bowel disease (IBD) diagnosed in 2010 in 31 centres from 14 Western and 8 Eastern European countries, covering 10 million in background population<sup>1</sup>.</p><p><bold>AIMS&METHODS:</bold> Patients were followed each 3<sup>rd</sup> month from diagnosis for 12 ± 3 months. Clinical data on surgery, biological treatment, hospitalization and medical treatment were captured throughout the follow-up period and entered in a web-based database, <ext-link ext-link-type="uri" xlink:href="www.epicom-ecco.eu">www.epicom-ecco.eu</ext-link>.</p><p><bold>RESULTS:</bold> A total of 1367 patients aged 15 years or older were eligible for follow-up of whom 710 (52%) had ulcerative colitis (UC), 509 (37%) had Crohn’s disease (CD), and 148 (11%) had IBD unclassified (IBDU). At 1-year follow up 104 patients had undergone 1<sup>st</sup> surgery (resection or colectomy) (14 from Eastern Europe, 90 from Western Europe), 137 had received biological therapy (7 from Eastern Europe, 130 from Western Europe) and 215 were hospitalized (32 from Eastern Europe, 183 from Western Europe). Crude annual rates for surgery, biological treatment and hospitalization are shown in Table 1. The cumulative probability for CD patients receiving treatment with 5-ASA within the first year of disease was 91% in Eastern Europe and 53% in Western Europe, 65% and 72% for prednisolone, 44% and 57% for immunomodulators, 5% and 21% for biological therapy and 11% and 15% for surgery, respectively. For UC patients the cumulative probability for receiving treatment with 5-ASA within the first year of disease was 99% in Eastern Europe and 91% in Western Europe, 38% and 49% for prednisolone, 15% and 22% for immunomodulators, 1% and 6% for biological therapy and 2% and 4% for surgery, respectively.</p><p>Table 1. Annual crude rates for surgery, biological therapy and hospitalization
<table-wrap id="table17-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="2" colspan="1"></th><th colspan="3" rowspan="1"><hr></hr>Eastern Europe</th><th colspan="3" rowspan="1"><hr></hr>Western Europe</th></tr><tr><th rowspan="1" colspan="1">CD</th><th rowspan="1" colspan="1">UC</th><th rowspan="1" colspan="1">IBDU</th><th rowspan="1" colspan="1">CD</th><th rowspan="1" colspan="1">UC</th><th rowspan="1" colspan="1">IBDU</th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">Surgery</td><td rowspan="1" colspan="1">12 (12%)</td><td rowspan="1" colspan="1">2 (1%)</td><td rowspan="1" colspan="1">0 (0%)</td><td rowspan="1" colspan="1">65 (16%)</td><td rowspan="1" colspan="1">20 (4%)</td><td rowspan="1" colspan="1">5 (4%)</td></tr><tr><td rowspan="1" colspan="1">Biological treatment</td><td rowspan="1" colspan="1">6 (6%)</td><td rowspan="1" colspan="1">1 (1%)</td><td rowspan="1" colspan="1">0 (0%)</td><td rowspan="1" colspan="1">86 (21%)</td><td rowspan="1" colspan="1">32 (6%)</td><td rowspan="1" colspan="1">12 (8%)</td></tr><tr><td rowspan="1" colspan="1">Hospitalization</td><td rowspan="1" colspan="1">20 (19%)</td><td rowspan="1" colspan="1">12 (8%)</td><td rowspan="1" colspan="1">0 (0%)</td><td rowspan="1" colspan="1">90 (22%)</td><td rowspan="1" colspan="1">80 (14%)</td><td rowspan="1" colspan="1">13 (9%)</td></tr></tbody></table></table-wrap></p><p><bold>CONCLUSION:</bold> In an era of more aggressive immunological therapy, including the use of biologicals, surgery rates at 1-year are comparable to previous population-based inception cohorts at the start of the millennium. The cumulative probability of receiving prednisolone or immunomodulators is similar in Eastern and Western Europe while the use of biological therapy in CD and UC patients and the use of 5-ASA in CD patients differs.</p><p><bold>REFERENCES:</bold></p><p>1. Burisch J, et al. East-West gradient in the incidence of inflammatory bowel disease in Europe: the ECCO-EpiCom inception cohort. Gut 2013;0:1–10</p><p><bold>Contact E-mail Address:</bold><email>burisch@dadlnet.dk</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> biological therapy, Cohort study, hospitalization, inflamatory bowel disease, medical treatment, surgery</p></sec><sec><title>OP115 LONG-TERM COMBINATION THERAPY WITH INFLIXIMAB AND AZATHIOPRINE PREDICTS SUSTAINED STEROID-FREE CLINICAL BENEFIT IN STEROID-DEPENDENT ULCERATIVE COLITIS</title><p><bold>A. Armuzzi</bold><sup>1</sup>, D. Pugliese<sup>1,*</sup>, S. Danese<sup>2</sup>, G. Rizzo<sup>1</sup>, M. Marzo<sup>1</sup>, C. Felice<sup>1</sup>, G. Andrisani<sup>1</sup>, G. Fiorino<sup>2</sup> O. M. Nardone I <sup>1</sup>, De Vitis<sup>1</sup>, G. L. Rapaccini<sup>1</sup>, A. Papa<sup>1</sup>, L. Guidi<sup>1</sup></p><p><italic><sup>1</sup>IBD UNIT, Complesso Integrato Columbus Catholic University , Rome, <sup>2</sup>IBD UNIT, Istituto Clinico Humanitas, Rozzano, Italy</italic></p><p><bold>INTRODUCTION:</bold> Anti-TNF alpha therapy is advised as second-line treatment after failure of thiopurines in steroid-dependent ulcerative colitis (UC). We recently reported more than 30% of steroid-free clinical remission and mucosal healing for steroid-dependent UC patients treated with infliximab (IFX) at 1 year.<sup> 1 </sup>Aims of our study were to describe the long-term outcome of IFX treatment in active steroid-dependent UC and to identify predictors of sustained clinical response and colectomy.</p><p><bold>AIMS&METHODS:</bold> Consecutive patients with active steroid-dependent UC were enrolled and treated with IFX. Co-primary endpoints were 1) sustained clinical response in patients who achieved complete or partial clinical benefit after induction and 2) colectomy free-survival. Sustained clinical response was defined as a persistent clinical improvement during the follow-up, with no need of a course of steroids. Secondary endpoints were to identify predictors of sustained clinical response and colectomy.</p><p><bold>RESULTS:</bold> 126 steroid-dependent UC patients were studied; 45% were naïve to thiopurines and 56% were started on concomitant thiopurines. The median duration of follow-up was 32 months (IQR 22-62), with a median number of infusion of 14 (IQR 7-24). 77% (97/126) of patients achieved clinical response after IFX induction and 47% (46/97) of them showed sustained clinical response during follow up. 46% (41/88) of patients who were on steroids at baseline were able to stop them during long-term treatment with IFX. Cox regression identified combination therapy (p<0.0001) as independent predictor of sustained clinical response. The colectomy rate was 23% (29/126), with a median time to colectomy of 16 months (IQR 9-30). Mayo endoscopic score≥2 (p=0.03) at baseline and high CRP after induction (p=0.001) were identified as independent predictors of colectomy, while thiopurine naïve status (p=0.03) was protective. Adverse events leading to IFX withdrawal were recorded in 11.1% of patients.</p><p><bold>CONCLUSION:</bold> Infliximab long-term treatment was effective and safe in steroid-dependent UC patients. Combination therapy with IFX and thiopurine predicts long-term sustained clinical benefit in steroid-dependent UC. The severity of endoscopic lesions at baseline and persistent high CRP are associated with higher rates of colectomy, while thiopurine naïve status is protective from colectomy.</p><p><bold>REFERENCES:</bold></p><p>1. Armuzzi A, et al. Inflamm Bowel Dis. 2013;19(5):1065-72</p><p><bold>Disclosure of Interest</bold>: A. Armuzzi Lecture fee(s) from: AbbVie, MSD, Chiesi, Ferring, Nycomed and Otsuka, Consultancy for: AbbVie, MSD, D. Pugliese: None Declared, S. Danese Lecture fee(s) from: Abbott Laboratories, Merck & Co/Schering Plough, UCB Pharma, Ferring, Cellerix, Millenium Takeda, Nycomed, Pharmacosmos, Actelion, Alphawasserman, Genentech, Pfizer, Astra Zeneca, Novo Nordisk, Cosmo Pharmaceuticals, Vifor, Johnson and Johnson., Consultancy for: Abbott Laboratories, Merck & Co/Schering Plough, UCB Pharma, Ferring, Cellerix, Millenium Takeda, Nycomed, Pharmacosmos, Actelion, Alphawasserman, Genentech, Pfizer, Astra Zeneca, Novo Nordisk, Cosmo Pharmaceuticals, Vifor, Johnson and Johnson., G. Rizzo: None Declared, M. Marzo: None Declared, C. Felice: None Declared, G. Andrisani: None Declared, G. Fiorino: None Declared, O. M. Nardone: None Declared, I. De Vitis: None Declared, G. L. Rapaccini: None Declared, A. Papa: None Declared, L. Guidi Financial support for research from: AbbVie, MSD</p><p><bold>Keywords:</bold> infliximab, long-term outcome, Steroid-dependent ulcerative colitis</p></sec><sec><title>OP116 INFLIXIMAB IS EFFECTIVE AND SAFE FOR BOTH STEROID-RESISTANT AND STEROID-DEPENDENT ULCERATIVE COLITIS: A “REAL LIFE “ EXPERIENCE IN A LARGE MULTICENTER SERIES</title><p><bold>M. Cappello</bold><sup>1,*</sup>, M. Mazza<sup>1</sup>, G. Costantino<sup>2</sup>, W. Fries<sup>2</sup>, A. C. Privitera<sup>3</sup>, M. Mastronardi<sup>4</sup>, F. Bossa<sup>5</sup>, F. Castiglione<sup>6</sup>, A. Rispo<sup>6</sup>, A. Lauria<sup>7</sup>, N. Buccianti<sup>8</sup>, R. Marasco<sup>9</sup>, L. Grossi<sup>10</sup>, P. L. Almasio<sup>11</sup></p><p><italic><sup>1</sup>Di.Bi.Mis - University of Palermo - Italy, UOC GASTROENTEROLOGIA ED EPATOLOGIA, Palermo, <sup>2</sup>Dipartimento di Medicina Interna, University of Messina, Messina, <sup>3</sup>Azienda Ospedaliera per l'Emergenza, Ospedale Cannizzaro, Catania, <sup>4</sup>UOC Gastroenterologia ed Endoscopia Digestiva, IRCSS, Castellana Grotte (BA), <sup>5</sup>Gastroenterologia, Casa Sollievo della Sofferenza, S. Giovanni Rotondo (FG), <sup>6</sup>Gastroenterologia, Università Federico II, Napoli, <sup>7</sup>Fastroenterologia ed Endoscopia Digestiva, A.O. Bianchi - Melacrino- Morelli, Reggio Calabria, <sup>8</sup>UOC Medicina Interna, AOS S. Carlo, Potenza, <sup>9</sup>UOC Gastroenterologia, Policlinico Catanzaro, Catanzaro, <sup>10</sup>Fisiopatologia Digestiva, Ospedale S. Spirito , Pescara, <sup>11</sup>Di.Bi.Mis, UOC GASTROENTEROLOGIA ED EPATOLOGIA - University of Palermo, Palermo, Italy</italic></p><p><bold>INTRODUCTION:</bold> Infliximab (IFX) has been shown effective both for induction and maintenance of remission in active ulcerative colitis (UC) in clinical trials.</p><p><bold>AIMS&METHODS:</bold> The aim of this retrospective multicenter study is to provide “real life” data on IFX efficacy and safety in UC. Consecutive patients with proven UC who received at least one infusion of IFX from January 2008 to June 2012 in ten referral centers from Southern Italy were recruited. Clinico-demographic characteristics, IFX indications, concomitant medications, disease activity (Mayo score), date of colectomy, and adverse events were registered. Outcomes of efficacy were clinical and endoscopic responses at week 14 and 52, steroid-free remission, mucosal healing and colectomy rate.</p><p><bold>RESULTS:</bold> 288 UC patients (61.1% males, mean age 35.7) were studied. Median duration of UC was 49.5 months;disease extent was pancolitis in 69.5%,left-sided colitis in 25%, proctosigmoiditis in 5.5%. Indication to IFX were steroid dependence in 75.1%, steroid-resistance in 17.4%, extra-intestinal complications in 2.1%. IFX was used as rescue therapy in 5.5% of patients. 40.7% received combo therapy. Patients received a median of 9 infusions. Median follow-up was 28 months. IFX optimization was necessary in 20%. Mayo score was 9 at enrolment, 4 at 14 weeks and 2 at 52 weeks (p<0.001). Remission rates were 29% at week 14, 43.5% at week 52. 47% of patients were on steroids at week 14, 26% at 52 weeks. Mucosal healing was obtained in 76.5%. Colectomy was performed in 24 patients (10.5%). Median time to colectomy was 5 months. There were no significant differences when comparing IFX monotherapy versus combo, long-lasting versus recent disease, steroid-dependent versus steroid-resistant patients. Colectomy rate was higher in steroid-resistant (p=0.002). Adverse events were observed in 23.6% of patients (25 infusion reactions, 37 opportunistic infections). 5 subjects developed “de novo” neoplasia (2 colo-rectal carcinoma).</p><p><bold>CONCLUSION:</bold> This multicenter survey represents one of the largest case series on IFX use in UC in “daily clinical practice”. IFX effectively induces short and long-term remission and mucosal healing and avoids early colectomy with a good safety profile.</p><p><bold>Contact E-mail Address:</bold><email>cmarica@tin.it</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Efficacy, infliximab, safety, ulcerative colitis</p></sec><sec><title>OP117 TWO-YEAR EFFICACY AND SAFETY OF AZATHIOPRINE TREATMENT IN THE MAINTAINANCE OF STEROID-FREE REMISSION IN INFLAMMATORY BOWEL DISEASE PATIENTS</title><p><bold>C. Claudio</bold><sup>1,*</sup>, R. Pica<sup>1</sup>, EV Avallone<sup>1</sup>, C. Corrado<sup>1</sup>, M. Zippi<sup>1</sup>, P. Vernia<sup>1</sup>, P. Paoluzi<sup>1</sup>, E. S. Corazziari<sup>1</sup></p><p><italic><sup>1</sup>Internal Medicine and Medical Specialties, “Sapienza” University of Rome, Rome, Italy</italic></p><p><bold>INTRODUCTION:</bold> Azathioprine (AZA) and thiopurine are widely used for induction and maintenance of remission in patients steroid-resistant or dependent with inflammatory bowel disease (IBD). The treatment must be withdrawn in 5-30% of patients due to the occurrence of adverse events.</p><p><bold>AIMS&METHODS:</bold> Aim of this study has been to investigate its efficacy and safety in maintaining steroid-free remission in steroid dependent/resistent IBD patients two year after the institution of treatment. Data from consecutive IBD outpatients referred in our Institution, between 1985-2011, were reviewed and all patients treated with AZA were included in this retrospective study. AZA was administered at the recommended dose of 2–2.5 mg/kg. Blood chemistry was analysed before administration of the drug, every 10-15 days for the first 3 months and then every 1-2 months following the institution of treatment.</p><p><bold>RESULTS:</bold> Out of 2396 consecutive IBD outpatients visited in the index period, AZA was prescribed to 347 patients, 182 (52.4%) were affected by Crohn's disease (CD) and 165 (47.6%) by ulcerative colitis (UC). Fifty-five patients with a follow-up <24 months were excluded from the study. Two hundred and ninety-two patients were evaluated, 158 (54.1%) with CD and 134 (45.9%) with UC. One hundred and sixty-one (55.1%) were male and 131 (44.9%) female (average age of 34.15 ± 14.34 SD years, range 12-76 y.). Two year after the institution of treatment, 188 (64.4%) patients still were in steroid-free remission (110 CD vs 78 UC, 69.6% and 58.2%, respectively, p=0.0499), 57 (19.5%) had a relapse requiring retreatment with steroids (35 UC vs 22 CD, 26.1% and 13.9%, respectively, p=0.0115), 47 (16.1%) discontinued the treatment due to side effects (26 CD vs 21 UC, 16.5% and 15.7%, respectively).</p><p><bold>CONCLUSION:</bold> The study confirms that AZA is an effective therapeutic tool for maintaining steroid-free remission in IBD patients. Two year after the onset of treatment about two/thirds of patients did not required further steroid courses. In the present series the maintenance of steroid-free remission was significantly higher in CD than in UC patients. The occurrence of side effects leading to the withdrawal of AZA treatment has been low.</p><p><bold>Contact E-mail Address:</bold><email>claudio.cassieri@libero.it</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> azathioprine, IBD, Steroid-dependent IBD, Steroid-resistent IBD</p></sec><sec><title></title><p><bold>MONDAY, OCTOBER 14, 2013 15:45-17:15</bold></p><p><bold>IBD: Top late breaking trials and other major advances – Hall Helsinki</bold></p></sec><sec><title>OP117-LB1 CLINICAL AND ENDOSCOPIC IMPROVEMENT FOLLOWING HEMOPOIETIC STEM CELL TRANSPLANTATION VS MOBILISATIION ALONE IN CROHN'S DISEASE</title><p><bold>C. J. Hawkey</bold><sup>1,*</sup> The ASTIC Trialists</p><p><italic><sup>1</sup>Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, United Kingdom</italic></p><p><bold>INTRODUCTION:</bold> The Autologous Stem Cell Transplantation International Crohn’s Disease (ASTIC) Trial is a randomised controlled trial co-sponsored by ECCO and EBMT, funded by the Broad Foundation investigating haemopoetic stem cell transplantation (HSCT) in patients with resistant Crohn’s disease (CD) causing impaired quality of life (QoL).</p><p><bold>AIMS & METHODS:</bold> Patients with impaired QoL and active CD, as measured by the EQ5D, McMaster Inflammatory Bowel Disease Questionnaire (IBDQ) or Karnofsky Index, were eligible if they had active disease and had failed to respond adequately to at least 3 immunosuppressive agents. All patients underwent mobilisation (iv cyclophosphamide 4gm/M<sup>2</sup> over 2 days followed by recombinant human granulocyte-colony stimulating factor [GCSF, filgrastim), 10µ/kg daily before randomisation to immediate (1 month) or delayed (1 year) immunoablation and HSCT. The conditioning regime was iv cyclophosphamide 50mg/kg per day for 4 days, anti-thymocyte globulin 2.5mg/kg/day and methyl prednisolone 1mg/kg on days 3–5. The bone marrow was reconstituted by infusion of an unselected graft of 3-8x10<sup>6</sup>/kg CD34 positive stem cells. Results in the two groups are compared one year after mobilisation, when those randomised to delayed transplantation form an untreated control group, using blinded adjudication of endoscopic activity (Simple Endoscopic Score, SES-CD), CDAI, QoL (EQ5D and IBDQ), CD Activity Index (CDAI) and serious adverse events (SAEs).</p><p><bold>RESULTS:</bold> Forty five patients were randomised to HSCT (n=23) or control (n=22). The groups were well matched for age, sex, duration and extent of disease, previous surgery, disease activity, and QoL. In patients undergoing HSCT The SES-CD fell by 7 (median, IQR 4-13) from 12 (8-23) to 3(1-8) compare to no change (-5 to +5) from 9 (5.5 to 16.5) to 7 (4.5 to 14) in the control group. The CDAI fell from 325 to 162 following HSCT vs 353 to 298 in the control group. The IBDQ score rose by 36 (-0.75 to 60.5) from 123 (102-143) to 138 (121 to 202) vs 10 (-6,5 to 21.5) . The EQ5D VAS score was 53 (40-65) at baseline and 80 after 1 year, a rise of 25 (-7 to 30) compared to a change of 6 (-15 to 11) from 53 (35-64) to 50 (39 to 62). Eight patients had a CDAI <italic><</italic> 150 for <italic>></italic> 3 months prior to the 1 year assessments, of whom 7 were off corticosteroids and immunosuppressive drugs compared to 2 (2) in the control group. During the year from the start of mobilisation there were 70 SAEs in patients undergoing HSCT vs 44 for the control group. One patient died following HSCT. Full results of this phase of the study will be available to be presented at UEGW in October 2013.</p><p><bold>CONCLUSION:</bold> HSCT improves endoscopic evidence of disease, clinical symptoms and quality of life.</p><p><bold>Contact E-mail Address:</bold><email>cj.hawkey@nottingham.ac.uk</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Crohn's disease, hemopoietic stem cell transplantation, randomised controlled trial</p></sec><sec><title>OP117-LB2 FAECAL CALPROTECTIN HELPS DETERMINE THE NEED FOR POST-OPERATIVE COLONOSCOPY IN CROHN’S DISEASE. PROSPECTIVE LONGITUDINAL ENDOSCOPIC VALIDATION. RESULTS FROM THE POCER STUDY.</title><p><bold>E. Wright</bold><sup>1,2,*</sup>, P. De Cruz<sup>1,2</sup>, M. Kamm<sup>1,2</sup>, A. Hamilton<sup>1,2</sup>, K. Ritchie<sup>1,2</sup>, S. Krejany<sup>1,2</sup>, S. Leach<sup>3</sup>, J. Keenan<sup>3</sup>, A. Gorelik<sup>1</sup>, L. Prideaux<sup>1,2</sup>, D. Liew<sup>1</sup>, J. Andrews<sup>1</sup>, I. Lawrence<sup>1</sup>, P. Bampton<sup>1</sup>, M. Sparrow<sup>1</sup>, T. Florin<sup>1</sup>, P. Gibson<sup>1</sup>, H. Debinski<sup>1</sup>, F. Macrae<sup>1</sup>, R. Leong<sup>1</sup>, I. Kronborg<sup>1</sup>, G. Radford-Smith<sup>1</sup>, W. Selby<sup>1</sup>, M. Johnston<sup>2</sup>, R. Woods<sup>2</sup>, P. Elliott<sup>2</sup>, S. Bell<sup>2</sup>, S. Brown<sup>2</sup>, W. Connell<sup>2</sup>, A. Day<sup>3</sup>, R. Gearry<sup>3</sup>, P. Desmond<sup>1,2</sup></p><p><italic><sup>1</sup>University of Melbourne, <sup>2</sup>St Vincent's Hospital, Melbourne, Australia, <sup>3</sup>University of Otago, Christchurch, New Zealand</italic></p><p><bold>INTRODUCTION:</bold> Surgery after “curative” resection for Crohn’s disease (CD) is common. The Post Operative Crohn's Endoscopic Recurrence (POCER) study demonstrated that optimal post-operative care entails drug treatment according to risk and colonoscopy with treatment step-up for recurrence. However colonoscopy is invasive. We tested whether faecal calprotectin (FC) can substitute for endoscopy to predict disease recurrence.</p><p><bold>AIMS & METHODS:</bold> 318 stool samples from 136 patients were tested for FC using ELISA (Buhlmann) pre-operatively and 6, 12, & 18 months after resection. Colonoscopy was performed at 6 &/or 18 months. Endoscopic recurrence was assessed using the Rutgeerts score. CRP and CDAI were assessed longitudinally.</p><p><bold>RESULTS:</bold> FC was elevated pre-operatively (median 1402 μg/g). At 6 months, FC fell (166 μg/g) but was higher in recurrence v remission (330 v 75μg/g, p<0.001). At 6 & 18 month observations the overall prevalence of endoscopic recurrence was 34%. FC>100μg/g indicated endoscopic recurrence (≥ i2) with a sens. of 0.89 and spec. of 0.59. PPV was 53% and NPV was 91%. The AUC was 0.77 based on ROC analysis. FC correlated with endoscopic score (r = 0.45, p<0.001). FC>100μg/g at 6 and/or 12 months predicted recurrence at 18 months with sens. 0.80, spec. 0.53, PPV 55% and NPV 79%. In patients with endoscopic recurrence at 6 months who stepped-up treatment, FC fell from 252μg/g at 6 months to 109μg/g at 18 months (p=0.004). At 18 months, in this step-up group FC discriminated between those in endoscopic remission (median change -158.5μg/g) and those with persistent recurrence (-79μg/g). CRP and CDAI did not correlate with FC or endoscopic recurrence.</p><p><bold>CONCLUSION:</bold> FC is sensitive to monitor for Crohn’s disease recurrence. FC >100μg/g indicates which patients require colonoscopic assessment. FC<100μg/g has a high NPV for endoscopic disease allowing avoidance of colonoscopy. Monitoring FC with treatment change provides a guide to response. FC>100μg/g predicts later recurrence and helps identify patients requiring observation and intervention. CRP and CDAI are insufficient for monitoring.</p><p><bold>Contact E-mail Address:</bold><email>emily.smith@svhm.org.au</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> biomarker, calprotectin, Crohn's disease, post-operative</p></sec><sec><title>OP117-LB3 LOW-DOSE BUDESONIDE IS AN EFFECTIVE MAINTENANCE THERAPY IN COLLAGENOUS COLITIS: RESULTS FROM THE RANDOMISED, PLACEBO-CONTROLLED BUC-63/COC-TRIAL</title><p><bold>A. Münch</bold><sup>1,*</sup>, J. Bohr<sup>2</sup>, S. Miehlke<sup>3</sup>, C. Benoni<sup>4</sup>, M. Olesen<sup>5</sup>, Å. Öst<sup>6</sup>, L. Strandberg<sup>7</sup>, P. M. Hellström<sup>8</sup>, E. Hertervig<sup>9</sup>, P. Armerding<sup>10</sup>, J. Stehlik<sup>11</sup>, G. Lindberg<sup>12</sup>, J. Björk<sup>12</sup>, A. Lapidus<sup>13</sup>, R. Löfberg<sup>14</sup>, O. Bonderup<sup>15</sup>, S. Avnström<sup>16</sup>, M. Roessle<sup>17</sup>, R. Mueller<sup>18</sup>, R. Greinwald<sup>18</sup>, C. Tysk<sup>2</sup>, M. Ström<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology, University hospital, Linköping, <sup>2</sup>Gastroenterology, University hospital, Örebro, Sweden, <sup>3</sup>Center for Digestive Disease, Hamburg, Germany, <sup>4</sup>Gastroenterology, <sup>5</sup>Pathology, University hospital, Malmö, <sup>6</sup>Pathology, Medilab, Stockholm, <sup>7</sup>Regional hospital, Falun, <sup>8</sup>Gastroenterology, University hospital, Uppsala, <sup>9</sup>Gastroenterology, University hospital, Lund, Sweden, <sup>10</sup>Gastroenterology, Private practice, Berlin, Germany, <sup>11</sup>Gastroenterology, Regional hospital, Usti nad Labem, Czech Republic, <sup>12</sup>Gastrocentrum, <sup>13</sup>Gastroenterology, University hospital, <sup>14</sup>IBD Unit, Sofiahemmet, Stockholm, Sweden, <sup>15</sup>Gastroenterology, Regional hospital, Silkeborg, <sup>16</sup>Gastroenterology, Regional hospital, Copenhagen, Denmark, <sup>17</sup>Gastroenterology, Private practice, <sup>18</sup>Dr Falk Pharma, Freiburg, Germany</italic></p><p><bold>INTRODUCTION:</bold> No controlled data exist so far showing the efficacy of longer treatment with lower dosages of budesonide in collagenous colitis (CC).</p><p><bold>AIMS & METHODS:</bold> BUC-63/COC is the first RCT comparing the efficacy of low-dose budesonide (Budenofalk<sup>®</sup> 3mg capsules; 2 capsules e.o.d, and 1 capsule e.o.d; average 4.5 mg/day) versus placebo for 12-months maintenance therapy. Patients were randomised after an 8-week induction treatment with budesonide 9 mg/day in tapering doses. Primary endpoint was the rate of continuous clinical remission over 52 weeks (intention-to-treat [ITT] population). Clinical remission was defined as a mean of <3 stools/day, thereof <1 watery stools/day [1]. Quality of Life (QoL) was assessed by Short Health Scale (SHS).</p><p><bold>RESULTS:</bold> Out of 148 screened patients, 110 were enrolled into open-label induction phase. 92 patients (78 females), who were in remission at the end of the induction phase, were randomised and evaluated in the double-blind maintenance phase. The mean (SD) age was 58.8 (11.0) years. Median (IQR) disease duration was 0.5 (0.1−3.8) years. At baseline, mean (SD) stool frequency was 1.7 (0.6)/day (budesonide) and 1.8 (0.9)/day (placebo); mean number of watery stools were 0.1 (0.2)/day (budesonide) and 0.2 (1.0)/day (placebo). After 52 weeks, 27 of 44 patients (61.4%) given budesonide and 8 of 48 patients (16.7%) given placebo were in clinical remission (ITT: difference 44.5%, 95% CI [26.9%; 62.7%]; p<0.0001 one sided). The QoL was unchanged after one year in budesonide group but showed clinically relevant deterioration in placebo group.</p><p><bold>CONCLUSION:</bold> Low-dose budesonide is an effective long-term maintenance therapy in CC and maintains patients’ QoL over 1-year of treatment.</p><p><bold>Contact E-mail Address:</bold><email>andreas.munch@lio.se</email></p><p><bold>Disclosure of Interest</bold>: A. Münch Financial Support from: Dr Falk Pharma, J. Bohr Financial Support from: Dr Falk Pharma, S. Miehlke Financial Support from: Dr Falk Pharma, C. Benoni: None Declared, M. Olesen: None Declared, Å. Öst: None Declared, L. Strandberg: None Declared, P. M. Hellström: None Declared, E. Hertervig: None Declared, P. Armerding: None Declared, J. Stehlik: None Declared, G. Lindberg: None Declared, J. Björk: None Declared, A. Lapidus: None Declared, R. Löfberg: None Declared, O. Bonderup Financial Support from: Dr Falk Pharma, S. Avnström: None Declared, M. Roessle: None Declared, R. Mueller Other: Employee of Dr Falk Pharma, R. Greinwald Other: Employee of Dr Falk Pharma, C. Tysk Financial Support from: Dr Falk Pharma, Lecture Fee(s) from: Tillots, Ferring, MSD, and AstraZeneca, M. Ström Financial Support from: Dr Falk Pharma</p><p><bold>Keywords:</bold> Budesonide, collagenous colitis, maintenance therapy</p></sec><sec><title>OP117-LB4 INFLIXIMAB AND ADALIMUMAB IN TNF-ΑNAÏVE CROHN`S DISEASE PATIENTS: AUSTRIAN MULTICENTRE COHORT STUDY</title><p><bold>P. Papay</bold><sup>1,*</sup>, S. Kainz<sup>1</sup>, W. Petritsch<sup>2</sup>, T. Haas<sup>3</sup>, T. Feichtenschlager<sup>4</sup>, G. Novacek<sup>1</sup>, A. Eser<sup>1</sup>, H. Vogelsang<sup>1</sup>, W. Reinisch<sup>1</sup></p><p><italic><sup>1</sup>Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical university Vienna,, Vienna, <sup>2</sup>Department of Internal Medicine, Medical University of Graz, Graz, <sup>3</sup>Department of Internal Medicine 1, Paracelsus Private Medical University, Salzburg, <sup>4</sup>Department of Internal Medicine 4, Hospital Rudolfstiftung, Vienna, Austria</italic></p><p><bold>INTRODUCTION:</bold> Tumor necrosis factor-α inhibitors (TNFi), infliximab (IFX) and adalimumab (ADA) revolutionized the treatment of Crohns disease (CD). However, despite their broad clinical use, studies comparing their efficacy in TNF-α naïve patients with CD are missing.</p><p><bold>AIMS & METHODS:</bold> Consecutive TNF-α naïve patients with luminal CD from four tertiary centers in Austria were retrospectively analyzed for short- and long-term efficacy of IFX and ADA. Stepwise logistic regression was performed to identify predictors of remission at week 12 and month 12. Cox-regression analysis was performed to evaluate time to loss of remission.</p><p><bold>RESULTS:</bold> In total 311 patients, 204 (65.6%) starting IFX and 107 (34.4%) ADA, were included. At baseline the median Harvey Bradshaw-Index score was 8 (5-29) and 8 (5-36), the mean CRP 2.4 ± 3.1 mg/dl and 2.2 ± 2.8 mg/dl for IFX and ADA, respectively. In total 155/311 (49.8%) subjects were on concomitant immunomodulators, 102/311 (32.8%) were on steroids at start of TNFi.</p><p>There was no difference regarding clinical remission as defined by HBI < 5 points (IFX 128/204; 62.7% vs. ADA 68/107; 63.6%, p=0.47) and steroid-free remission (IFX 110/204; 53.9% vs. ADA 61/107; 57.0%, p=0.60) at week 12. Duration of disease was identified as predictor of response at week 12, defined as HBI drop ≥ 3 points (OR 1.06; 95%CI 1.026-1.098).</p><p>After 12 months there were 77/204 (37.7%) patients treated with IFX and 47/107 (43.9%) with ADA in remission (p=0.48). Baseline CRP ≥ 0.7 mg/dl (OR 0.24; 95%CI 0.07-0.77, p=0.01) was the only predictor of remission at month 12 in patients without TNFi intensification. There was a trend in favour of ADA (OR 2.96; 0.87-10.07, p=0.08), and smoking (OR 2.12; 95%CI 0.89-5.04, p=0.09).</p><p><bold>CONCLUSION:</bold> IFX and ADA appear comparable regarding short and long-term remission in TNFa naïve luminal CD patients. Shorter disease duration and CRP ≥0.7 mg/dl are associated with higher rate of short- and long-term remission, respectively.</p><p><bold>Contact E-mail Address:</bold><email>pavol.papay@meduniwien.ac.at</email></p><p><bold>Disclosure of Interest</bold>: P. Papay Lecture Fee(s) from: AbbVie,MSD, Consultancy for: AbbVie,MSD, S. Kainz: None Declared, W. Petritsch Lecture Fee(s) from: AbbVie,MSD, Consultancy for: AbbVie,MSD, T. Haas Lecture Fee(s) from: Abbvie, MSD, Consultancy for: AbbVie,MSD, T. Feichtenschlager Lecture Fee(s) from: AbbVie,MSD, Consultancy for: AbbVie,MSD, G. Novacek Lecture Fee(s) from: AbbVie,MSD, Consultancy for: AbbVie,MSD, A. Eser Lecture Fee(s) from: AbbVie,MSD, Consultancy for: AbbVie,MSD, H. Vogelsang Lecture Fee(s) from: AbbVie,MSD, Consultancy for: AbbVie,MSD, W. Reinisch Lecture Fee(s) from: AbbVie,MSD, Consultancy for: AbbVie,MSD</p><p><bold>Keywords:</bold> adalimumab, crohns disease, infliximab</p></sec><sec><title>OP117-LB5 VOLATILE ORGANIC COMPOUNDS IN BREATH AS NEW TEST FOR CROHN’S DISEASE ACTIVITY</title><p><bold>A. Bodelier</bold><sup>1,2,*</sup>, A. Smolinska<sup>3</sup>, J. Dalinga<sup>3</sup>, A. Masclee<sup>2</sup>, D. Jonkers<sup>2</sup>, M. Pierik<sup>2</sup>, F.-J. van Schooten<sup>3</sup></p><p><italic><sup>1</sup>Internal Medicine & Gastroenterology, Amphia Hospital Breda, Breda, <sup>2</sup>Internal Medicine & Gastroenterology, Maastricht University Medical center, <sup>3</sup>Health Risk Analysis & Toxicology, Maastricht University, Maastricht, Netherlands</italic></p><p><bold>INTRODUCTION:</bold> Monitoring of mucosal inflammation is of major importance in IBD. Ileocolonoscopy is gold standard but invasive and expensive. Clinical activity indices do not correlate well with endoscopic findings and available non-invasive markers show low sensitivities. Volatile organic compounds (VOCs) in exhaled breath may be related to inflammation. Therefore we measured total amount of exhaled VOCs (volatome) to select those relevant for disease. The aim of the study is to find VOC profiles that accurately differentiate between patients with active CD and remission.</p><p><bold>AIMS & METHODS:</bold> CD patients visiting the outpatient clinic were included in a prospective 1-year study. At 3 monthly visits or when a flare occurred Harvey Bradshaw index (HBI), blood, fecal and breath samples were collected. Patients were divided in 3 groups; healthy controls, active disease (HBI>4 and CRP>5mg/l or Fecal Calprotectin (FC)>250µg/g) and inactive disease (HBI<4 and CRP<5 and FC<100). Breath samples were analyzed by gas chromatography combined with <italic>time-of-flight</italic> mass spectrometry (GC-<italic>tof</italic>-MS) to obtain breathograms. Random Forests (RF) method was used to find the most discriminatory VOCs to classify healthy controls, active CD and remission. Principal Component Analysis was performed on proximity matrix obtained from the RF model.</p><p><bold>RESULTS:</bold> 835 GC-<italic>tof</italic>-MS spectra were measured (725 CD, 110 healthy controls). The dataset contained 110 healthy controls, 135 CD remission and 140 active CD after assignement to the 3 groups. First RF model showed a set of 6 discriminatory VOCs with an overall correct prediction of healthy controls vs CD remission of 92.3% (sens 0.96, spec 0.97, AUC 0.99). Second RF analysis (healthy controls/active CD) showed overall accuracy of 97.3% for diagnosis of active CD (sens 0.96, spec 0.97 and AUC 0.98). Finally, 10 discriminatory VOCs gave correct prediction of 81.5% for active CD and 86.4% for remission (sens 0.81, spec 0.80, AUC 0.80). For further validation, the 10 discriminatory VOCs were combined in a single disease activity score. This new score showed significant differences between active CD and remission (p<0.001) and was able to classify disease activity in more than 60% of previously undetermined individuals, only 22% of patients remained unclassified.</p><p><bold>CONCLUSION:</bold> We showed that it’s possible to separate patients with CD from healthy controls and active CD from CD in remission with VOC analyses in a real life cohort of CD patients. The VOCs activity score could classify disease activity better than a combination of HBI, CRP and FC.</p><p><bold>Contact E-mail Address:</bold><email>abodelier@amphia.nl</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> breath test, Crohn`s disease, Disease activity, non-invasive tests</p></sec><sec><title>OP117-LB6 CXCR3 DEFICIENCY INCREASES SUSCEPTIBILITY TO INTESTINAL INFLAMMATION IN EXPERIMENTAL IBD</title><p><bold>G. Pickert</bold><sup>1,*</sup>, I. Tegeder<sup>2</sup>, D. Schuppan<sup>3,4</sup></p><p><italic><sup>1</sup>Department of Medicine I, Institute of Translational Immunology, Mainz, <sup>2</sup>Goethe-University, Medical faculty, Institute of clinical pharmacology, 60590 Frankfurt , <sup>3</sup>Dept. of Medicine I, Institute of Translational Immunology , Mainz, Germany, <sup>4</sup>Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States</italic></p><p><bold>INTRODUCTION:</bold> Crohn's disease (CD) and ulcerative colitis (UC) are characterized by a chronic clinical course of relapse and remission associated with self-destructive inflammation of the gastrointestinal tract. In both UC and CD, leukocyte infiltration into the intestine is fundamental event in disease development and progression. Chemokines and their receptors are orchestrating tissue- and cell type-specific trafficking of leukocytes in CD and UC. Signaling of the chemokine receptor CXCR3 is central for the chemoattraction of activated Th1 cells, CTLs, NK cells, macrophages and DCs to inflammatory sites. CXCR3 and its ligands CXCL9, CXCL10 and CXCL11 are highly expressed in IBD, CXCR3’s role in IBD remains unexplored.</p><p><bold>AIMS & METHODS:</bold> To elucidate the role of CXCR3 in the intestinal inflammation, wild type and CXCR3 deficient mice were studied in the model of dextran sodium sulphate (DSS) induced colitis (2.5% DSS in drinking water for 10 days). The inflammation was studied endoskopically, histologically and with FACS-analysis.</p><p><bold>RESULTS:</bold> CXCR3 deficiency strongly enhanced the development of colonic inflammation, with significantly increased intestinal inflammatory infiltrates accelerated weight loss and more severe epithelial erosions compared to the wildtype controls. FACS-analysis and immunohistochemistry revealed significantly increased infiltration by of CD11b+ inflammatory cells and recruitment of F4/80+ macrophages in the colonic mucosa and in the intraepithelial compartment of CXCR3-/- mice. Furthermore, the exacerbated inflammation in CXCR3-/- mice was associated with elevated levels of certain lipid mediators like C16-ceramide, LPAs, and prostaglandins like 6-keto-PGF in inflamed tissue and in the plasma.</p><p><bold>CONCLUSION:</bold> Chemokine receptor CXCR3 plays an important role in inflammatory bowel disease. Deficiency of CXCR3 enhances intestinal inflammation in a mouse model of DSS induced colitis. CXCR3 activation could be an attractive target to attenuate inflammation in IBD.</p><p><bold>Contact E-mail Address:</bold><email>gpickert@uni-mainz.de</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> IBD, Inflammation</p></sec><sec><title>OP117-LB7 IL-33 TREATMENT ACCELERATES EPITHELIAL REPAIR AND GUT MUCOSAL WOUND HEALING IN DSS-COLITIC MICE</title><p><bold>L. R. Lopetuso</bold><sup>1,2,*</sup>, H. Senkfor<sup>1</sup>, C. De Salvo<sup>1</sup>, X.-M. Wang<sup>1</sup>, D. W. Abbott<sup>3</sup>, F. Scaldaferri<sup>4</sup>, A. Gasbarrini<sup>4</sup>, T. T. Pizarro<sup>1</sup></p><p><italic><sup>1</sup>Pathology, Case Western Reserve University - School of Medicine, Cleveland, United States, <sup>2</sup>Internal Medicine, Gastroenterology Division, Catholic University of Sacred Heart, Rome, Italy, <sup>3</sup>Case Western Reserve University - School of Medicine, Cleveland, United States, <sup>4</sup>Internal Medicine, Gastroenterology Division, Catholic University of Sacred Heart, Rome, Italy</italic></p><p><bold>INTRODUCTION:</bold> Increasing evidence confirms that IL-33 and its receptor, ST2, are important factors in the pathogenesis of IBD.However, animal studies to uncover their mechanistic functions during gut mucosal inflammation have yielded ambiguous results, reporting both pathogenic as well as protective functions.</p><p><bold>AIMS & METHODS:</bold> To characterize the role of the IL-33/ST2 axis following acute epithelial injury and mucosal repair in DSS-induced colitic mice.3% DSS was administered for 5d to BL6 wild-type (WT) and IL-33 KO mice.DSS was replaced with regular drinking water for 2 wks (recovery period).Another group of WT mice received DSS for 5d and IL-33 or vehicle (VEH) every other day during the recovery period.Mice were sacrificed either after DSS challenge or after 1 or 2 wks of recovery; control mice (CT) not exposed to DSS were sacrificed at similar time points.Disease Activity Index (DAI) was daily calculated, and endoscopic and histological evaluation of colons were performed.IHC, qPCR and Western blots were done on full-thickness colons for IL-33 and ST2 localization, mRNA expression, and evaluation of protein isoforms, respectively.</p><p><bold>RESULTS:</bold> DSS administered to WT mice resulted in increased body weight loss and DAI.More severe colitis was observed following DSS+1wk recovery vs. after 5d of DSS, which decreased after DSS+2wks recovery.IL-33 mRNA transcripts were dramatically elevated after DSS, and even more so following DSS+recovery vs. CT.ST2 mRNA expression was also increased after DSS+recovery vs. CT, while no difference was found between 5d of DSS challenge and CT.Full-length, bioactive IL33, ST2L and sST2 were expressed in all experimental groups; the cleaved, less active form of IL33 was increased in only DSS exposed mice vs. CT.IHC showed intense IL-33 and ST2 staining within the inflamed and ulcerated mucosa of DSS-treated mice.ST2 staining was more evident during the recovery phase following DSS, notably localized to subepithelial myofibroblasts in close proximity to areas of re-epithelialization. Remarkably, IL-33 KO mice showed increased colonic inflammation even after 2 wks recovery compared to after 5d DSS, suggesting the importance of IL-33 in mucosal healing.Likewise, IL-33 treatment of WT mice resulted in increased body weight, reduced DAI, and decreased colonic inflammation after 2 wks recovery vs.VEH.</p><p><bold>CONCLUSION:</bold> Our results suggest that activation of the IL-33/ST2 axis promotes epithelial repair and mucosal healing following acute epithelial injury during DSS-induced colitis.</p><p><bold>Contact E-mail Address:</bold> Dr. Loris Riccardo Lopetuso</p><p>lopetusoloris@libero.it</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> DSS-Colitis, Epithelial Repair, IL-33/ST2 axis, Mucosal Healing</p></sec><sec><title></title><p><bold>MONDAY, OCTOBER 14, 2013 15:45-17:15</bold></p><p><bold>Clinical management of pancreatic diseases: Important updates – Hall 8</bold></p></sec><sec><title>OP118 COMPARISON OF CHEMORADIOTHERAPY (CRT) AND CHEMOTHERAPY (CT) IN PATIENTS WITH LOCALLY ADVANCED PANCREATIC CANCER (LAPC) CONTROLLED AFTER 4 MONTHS OF GEMCITABINE WITH OR WITHOUT ERLOTINIB: FINAL RESULTS OF THE INTERNATIONAL PHASE III LAP 07 STUDY</title><p><bold>P. Hammel</bold><sup>1,*</sup>, F. Huguet<sup>2</sup>, J.-L. van Laethem<sup>3</sup>, D. Goldstein<sup>4</sup>, B. Glimelius<sup>5</sup> P. Artru I <sup>6</sup>, Borbath<sup>7</sup>, O. Bouché<sup>8</sup>, J. Shannon<sup>9</sup>, T. André<sup>10</sup>, F. Bonnetain<sup>11</sup>, C. Louvet<sup>12</sup></p><p><italic><sup>1</sup>Gastroenterologie-Pancreatology, hôpital Beaujon, APHP, Clichy, <sup>2</sup>radiotherapy, hopital Tenon, Paris, France, <sup>3</sup>Gastroenterologie-Pancreatology, hospital Erasmus, Bruxelles, Belgium, <sup>4</sup>oncology, princess Wales hospital, Sydney, Australia, <sup>5</sup>Oncology, University of Upsala, Upsala, Sweden, <sup>6</sup>Oncology, hôpital Mermoz, Lyon, France, <sup>7</sup>Gastroenterologie-Pancreatology, Clinique universitaire st Luc, Bruxelles, Belgium, <sup>8</sup>Gastroenterologie-Pancreatology, hôpital Robert Debré, Reims, France, <sup>9</sup>Oncology, Nepean center, Sydney, Australia, <sup>10</sup>Oncology, hôpital st Antoine, Paris, <sup>11</sup>Methodology & Quality of life unit, EA 3181, Besançon, <sup>12</sup>Oncology, Institut Mutualiste Montsouris, Paris, France</italic></p><p><bold>INTRODUCTION:</bold> CRT in patients with LAPC controlled after induction CT could be superior to continue CT alone (Huguet, JCO 2007). The role of erlotinib in LAPC is unknown.</p><p><bold>AIMS&METHODS:</bold> We aimed to define the role of 1) CRT after disease control with gemcitabine, 2) erlotinib in LAPC.</p><p>LAPC PS 0-2 patients were first randomized to gemcitabine alone or plus erlotinib 100 mg/d (R1, stratification: center, PS). Patients with controlled disease after 4 months were then randomized to 2 additional months of CT (Arm 1) or CRT (Arm 2) 54 Gy and capecitabine 1600 mg/m<sup>2</sup>/d (R2, stratification: center, initial arm). Patients receiving erlotinib at R1 had maintenance therapy after protocol completion. Quality control for radiotherapy included dummy runs and assessment of treated patients. Primary objective; overall survival (OS) in R2 patients. Secondary objectives; role of erlotinib on OS (R1), tolerance, predictive markers, and circulating tumor cells. Taking into account a 30% progression rate between R1 and R2, and 5% lost to follow-up, 722 patients were required to observe 392 deaths to demonstrate a median OS increase from 9 to 12 months (HR=0.75) in the CRT arm (2 sided a=5% and b=20%) with planned interim analyses using alpha spending function and O´Brien Fleming boundaries (to reject H0 or H1). Kaplan-Meier, log rank and univariate Cox tests were used.</p><p><bold>RESULTS:</bold> From 442 pts included for R1, 269 pts reached R2 (arm1: 136; arm 2: 133). Main baseline characteristics in arms 1/2: female 44%/56%, mean age 63/62, head tumor 65%/62%, PS 0 56%/48%. After a median follow-up of 36 m, 221 deaths had occurred allowing the planned interim analysis (information fraction 56.4%). OS in R2 pts was 16.5 m [15.5-18.5] and 15.3 m [13.9–17.3] in arms 1 and 2, respectively (HR=1.03 [0.79-1.34], p=0.83). IDMC has confirmed that the futility boundary for the hypothesis of CRT superiority was crossed and considered this as the final analysis of the study.oao</p><p><bold>CONCLUSION:</bold> Administrating CRT is not superior to continue CT in patients with controlled LAPC after 4 months of CT.</p><p><bold>Contact E-mail Address:</bold><email>pascal.hammel@bjn.aphp.fr</email></p><p><bold>Disclosure of Interest</bold>: P. Hammel Financial support for research from: Roche, Other: travel organisation, F. Huguet: None Declared, J.-L. van Laethem: None Declared, D. Goldstein: None Declared, B. Glimelius: None Declared, P. Artru: None Declared, I. Borbath: None Declared, O. Bouché Consultancy for: Roche, J. Shannon: None Declared, T. André: None Declared, F. Bonnetain: None Declared, C. Louvet: None Declared</p><p><bold>Keywords:</bold> chemotherapy, erlotinib, pancreatic adenocarcinoma, radiotherapy</p></sec><sec><title>OP119 THE IMPACT OF EXTRACORPOREAL SHOCKWAVE LITHOTRIPSY ON LARGE PANCREATIC CALCULI</title><p><bold>M. Tandan</bold><sup>1,*</sup>, D. Nageshwar Reddy<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology, Asian Institute Of Gastroenterology, Hyderabad, India</italic></p><p><bold>INTRODUCTION:</bold> Large pancreatic calculi are a sequalae of chronic pancreatitis (CP) and a challenge to the treating gastroenterologist. They produce disabling pain in most patients and are difficult to extract. ESWL is now accepted as the standard of care for large pancreatic calculi not amenable to the standard techniques</p><p><bold>AIMS&METHODS:</bold> A total of 1006 patients with large PD calculi were subjected to ESWL at Asian Institute of Gastroenterology, Hyderabad, India a high volume tertiary referral center. ESWL was performed with III generation electromagnetic lithotripter. A maximum of 5000 shocks were given per session and the aim was to fragment the calculi to <3mm size. Post ESWL, an Endoscopic Retrograde Cholangio Pancreatography (ERCP) was performed to clear the calculi. Follow up in terms of pain relief, analgesic use hospitalization and quality of life was noted. Short term follow up of 6 months, intermediate follow up between 24-60months and long term follow up beyond 60months (maximum 96months) was noted, which included 830, 364 and 272 patients respectively.</p><p><bold>RESULTS:</bold> Complete clearance was achieved in 76% and partial in another 17% following the initial ESWL and ERCP. 84% of patients were relieved of pain on short term follow up. An intermediate follow up revealed complete pain relief in 68.7% while 25.4% had mild to moderate pain. In the long term group, complete pain relief was seen 60% while 35% had mild to moderate pain. There was significant improvement in weight and quality of life in these groups. Though the numbers are small, a few patients also revealed improvement in their endocrine functions.</p><p><bold>CONCLUSION:</bold> ESWL is useful modality for large pancreatic duct calculi and offers good pain relief on short, intermediate and long term follow up. It should be offered as first line therapy in selected patients with large PD calculi.</p><p><bold>Contact E-mail Address:</bold><email>mantan_05@rediffmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> extracorporeal shockwave lithotripsy, large pancreatic ductal calculi, , long term follow up</p></sec><sec><title>OP120 PANCREATIC DUCT STENTING THERAPY IN CHILDREN WITH CHRONIC PANCREATITIS.</title><p><bold>G. Oracz</bold><sup>1,*</sup>, J. Pertkiewicz<sup>2</sup>, J. Kierkus<sup>1</sup>, M. Dadalski<sup>1</sup>, J. Ryzko<sup>1</sup></p><p><italic><sup>1</sup>Dep. of Gastroenterology, Hepatology and Feeding Disorders, The Childrens Memorial Health Institute, <sup>2</sup>Endotherapy, Warsaw, Poland</italic></p><p><bold>INTRODUCTION:</bold> Chronic pancreatitis (CP) is a rare disease in childhood. Because of the infrequent occurrence of this disease in childhood, the clinician may be unfamiliar with optimal diagnostic and management strategies. Although Endoscopic Retrograde Cholangiopancreatography (ERCP) is commomnly performed in children, the effect of pancreatic duct stenting therapy in children with CP is unknown.</p><p><bold>AIMS&METHODS:</bold> The aim of the study was to elaborate efficiency of endoscopic treatment (pancreatic duct stenting) in children with chronic pancreatitis.</p><p>208 children with CP hospitalized since 1988 to 2012 were enrolled into the study. ERCP was performed in 157 patients (75.5%). In 86 cases (55.5%) ERCP was done at least 2 times (from 2 to 21 examinations). Clinical and epidemiological data were recorded and analyzed. Results of endoscopic therapy were documented.</p><p>Number of pancreatitis episodes/year before and after treatment was analyzed.</p><p><bold>RESULTS:</bold> A total of 481 ERCP were performed. ERCP was successful in 475 cases (98.7%) with a complication rate 1.9% (9/475 procedures). ERCP showed mean 1.68 grade according to the Cambridge Classification System.</p><p>The total number of 223 pancreatic duct stenting procedures were performed in 72 children (34,6%) (41 girls and 31 boys; mean age 11.5 years, range: 3.5-17.9 years). In 26 cases (11,6%) 2 stents at the same time were inserted. Median number of stent replacement was 3 (from 1 to 21). Median interwal between stent replacement was 4.5 months (range 1-24 months). Stents obliteration occurred in 25 cases (11%). 3 of 72 patients still had their stents in place.</p><p>We observed statistically significant decrease in the number of pancreatitis episodes/year from 1.75 /year to 0.23 /year after endoscopic treatment <italic>(p<0.05).</italic></p><p>Pancreatic duct stenting was performed more frequently in the patients with hereditary pancreatitis (61.5%; <italic>p<0.05</italic>) and in the children with CP and anatomic anomalies of pancreatic duct (65%; <italic>p<0.05</italic>).</p><p><bold>CONCLUSION:</bold> 1. Pancreatic duct stenting therapy is a safe and effective procedure in children with CP.</p><p>2. This therapy should be especially recommended for children with hereditary pancreatitis and patients with anatomic anomalies of pancreatic duct.</p><p><bold>Contact E-mail Address:</bold><email>agoracz@wp.pl</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> children, Chronic Pancreatitis, ERCP</p></sec><sec><title>OP121 ACUTE PANCREATITIS: IS THE NEW ATLANTA CLASSIFICATION USEFUL IN CLINICAL PRACTICE?</title><p><bold>A. I. Fernandes</bold><sup>1,*</sup>, N. Almeida<sup>1</sup>, A. M. Ferreira<sup>1</sup>, A. Casela<sup>1</sup>, E. Camacho<sup>1</sup>, P. Amaro<sup>1</sup>, M. Ferreira<sup>1</sup>, J. M. Romãozinho<sup>1</sup>, C. Sofia<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal</italic></p><p><bold>INTRODUCTION:</bold> Acute pancreatitis (AP) is a common condition in clinical practice and a classification that standardizes concepts and establishes criteria of severity more accurately would be very useful.</p><p><bold>AIMS&METHODS:</bold> To evaluate the applicability of the new Atlanta classification in clinical practice and determine its correlation with the original one published in 1992. Retrospective study that included all admissions to the gastroenterology department due to AP during the year 2012 (106 episodes, 99 patients; M/F – 60/39, Mean age: 63±17 years). Clinical, analytical and imaging parameters were evaluated and different scores of severity were applied. Organ failure was defined according to the modified Marshall scoring system. We applied the original Atlanta classification of AP and its new revision. Statistical analysis was performed with SPSS v20.0.</p><p><bold>RESULTS:</bold><italic>Aetiologies</italic>: lithiasis-31.1%; alcohol-17%; post-ERCP-5.7%; hypertriglyceridemia-4.7%, Other-0.9%, Idiopathic-40.6%. <italic>Exacerbation of co-morbidities</italic> – 19.8%. <italic>Presence of Systemic Inflammatory Response Syndrome </italic>– 36.8%. <italic>Organ failure</italic>: 31 admissions (29.2%); transient (≤48h) – 35.5%, persistent (>48h) – 64.5%. <italic>Types of organ failure</italic>: respiratory – 26.4%; renal – 10.4%; cardiovascular – 5.7%. <italic>Severity scoring systems</italic>: Ranson ≥3 – 34%; APACHE II ≥8 – 43.4%; BISAP ≥3 – 24.5%. <italic>Local complications</italic>: acute peripancreatic fluid collection – 29.2%; acute necrotic collection – 13.2%; pseudocyst – 2.8%; walled-off necrosis – 2.8%. <italic>Need for surgical treatment</italic> – 6.6%. <italic>Mortality</italic> – 4.7%. <italic>Original Atlanta classification</italic>: mild AP – 49.1%; severe AP – 50.9%. <italic>Revised Atlanta classification</italic>: mild AP – 52.8%; moderately severe AP – 28.3%; severe AP – 18.9%. <italic>Concordance of the two classifications</italic>: 54.7% considering all admissions; 76.3% excluding the moderately severe AP in the revised classification. The disagreements occurred because a significant number of patients with mild AP in the new classification had positive traditional severity scores (Ranson ≥3 – 16.1%; APACHE II ≥8 – 32.5%). Statistically significant differences between severe, moderately severe and mild AP were: length of hospital stay (31.1±29.5 vs 14.5±6.1 vs 9.3±4 days), referral to surgery (25% vs 6.7% vs 0%) and mortality (25% vs 0% vs 0%).</p><p><bold>CONCLUSION:</bold> The new Atlanta classification is useful in clinical practice since it demonstrated a good correlation with the length of hospital stay, need for surgical treatment and mortality. However, in some cases, a correct classification of severity can only be established at the end of hospitalization. Moreover, the disagreement with the traditionally used severity scores could be problematic.</p><p><bold>Contact E-mail Address:</bold><email>xanafmuc@hotmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Acute Pancreatitis, Atlanta Classification, organ failure</p></sec><sec><title>OP122 PANCREATIC CYST WALL STUDY WITH CONFOCAL ENDOMICROSCOPY (NCLE): IS IT POSSIBLE TO DISTINGUISH MUCINOUS VS NON-MUCINOUS CYST?</title><p><bold>H. Bertani</bold><sup>1,*</sup>, V. G. Mirante<sup>1</sup>, R. Manta<sup>1</sup>, M. Manno<sup>1</sup>, A. Caruso<sup>1</sup>, R. Conigliaro<sup>1</sup></p><p><italic><sup>1</sup>Endoscopy Unit, Nuovo Ospedale Civile S.Agostino Estense, Modena, Italy</italic></p><p><bold>INTRODUCTION:</bold> Preoperative diagnosis of pancreatic cysts benefits from integrating the clinical, radiological, and cytological features. As patient management algorithms evolve to increasingly nonsurgical options, accuracy in distinguishing mucinous from nonmucinous and benign from malignant mucinous cysts is important.. EUS-FNA represents one of the step in the work up of cystic lesions to differentiate between mucinous and non mucinous lesions, however its diagnostic accuracy still remains low. Confocal laser endomicroscopy is now well established as a valid technique to differentiate neoplastic vs non-neoplastic tissue in the GI tract. A novel needle based confocal laser endomicropscy probe (nCLE), introduced through an FNA needle has been presented as able to visualize epithelial layer of cystic wall and consequently to differentiate between non-mucinous, mucinous non- malignant and malignant lesions.</p><p><bold>AIMS&METHODS:</bold> The aim of the study was to identify specific imaging criteria to differentiate mucinous vs non mucinous cysts. After nCLE procedure, all patients underwent aspiration of cystic fluid for CEA, amylase and cytology analysis.</p><p>All nCLE findings were compared to cytology, Cystic fluid analysis and EUS findings if surgical specimen was not available and discussed with pathologist in order to recognize typical findings of mucinous vs non mucinous.</p><p>Aim: In this pilot study 6 patients undergoing EUS for pancreatic cysts were evaluated using the nCLE.</p><p><bold>RESULTS:</bold> In all six patients nCLE was able to identify the epithelial layer of the cysts. In 5 of 6 patients nCLE images featured finger-like projection suitable with papillary structures typical for mucinous neoplasm. In this 5 patients CEA levels, amylase and cytology confirmed the suspicion for mucinous lesion.</p><p><bold>CONCLUSION:</bold> In this pilot study, nCLE was able to differentiate mucinous vs non-mucinous cysts with high accuracy and confidence. Mulitcentric studies on this topic are ongoing.</p><p><bold>Contact E-mail Address:</bold><email>helga.bertani@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Confocal Laser Microscopy, Pancreatic cyst </p></sec><sec><title>OP123 THE EFFICACY OF SUPPOSITORY NAPROXAN TO PREVENT POST ERCP PANCREATITIS: A DOUBLE BIND PLACEBO CONTROLED TRIAL.</title><p><bold>F. Mansour-Ghanaei</bold><sup>1,*</sup>, Z. Taherzadeh<sup>1</sup>, F. Joukar<sup>1</sup></p><p><italic><sup>1</sup>Gastrointestinal and Liver Diseases Research Cente, GUILAN UNIVERSITY OF MEDICAL SCIENCES, Rasht, Iran, Islamic Republic Of</italic></p><p><bold>INTRODUCTION:</bold> Acute pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). Despite significant advances in endoscopic technology, equipment, and accessory in ERCP the incidence has not changed over the past thirty yea rs .We aimed to evaluate the efficacy of rectally administered naproxen 500mg for the prevention of post-ERCP pancreatitis</p><p><bold>AIMS&METHODS:</bold> In a prospective, single-center, randomized, double-blind controlled trial during February 2011 to March 2012, 203 eligible patients who underwent ERCP were enrroled in this study, then patients with random block were divided to drug or placebo group . Of this 105 patients were in drug and 98 patients were in placebo groups received a suppository containing naproxen, 500 mg, or an inert placebo immediately before ERCP respectively .At the end of each procedure, the endoscopists recorded the total time of the procedure, the number of attempts at cannulation, the number of pancreatic duct cannulations, pancreatic acinarization on radiography, and whether a sphincterotomy, a needle knife papillotomy, or stent placement were performed, and final diagnosis. The main outcome of the study was complicated pancreatitis. All patients in clinical protests: abdominal pain typical for pancreatitis, increased more than 3-fold amylase enzyme were monitored for 24 hours after procedure.</p><p><bold>RESULTS:</bold> Of 203 patients participated in the project, 28 (13.7%) developed post ERCP pancreatitis. Of this, 19 patients (19.4%) in the placebo group and 9 patients (8.6%) in the Naproxan group developed pancreatitis. Using the chi square test showed significant reduction of post ERCP pancreatitis after taking Naproxan group in comparetion to placebo groups were observed at p = (0.02).In this study, a known risk factor in the incidence of pancreatitis after ERCP were: increas age prolong procedure time and number of pancreatic duct injection.</p><p><bold>CONCLUSION:</bold> This trial showed that rectal Naproxen given immediately before ERCP can reduce the incidence and severity of post-ERCP pancreatitis as shown in other similar study with other NSAIDS</p><p><bold>Contact E-mail Address:</bold><email>ghanaie@yahoo.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Pancreatitis, post ERCP , Suppository Naproxenz</p></sec><sec><title></title><p><bold>MONDAY, OCTOBER 14, 2013 15:45-17:15</bold></p><p><bold>Update on Barrett's oesophagus – Hall 7</bold></p></sec><sec><title>OP124 THE COMBINATION OF AUTOFLUORESCENCE IMAGING AND PROBE-BASED CONFOCAL LASER ENDOMICROSCOPY CAN ACCURATELY DIAGNOSE DYSPLASIA IN BARRETT’S OESOPHAGUS</title><p><bold>M. Di Pietro</bold><sup>1,*</sup>, E. Bird-Lieberman<sup>1</sup>, X. Liu<sup>1</sup>, M. O'Donovan<sup>2</sup>, R. C. Fitzgerald<sup>1</sup></p><p><italic><sup>1</sup>HUTCHISON MRC Cancer Cell Unit, <sup>2</sup>Histopathology, Cambridge University Hospitals, Cambridge, United Kingdom</italic></p><p><bold>INTRODUCTION:</bold> Probe-based confocal laser endomicroscopy (pCLE) and narrow band imaging with zoom (NBI-Z) allow real time prediction of histology in Barrett’s oesophagus (BO), but have a narrow field of view. Autofluorescence imaging (AFI) can locate areas of potential dysplasia.</p><p><bold>AIMS&METHODS:</bold> The aims of the study were to evaluate the diagnostic accuracy for dysplasia of the combination of AFI and pCLE and to compare pCLE with NBI-Z for the prediction of the dysplasia status. 39 patients with BO were recruited at a single tertiary referral centre (non-dysplastic BO n=18, indefinite for dysplasia (ID) n=4, BO with low grade dysplasia (LGD) n=8, BO with high grade dysplasia (HGD) n=3, BO with intramucosal cancer (IMC) n=6). AFI positive (AFI+) areas were assessed as regular or irregular by NBI-Z and pCLE, according to published criteria (1, 2). If pCLE irregularity relied on at most 2/6 criteria on 1 glandular structure only this was recorded as focal irregularity. Targeted biopsies were taken from AFI+ areas as well as from random quadrantic locations (Seattle protocol). Correlation between imaging and histological outcomes was analysed on a per-location (AFI+ areas individually) and per-patient (overall histology) basis. Statistical analyses were performed using chi-square test and paired t-test.</p><p><bold>RESULTS:</bold> 130 AFI-targeted areas were included in the analysis. Both NBI-Z and pCLE irregularity correlated with any grade of dysplasia (p<0.0001). Also pCLE focal irregularity associated with any grade of dysplasia (p=0.017), but failed to differentiate lower from higher degrees of dysplasia (ID/LGD vs HGD/EC, p=0.61). In the per-location analysis, sensitivity and specificity of pCLE were 100% and 69% respectively for a diagnosis of HGD/IMC; and 71% and 80% for a diagnosis of any grade of dysplasia. pCLE had a higher sensitivity for dysplasia (P=0.0004) than NBI, but a lower specificity (p=0.004). In the per-patient analysis, pCLE correctly classified all dysplastic patients, except one with ID, leading to a higher diagnostic accuracy than NBI-Z (table 1). pCLE analysis required shorter time than the Seattle protocol (p=0.0021).</p><p>Table 1. Per-patient analysis
<table-wrap id="table18-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="2" colspan="1"></th><th colspan="2" rowspan="1"><hr></hr>HGD/EC</th><th rowspan="2" colspan="1">p value pCLE vs NBI-Z</th><th colspan="2" rowspan="1"><hr></hr>Any dysplasia</th><th rowspan="2" colspan="1">p value pCLE vs NBI-Z</th></tr><tr><th rowspan="1" colspan="1">AFI + NBI-Z</th><th rowspan="1" colspan="1">AFI + pCLE</th><th rowspan="1" colspan="1">AFI + NBI-Z</th><th rowspan="1" colspan="1">AFI + pCLE</th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">Sensitivity</td><td rowspan="1" colspan="1">87%</td><td rowspan="1" colspan="1">100%</td><td rowspan="1" colspan="1">Ns</td><td rowspan="1" colspan="1">60%</td><td rowspan="1" colspan="1">95%</td><td rowspan="1" colspan="1">0.007</td></tr><tr><td rowspan="1" colspan="1">Specificity</td><td rowspan="1" colspan="1">70%</td><td rowspan="1" colspan="1">55%</td><td rowspan="1" colspan="1">ns</td><td rowspan="1" colspan="1">78%</td><td rowspan="1" colspan="1">82%</td><td rowspan="1" colspan="1">ns</td></tr><tr><td rowspan="1" colspan="1">Accuracy</td><td rowspan="1" colspan="1">74%</td><td rowspan="1" colspan="1">64%</td><td rowspan="1" colspan="1">ns</td><td rowspan="1" colspan="1">67%</td><td rowspan="1" colspan="1">87%</td><td rowspan="1" colspan="1">0.03</td></tr></tbody></table></table-wrap></p><p><bold>CONCLUSION:</bold> The combination of AFI and pCLE allows accurate in vivo diagnosis of dysplasia in BO and has the potential to enable clinicians to dispense with multiple random biopsies currently taken during endoscopic surveillance</p><p><bold>REFERENCES:</bold></p><p>1. Kara MA, Ennahachi M, Fockens P, ten Kate FJ, Bergman JJ. Detection and classification of the mucosal and vascular patterns (mucosal morphology) in Barrett's esophagus by using narrow band imaging. Gastrointest Endosc. 2006 Aug;64(2):155-66.</p><p>2. Gaddam S, Mathur SC, Singh M, Arora J, Wani SB, Gupta N, et al. Novel probe-based confocal laser endomicroscopy criteria and interobserver agreement for the detection of dysplasia in Barrett's esophagus. Am J Gastroenterol. 2011 Nov;106(11):1961-9.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> autofluorescence imaging, Barrett's oesophagus, confocal laser endomicroscopy, Dysplasia, Narrow-band imaging, oesophageal adenocarcinoma</p></sec><sec><title>OP125 ENDOSCOPIC FOLLOW-UP INTERVALS OF INDEFINITE FOR DYSPLASIA IN BARRETT’S ESOPHAGUS SHOULD BE SIMILAR TO THOSE RECOMMENDED FOR LOW-GRADE DYSPLASIA: A DUTCH NATIONWIDE COHORT STUDY</title><p><bold>C. Kestens</bold><sup>1,*</sup>, M. Leenders<sup>1</sup>, G. J. A. Offerhaus<sup>2</sup>, L. I. H. Overbeek<sup>3</sup>, J. W. P. M. van Baal<sup>1</sup>, P. D. Siersema<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology and Hepatology, <sup>2</sup>Pathology, University Medical Center Utrecht, <sup>3</sup>Stichting Palga, Utrecht, Netherlands</italic></p><p><bold>INTRODUCTION:</bold> Histological assessment of Barrett’s esophagus (BE) is the only diagnostic tool for risk stratification of the progression to esophageal adenocarcinoma (EAC). The histological diagnosis indefinite for dysplasia (IND) in BE is used when the decision regarding non-dysplastic or dysplastic cannot be made. Due to this uncertainty combined with the unknown risk of progression of IND to low-grade dysplasia (LGD), high-grade dysplasia (HGD) or EAC, follow-up includes repeat endoscopy with biopsies.</p><p><bold>AIMS&METHODS:</bold> The aim of the present study was to assess the neoplastic progression rate of IND in a nationwide cohort of patients with IND in BE in the Netherlands.Patients with a first diagnosis of IND in BE were selected between 2002-2011 using PALGA, a nationwide registry of histopathology diagnoses in the Netherlands. Exclusion criteria were gastric type BE or intestinal with dysplasia prior to or simultaneously with initial IND diagnosis. Patients were followed during surveillance until treatment for HGD, detection of EAC or the last pathology report in the database.</p><p><bold>RESULTS:</bold> In total, 1258 patients met the in- and exclusion criteria of whom 842 (67%) had endoscopic follow-up. Of these, 70% were male, 17.6% were diagnosed in a university center and in 7%, the diagnosis was based on histological revision. Patients who had endoscopic follow-up were significantly younger than those without. Patients were followed-up for a total of 2585 person-years (mean 3.01, SD 2.6), during which 189 (22%) patients progressed to LGD (138), HGD (21) or EAC (30) (incidence 7.3(95% CI 6.3-8.4)), while the incidence from IND to HGD/EAC was 2.0(95% CI 1.5-2.6) per 100 person years. After excluding cases with HGD/EAC within 1 year after IND diagnosis (n=16), the incidence rates were 6.7(95% CI 5.8-7.8) and 1.4(95% CI 1.0-1.9), respectively. Older age was an independent risk factor for neoplastic progression (HR 1.36, 95%CI 1.2-1.6) in contrast to gender, university setting and histological revision.</p><p><bold>CONCLUSION:</bold> In this large cohort of patients with BE, the incidence rate of HGD/EAC following a diagnosis of IND was 1.4 per 100 person-years. This is not different from reported incidence rates of LGD to HGD/EAC in the literature and suggests that surveillance intervals in patients with IND should not be different from those in patients with LGD.</p><p><bold>Contact E-mail Address:</bold><email>c.kestens@umcutrecht.nl</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Barrett's esophagus, Indefinite for dysplasia, Neoplastic progression </p></sec><sec><title>OP126 INCREASING INCIDENCE OF BARRETT’S ESOPHAGUS AND ESOPHAGEAL ADENOCARCINOMA IN THE GENERAL POPULATION</title><p><bold>G. M. Masclee</bold><sup>1,2,*</sup>, P. Coloma<sup>1</sup>, E. Kuipers<sup>2</sup>, M. Sturkenboom<sup>1</sup></p><p><italic><sup>1</sup>Medical Informatics, <sup>2</sup>Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, Netherlands</italic></p><p><bold>INTRODUCTION:</bold> Barrett’s esophagus (BE) is an established risk factor for the development of esophageal adenocarcinoma (EAC). Several studies have reported an increasing incidence of BE, but estimates vary substantially. There are limited data on the incidence of EAC among BE patients in a population setting. Our study aimed to determine trends in age- and sex-stratified incidence of BE and EAC in the general population and incidence of EAC among patients with BE.</p><p><bold>AIMS&METHODS:</bold> Data were retrieved from The Health Improvement Network (THIN) database (DB), a primary care DB containing electronic medical records of 11.1 million patients from the United Kingdom (UK). BE and EAC cases were identified using disease-specific READ codes. The study period was from January 1st 1995 to December 31st 2012. Analyses using standardized software provided age-and sex-specific incidence rates (IR) both for BE and for EAC.</p><p><bold>RESULTS:</bold> From a study population of 6,707,493 subjects, we identified 11,616 incident BE cases and 1,606 incident EAC cases corresponding to 56,294,380 person-years (PYs). IR of BE increased linearly with age: IR was 13.5/100,000 PYs for patients >40 years of age up to 79.5/100,000 PYs for 70-74 years, after which IRs remained stable. IR of BE was 2-3 times higher for males than females across all age groups. IR for BE increased seven-fold from 1995 to 2003 and thereafter remained fairly stable up to 2012. Similar increases were observed for males and females. IRs of EAC in the general population increased from 0.53/100,000 PYs for 40-44 years of age to 14.1/100,000 PYs for those aged 80-84 years; this increase was more pronounced in males. Among BE patients, 49 (0.4%) were diagnosed with EAC at least one year after BE diagnosis. IR of EAC among BE patients increased from 9.9/100,000 PYs for those aged 40-44 years to 58.7/100,000 PYs for those aged 75-79 years. This increase was especially seen for males >65 years.</p><p><bold>CONCLUSION:</bold> The incidence rate of BE in the UK has increased substantially in both males and females from 1995 to 2003, but has remained stable thereafter. Less than 1% of patients with BE are diagnosed with EAC one year after BE diagnosis. The incidences of both BE and EAC increase with advancing age, particularly in males aged >65 years. These findings may help tailor endoscopic surveillance strategies among patients with BE.</p><p><bold>Contact E-mail Address:</bold><email>g.masclee@erasmusmc.nl</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> BARRETT´S ESOPHAGUS, Clinical Epidemiology, esophageal adenocarcinoma, Incidence</p></sec><sec><title>OP127 HIGH DEFINITION MAGNIFICATION ENDOSCOPY WITH MULTIPLE BAND IMAGING VERSUS STANDARD WHITE LIGHT ENDOSCOPY IN BARRETTS ESOPHAGUS. A PROSPECTIVE RANDOMIZED BLINDED CROSS-OVER STUDY.</title><p><bold>S. O. Bratlie</bold><sup>1,*</sup>, A. Edebo<sup>1</sup>, E. Johnsson<sup>1</sup>, C. Jönson<sup>1</sup></p><p><italic><sup>1</sup>Sahlgrenska University Hospital, Göteborg, SWEDEN, DEP OF CLINICAL RESEARCH, Gothenburg, Sweden</italic></p><p><bold>INTRODUCTION:</bold> Barretts Esophagus (BE) is a metaplastic mucosal transformation adjacent to the esophagogastric junction (EGJ), due to Gastro Esophageal Reflux Disease (GERD). Specialized Intestinal Metaplasia (SIM) is associated to the development of esophageal adenocarcinoma (EAC). The prevalence of EAC is rising compared to other malignancies. The poor prognosis of an invasive cancer in the esophagus advocates surveillance. Traditionally, surveillance for BE is standard White Light Endoscopy (WLE) and 4 quadrant biopsies every 1-2 cm of metaplastic mucosa oral to the EGJ[1]. Technical improvements like High Definition Magnification Endoscopy (HDME) and Multiple Band Imaging (MBI) may improve diagnostic outcome of surveillance, but has not yet been thoroughly investigated[2].</p><p><bold>AIMS&METHODS:</bold> The aim was to compare the yield of neoplasia in targeted biopsies (HDME (Fujinon EG-590ZW) + MBI) versus 4-quadrant biopsies (WLE (Olympus GIF-Q160)). A prospective single-centre investigator- and pathologist-blinded randomized cross-over trial was performed on patients with confirmed SIM in a tertiary referral centre. Macroscopic extent of BE according to the Prague C&M Criteria, yield of neoplasia, number of biopsies and time-consumption was measured[3].</p><p><bold>RESULTS:</bold> Of 255 referred patients, 111 patients were enrolled for the study. 107 patients completed the study. 59 were randomized to HDME with MBI and 51 to WLE as the first investigating procedure. 4 out of 107 patients showed HGN in the BE. 3 in the HDME-group and 1 in the WLE-group. The HGN found in the WLE-group were diagnosed as a type 0-IIa polyp at HDME-MBI, but histology only showed LGN. There was no significant difference regarding the yield of LGN. BE extent according to the Prague C & M Criteria was significantly longer when measured by WLE. The number of biopsies taken during WLE was 3 times as high as HDME-MBI (mean 11,7 vs 3,8). Time-consumption was equal.</p><p><bold>CONCLUSION:</bold> The relevance of endoscopic BE-surveillance has been questioned. General recommendations have until now been WLE with 4-quadrant biopsies depending on prior surveillance results. In this randomized cross-over study, we found equal or more neoplasia with HDME-MBI despite less biopsies taken. The finding of 4 HGN among 107 referred patients without prior known neoplasia supports the recommendation of surveillance being performed, and we conclude that future BE surveillance should be performed with HDME in a BE-specialized setting. Whether an additional 4-quadrant biopsy regimen is necessary to even further avoid EAC-development remains to be investigated.</p><p><bold>REFERENCES:</bold></p><p>1. Spechler, S.J., et al., <italic>American Gastroenterological Association medical position statement on the management of Barrett's esophagus.</italic> Gastroenterology, 2011. 140(3): p. 1084-91.</p><p>2. Sharma, P., et al., <italic>Magnification chromoendoscopy for the detection of intestinal metaplasia and dysplasia in Barrett's oesophagus.</italic> Gut, 2003. 52(1): p. 24-7.</p><p>3. Sharma, P., et al., <italic>The development and validation of an endoscopic grading system for Barrett's esophagus: the Prague C & M criteria.</italic> Gastroenterology, 2006. 131(5): p. 1392-9.</p><p><bold>Contact E-mail Address:</bold><email>svein.olav.bratlie@vgregion.se</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Barrett’s esophagus, cancer, Endoscopy, surveillance</p></sec><sec><title>OP128 RADIOFREQUENCY ABLATION COMBINED WITH ENDOSCOPIC MUCOSAL RESECTION IS SAFE AND EFFECTIVE IN ERADICATING DYSPLASTIC BARRETT'S OESOPHAGUS: UPDATED OUTCOMES FOR THE LARGEST REPORTED AUSTRALIAN EXPERIENCE WITH RFA</title><p><bold>G. Cameron</bold><sup>1</sup>, C. Jayasekera<sup>2</sup>, R. Williams<sup>3</sup>, F. Amico<sup>2</sup>, F. Macrae<sup>2</sup>, P. Desmond<sup>1</sup>, A. Taylor<sup>1,*</sup></p><p><italic><sup>1</sup>Gastroenterology Department, St Vincent's Hospital, <sup>2</sup>Gastroenterology Department, Royal Melbourne Hospital, <sup>3</sup>Pathology Department, St Vincent's Hospital , Melbourne, Australia</italic></p><p><bold>INTRODUCTION:</bold> Radiofrequency ablation (RFA) combined with endoscopic mucosal resection (EMR) for visible lesions is effective in eradicating dysplastic Barrett’s oesophagus (BE) providing a credible alternative to surgery for high grade dysplasia (HGD) and early mucosal cancer (IMC) in BE.<sup>1</sup></p><p><bold>AIMS&METHODS:</bold> To report latest efficacy and safety outcomes of RFA combined with EMR in patients with dysplastic BE treated at Melbourne’s two quaternary referral centres. Methods: Patients referred from 2008-April 2013 for treatment of BE were entered prospectively into a central database. Patients underwent assessment endoscopy with white light, narrow band +/- confocal endomicroscopy and had EMR of visible lesions. Subsequent clinical and histological outcomes were recorded. Patients deemed appropriate for RFA (treatment group) were treated at ∼3 monthly intervals until remission of dysplasia (CR-D) and/or Barrett’s (CR-BE) was achieved. Remission rates of CR-D (=no dysplasia on biopsy) and CR-BE (=no intestinal metaplasia on biopsy and no visible BE) were assessed. Time to achieve remission and number of RFA treatments required to reach these endpoints were recorded. Adverse events were defined as surgery, hospital admission, bleeding requiring blood transfusion, unplanned endoscopic intervention.</p><p><bold>RESULTS:</bold> 209 patients have been assessed to date. 165 were amenable to combined endoscopic therapy (24 await RFA, 18 required EMR only). Of 123 patients (108M) in the treatment group (RFA+/-EMR (69)) median age was 66 (39-87); median M length 5cm (0.5-18); 86 (70%) had HGD or IMC as worst prior pathology. Kaplan-Meier analysis showed 97% of the treatment group achieved CR-D within 30m and 74% achieved CR-BE within 36m. Median time to CR-D was 7.4m (0.4-41.5), median RFA=2 (1-6). Median time to CR-BE=13.2 (2.9-34.4); median RFA=2(1-6). Of 182 EMR procedures there was 1 perforation requiring surgery, 13 hospital admissions for observation or unplanned endoscopic procedure. Of 262 RFA procedures there were 5 complications requiring admission (2 mucosal tears, 3 post-RFA bleeds).</p><p><bold>CONCLUSION:</bold> Our updated data supports that RFA combined with EMR is effective in achieving CR-D and CR-BE in the majority of patients with dysplastic BE with low risk of serious complication. A subgroup of patients with dysplastic BE have poorer response to RFA. Further studies are needed to determine risk factors for poor responders.</p><p><bold>REFERENCES:</bold></p><p>1. Shaheen et al. Radiofrequency Ablation in Barrett’s Esophagus with Dysplasia. N Engl J Med 2009;360:2277-88.</p><p><bold>Contact E-mail Address:</bold><email>georgina.cameron@svhm.org.au</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Barrett's oesophagus, Outcomes, Radiofrequency ablation, Treatment response</p></sec><sec><title>OP129 ACETIC-ACID GUIDED ENDOSCOPIC RESECTION OF DYSPLASTIC BARRETT’S EPITHELIUM IN A LARGE UK SERIES – IS ROUTINE RFA REQUIRED?</title><p><bold>P. J. Basford</bold><sup>1,*</sup>, G. Longcroft-Wheaton<sup>2</sup>, R. Bhattacharyya<sup>1</sup>, P. Bhandari<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology, PORTSMOUTH HOSPITALS NHS TRUST, <sup>2</sup>Gastroenteroloy, Portsmouth Hospitals NHS Trust, Portsmouth, United Kingdom</italic></p><p><bold>INTRODUCTION:</bold> Endoscopic resection (ER) is an established effective treatment for high grade intraepithelial neoplasia (HGIN) and intramucosal cancer (IMC) arising in Barrett’s oesophagus. ER can lead to recurrence so it is suggested that all patients should undergo radiofrequency ablation (RFA) after ER as a complimentary treatment strategy. However no comparative study to support this concept has been performed. Acetic acid chromoendoscopy has been shown to be an effective method of localising and delineating dysplastic areas of Barrett’s oesophagus in a high risk population.</p><p><bold>AIMS&METHODS:</bold> All ER procedures between January 2005 and April 2013 were recorded in a prospective database which was analysed. Demographic data, histology, procedure success, long-term outcome and complications were assessed. Acetic-acid guided ER was the predominant treatment strategy with the aim of removing all neoplasia visible with acetic acid chromoendoscopy. Routine RFA was not used.</p><p><bold>RESULTS:</bold> 103 patients were treated for dysplastic Barrett’s oesophagus or early Barrett’s cancer by ER. The mean age at first procedure was 69 years and 85% of the patients were male. Mean initial Barrett’s length was 5.3cm. 22 of 103 patients had advanced histological features on the initial ER specimen and were referred for surgical or oncological treatment. Of the remaining 81 cases the initial ER specimen showed intramucosal cancer (IMC) in 34, high grade dysplasia (HGD) in 45 and low grade dysplasia in 2. 67 of these 81 cases have follow-up data with a mean duration of 36.5 months. 58 of 67 cases (86.6%) have sustained eradication of HGIN/IMC by ER with follow-up. 53 of 67 (79.1%) cases have complete remission of all dysplasia. 5 patients were referred for surgery for advanced disease (4) or extensive bulky low grade dysplasia not amenable to ER/ablation (1). ER was successful in a mean of 1.45 procedures per patient (range 1-3). Complication rate was 4.7% (4 bleeds, 1 microperforation, 2 strictures). Additional RFA was used in 14 cases.</p><p><bold>CONCLUSION:</bold> Acetic-acid guided ER is an effective and safe treatment for HGIN/IMC within Barrett’s oesophagus without the need for routine RFA and can be performed successfully in a UK centre. The results for clearance rate of HGD/IMC and of all dysplasia in this series are almost identical to those reported in the UK RFA registry in which routine RFA was used.</p><p><bold>REFERENCES:</bold></p><p>1. Haidry et al Gastroenterology 2013 doi: 10.1053/j.gastro.2013.03.045 [Epub ahead of print]</p><p><bold>Contact E-mail Address:</bold><email>petebasford@hotmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Barrett's neoplasia, Endoscopic resection, radiofrequency ablation</p></sec><sec><title></title><p><bold>MONDAY, OCTOBER 14, 2013 15:45-17:15</bold></p><p><bold>Endoscopic techniques which will change tomorrow's practice – Hall 6</bold></p></sec><sec><title>OP130 COMPARISON OF BLOC BIOPSY USING SUBMUCOSAL ENDOSCOPY WITH MUCOSAL FLAP METHOD VERSUS EUS-FNA FOR GASTROINTESTINAL SUBEPITHELIAL TUMOR TISSUE SAMPLING: A PROSPECTIVE STUDY WITH CROSSOVER DESIGN</title><p><bold>H. Kobara</bold><sup>1,*</sup>, H. Mori<sup>1</sup>, S. Fujihara<sup>1</sup>, N. Nishiyama<sup>1</sup>, M. Ayaki<sup>1</sup>, T. Yachida<sup>1</sup>, K. Kato<sup>1</sup>, Y. Aritomo<sup>1</sup>, M. Ono<sup>1</sup>, H. Kamada<sup>1</sup>, M. Oryu<sup>1</sup>, K. Tsutsui<sup>1</sup>, R. Haba<sup>2</sup>, T. Masaki<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology and Neurology, <sup>2</sup>Diagnotic Pathology, Kagawa University , Kagawa, Japan</italic></p><p><bold>INTRODUCTION:</bold> The diagnostic procedure acquiring adequate tissue sampling for gastrointestinal subepithelial tumors (SETs) is not reliable because of small sample size and technical failure. Appropriate new techniques are required to obtain adequate specimens for immunohistochemical analysis in this field. We have demonstrated the usefulness of bloc biopsy using submucosal endoscopy with mucosal flap method (SEMF) as a novel method for collecting tumor tissue under direct vision to assist in the diagnosis of SETs.</p><p><bold>AIMS&METHODS:</bold> We enrolled a total of 20 patients with SETs presenting primarily endoluminal growth between November 2011 and April 2013 (our hospital ethics committee approval, UMIN registration No. 000006754) in this prospective study with crossover design. This bloc biopsy with SEMF consists of five major procedures; the ESD procedure, the short mucosal flap method, the bloc biopsy acquiring a specimen of sufficient size (∼5 mm), and the clip closure from the tumor side. Our aim was to investigate the safety and histological diagnosis of bloc biopsy with SEMF compared to EUS-FNA for SETs. The immunohistological diagnostic rate and complication rate by both methods were evaluated .</p><p><bold>RESULTS:</bold> The immunohistological diagnostic rate of all 20 cases were 100% (20/20) in bloc biopsy and 35% (7/20) in EUS-FNAB. (P<0.05) The results of the immunopathological analysis provided 12 GISTs, 3 leiomyomas, 2 aberrant pancreases, 1 schwannoma, 1 duplication cyst and 1 lipoma among SETs. No complications, such as bleeding requiring blood transfusion or perforation, occurred during or after the procedures (complication rate: 0%) in both methods.</p><p><bold>CONCLUSION:</bold> Bloc biopsy with SEMF exhibited significantly a higher advantage over EUS-FNA for determining the definitive pathological diagnosis, guiding decisions regarding therapeutic planning.</p><p><bold>REFERENCES:</bold></p><p>1. Hideki Kobara. Bloc biopsy by tunneling method using the endoscopic submucosal dissection for upper gastrointestinal submucosal tumor. Endoscopy 2012; 44: E197–E198</p><p>2. Hideki Kobara. Bloc biopsy by using submucosal endoscopy with a mucosal flap method for gastric subepithelial tumor tissue sampling (with video). Gastrointest Endosc 2013;77:141-145</p><p><bold>Contact E-mail Address:</bold><email>kobara@med.kagawa-u.ac.jp</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> bloc biopsy , immunohistological diagnosis, subepithelial tumors, submucosal endoscopy, tissue sampling method</p></sec><sec><title>OP131 IMAGE-GUIDED CELL THERAPY ON A MODEL OF ENTEROCUTANEOUS FISTULA IN MICE.</title><p><bold>G. Rahmi</bold><sup>1,2,*</sup>, L. Pidial<sup>3</sup>, A. Andriola<sup>4</sup> G. Autret V <sup>2</sup>, Fitoussi<sup>2</sup>, F. gazeau<sup>5</sup>, C. wilhelm<sup>5</sup>, C. Cellier<sup>1</sup>, O. Clément<sup>2,6</sup></p><p><italic><sup>1</sup>Hepatogastroenterology, <sup>2</sup>Laboratoire de Recherche en Imagerie. INSERM U970., <sup>3</sup>hôpital européen georges pompidou, <sup>4</sup>Laboratoire Matière et Systèmes Complexes, <sup>5</sup>Laboratoire Matière et Systèmes Complexes, Université Paris Diderot, <sup>6</sup>Radiologie, hôpital européen georges pompidou, Paris, France</italic></p><p><bold>INTRODUCTION:</bold> The failure rate in the treatment of digestive fistula either postoperative or related to Crohn's disease remains high. The aim was to evaluate the efficacy of an image-guided treatment with dual labeled mesenchymal stem cell (MSC) sheets from human bone marrow in the healing process of a post-surgical fistula model (tract connecting the cecum and the skin) in nude mice.</p><p><bold>AIMS&METHODS:</bold> Prospective randomized controlled trial from March to August 2012. At D3 after surgery, 3 groups: control mice (CM=10), mice grafted with unlabeled cell sheets (UCS=10) and mice grafted with dual-labeled cell sheets (superparamagnetic nanoparticles of iron oxide and PKH67 fluorochrome) (LCS=8). Cell sheets consisted of a MSC double layer obtained by the detachment of confluent cells from commercial thermo-responsive culture surfaces . Imaging evaluation at D3, D10, D17. MRI (Bruker4.7T cryoprobe) and a video-confocal microscopy miniprobe (VCF) named Cellvizio were performed.</p><p><bold>RESULTS:</bold> Treated mice presented mild or absent inflammatory clinical response compared to control mice (6% vs 60%). 2 cases of complete fistula healing, both for the treated groups (1 LSC and 1 UCS). No complete healing was observed for the control group. Punctiform fistula aspect was more frequently observed in the treated group (56%vs10%). MRI analysis confirmed the appropriate positioning of the LCS after the graft. Ratio final/initial fistula opening surface on MRI-based measurements indicated statistically significant decrease for the treated group (12%vs59.5%,p<0.001). The decrease was comparable for both treated groups (LCS or ULC) (12.1%vs12%,p=0.73). According to VCF, the microvasculature density was enhanced for treated mice compared to control ones (8.9%vs1.6%,p=0.01). Histology revealed that the presence of a fibro-inflammatory infiltrate was more important around the fistula opening of control mice compared to treated mice transplanted. Histology confirmed the two cases of complete healing in the treated groups while Pearl’s staining enabled the detection of iron co-localized with inflammatory infiltrate in the group of mice treated with LCS.</p><p><bold>CONCLUSION:</bold> The clinical and imaging evaluation demonstrated improved healing with higher micro-vasculature density and enhanced fistula closure in the treated mice group. Further studies are in the pipeline to confirm these results in a swine model.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Cellular therapy, Enterocutaneous fistula, Mice model</p></sec><sec><title>OP132 IN VIVO MOLECULAR IMAGING USING FLUORESCENT ANTI-TNF ANTIBODIES AND CONFOCAL LASER ENDOMICROSCOPY PREDICTS RESPONSE TO ANTI-TNF THERAPY IN CROHN'S DISEASE</title><p><bold>R. Atreya</bold><sup>1,*</sup>, H. Neumann<sup>1</sup>, C. Neufert<sup>1</sup>, M. J. Waldner<sup>1</sup>, U. Billmeier<sup>1</sup>, Y. Zopf<sup>1</sup>, M. Willma<sup>1</sup>, C. App<sup>1</sup>, T. Münster<sup>1</sup>, H. Kessler<sup>1</sup>, S. Maas<sup>1</sup>, B. Gebhardt<sup>1</sup>, R. Heimke-Brinck<sup>1</sup>, E. Reuter<sup>1</sup>, F. Doerje<sup>1</sup>, T. T. Rau<sup>1</sup>, W. Uter<sup>1</sup>, T. D. Wang<sup>2</sup>, R. Kiesslich<sup>3</sup>, M. Vieth<sup>4</sup>, E. Hannappel<sup>1</sup>, M. F. Neurath<sup>1</sup></p><p><italic><sup>1</sup>UNIVERSITY OF ERLANGEN, Erlangen, Germany, <sup>2</sup>UNIVERSITY OF MICHIGAN, Ann Arbor, United States, <sup>3</sup>ST. MARY'S HOSPITAL, Frankfurt, <sup>4</sup>KLINIKUM BAYREUTH, Bayreuth, Germany</italic></p><p><bold>INTRODUCTION:</bold> As anti-tumour necrosis factor (TNF) antibodies suppress immune responses in Crohn’s disease (CD) by binding to membrane-bound TNF (mTNF) expressing mucosal cells, we hypothesized that<italic> in vivo</italic> detection of such cells via fluorescent anti-TNF antibodies might be used as a predictor of response to anti-TNF therapy.</p><p><bold>AIMS&METHODS:</bold> Aim of our clinical study was to visualize mucosal mTNF expression in humans using confocal laser endomicroscopy (CLE) with topical application of a fluorescent anti-TNF antibody (FITC-Adalimumab). This novel <italic>in vivo</italic> diagnostic modality was used to predict clinical response to subsequent anti-TNF therapy in 25 CD patients.</p><p>The GMP-conform fluorescent anti-TNF antibody was topically applied onto the inflamed mucosa of CD patients during a colonoscopy prior to anti-TNF therapy. Fluorescein expression on a cellular level, indicating mucosal mTNF+ cells, was quantified via CLE. CD patients were then treated with an anti-TNF antibody and changes of the CDAI score was correlated to the amount of mucosal mTNF+ cells. Response to treatment was defined as a decrease in the CDAI ≥ 100 points after 12 weeks of therapy.</p><p><bold>RESULTS:</bold> The binding of the antibody to mTNF+ intestinal cells and visualization of the FITC moiety during CLE enabled assessment of mTNF expression in CD patients<italic> in vivo</italic>. No serious adverse events were observed. Patients with high amounts of mTNF+ cells showed significantly higher response rates at week 12 (92%) upon subsequent anti-TNF therapy as compared to patients with low amounts of mTNF+ cells (15%). This clinical response in the former patients was sustained over a follow-up period of one year. The significant difference of the mean number of mTNF+ cells per image was 30 for anti-TNF responders and 11 for non-responders. Sensitivity for the prediction of therapeutic responses based on a discriminative factor of 20 positive cells was 92%.</p><p><bold>CONCLUSION:</bold> Our data indicate a significant correlation between the efficacy of anti-TNF therapy and prior <italic>in vivo</italic> detected expression of mucosal mTNF+ cells in CD patients. These data indicate for the first time that molecular imaging with fluorescent antibodies <italic>in vivo</italic> has the potential to predict therapeutic responses and opens new avenues for individualized therapy.</p><p><bold>Contact E-mail Address:</bold><email>raja.atreya@uk-erlangen.de</email></p><p><bold>Disclosure of Interest</bold>: R. Atreya Financial support for research from: Abbvie, H. Neumann: None Declared, C. Neufert: None Declared, M. Waldner: None Declared, U. Billmeier: None Declared, Y. Zopf: None Declared, M. Willma: None Declared, C. App: None Declared, T. Münster: None Declared, H. Kessler: None Declared, S. Maas: None Declared, B. Gebhardt: None Declared, R. Heimke-Brinck: None Declared, E. Reuter: None Declared, F. Doerje: None Declared, T. Rau: None Declared, W. Uter: None Declared, T. Wang: None Declared, R. Kiesslich: None Declared, M. Vieth: None Declared, E. Hannappel: None Declared, M. Neurath Consultancy for: Abbvie</p><p><bold>Keywords:</bold> anti TNF therapy, Crohn`s disease, Endoscopy, Inflammatory bowel disease (IBD), molecular imaging</p></sec><sec><title>OP133 THE BEGINNING OF NEW ENDOSCOPIC TREATMENT: ESTABLISHMENT OF PURE ENDOSCOPIC FULL-THICKNESS RESECTION AND SUTURING OF GASTRIC WALL WITH INNOVATIVE NEW ENDOSCOPIC DEVICES</title><p><bold>H. Mori</bold><sup>1,*</sup>, H. Kobara<sup>1</sup>, S. Fujihara<sup>1</sup>, N. Nishiyama<sup>1</sup>, T. Yachida<sup>1</sup>, T. Masaki<sup>1</sup>, M. Ayaki<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology and Neurology, Kagawa university, Kagawa, Japan</italic></p><p><bold>INTRODUCTION:</bold> An endoscopic full thickness resection (EFTR) requires a reliable full-thickness suturing device and endoscopic counter traction device against collapse of the digestive tract. This presentation focused on assessing the reliability of newly developed flexible endoscopy suturing devices.</p><p><bold>AIMS&METHODS:</bold> A total of thirty EFTRs were performed and allocated into 3 groups (n=10 for each group). The full-thickness sutures were performed with over-the-scope clip (OTSC), hand-sewn suture and Double-arm-bar Suturing System (DBSS). Air leak tests were conducted among the three groups. The time required for 1 OTSC suture, and for single-stitch simple interrupted sutures (hand-sewn and DBSS) were also compared. Furthermore, we conducted EFTR of 3 Beagles dogs to confirm the safety of these devices.</p><p><bold>RESULTS:</bold> All thirty full thickness suturing were completely and successfully performed. With regard to air leak test, Mann-Whitney U test showed significant differences between OTSC and hand-sewn sutures (<italic>P</italic>=0.003). There was also a significant difference between OTSC and DBSS (<italic>P</italic>=0.023). There was no significant difference between hand-sewn sutures and DBSS (<italic>P</italic>=0.542). A significant difference was found in the suture time for single-stitch simple interrupted sutures among the OTSC, hand-sewn, and DBSS. Mann-Whitney U test showed a significant difference between OTSC and hand-sewn suture (<italic>P</italic>=0.0001). There was no significant difference between OTSC and DBSS (<italic>P</italic>=0.533). A significant difference was found between hand-sewn sutures and DBSS (<italic>P</italic>=0.0001). All dogs experiments were succeeded and alive without any complications.</p><p><bold>CONCLUSION:</bold> The high safety of full-thickness resection and full-thickness suturing allows for clinical applications of this method.</p><p><bold>REFERENCES:</bold></p><p>1. Hirohito Mori, Innovative non-insufflation EFTR: sufficient endoscopic operative field by mechanical counter traction device (with video) Surgical Endoscopy Jan 2013 accept in press</p><p>2. Hirohito Mori, New flexible endoscopic full thickness suturing device: A Triple-arm-bar Suturing System (with video)</p><p><bold>Contact E-mail Address:</bold><email>hiro4884@med.kagawa-u.ac.jp</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> air leak test, clinical applications, endoscopic counter traction device, endoscopic full thickness resection (EFTR), full-thickness suturing device, in vivo experiments</p></sec><sec><title>OP134 NOTES GASTROENTERIC BYPASS USING A TISSUE-APPOSING STENT: A REPRODUCIBLE AND EFFICIENT PROCEDURE IN PIGS.</title><p><bold>G. Vanbiervliet</bold><sup>1,*</sup>, R. Garces<sup>2</sup>, S. Berdah<sup>2</sup>, E. Garnier<sup>2</sup>, M. Barthet<sup>2</sup></p><p><italic><sup>1</sup>gastroenterology, CHU Archet 2, Nice, <sup>2</sup>gastroenterology, HOPITAL NORD, Marseille cedex 20, France</italic></p><p><bold>INTRODUCTION:</bold> Natural orifice translumenal endoscopic surgery (NOTES) is a less invasive surgical technique than regular surgical procedures and creates a gastrojejunal anastomosis without the need of parietal incisions.</p><p><bold>AIMS&METHODS:</bold> The aim of this study is to determine feasibility, efficacy and safety of a pure endoscopic NOTES gastrojejunal anastomosis procedure (GJA). This prospective animal study was carried out under the Aix-Marseille Universite ethical committee approval. All procedures were performed on 20 to 45 kg domestic pigs, The NOTES procedure has been previously established according to our preliminary experiences of performing a pure GJA on 16 animals . For this study, we made the incision of the loop with a Cremer cystostome, introduced a guide wire, deployed the distal stent, transferred the loop into the stomach and finally deployed the proximal stent. The endoscope was passed through the stent and into the jejunal lumen to check the permeability of the loop.</p><p>Animals were reefed after 2 days and euthanasia was performed after 21 days of follow-up. All resected surgical specimens were analyzed for anastomotic patency and a histological analysis was carried out.</p><p><bold>RESULTS:</bold> In total, six pure NOTES gastrojejunal by-pass procedures were performed. All the procedures were successfully achieved. The mean operative time was 26 minutes (CI 6,2). There was only one complication during the procedures in one pig with a leakage of the GJA at the checking step. The stent was recovered and replaced successfully with the same procedure.</p><p>The pigs were reefed after 2 days without any complications or sepsis, and they all survived for 21 days. Their mean gain weight during the three weeks follow up was 0.85 kg (CI 2,56) instead of 5,2 kg (CI 1,6) in animal controls. There were no complications observed during the clinical follow up. At the autopsy the GJA was always permeable with the stent still in place in all the cases, without evidence of stricture after the removal of the stent and no signs of peritonitis.</p><p>Pathological examination showed a complete fusion of both gastric and jejunal walls without any dehiscence.</p><p><bold>CONCLUSION:</bold> GJA with a lumen-apposing stent is feasible and reproducible in all the cases using a pure NOTES approach and standard endoscopic equipment. This procedure is efficient resulting in a constant patent anastomosis and a weight loss versus the normal growth curve.</p><p><bold>REFERENCES:</bold></p><p>1. ESGE grant 2012</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> experimental endoscopy, Gastrojejunal anastomosis, NOTES, Stents</p></sec><sec><title>OP135 A PROSPECTIVE EVALUATION UTILIZING AN ENDOSCOPIC APPROACH TO PLICATE TISSUE FOR THE TREATMENT OF PRIMARY OBESITY: OUR FIRST 100 POSE (PRIMARY OBESITY SURGERY, ENDOSCOPIC) PATIENTS</title><p><bold>R. Turro</bold><sup>1,1,*</sup>, J. Espinos<sup>1</sup>, A. Mata<sup>1</sup>, J. Turro<sup>1</sup></p><p><italic><sup>1</sup>Unidad Endoscopia Digestiva, Centro Medico Teknon, Barcelona, Spain</italic></p><p><bold>INTRODUCTION:</bold> The Incisionless Operating Platform™ (USGI Medical, San Clemente, CA, USA) utilizes the g-Cath EZ ™ suture anchor, which can be used to plicate gastric tissue endoscopically. We report on use of these suture anchors for the treatment of primary obesity.</p><p><bold>AIMS&METHODS:</bold> 100 study subjects were enrolled prospectively after institutional approval. Diet was advanced post procedure to full solids over 4-6 weeks to allow time for suture plication healing in all patients. Weights were recorded at 1, 2, 3, 4, 6, 9 and 12 months. Patients will be followed through 2 years.</p><p><bold>RESULTS:</bold> Subject demographics: (76%F/24%M). Mean age =42.4 (21-64). At baseline: mean weight was 101.8±12.5 Kg; mean body mass index (BMI) = 37.5±3.9 (Range 28-47). A mean of approximately 9.3 plications were placed in the fundus, 3.5 at the distal gastric body. Mean operative time, 64 minutes (29.0–126). Last 50 cases were done in a mean of less than 50 minutes. There were no mortalities. There was 1 SAE which involved readmission for fever 1 week post-procedure at which time a peri-splenic abcess was discovered and resolved conservatively with antibiotics. 6 month mean weight loss = 16.9 ±7.5 Kg (N=67); %Total Body Weight Loss was 16.6%. 9 month weight loss (N=41) revealed %EWL at 58.2% with %TBWL at 17.8%. Early 1 year Data (N=18) revealed %EWL/%TBWL at 64.1%/19.5% respectively. All patients with baseline and 2/6 month data demonstrated reduced capacity and earlier satiety (p<0.001).</p><p><bold>CONCLUSION:</bold> At early follow-up, this procedure appears to provide a safe and effective short term weight loss solution, and also may decrease gastric capacity and produce earlier fullness through either a mechanical and/or physiologic mechanism. Longer-term follow-up and further study are required.</p><p><bold>Contact E-mail Address:</bold><email>romanturro@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: R. Turro Lecture fee(s) from: USGI Medical, J. Espinos Consultancy for: USGI Medical, A. Mata: None Declared, J. Turro Financial support for research from: USGI Medical</p><p><bold>Keywords:</bold> Obesity surgery, Therapeutic endoscopy</p></sec><sec><title></title><p><bold>MONDAY, OCTOBER 14, 2013 15:45-17:15</bold></p><p><bold>Today's science; tomorrow's medicine: Genetics and pathogenesis – Hall 9</bold></p></sec><sec><title>OP136 THE IMPACT OF SPRED-2 ON COLONIC MUCOSAL REPAIR IN MICE WITH DSS-INDUCED COLITIS</title><p><bold>S. Takahashi</bold><sup>1,2,*</sup>, S. Fushimi<sup>2</sup>, T. Ito<sup>2</sup>, R. Kimura<sup>2</sup>, T. Inokuchi<sup>1</sup>, A. Nakarai<sup>1</sup>, M. Akita<sup>1</sup>, K. Harada<sup>3</sup>, S. Hiraoka<sup>1</sup>, H. Okada<sup>3</sup>, K. Yamamoto<sup>1</sup>, A. Matsukawa<sup>2</sup></p><p><italic><sup>1</sup>Department of Gastroenterology and Hepatology, <sup>2</sup>Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, <sup>3</sup>Department of Endoscopy, Okayama University Hospital, Okayama, Japan</italic></p><p><bold>INTRODUCTION:</bold> Intestinal barrier dysfunction is a main feature of the inflammatory bowel diseases (IBD), Crohn’s disease and ulcerative colitis. Rapid and adequate mucosal healing is one of the important prognostic factors for long-term remission in IBD patients. Ras/Raf/ERK pathway play critical roles in colon epithelial regeneration. Sprouty-related EVH1-domain-containing protein (Spred) is a family of proteins that inhibit Ras/Raf/MEK/ERK pathway. Spred-2 is ubiquitously expressed in various tissues including colon whereas Spred-1 and Spred-3 are preferentially expressed in the brain and cerebellum. Spred-2 is considered as a negative regulator of several growth factors.</p><p><bold>AIMS&METHODS:</bold> We hypothesized that knock down of Spred-2 may reinforce EGF signalling and promote colon epithelial repair. Spred-2-knockout (KO) and wild-type (WT) mice were given 2% DSS dissolved in drinking water for five days. The body weight and clinical activity of colitis were evaluated by day 0, 2, 5, 8, 13 and 20 after DSS administration. Additionally, mice were sacrificed at various time points, and their colons were removed for histological and mechanistic analyses. To evaluate epithelial cell proliferation, mice were injected with BrdU intraperitoneally two hour before sacrifice.</p><p><bold>RESULTS:</bold> Reduction of colitis and rapid epithelium repair was observed in Spred-2 KO mice. No significant differences in the levels of TNF-alpha, IL-6 and MPO in the colon were found between WT and Spred-2 KO mice. BrdU-positive cells were significantly higher in the colon epithelium in Spred-2 KO mice than that in WT mice. ERK activity was increased in Spred-2 KO mice relative to the WT mice.</p><p><bold>CONCLUSION:</bold> These results suggest that the colonic epithelial regeneration is dependent on Ras/Raf/ERK pathway and Spred-2 may be a new therapeutic target for the treatment of IBD.</p><p><bold>Contact E-mail Address:</bold><email>saqi@yahoo.co.jp</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> colitis, colon epithelium, DSS, MAPK signaling, spred-2 </p></sec><sec><title></title><p><bold>MONDAY, OCTOBER 14, 2013 15:45-17:15</bold></p><p><bold>TSTM: Genetics and pathogenesis – Hall 9</bold></p></sec><sec><title>OP137 MICRORNA MIR-19B TARGETING SOCS3 IN COLONIC EPITHELIAL CELLS AND IS ASSOCIATED WITH THE PATHOGENESIS OF CROHN’S DISEASE</title><p><bold>H. Zhang</bold><sup>1,*</sup>, X. Zhang<sup>1</sup>, W. Jiang<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China</italic></p><p><bold>INTRODUCTION:</bold> Cytokine signaling (SOCS)-3 plays an important role in autoimmune disorders. High levels of SOCS-3 were observed in Crohn’s disease(CD). microRNAs (miRNAs) can regulate gene expression during immune responses.</p><p><bold>AIMS&METHODS:</bold> The aim of our study was to investigate the contribution of SOCS-3 expression-associated miRNA to the regulation of chemokines production in colonic epithelial cells(CECs) in active CD. Targetscan Human 6.2 was used to screen miRNAs which may be target the 3’ untranslated region (3’ UTR) of SOCS3, and quantitative PCR was used to detect these miRNAs levels in active CD and healthy subjects. The luciferase reporter assay was performed to confirm the target gene. The expressions of SOCS3 mRNA and protein were determined by quantitative PCR and western blot. Caco2 cells were stimulated with IL-6 for 24h and 72h after over-expression or down-regulation miRNA and SOCS3. The levels of chemokines were measured by enzyme linked immunosorbent assay (ELISA).</p><p><bold>RESULTS:</bold> miRNA-19b expression was decreased, while SOCS3 protein expression was increased in affected area of colonic mucosa tissue in active CD. There was an inverse correlation between the expression of miR-19b and SOCS3 protein. Bioinformatic prediction showed that SOCS3 was the target gene of miR-19b. Next, we verified that among the targetscan screened miRNAs, only miR-19b expression was significantly lower than the controls. The luciferase reporter assay confirmed that miR-19b directly recognized 3’ UTR of SOCS3. In vitro, knockdown of miR-19b increased SOCS3 expression, and over-expression of miR-19b decreased SOCS3 expression. Furthermore, down-regulation of miR-19b decreased MIP-3αproduction induced by IL-6 modulated by SOCS3. MIP-3αcan induce restitutive migration of intestinal epithelium. So miR-19b may also play a protective role for CD patients, and participate in the repair of intestinal mucosa.</p><p><bold>CONCLUSION:</bold> miR-19b plays a critical role in regulating production of chemokines by targeting SOCS3 in colonic epithelial cells.</p><p><bold>Contact E-mail Address:</bold><email>hjzhang06@163.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> chemokines, colonic epithelial cells, Crohn’s disease, Cytokine signaling (SOCS)-3, MicroRNA miR-19b</p></sec><sec><title>OP138 TISSUE SPECIFIC DELETION OF MITOCHONDRIAL HSP60 ACTIVATES UNFOLDED PROTEIN RESPONSES IN THE INTESTINE ASSOCIATED WITH FOCAL HYPERPROLIFERATION OF EPITHELIAL STEM CELLS</title><p><bold>E. Berger</bold><sup>1,*</sup>, D. Yuan<sup>2</sup>, N. Waldschmitt<sup>1</sup>, E. Rath<sup>1</sup>, N. Simonavicius<sup>2</sup>, O. Staszewski<sup>3</sup>, M. Boekschoten<sup>4</sup>, M. Prinz<sup>3</sup>, M. Müller<sup>4</sup>, A. Weber<sup>5</sup>, K.-P. Janssen<sup>6</sup>, M. Heikenwälder<sup>2</sup>, D. Haller<sup>1,7</sup></p><p><italic><sup>1</sup>Chair of Immunology and Nutrition, Technische Universität München, Freising-Weihenstephan, <sup>2</sup>Institute of Virology, Technische Universität München, München, <sup>3</sup>Institute of Neuropathology, University of Freiburg, Freiburg, Germany, <sup>4</sup>Chair Nutrition, Metabolism&Genomics, Wageningen University, Wageningen, Netherlands, <sup>5</sup>Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland, <sup>6</sup>Department of Surgery, Technische Universität München, München, <sup>7</sup>ZIEL – Research Center for Nutrition and Food Science, Technische Universität München, Freising-Weihenstephan, Germany</italic></p><p><bold>INTRODUCTION:</bold> Heat shock protein (HSP) 60, a mitochondrial (mt) unfolded protein response (UPR)-associated chaperone, is implicated in the pathogenesis of chronic intestinal inflammation.</p><p><bold>AIMS&METHODS:</bold> This study investigates the role of HSP60 in intestinal epithelial cell (IEC) homeostasis using novel tissue-specific knockout mouse models.</p><p><bold>RESULTS:</bold> Generation of epithelial-specific <italic>Hsp60</italic> knockout mice (<italic>Hsp60<sup>flox/flox</sup></italic>XVillinCre) antagonized embryonic development upon day eleven after conception and induced embryolethality. Postnatal induction of an epithelial specific <italic>hsp60</italic> knockout (<italic>Hsp60<sup>flox/flox</sup></italic>XVillinCreERT2) caused a severe phenotype with rapid weight loss and mortality. Histological evaluation of intestinal gut sections revealed aberrations in villus-crypt architecture including focal crypt hyper-regeneration dominantly in the upper small intestine. While HSP60-negative crypt epithelial cells showed an abrogated expression of the proliferation marker KI67, hyper-regenerative crypts were positive for HSP60 and KI67. These crypt foci originate from few HSP60-positive cells which express the stem cell marker olfactomedin (OLFM) 4 and escaped from the genetic knock out in the crypt. Although a loss of HSP60 led to an abrogated KI67 expression in colonic epithelium as well, this did not cause overall tissue pathology. Absence of HSP60 both in jejunal and colonic epithelium induced hallmarks of the mtUPR in IEC, suggesting the presence of compensatory mechanisms upon loss of HSP60 at early phases of mtUPR. These include induction of mitochondrial chaperones like mtHSP70, proteases like the ATP dependent caseinolytic peptidase and transcription factors like C/EBP-homologous-protein. Mitochondria showed spherical deposits in the matrix and a decreased expression of functionality markers like the mitochondrial encoded cytochrome c oxidase (COX) I.</p><p><bold>CONCLUSION:</bold> Tissue-specific deletion of <italic>Hsp60</italic> disrupts epithelial cell homeostasis both pre- and postnatally leading to crypt aberrations and compartmentalized pathologies in the small intestine.</p><p><bold>Contact E-mail Address:</bold><email>dirk.haller@tum.de</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Hyper-regenerative crypts, Intestinal epithelial cells, Mitochondrial HSP60, Stem Cells, Unfolded Protein Response</p></sec><sec><title>OP139 GENETIC AND CLINICAL DIFFERENCES IN PRIMARY SCLEROSING CHOLANGITIS PATIENTS WITH HIGH IGG4</title><p><bold>N. L. Berntsen</bold><sup>1,*</sup>, O. Klingenberg<sup>2</sup>, K. M. Boberg<sup>1</sup>, T. H. Karlsen<sup>1</sup>, J. R. Hov<sup>1</sup></p><p><italic><sup>1</sup>Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Rikshospitalet, <sup>2</sup>Department of Medical Biochemistry and Institute of Clinical Biochemistry, Oslo University Hospital, Oslo, Norway</italic></p><p><bold>INTRODUCTION:</bold> Elevated serum concentration of IgG4 is reported in up to 10% of patients with primary sclerosing cholangitis (PSC), a heterogeneous disorder of unknown aetiology. High IgG4 is associated with more severe disease, yet with some extent of corticosteroid responsiveness. We hypothesized that these patients represent a distinct subgroup of PSC and aimed to explore clinical and genetic aspects of high IgG4 in a large Norwegian cohort.</p><p><bold>AIMS&METHODS:</bold> We included 263 PSC patients with stored DNA and serum available. Patients with high IgG4 were defined by cut-off levels of a) 1.35g/l (as applied in previous studies on IgG4 related disease) and b) 2.01g/l (upper reference limit defined for the N IgG4 assay from Siemens Healthcare Diagnostics). Genotypes of the strongest genetic risk factors in PSC, <italic>HLA-B </italic>and <italic>HLA-DRB1</italic> were available from the patients and 368 healthy controls.</p><p><bold>RESULTS:</bold> N<bold>=</bold>47 (18%) and n=23 (9%) PSC patients had high IgG4 when applying cut-off levels of IgG4>1.35 and IgG4>2.01 respectively. The HLA-B*08 allele, consistently observed as the top genetic risk factor in PSC, was less prevalent in patients with high than low IgG4 (29% vs 42%, P=0.02, for cut-off IgG4>1.35 and 26% vs 41%, P=0.05, for cut-off IgG4>2.01). In contrast, the PSC-associated alleles HLA-B*07 and DRB1*15 were more prevalent in PSC with high than low IgG4, but only when applying the IgG4>2.01 cut-off (HLA-B*07: 24% vs 13%, P=0.04 and DRB1*15: 26% vs 14%, P=0.04, for high vs low IgG4, respectively). When comparing the patients with healthy controls, HLA-DRB1*15 was significantly associated only with PSC with IgG4>2.01 (26% vs 15%, P=0.05), while there was no association with HLA-DRB1*15 in this PSC population as a whole (P=0.90). Clinically, IgG4>1.35 was associated with shorter liver transplantation free survival (P=0.05) and shorter survival to the end-point of death only (P=0.007), while there were no differences between high and low IgG4 regarding gender (87% vs 75% male, P=0.09) or inflammatory bowel disease (82% vs 82%).</p><p><bold>CONCLUSION:</bold> We report for the first time on genetic associations for elevated IgG4 levels in PSC. Our findings suggest that the phenotypic heterogeneity represented by the IgG4 response contribute to the complex HLA associations observed in PSC. The possibility that elevated IgG4 concentration designates a genetic as well as clinical subgroup should be taken into account in further studies, ultimately aiming to identify patients suitable for immunosuppressive therapy or other treatment options.</p><p><bold>Contact E-mail Address:</bold><email>n.l.berntsen@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> genetics, IgG4, Primary sclerosing cholangitis</p></sec><sec><title>OP140 EXOME SEQUENCING IDENTIFIES LRP5 MUTATIONS IN POLYCYSTIC LIVER DISEASE</title><p><bold>W. R. Cnossen</bold><sup>1,*</sup>, R. H. te Morsche<sup>1</sup>, A. Hoischen<sup>2</sup>, C. Gilissen<sup>2</sup>, M. Chrispijn<sup>3</sup>, H. Venselaar<sup>4</sup>, S. Mehdi<sup>5</sup>, C. Bergmann<sup>6,7</sup>, J. A. Veltman<sup>2</sup>, J. P. Drenth<sup>1</sup> Institute for Genetic and Metabolic Disease (IGMD); Genomic Disorders Group (GDG)</p><p><italic><sup>1</sup>Gastroenterology and Hepatology, <sup>2</sup>Human Genetics, <sup>3</sup>Radiology, <sup>4</sup>Center for Molecular and Biomolecular Informatics, Radboud University Medical Center, Nijmegen, Netherlands, <sup>5</sup>Surgery, University Mohammed First, d’Oujda, Morocco, <sup>6</sup>Center for Clinical Research, University Hospital Freiburg, Freiburg, <sup>7</sup>Center for Human Genetics, Bioscientia, Ingelheim, Germany</italic></p><p><bold>INTRODUCTION:</bold> Hepatic cystogenesis is characterized by multiple fluid filled cysts originating from biliary epithelium cells causing hepatomegaly. Polycystic livers are present in isolated polycystic liver disease (PCLD) and are a major extrarenal manifestation (83%) in autosomal dominant polycystic kidney disease (ADPKD). Mutations in the <italic>PRKCSH</italic> or <italic>SEC63</italic> gene cause autosomal dominant PCLD, while mutations in the <italic>PKD1</italic> or <italic>PKD2</italic> gene cause ADPKD. There is considerable genetic heterogeneity and ∼80% of polycystic liver patients lack mutations in hitherto identified genes.</p><p><bold>AIMS&METHODS:</bold> We hypothesized that another gene is involved in hepatic cystogenesis. We assessed a 40-member family with PCLD. Mutation analysis for the 4 disease-related genes was followed by whole-exome sequencing. Candidate genes were prioritized according to a dominant model of inheritance (ref.1,2) and validated by Sanger sequencing in all members. Next, candidate variants were excluded in 1,000 Dutch DNAs from healthy, unrelated individuals; and in genome-wide sequence data of 6,500 individuals from the NHLBI Exome Sequencing Project, the 1,000 Genomes Project and 1,300 individuals of predominantly European ancestry sequenced in-house. Functional studies were conducted to elucidate the molecular mechanism.</p><p><bold>RESULTS:</bold> A private variant<italic> c.3562C>T </italic>at a highly conserved amino acid residue in the <italic>Low density lipoprotein Receptor-related Protein 5 </italic>(<italic>LRP5</italic>) gene was present in all affected relatives. This variant was absent in 1,000 controls and predicted to be damaging according to PolyPhen2, MutPred and SIFT with profound structural effects by homology modeling. There was highly significant linkage with the <italic>LRP5</italic> locus (LOD score 4.62).</p><p>Screening of all <italic>LRP5</italic> exons in a PCLD cohort identified 3 independent mutations (2 Dutch and 1 Moroccan family), again all undetected in controls and predicted to be damaging.</p><p>Immunohistochemistry of liver cyst tissue showed that the protein is present. We performed luciferase activity assays to investigate the effect of <italic>LRP5</italic> mutants on the canonical Wnt signaling. Activation of the Wnt signaling was significantly decreased compared to the wild type.</p><p><bold>CONCLUSION:</bold> Germline <italic>LRP5</italic> mutations are associated with polycystic liver disease. This study provides new insights for the study of hepatic cystogenesis and a molecular link for canonical Wnt signaling pathway in PCLD.</p><p><bold>REFERENCES:</bold></p><p>1. Hoischen A. et al. <italic>De novo</italic> mutations of <italic>SETBP1</italic> cause Schinzel-Giedion syndrome. Nat Genet 2010;42:483-485.</p><p>2. Gilissen C. et al. Exome sequencing identifies <italic>WDR35</italic> variants involved in Sensenbrenner syndrome. Am J Hum Genet 2010;87:418-423.</p><p><bold>Contact E-mail Address:</bold><email>w.cnossen@mdl.umcn.nl</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> cystogenesis, exome sequencing, genetics, polycystic liver disease, Wnt signaling pathway</p></sec><sec><title>OP141 COMPARATIVE EFFECTIVENESS OF IMMUNE-CELL DEPLETION IN THE TREATMENT OF AUTOIMMUNE PANCREATITIS</title><p><bold>G. M. Seleznik</bold><sup>1,*</sup>, T. Reding<sup>1</sup>, J. Browning<sup>2</sup>, S. Segerer<sup>3</sup>, M. Heikenwälder<sup>4</sup>, R. Graf<sup>1</sup></p><p><italic><sup>1</sup>Swiss HPB Center, University Hospital Zurich, Zurich, Switzerland, <sup>2</sup>Department of Immunology, Biogen-Idec, Boston, United States, <sup>3</sup>Division of Nephrology, University Hospital Zurich, Zurich, Switzerland, <sup>4</sup>Helmholtz-Zentrum , Institute for Virology, München, Germany</italic></p><p><bold>INTRODUCTION:</bold> The long-term management of autoimmune pancreatitis (AIP) - a relapsing steroid-responsible disorder - is still elusive. We previously demonstrated that acinar specific Lymphotoxin expression in mice Tg(Ela1-Lta,b) induces autoimmunity with features reminiscent of human AIP. This includes formation of tertiary lymphoid organs, increased serum IgGs, anti-nuclear antibodies and immune-complex glomerulonephritis. Mice were responsive for corticosteroid treatment but it did not revert the autoimmune repertoire. In contrast, inhibition of Lymphotoxin beta receptor (LTβR) signaling pathway (LTβR-Ig) dampened auto-antibody production, chemokine expression, and renal immune-complex deposition and abrogated AIP.</p><p><bold>AIMS&METHODS:</bold> Tg(Ela1-Lta,b) mice with established AIP were treated with anti-CD20 mAb (Rituximab) and anti-CD4 mAb in order to deplete B- and CD4<sup>+</sup> T-cells respectively. Histology, autoantibody production, chemokine expression and renal immune complex formation was tested, and compared to LTβR-Ig treatment.</p><p><bold>RESULTS:</bold> Rituximab and LTβR-Ig treatment led to a significant decrease in autoantibody production and inflammatory cell infiltration. The molecular mechanism of this beneficial effect possibly involves the down regulation of Stat3 activation. Additionally, in contrast to Rituximab treatment blocking LTβR- signalling reverted acinar cell proliferation and acinar-to-ductal metaplasia formation and also prevented the activation of the non-canonical NF-κb signalling.</p><p><bold>CONCLUSION:</bold> In this unique genetic mouse model of AIP, we demonstrate that therapy with LTβR-Ig and Rituximab is superior to CD4<sup>+</sup> T-cell depletion. We reveal novel mechanisms of anti-inflammatory and anti-autoimmune effects throughout repressing Stat3 activation and the non-canonical NF-κb pathway upon LTβR-Ig treatment. Therefore, inhibition of the LTβR-signalling pathway could become an alternative or supplementary approach for AIP treatment.</p><p><bold>Contact E-mail Address:</bold><email>gittamaria.seleznik@usz.ch</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> autoimmune pancreatitis, transgenic mouse model</p></sec><sec><title>OP142 EXOCRINE PANCREATIC CELLS DERIVED FROM PLURIPOTENT STEM CELLS – NEXT GENERATION DISEASE MODELING</title><p><bold>A. Kleger</bold><sup>1,*</sup>, M. Hohwieler<sup>2</sup>, A. Illing<sup>2</sup>, T. Seufferlein<sup>2</sup></p><p><italic><sup>1</sup>Department of Internal Medicine 1, <sup>2</sup>Ulm University Hospital, Ulm, Germany</italic></p><p><bold>INTRODUCTION:</bold> Human induced pluripotent stem (iPS) cells can be generated from easily accessible tissues such as skin or plucked hair. In particular keratinocytes can be reprogrammed faster and more efficient than fibroblasts. In case of applying this tool to patients who are classified into a disease group, it enables the generation of disease-specific iPS cells. iPS cells have proven a significant tool to elucidate pathophysiological mechanisms in various diseases such as diabetes, blood disorders, defined neurological disorders and genetic liver disease. However, differentiation of hiPS cells towards the pancreatic lineage remains inefficient and variable. Moreover, current protocols are mostly aiming to generate endocrine cells while exocrine differentiation protocols remain elusive.</p><p><bold>AIMS&METHODS:</bold> For the current studies we utilized keratinocyte cultures from plucked human hair. With the use of a lentiviral, multicistronic four-factor reprogramming system (encoding Oct4, Sox2, c-Myc, and Klf4), human keratinocytes were successfully reprogrammed to human induced pluripotent stem cells displaying all hallmarks of embryonic stem cells.</p><p><bold>RESULTS:</bold> Herein, we report the generation of plucked human hair derived induced pluripotent stem cells from healthy donors and patients suffering form a series of genetic pancreatic disorders. We successfully applied a novel and stepwise pancreatic differentiation protocol to generate exocrine pancreatic cells: Briefly, this includes the generation of virtually pure populations of definitive and forgut endoderm as assessed by positivity for Sox17 and Foxa2. Further differentiation clues induce Pdx1-positive pancreatic progenitor cells, which can be subsequently matured towards amylase positive exocrine cells.</p><p><bold>CONCLUSION:</bold> This set up will provide the basis for future studies dissecting the pathophysiology of exocrine pancreatic disease in a dish but patient specific context.</p><p><bold>Contact E-mail Address:</bold><email>alexander.kleger@uni-ulm.de</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Differentiation, Disease model, Induced pluripotent stem cells</p></sec><sec><title></title><p><bold>MONDAY, OCTOBER 14, 2013 15:45-17:15</bold></p><p><bold>New developments in upper GI imaging – Hall 10</bold></p></sec><sec><title>OP143 THE DIAGNOSTIC PERFORMANCE OF CONVENTIONAL ENDOSCOPY FOR MAKING A DIAGNOSIS OF SUBMUCOSAL INVASION BY EARLY GASTRIC CANCER: A SIMPLE DIAGNOSTIC CRITERION OF “NON-EXTENSION SIGNS”</title><p><bold>T. Nagahama</bold><sup>1,*</sup>, K. Yao<sup>1</sup>, T. Matsui<sup>1</sup>, H. Tanabe<sup>2</sup>, K. Imamura<sup>2</sup>, A. Iwashita<sup>2</sup></p><p><italic><sup>1</sup>Gastroenterology, Fukuoka university chikushi hospital, <sup>2</sup>Pathology, Fukuoka University Chikushi Hospital, Chikushino-city, Japan</italic></p><p><bold>INTRODUCTION:</bold> Differential diagnosis of mucosal (M) or microinvasive submucosal (SM1: <500 μm) carcinoma and invasive submucosal (SM2: ≧500 μm) carcinoma as an indicator of invasion depth is an important method for determining how to treat early gastric carcinoma (EGC). The present study sought to determine the ability of conventional endoscopy to diagnose SM2 carcinoma.</p><p><bold>AIMS&METHODS:</bold> This study comprised all lesions of successive patients who underwent conventional endoscopy prior to either endoscopic or surgical resection between 2005 and 2012. EGC detected during endoscopic examination were diagnosed according to invasion depth as M/SM1 or SM2, and were then recorded in a database upon completion of endoscopy. SM2 was diagnosed when one of two criteria is fulfilled according to the standard endoscopy findings: (i) massive surround elevation; or (ii) mucosal convergence with elevation [1]. These non-extension signs (NES) findings relate to the increased thickness and rigidity caused by massive submucosal invasion. In order to obtain reproducible findings, the stomach was insufflated with a large volume of air to detect non-extensibility. In terms of the endoscopic diagnostic criterion, lesions that were positive for NES were diagnosed as SM2, and those without NES were classified as M/SM1. Histological findings were used as the gold standard.</p><p><bold>RESULTS:</bold> The study investigated a total of 863 lesions from 704 patients (male/ female= 494/ 210, average age 69.6 years, average tumor size 21.8 mm, macroscopic-type; elevated/ depressed or flat= 554/ 309, histological depth of invasion; M/ SM1/ SM2= 655/ 87/ 121, histological type; differentiated type/ undifferentiated type= 727/ 136). Accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of SM2 diagnosis based on the criterion of NES were 96.6% (834/863), 89.7% (104/116), 97.7% (730/747), 86% (104/121), and 98.4% (730/742), respectively.</p><p><bold>CONCLUSION:</bold> In the present study, the diagnostic criterion of NES possessed significantly high accuracy, specificity, and negative predictive value. NES that can be detected in conventional endoscopy are a straightforward and effective means for accurately determining the suitability of minimally-invasive endoscopic treatment.</p><p><bold>REFERENCES:</bold></p><p>1. Yao T, Tanabe H, Nagahama T et al. Clinicopathological study for accurate endoscopic diagnosis of submucosal invasion by early cancer of depressed type. Stom. Intest. (Tokyo) 2008; 43: 1109–25.</p><p><bold>Contact E-mail Address:</bold><email>nagahamagogo@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Early gastric cancer , Diagnosis, Endoscopy, Invasion depth, Non-extension signs</p></sec><sec><title>OP144 INTRA- AND INTEROBSERVER AGREEMENT BETWEEN ENDOSCOPISTS AND PATHOLOGISTS FOR DETECTION OF GASTRIC INTESTINAL METAPLASIA BY MEANS OF NARROW BAND IMAGING WITH MAGNIFYING ENDOSCOPY.</title><p><bold>L. Gemignani</bold><sup>1,*</sup>, P. Dulbecco<sup>1</sup>, M. Corbo<sup>1</sup>, E. Giambruno<sup>1</sup>, G. Bodini<sup>1</sup>, M. Furnari<sup>1</sup>, M. Giacchino<sup>1</sup>, F. E. Gianiorio<sup>1</sup>, L. Mastracci<sup>2</sup>, F. Grillo<sup>2</sup>, V. Savarino<sup>3</sup>, E. Savarino<sup>3,4</sup></p><p><italic><sup>1</sup>Department of Internal Medicine, University of Genoa, Italy, <sup>2</sup>Department of Anatomic Pathology, <sup>3</sup>Department of Internal Medicine, University of Genoa, Genoa, <sup>4</sup>Gastroenterology Unit, Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Padua, Italy</italic></p><p><bold>INTRODUCTION:</bold> Narrow Band Imaging with Magnifying Endoscopy (NBI-ME) has been recently shown to be able to accurately detect gastric intestinal metaplasia (GIM) through the visualization of a light blue crest (LBC) on the epithelial surface. However, limited data are available on the reliability of this technique among different observers.</p><p><bold>AIMS&METHODS:</bold> The aim was to define the observer agreement among different endoscopists in identifying GIM using NBI-ME. We prospectively evaluated consecutive patients undergoing upper GI endoscopy (UGIE). Patients underwent UGIE with NBI-ME performed by experienced endoscopists, and a five biopsy set (2 antrum+1 angulus+2 corpus), examined by two pathologists unaware of endoscopic findings. In all endoscopic examinations, at biopsy sites, five photographs were taken and recorded. A total of 100 pictures with related histological diagnosis were selected. Then, seven endoscopists with different experience with NBI-ME (n=3 with >1500 UGIEs with NBI-ME, n=2 with >500 and <1500 and n=2 with <500) blinded to the histological diagnosis and to the results of the other observers, were asked to independently assess the pictures before and after a short training program (visualization of 160 images). An eight more experienced endoscopist (>1500 UGIEs with NBI-ME) repeated four consecutive assessments of the same images shown in different orders, at weekly interval. The patient was defined as GIM-positive if LBC was seen in any of the image fields.</p><p><bold>RESULTS:</bold> Comparing to the histological assessment, the NBI-ME observation had an accuracy of 90% (95% CI, 88-95%), a positive predictive value of 81% (95% CI, 74-94%) and a negative predictive value of 93% (95% CI, 92-99%) in detecting GIM. By using Fleiss’ kappa analysis, a very good intra-observer agreement was found (k=0.86). The agreement among endoscopists and among endoscopists and pathologists was moderate (k=0.60 and 0.67, respectively) after the first observation, but it improved significantly after the training program (k=0.79 and 0.85, respectively).</p><p><bold>CONCLUSION:</bold> Intra-observer agreement in detecting GIM using NBI-ME was very good, while the inter-observer agreement among endoscopists with different experienced with NBI-ME without adequate training was moderate. However, a very short imaging training permitted to obtain a good level of concordance among different experienced endoscopists in detecting GIM.</p><p><bold>Contact E-mail Address:</bold><email>alphaone81@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> agreement, Endoscopy, gastric intestinal metaplasia, light blue crests, Pathology, stomach</p></sec><sec><title>OP145 THE LEARNING CURVE OF PROBE-BASED CONFOCAL LASER ENDOMICROSCOPY FOR THE DIAGNOSIS OF ESOPHAGEAL AND COLORECTAL LESIONS IS SHORT AND INDEPENDANT OF PREVIOUS ENDOSCOPIC EXPERIENCE</title><p><bold>E. Coron</bold><sup>1,*</sup>, F. Prat<sup>2</sup></p><p><italic><sup>1</sup>CHU Nantes, Nantes, <sup>2</sup>CHU Cochin, Paris, France</italic></p><p><bold>INTRODUCTION:</bold> Probe-based Confocal Laser Endomicroscopy (pCLE) is an imaging technology enabling <italic>in vivo</italic> microscopic evaluation of live tissues, in real-time, during an endoscopic procedure. Few studies have addressed the evaluation of the learning curve for this technology.</p><p><bold>AIMS&METHODS:</bold> Our aims were: 1) to evaluate the learning curve in a large sample of gastroenterologists naive to pCLE, 2) to compare trainees (with limited endoscopic experience) and confirmed GI specialists (with large endoscopic experience).</p><p>A set of 10 pCLE video sequences were used for study purpose. The sequences included typical images of healthy GI tract (oesophagus, n=2 ; colon, n=2) and various pathological conditions (in the esophagus, Barrett's esophagus (BE) intestinal metaplasia (n=2), BE gastric metaplasia (n=2), BE dysplasia and/or cancer (n=3) and in the colon, hyperplastic polyp (n=2), adenomatous polyp (n=2), adenocarcinoma (n=2), and ulcerative colitis (n=2)). During the first phase of experiments, the participants (81 trainees and 37 GI specialists) reviewed 10 sequences without any previous training. For each sequence, the participants were asked to choose a presumptive diagnosis between multiple choices, given here above. Then, they underwent a short training session where elemental lesions were described, using an independant set of typical examples. Finally, the same review evaluation was repeated using the first set of videos re-arranged randomly. Diagnostic accuracy was assessed for each main diagnosis.</p><p><bold>RESULTS:</bold> The results were analyzed considering the percentage of correct answers before and after the training session, for each group of participants. Results are indicated in table 1. Before and after training, the diagnostic accuracy increased from 56 % to 89 % for BE lesions and from 24 % to 68 % for colorectal lesions (Table 1). Regarding esophageal lesions, the most significant improvement post teaching was observed for the interpretation of normal squamous epithelium (37 % to 95%). Regarding colorectal lesions, the most significant improvement post teaching was observed for the interpretation of hyperplastic polyps (7 % to 81 %) and ulcerative colitis (12 % to 73 %).
<table-wrap id="table19-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="2" colspan="1"></th><th colspan="3" rowspan="1"><hr></hr>Esophageal lesions</th><th colspan="3" rowspan="1"><hr></hr>Colorectal lesions</th></tr><tr><th rowspan="1" colspan="1">All (n=64)</th><th rowspan="1" colspan="1">Residents (n=46)</th><th rowspan="1" colspan="1">Experienced GI specialists (n=18)</th><th rowspan="1" colspan="1">All (n=54)</th><th rowspan="1" colspan="1">Residents (n=35)</th><th rowspan="1" colspan="1">Experienced GI specialists (n=19)</th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">Accuracy before training</td><td rowspan="1" colspan="1">56</td><td rowspan="1" colspan="1">59</td><td rowspan="1" colspan="1">48</td><td rowspan="1" colspan="1">24</td><td rowspan="1" colspan="1">23</td><td rowspan="1" colspan="1">28</td></tr><tr><td rowspan="1" colspan="1">Accuracy after training</td><td rowspan="1" colspan="1">89</td><td rowspan="1" colspan="1">91</td><td rowspan="1" colspan="1">84</td><td rowspan="1" colspan="1">68</td><td rowspan="1" colspan="1">69</td><td rowspan="1" colspan="1">57</td></tr></tbody></table></table-wrap></p><p><bold>CONCLUSION:</bold> 1) The learning curve for pCLE image interpretation is fast, and interpretation can be learned easily after a short and structured training.</p><p>2) The learning curve is independant of endoscopic experience.</p><p><bold>Contact E-mail Address:</bold><email>emmanuel.coron@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> colon, endomicroscopy, Esophagus, learning curve</p></sec><sec><title>OP146 A PRELIMINARY STUDY OF STEREOVISION OF VASCULAR STRUCTURE IN GASTRIC MUCOSA</title><p><bold>R. Yamakawa</bold><sup>1,*</sup>, M. Iwata<sup>1</sup>, S. Nyuzuki<sup>1</sup>, M. Harada<sup>1</sup>, K. Kawauchi<sup>1</sup>, S.-I. Oyama<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology, KAETSU HOSPITAL, Niigata, Japan</italic></p><p><bold>INTRODUCTION:</bold> Magnification endoscopy with narrow band imaging (ME-NBI) enhances the visualization of mucosal glandular and vascular structure. But it do not provide real-time 3D image.</p><p>We reported previously that a pair of images taken by ME-NBI from a position slightly away could provide non real-time 3D image (anaglyph image) if the tilt and size differences of one image to another were corrected by projective transformation. We also reported that making multiple images (3D rendering) of gastric mucosa from different directions was possible, and these images were useful for the simultaneous examination of gastric mucosal glandular and vascular structure by many person.</p><p><bold>AIMS&METHODS:</bold> The aims of this study were to clarify the possibility and the usefulness of stereoscopic examination of vascular structure in gastric mucosa. A total of 22 patients were analyzed between July 2009 and May 2013: two gastritis, two gastric adenoma, 15 well-differentiated early gastric carcinoma, two undifferentiated early gastric carcinoma, and one MALT lymphoma. A total of 10,191 patients underwent upper GI endoscopy and 140 patients were examined by anaglyph method at our hospital in this period.</p><p>We took a pair of images by ME-NBI from a position slightly away and specified four pairs of points in these two images. The tilt and size differences of one image to another were deformed by projective transformation. We identified multiple same points on vascula in these two images, and calculated the height of these points. Then multiple line-drawing of vascula from different directions were made. We examined the usefulness of these images for the understanding of vascular structure in gastric mucosa, and the problems of this method.</p><p><bold>RESULTS:</bold> The stereoscopic observation of vascula in gastric mucosa was possible. The differences in vascular structure of gastric mucosa were more clear in 3D image than in 2D. But it was difficult to automatically pick out vascula in an image. Small vascula in an image were sometimes invisible in another image because real-time 3D image could not be obtained.</p><p><bold>CONCLUSION:</bold> The stereoscopic observation of vascula in gastric mucosa was useful for the understanding of vascular structure. But to pick out vascula automatically in an image was difficult. The examination of all vascula in an image was impossible.</p><p>The development of magnification endoscopy system which provide real-time 3D image is desired.</p><p><bold>Contact E-mail Address:</bold><email>yamakawa_r@niigata-min.or.jp</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> gastric mucosa, magnification endoscopy, NBI, stereovision </p></sec><sec><title>OP147 VISUALIZING INTRAGASTRIC STRUCTURING OF FAT EMULSIONS AND ITS IMPACT ON GASTRIC MOTOR FUNCTION BY MAGNETIC RESONANCE IMAGING (MRI)</title><p><bold>T. Radovic</bold><sup>1,*</sup>, S. Buetikofer<sup>1</sup>, T. J. Wooster<sup>2</sup>, J. Curcic<sup>1</sup>, O. Goetze<sup>1</sup>, M. Fried<sup>1</sup>, W. Schwizer<sup>1</sup>, A. Steingoetter<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland, <sup>2</sup>CSIRO Preventative Health Flagship, Werribee, Australia</italic></p><p><bold>INTRODUCTION:</bold> The most recent approach to counteract nutrition-related diseases, e.g. obesity and type 2 diabetes is designing functional foods that will increase satiety, reduce fat synthesis and absorption. Spatial distribution of fat within the gastric lumen is a critical factor that influences the rate of fat delivery to the small intestine and subsequent fat digestion process. Studies using marker tracer techniques showed that different compositions of fat emulsions (FE) can alter gastric emptying and maximize satiety signals. MRI is a reliable non-invasive imaging modality that has been applied to assess gastric motor function and visualize gastric fat-water distribution. The current study applied MRI to investigate the (de)structuring of different FE in the stomach and its impact on gastric emptying and motility.</p><p><bold>AIMS&METHODS:</bold> The randomized, double-blind, three-way crossover study assessed the impact of three FE of different acid stability and fat composition (table) on gastric emptying (GE), motility and post-prandial visceral perception. 17 healthy volunteers (6 m, age 25 ± 7, BMI 22 ± 1) orally ingested the FE on separate occasions. MRI scans (1.5TAchieva, Philips Healthcare, Netherlands) assessing gastric content volume (GCV) and peristaltic frequency (f) were performed and hunger/fullness scores were registered at fasted state, directly and at 15, 30, 50, 65, 80, 140, 190, 225 min after end of FE intake. Parameters were compared by linear mixed model.</p><p><bold>RESULTS:</bold> Acid stability and fat composition of FE had an impact on all parameters. The stable FE (sFE) resulted in slowest GE with highest meanGCV (p <0.001), highest f (p <0.001), lowest hunger (p <0.003) and highest fullness score (p <0.05). Unstable FE (uFE1 and uFE2) manifested with rapid intragastric water-fat separation, resulting in strikingly different intragastric fat distributions/structures: uFE1 resulted in large solid fat particles present in the stomach and surprisingly also the duodenum, uFE2 exhibited a distinct fat layer and water phase forming in fundus and antrum, respectively.
<table-wrap id="table20-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1"></th><th rowspan="1" colspan="1">sFE</th><th rowspan="1" colspan="1">uFE1</th><th rowspan="1" colspan="1">uFE2</th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">Acid stable</td><td rowspan="1" colspan="1">Y</td><td rowspan="1" colspan="1">N</td><td rowspan="1" colspan="1">N</td></tr><tr><td rowspan="1" colspan="1">Initial droplet size [µm]</td><td rowspan="1" colspan="1">0.6</td><td rowspan="1" colspan="1">0.6</td><td rowspan="1" colspan="1">0.6</td></tr><tr><td rowspan="1" colspan="1">Fat composition</td><td rowspan="1" colspan="1">Liquid oil</td><td rowspan="1" colspan="1">Solid fat</td><td rowspan="1" colspan="1">Liquid oil</td></tr><tr><td rowspan="1" colspan="1"> MRI</td><td rowspan="1" colspan="1"></td><td colspan="2" rowspan="1">Differences to sFE</td></tr><tr><td rowspan="1" colspan="1">MeanGCV [ml]</td><td rowspan="1" colspan="1">310±6</td><td rowspan="1" colspan="1">-111±8 <sup>#</sup></td><td rowspan="1" colspan="1">-78±8 <sup>#</sup></td></tr><tr><td rowspan="1" colspan="1">f [1/min]</td><td rowspan="1" colspan="1">0.9±0.04</td><td rowspan="1" colspan="1">-0.1±0.05<sup> *</sup></td><td rowspan="1" colspan="1">-0.2±0.05<sup> #</sup></td></tr></tbody></table></table-wrap></p><p>Table: acid stability, fat composition of FE; values for sFE and differences in meanGCV and f compared to sFE (estimate±SE). *p <0.01; <sup>#</sup>p <0.001</p><p><bold>CONCLUSION:</bold> Intragastric structuring of acid unstable emulsions can be visualized by MRI and has an impact on gastric emptying, motility and visceral perception scores.</p><p><bold>Contact E-mail Address:</bold><email>steingoetter@biomed.ee.ethz.ch</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Fat emulsion, Gastric function, MRI, Satiation</p></sec><sec><title>OP148 SCHEDULED SECOND-LOOK ENDOSCOPY IS NOT NECESSARY AFTER ENDOSCOPIC SUBMUCOSAL DISSECTION FOR GASTRIC NEOPLASMS: A MULTICENTER PROSPECTIVE RANDOMIZED CONTROLLED TRIAL (THE SAFE TRIAL)</title><p><bold>T. Yamashina</bold><sup>1,*</sup>, S. Mochizuki<sup>2</sup>, I. Oda<sup>3</sup>, K. Kaneko<sup>4</sup>, Y. Yamamoto<sup>5</sup>, N. Uedo<sup>1</sup>, H. Suzuki<sup>3</sup>, T. Yano<sup>4</sup>, S. Kodashima<sup>2</sup>, N. Yamamichi<sup>2</sup>, O. Goto<sup>6</sup>, M. Fujishiro<sup>2</sup>, K. Koike<sup>2</sup></p><p><italic><sup>1</sup>Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, <sup>2</sup>The University of Tokyo, <sup>3</sup>National Cancer Center Hospital, Tokyo, <sup>4</sup>National Cancer Center Hospital East, Kashiwa, <sup>5</sup>Cancer Institute Hospital, <sup>6</sup>Keio University, Tokyo, Japan</italic></p><p><bold>INTRODUCTION:</bold> Postoperative bleeding is a major complication after endoscopic submucosal dissection (ESD) for gastric neoplasms and it accounts up to 11.3% of cases. To reduce incidence of the bleeding, second-look endoscopy (SLE) is usually scheduled on the day after ESD. However, the effectiveness of SLE in prevention of post-ESD bleeding remains controversial.</p><p><bold>AIMS&METHODS:</bold> To clarify the effectiveness of a SLE after gastric ESD, this open-label multicenter prospective randomized controlled non-inferiority trial was undertaken in 5 sites across Japan. Patients with one gastric neoplasm were enrolled in this study with limited exclusion criteria (no history of esophagogastric surgery or radiation therapy, no antithrombotics or steroids use during the perioperative period). Immediately after the completion of ESD, all visible vessels and adherent clots on the mucosal defect were routinely coagulated. Then, the patients were allocated (1:1) to either SLE group or non-SLE group by computer-generated random sequence via a web response system. In the SLE group, patients received SLE on the day after ESD, and when an endoscopist found active bleeding, visible vessels or adherent clots on the post-ESD ulcer, prophylactic cauterization was performed. All patients received proton pump inhibitor from the day before the ESD and continued for 4 weeks. When a patient presented with hematemesis, melena or drop of Hb >2g/dl, emergency endoscopy was performed. The primary endpoint was non-inferiority of the post-ESD bleeding rate, which was defined as endoscopically proven hemorrhage, in the non-SLE group to that in the SLE group. (Trail registration number: UMIN-CTR 000007170)</p><p><bold>RESULTS:</bold> A total of 130 patients were assigned to the SLE group and 132 to the non-SLE group; 126 and 132 were included in analysis of the primary endpoint. Post-ESD bleeding occurred in 7 (5.5%) patients in the SLE group and 5 (3.8%) in the non-SLE group (risk difference, -1.8% [90%CI: -6.10-2.56]; <italic>P</italic><sub>non-inferiority</sub>=0.0003), meeting the predefined non-inferiority criterion of 7%. All bleeding cases and one case of postoperative perforation were successfully managed with conservative treatments without blood transfusion or surgery.</p><p><bold>CONCLUSION:</bold> SLE after gastric ESD is not recommended because it contributes little to the prevention of post-ESD bleeding.</p><p><bold>Contact E-mail Address:</bold><email>satoshi-jp@umin.ac.jp</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> endoscopic submucosal dissection (ESD), gastric neoplasm, Post ESD bleeding, second look endoscopy</p></sec><sec><title></title><p><bold>MONDAY, OCTOBER 14, 2013 15:45-17:15</bold></p><p><bold>Basic mechanisms of GI motor and sensory dysfunction – Salon 11/12</bold></p></sec><sec><title>OP149 INTEGRATION OF ENTERIC NEURAL CREST CELLS AFTER COLONIC TRANSPLANTATION.</title><p><bold>C. McCann</bold><sup>1,*</sup>, J. Cooper<sup>1</sup>, D. Natarajan<sup>1</sup>, J.-M. Delalande<sup>1</sup>, W. Boesmans<sup>2</sup>, P. Vanden Berghe<sup>2</sup>, A. Burns<sup>1</sup>, N. Thapar<sup>1,3</sup></p><p><italic><sup>1</sup>Birth Defects Research Centre, Institute of Child Health, University College London, London, United Kingdom, <sup>2</sup>TARGID, KU Leuven, Leuven, Belgium, <sup>3</sup>Gastroenterology Unit, Great Ormond Street Hospital, London, United Kingdom</italic></p><p><bold>INTRODUCTION:</bold> Recent work has focused on the development of cellular therapies for severe enteric neuropathies such as Hirschsprung disease. Neural crest (NC) derived enteric neural stem cells (ENSC) have been identified as a possible source for neural replenishment. Previous work has shown that after isolation and transplantation, ENSC can successfully colonise recipient gut both <italic>in vitro</italic> and <italic>in vivo.</italic> However, the integration and functionality of transplanted cells within the host neuromusculature remains unclear.</p><p><bold>AIMS&METHODS:</bold> Our aim was to determine the functional integration of ENSC within recipient mouse colonic tissue.</p><p>We utilized donor ENSC from transgenic mice (<italic>Wnt1-cre;YFP - </italic>all NCC express yellow fluorescent protein) as a way of fate mapping cells. Transplantations were performed into both ganglionic and aganglionic colon. Transplanted cells were characterised post transplantation to assess integration and functionality, using immunolabeling and both cellular and tissue physiology.</p><p><bold>RESULTS:</bold> In ganglionic colon, YFP<sup>+</sup> transplanted cells showed differentiation into enteric neurons (β-III tubulin) and glia (GFAP). Mature neuronal subtypes (nNOS, ChaT, VIP) were also evident. YFP<sup>+</sup> cells co-localised within the endogenous neuronal plexuses and appeared to form synaptic contacts (synaptophysin) with endogenouscells.</p><p>Functionality was assessed via calcium imaging. Transplanted YFP<sup>+</sup> cells displayed calcium transients upon electrical train stimulation (2s, 20Hz of 300ms electrical pulses) of endogenous neuronal fibres, suggesting functional integration within the endogenous neural circuitry. These responses were blocked in the presence of tetrodotoxin (TTX; 1μM) confirming neuronal origin.</p><p>Similar <italic>in vivo</italic> studies on aganglionic bowel are limited by poor survival of recipient animals (4 days post transplant). We therefore developed an <italic>ex vivo</italic> culture system that enables characterization up to 2 weeks post transplantation. These show similar integration and differentiation, of transplanted cells, into enteric neurons (β-III tubulin) as with ganglionic colon.</p><p>We are currently studying functionality in transplanted aganglionic gut in the context of this <italic>ex vivo </italic>system.</p><p><bold>CONCLUSION:</bold> The experiments described provide key evidence of functional integration of transplanted ENSC within recipient gut. Transplanted ENSC show appropriate migration and differentiation along with displaying functional neuronal properties. Thus, providing proof of concept for the use of ENSC for enteric neuropathies.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Enteric nervous system, Hirschsprung Disease, Stem Cells, Transplantation</p></sec><sec><title>OP150 INTERSTITIAL CELLS OF CAJAL INTEGRATE EXCITATORY AND INHIBITORY NEUROTRANSMISSION WITH INTESTINAL SLOW WAVE ACTIVITY</title><p><bold>S. Klein</bold><sup>1,*</sup>, B. Seidler<sup>1</sup>, A. Kettenberger<sup>1</sup>, A. Sibaev<sup>2</sup>, M. A. Storr<sup>2</sup>, M. Schemann<sup>3</sup>, R. M. Schmid<sup>1</sup>, G. Schneider<sup>1</sup>, D. Saur<sup>1</sup></p><p><italic><sup>1</sup>Department of Internal Medicine 2, TUM, <sup>2</sup>Department of Internal Medicine 2, Ludwig-Maximilian Universität München, München, <sup>3</sup>Lehrstuhl für Humanbiologie, TUM, Freising-Weihenstephan, Germany</italic></p><p><bold>INTRODUCTION:</bold> The enteric nervous system contains excitatory and inhibitory neurons which control contraction and relaxation of smooth muscle cells (SMC) and gastrointestinal (GI) motor activity. Interstitial cells of Cajal (ICC) act as pacemaker in the GI tract and orchestrate GI motility by generating waves of depolarisation which induce rhythmic contraction of SMC. The role of ICC in neurotransmission is highly controversial and hampered by the lack of genetically defined models enabling time-specific targeting of ICC in adult animals.</p><p><bold>AIMS&METHODS:</bold> To analyse ICC function in adult mice <italic>in vivo</italic>, we generated a <italic>c-Kit<sup>CreERT2</sup></italic> knock-in allele at the endogenous c-Kit locus. This mouse line enables for the first time genetic manipulation of ICC at defined time points during development and in adults <italic>in vivo</italic>. With the help of this novel model, we analyzed the specific role of ICC in enteric excitatory and inhibitory neurotransmission by genetic loss of function studies. We crossed <italic>c-Kit<sup>CreERT2/+</sup></italic> mice with conditional <italic>LSL-R26DTA/+</italic> animals, which carry a latent diphtheria toxin A (DTA) expression cassette to deplete ICC. To test whether ICC modulate inhibitory neurotransmission, we deleted <italic>cGMP-dependent protein kinase I</italic> (<italic>Prkg1</italic>), a central mediator of the non-adrenergic, non-cholinergic neurotransmission, in ICC by using floxed <italic>Prkg1<sup>lox/lox</sup></italic> mice.</p><p><bold>RESULTS:</bold> Tamoxifen induced depletion of >50% of the ICC network was observed in c-Kit<sup>CreERT2</sup>;<italic> LSL-R26DTA/+</italic> mice. ICC network disruption in healthy adult animals resulted in severely disturbed GI motility with significantly increased GI transit time. Importantly, all parts of the GI tract were equally affected by ICC depletion. The disturbed motility is caused by dysrhythmic spontaneous phasic myogenic contractions and lack of slow-wave type electrical activity in circular small intestinal SMC. Organ bath experiments showed a significant reduction of neuronal induced colonic SM contractions after electrical field stimulation in tamoxifen treated animals. A loss of Prkg1 expression in ∼40% of all ICC resulted in disturbed GI motility and abolished specifically the NO-dependent component of the inhibitory junction potential in colonic circular SMC.</p><p><bold>CONCLUSION:</bold> Time specific inducible depletion of the ICC network is feasible in adult animals using the novel c-Kit<sup>CreERT2</sup> expression model. In addition, we demonstrate for the first time a role for ICC in excitatory and inhibitory neurotransmission in phenotypic normal adult animals.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Interstitial cells of Cajal, neurotransmission</p></sec><sec><title>OP151 ACTIVATION OF THE GUANYLATE CYCLASE-C/CGMP PATHWAY DECREASES GASTROINTESTINAL PAIN</title><p><bold>I. Silos-Santiago</bold><sup>1,*</sup>, J. Castro<sup>2</sup>, P. Ge<sup>1</sup>, H. Jin<sup>1</sup>, M. M. Kessler<sup>1</sup>, A. L. Blackshaw<sup>3</sup>, C. B. Kurtz<sup>1</sup>, M. G. Currie<sup>1</sup>, G. Hannig<sup>1</sup>, S. M. Brierley<sup>2</sup></p><p><italic><sup>1</sup>Ironwood Pharmaceuticals, Inc, Cambridge, United States, <sup>2</sup>Nerve-Gut Research Laboratory - Dicipline of Medicine, University of Adelaide, Adelaide, Australia, <sup>3</sup>Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom</italic></p><p><bold>INTRODUCTION:</bold> The 14-amino acid peptide linaclotide is a guanylate cyclase-C (GC-C) agonist related to the hormones guanylin and uroguanylin. In animal models, linaclotide reduced colonic hypersensitivity in a GC-C dependent manner, a mechanism not previously linked to the GC-C/cGMP pathway. It has been hypothesized that the analgesic effects of linaclotide are mediated by extracellular cGMP, following GC-C activation.</p><p><bold>AIMS&METHODS:</bold> In this study, we investigated the effects of the endogenous GC-C/cGMP pathway on modulating gastrointestinal sensory signaling. Analgesic effects of uroguanylin and cGMP were assessed in a rat model of inflammation-induced colonic hypersensitivity. Linaclotide, uroguanylin and cGMP effects on mouse splanchnic colonic nociceptors were measured using <italic>in vitro</italic> single-unit afferent recordings. GC-C expression in mice was determined by <italic>in situ</italic> hybridization.</p><p><bold>RESULTS:</bold> During inflammation-induced colonic hypersensitivity, orally administered uroguanylin elicited significant anti-hyperalgesic effects increasing the pain threshold to colorectal distension. In addition, linaclotide, and uroguanylin <italic>in vitro</italic> significantly inhibited the mechanical responsiveness of mouse colonic nociceptors, an effect that became particularly pronounced during chronic visceral hypersensitivity. These effects were mimicked by cGMP, suggesting a direct link between activation of the GC-C/cGMP pathway and analgesic effects in this model. Incubation of colonic afferent preparations with the cGMP efflux inhibitor, probenecid, eliminated the inhibitory effect of linaclotide on colonic nociceptors. This suggests that extracellular cGMP, released upon activation of GC-C from intestinal epithelial cells, underlies the anti-hyperalgesic effects of these GC-C agonists. Since we detected high levels of GC-C expression in the intestine but not dorsal root ganglion neurons this is consistent with a local, peripheral mechanism linking analgesic effects to activation of the GC-C/cGMP pathway.</p><p><bold>CONCLUSION:</bold> GC-C agonists, such as linaclotide, have pronounced anti-hyperalgesic effects in animal models of abdominal pain. These effects have also translated into the clinic, where in patients with irritable bowel syndrome with constipation, linaclotide treatment improved abdominal pain. These findings suggest that targeting the GC-C/cGMP pathway is linked to analgesic effects in these patients</p><p><bold>Contact E-mail Address:</bold><email>isilos-santiago@ironwoodpharma.com</email></p><p><bold>Disclosure of Interest</bold>: I. Silos-Santiago Shareholder of: Ironwood Pharmaceuticals, Inc., J. Castro Financial support for research from: Ironwood Pharmaceuticals, Inc., P. Ge Shareholder of: Ironwood Pharmaceuticals, Inc., H. Jin Shareholder of: Ironwood Pharmaceuticals, Inc., M. Kessler Shareholder of: Ironwood Pharmaceuticals, Inc., A. Blackshaw Financial support for research from: Ironwood Pharmaceuticals, Inc., C. Kurtz Shareholder of: Ironwood Pharmaceuticals, Inc., M. Currie Shareholder of: Ironwood Pharmaceuticals, Inc., Directorship(s) for: Ironwood Pharmaceuticals, Inc., G. Hannig Shareholder of: Ironwood Pharmaceuticals, Inc., S. Brierley Financial support for research from: Ironwood Pharmaceuticals, Inc.</p><p><bold>Keywords:</bold> abdominal pain, cGMP, Guanylate Cyclase-C, linaclotide</p></sec><sec><title>OP152 THE GPR30-ESTROGEN RECEPTOR CONTROLS GASTROINTESTINAL CHOLINERGIC NEUROTRANSMISSION IN THE REGULATION OF MOTILITY AND VISCERAL SENSATION</title><p><bold>J. Fichna</bold><sup>1,2,*</sup>, A. Sibaev<sup>3</sup>, S. Habibi<sup>1</sup>, M. Bashashati<sup>1</sup>, M. Storr<sup>3</sup></p><p><italic><sup>1</sup>Department of Medicine, Division of Gastroenterology, University of Calgary, Calgary, Canada, <sup>2</sup>Department of Biomolecular Chemistry, Medical University of Lodz, Lodz, Poland, <sup>3</sup>Department of Medicine, Ludwig Maximilians University of Munich, Munich, Germany</italic></p><p><bold>INTRODUCTION:</bold> Irritable bowel syndrome (IBS) is more common among women. Among female hormones, estrogen plays a crucial role at transcriptional levels through stimulating its classical nuclear receptors: ERα and ERβ. We designed this study to identify whether estrogen alters GI motility and sensation and whether these effects involve a recently introduced G protein coupled receptor GPR30.</p><p><bold>AIMS&METHODS:</bold> CD1 female mice (4-5 weeks old) were used. The effects of β-Estradiol and a selective GPR30 agonist G-1 (both 100 nM-3µM) on the contractility of colonic preparations induced by electrical field stimulation (EFS; 4 Hz, 10 sec, 24 V, 50 sec intervals) and the muscarinic agonist bethanechol (10µM) were studied <italic>in vitro</italic>. Intracellular recordings of colonic circular smooth muscle cells were performed to evaluate the effects of GPR30 activation on excitatory and inhibitory junction potentials (EJP; IJP). Colonic propulsion of a glass bead in the presence of β-Estradiol or G-1 was studied <italic>in vivo</italic>. The effects of either compound on visceral hyperalgesia induced by intracolonic (i.c.) mustard oil (MO) were tested by recording spontaneous behaviours.</p><p><bold>RESULTS:</bold> G-1 or β-Estradiol inhibited colonic EFS and bethanechol induced contractilities. G-15, a selective GPR30 antagonist, blocked the effects of G-1 but not the effects of β-Estradiol on colonic contractility. MPP dihydrochloride a highly selective ERα antagonist partially reversed the effects of G-1 and β-Estradiol; PHTPP, an ERβ antagonist, did not alter the effects of G-1 or β-Estradiol. Intracellular recordings showed that G-1 reduced the cholinergic mediated EJP without any influence on the nitrergic or purinergic phases of IJP. β-Estradiol and G-1 (10-20 mg. i.v.) prolonged colonic propulsion in vivo. The effects of β-Estradiol on colonic propulsion were reversed by G-15 or MPP dihydrochloride. For G-1, G-15 or the ER antagonists reversed the effects on colonic propulsion. MO induced visceral hyperalgesia was inhibited by G-1 or β-Estradiol (20 mg, i.v.). G-15 and MPP dihydrochloride but not PHTPP reversed the effects of G-1 on visceral hyperalgesia. The effects of β-Estradiol on visceral hyperalgesia were blocked by G-15 but not by the ER antagonists.</p><p><bold>CONCLUSION:</bold> Our data suggest that GPR30 may become a promising target for the treatment of functional GI disorders where motility disturbances and visceral pain are involved.</p><p><bold>Contact E-mail Address:</bold><email>jakub.fichna@umed.lodz.pl</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Estrogen, G protein-coupled receptor, GPR30, Irritable bowel syndrome</p></sec><sec><title>OP153 EXTRACELLULAR MATRIX PROTEIN TENASCIN-X IN MOUSE AND HUMAN NERVE-GUT INTERACTIONS</title><p><bold>R. Aktar</bold><sup>1,*</sup>, A. Fikree<sup>1</sup>, M. Peiris<sup>1</sup>, Q. Aziz<sup>1</sup>, L. A. Blackshaw<sup>1</sup></p><p><italic><sup>1</sup>Digestive Diseases, QUEEN MARY UNIVERSITY OF LONDON, London, United Kingdom</italic></p><p><bold>INTRODUCTION:</bold> Joint hypermobility syndrome (JHS) affects 1 in 20 people, characterised by joint and skin hyperflexibility, chronic pain, rectal evacuatory dysfunction (Mohammed<italic>,</italic> NGM 2010, 22, 1085), prolapse and unexplained gastrointestinal (GI) symptoms (Zarate, NGM 2010, 22, 252). There is also increased prevalence of alternating bowel habit, postprandial fullness, bloating and dysphagia (Fikree, NGM 2012, 24, S2, 19). A severe form of JHS - Ehlers Danlos Syndrome type III - is caused by absence of the extracellular matrix (ECM) glycoprotein Tenascin X (TNX). It is reproduced in TNX knockout mice (Mao<italic>,</italic> Nat Genet 2002 30:421). We hypothesise that GI disturbances and JHS may share a common disorder of the extracellular matrix.</p><p><bold>AIMS&METHODS: Aim:</bold> To establish TNX distribution in the gut, and how it relates to the extrinsic and enteric nervous system. <bold>Methods</bold>: Fluorescent immunohistochemistry was performed on whole-mount mouse tissue (n=7). Colon and gastric fundus were co-labelled for CGRP (calcitonin gene related peptide) - a marker for nociceptive primary extrinsic afferents, or Calretinin – a vagal afferent and enteric neuronal marker, plus TNX. These markers were also used in full thickness sections of human colon.</p><p><bold>RESULTS:</bold> Mouse: TNX-IR was surprisingly not found in connective tissue, but often in neural and vascular tissue. In stomach, immunoreactivity (IR) for TNX or calretinin was not observed in enteric neurones. However, both were seen in intramuscular arrays (IMA), a specific subtype of vagal afferent endings (Phillips, Brain Res Rev 2000, 34, 1-26). Blood vessels were TNX-IR, with CGRP positive nerve fibres running separately alongside, as also found in the colon. In colonic enteric neurones, TNX-IR was found on ∼50% of calretinin-IR neuronal cell bodies, and on calretinin-negative neurones. TNX-IR nerve endings were common in longitudinal muscle layer, but showed less overlap with calretinin. The same pattern of labelling for calretinin and TNX was found in human colonic enteric neurones, indicating this pattern is conserved amongst species. Observations in both species indicated calretinin was cytoplasmic, whilst TNX was confined to the membrane, as would be expected for an extracellular anchoring role (Kwok, Dev Neurobiol 2011, 71:1073-89).</p><p><bold>CONCLUSION: Conclusion:</bold> We provide new evidence that TNX associates with nerves in the gut. Our data imply that TNX may be involved in colonic enteric neural function and gastric vagal afferent function, but not in nociceptor function. Further anatomical work is needed on JHS tissue, and functional studies on TNX knockout mice to help elucidate importance of TNX in sensory and motor function.</p><p><bold>Contact E-mail Address:</bold><email>r.aktar@qmul.ac.uk</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> extracellular matrix, nerve-gut interactions</p></sec><sec><title>OP154 THE NON-DIABETIC BB-RAT: A SPONTANEOUS MODEL FOR INFLAMMATION-RELATED IMPAIRED GASTRIC ACCOMMODATION.</title><p><bold>C. Vanormelingen</bold><sup>1,*</sup>, R. Farré<sup>1</sup>, T. Vanuytsel<sup>1</sup>, T. Masaoka<sup>1</sup>, P. Vanden Berghe<sup>1</sup>, J. Tack<sup>1</sup></p><p><italic><sup>1</sup>TARGID, Leuven, Belgium</italic></p><p><bold>INTRODUCTION:</bold> Symptoms in post-infectious functional dyspepsia have been attributed to impaired gastric accommodation resulting from dysfunction of nitrergic myenteric neurons.<sup>1 </sup>To date, a spontaneous animal model to study the relationship between these changes is lacking. The Biobreeding (BB) rat consists of a diabetes-resistant (BBDR), control strain, and a diabetes-prone (BBDP) strain. In our facility, 50% of the BBDP rats become diabetic after the age of 90 days. BBDP rats develop ganglionic inflammation, loss of neuronal nitric oxide synthase (nNOS) and impaired nitrergic motor control in the intestine, independently of hyperglycemia.</p><p><bold>AIMS&METHODS:</bold> Our aim was to evaluate neuromuscular function, gastric accommodation and presence of inflammation in the gastric fundus of different BB rat strains. Responses to electrical field stimulation (1-4Hz) were evaluated in gastric fundus circular muscle strips from rats 30 and 220 days old (control (BBDR), non-diabetic (BBDP) and diabetic (BBDP-H) (N=6)). This was done under NANC conditions and in the presence of NO synthase inhibitor L-NAME (10-4M). Relaxation was evaluated as area under the curve and corrected for cross-sectional area and weight. Statistics were done using mixed model analysis. Gastric accommodation was studied in vivo by measuring changes in intragastric pressure (IGP) during infusion of liquid nutrient meal via a gastric fistula.<sup>2</sup> Expression of nNOS was quantified by Western blot relative to PGP9.5. Inflammation was evaluated histologically and by myeloperoxidase (MPO)-activity for mucosa and muscularis propria.</p><p><bold>RESULTS:</bold> No differences were seen between BBDP and control rats at 30 days. The nitrergic component of the relaxation under NANC conditions was reduced in BBDP and BBDP-H rats of 220 days compared to age-matched controls (P<0.01). This was accompanied by a loss of nNOS proteins (P<0.01). MPO activity increased in the fundic mucosa and muscularis propria of 220 days BBDP and BBDP-H rats. This inflammation was histologically confirmed by significant infiltration of polymorphonuclear cells, whitout lesions. IGP during nutrient infusion significantly increased in BBDP rats of 220 days compared to controls. Only in controls, IV administration of L-NAME increased IGP during nutrient infusion.</p><p><bold>CONCLUSION:</bold> BBDP rats of 220 days display altered fundic motor control and impaired accommodation, which is partially explained by loss of nitrergic function in the myenteric plexus, and which may be related to low grade inflammation in the neuromuscular layer. Changes develop independently from diabetes. The non-diabetic BBDP rat may provide a spontaneous model for inflammation-induced impaired gastric accommodation.</p><p><bold>REFERENCES:</bold></p><p>1. Tack J, Demedts I, Dehondt G, <italic>et al</italic>. Clinical and pathophysiological characteristics of acute-onset functional dyspepsia. Gastroenterology. 2002 Jun;122(7):1738-47.</p><p>2. Janssen P, Nielsen MA, Hirsch I, <italic>et al</italic>. A novel method to assess gastric accommodation and peristaltic motility in conscious rats. Scand J Gastroenterol 2008;43:34-43.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Biobreeding rat, gastric accomodation, neuromuscular inflammation, Nitrergic function</p></sec><sec><title></title><p><bold>TUESDAY, OCTOBER 15, 2013 8:30-10:30</bold></p><p><bold>New treatments for functional GI disorders – Hall Prague</bold></p></sec><sec><title>OP155 ACCELERATION OF TIME TO FIRST BOWEL MOVEMENT IN CHRONIC IDIOPATHIC CONSTIPATION (CIC) PATIENTS RECEIVING PLECANATIDE IN A LARGE, MULTICENTER, DOSE-RANGING STUDY</title><p><bold>P. B. Miner</bold><sup>1,*</sup>, L. Barrow<sup>2</sup>, R. Fogel<sup>3</sup>, A. Joslyn<sup>2</sup>, G. Jacob<sup>2</sup></p><p><italic><sup>1</sup>Oklahoma Institution for Digestive Research,, Oklahoma City, <sup>2</sup>Synergy Pharmaeuticials, Inc, New York, <sup>3</sup>Clinical Research Institute of MI, Chesterfield, United States</italic></p><p><bold>INTRODUCTION:</bold> Plecanatide, a new guanylate-cyclase C receptor agonist, restores intestinal fluid balance in CIC patients resulting in increased number of bowel movements (BM). Time to first BM data were examined several ways as part of the analysis of the study results from a recently completed large multicenter study. The aim was to better understand the potential impact of rescue medication (RM) on the time to first BM.</p><p><bold>AIMS&METHODS:</bold> This double-blind, placebo-controlled dose-ranging study enrolled 951 CIC patients at 113 sites in the U.S. Patients who met modified CIC Rome III criteria, and demonstrated <3 Complete Spontaneous Bowel Movements (CSBMs)/week during pre-treatment were randomized to 0.3, 1.0, or 3.0 mg plecanatide, or placebo QD for 12 weeks. Bisacodyl (Dulcolax®) 5 mg was allowed as RM. Efficacy data was collected daily by an interactive telephone system. The four endpoints measured were: Time to first spontaneous bowel movement (SBM) and CSBM, and % of patients with SBM and CSBM in the first 24 hr post-dose.</p><p><bold>RESULTS:</bold> All four endpoints demonstrated a dose response. In a subset of 495 patients who had not taken RM for 72 hr before and after first dose of study drug, time to first CSBM and SBM demonstrated dose-related, even faster, onset of effect (Table).
<table-wrap id="table21-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1">MEASURE</th><th rowspan="1" colspan="1">Placebo</th><th rowspan="1" colspan="1">0.3 mg</th><th rowspan="1" colspan="1">1.0 mg</th><th rowspan="1" colspan="1">3.0 mg</th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">Median Time to First CSBM (hours)</td><td rowspan="1" colspan="1">124.5</td><td rowspan="1" colspan="1">96.9</td><td rowspan="1" colspan="1">82 (p<0.05)</td><td rowspan="1" colspan="1">54.7 (p<0.001)</td></tr><tr><td rowspan="1" colspan="1">Median Time to First SBM (hours)</td><td rowspan="1" colspan="1">27.3</td><td rowspan="1" colspan="1">21 (p<0.01)</td><td rowspan="1" colspan="1">21.3 (p<0.01)</td><td rowspan="1" colspan="1">12.5 (p<0.001)</td></tr><tr><td rowspan="1" colspan="1">Median Time to First CSBM w/out Rescue within 72 hours (hours)</td><td rowspan="1" colspan="1">124.5</td><td rowspan="1" colspan="1">93.3</td><td rowspan="1" colspan="1">71.1 (p<0.05)</td><td rowspan="1" colspan="1">51.3 (p<0.001)</td></tr><tr><td rowspan="1" colspan="1">Median Time to First SBM w/out Rescue within 72 hours (hours)</td><td rowspan="1" colspan="1">25.1</td><td rowspan="1" colspan="1">20.3 (p<0.05)</td><td rowspan="1" colspan="1">18.1 (p<0.01)</td><td rowspan="1" colspan="1">9.6 (p<0.001)</td></tr><tr><td rowspan="1" colspan="1">% Patients with CSBM within 24 hours</td><td rowspan="1" colspan="1">11.5</td><td rowspan="1" colspan="1">20.7 (p<0.01)</td><td rowspan="1" colspan="1">23.1 (p<0.001)</td><td rowspan="1" colspan="1">31.2 (p<0.001)</td></tr><tr><td rowspan="1" colspan="1">% Patients with SBM within 24 hours</td><td rowspan="1" colspan="1">41.5</td><td rowspan="1" colspan="1">55.7 (p<0.01)</td><td rowspan="1" colspan="1">53.8 (p<0.01)</td><td rowspan="1" colspan="1">67.5 (p<0.001)</td></tr></tbody></table></table-wrap></p><p><bold>CONCLUSION:</bold> Plecanatide produced a dose-related reduction in time to first SBM and CSBM compared to placebo, and a dose-related increase in the percent of patients achieving first SBM and CSBM within 24 hr following first dose. In patients not taking RM 72 hr before or after first dose, the time to first CSBM and SBM continued to show a dose-related decrease in time to first BM , therefore the ingestion of RM did not dramatically influence the analysis of the first dose effects of plecanatide on BM.</p><p><bold>Contact E-mail Address:</bold><email>ajoslyn@sentinellapharma.com</email></p><p><bold>Disclosure of Interest</bold>: P. Miner: None Declared, L. Barrow Shareholder of: Synergy Pharma, Other: Employee Synergy Pharma, R. Fogel: None Declared, A. Joslyn Consultancy for: Synergy Pharma, G. Jacob Shareholder of: Synergy Pharma, Other: Employee Synergy Pharma</p><p><bold>Keywords:</bold> chronic idiopathic constipation, constipation, GC-C, plecanatide</p></sec><sec><title>OP156 PLACEBO INTERVENTIONS IN STUDIES WITH PSYCHOLOGICAL TREATMENTS OF IRRITABLE BOWEL SYNDROME: A SYSTEMATIC REVIEW</title><p><bold>C. Flik</bold><sup>1,*</sup>, L. Bakker<sup>1</sup>, W. Laan<sup>1</sup>, N. de Wit<sup>1</sup></p><p><italic><sup>1</sup>Julius Center, Health Sciences and Primary Care, UNIVERSITY MEDICAL CENTER, Utrecht, Netherlands</italic></p><p><bold>INTRODUCTION:</bold> The reported placebo response (PR) in RCT’s on therapeutic interventions for Irritable Bowel Syndrome (IBS) ranges from 37.5 to 42.6%. In studies with psychological interventions designing an adequate placebo comparison is difficult. Due to the subjective perception of the intervention and the important role of the therapist the size of the PR may be different as compared to drug interventions.</p><p><bold>AIMS&METHODS:</bold> We aimed to assess the design and the effect size of placebo interventions used in RCTs on psychological treatments for IBS.</p><p>Randomized Controlled Trials comparing psychological interventions for the treatment of IBS with an adequate placebo treatment, defined as an intervention that included consultation of a therapist, had a possible benefit for the patient and took as much therapeutic time as the psychological intervention itself, were systematically reviewed.</p><p>Studies published full text in Dutch and English language in peer-reviewed journals, concerning adult IBS patients diagnosed according to the Manning, Rome I, II or III criteria were selected.</p><p><bold>RESULTS:</bold> Six studies, with a total of 545 patients met the inclusion criteria. The PR ranged from 25% till 71.4% with a pooled mean of 42.2%.</p><p> Four studies, three with C(B)T and one with autogenic training, used an educational intervention as placebo control (PR: 56%; 37.3%; 25%; 30%). One study used imaginative and active visualization as control intervention for stress and contingency management (PR: 71.4%). One study on mindfulness used a support group as placebo control (PR:68.8%).</p><p><bold>CONCLUSION:</bold> Different placebo interventions are used as comparison in studies on psychological interventions in IBS, but the pooled effect size is comparable to that of drug studies. Possibly the PR is more determined by patient related factors such as expectations and disease perception than by the actual content of the placebo intervention.</p><p><bold>Contact E-mail Address:</bold><email>c.e.flik@umcutrecht.nl</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Irritable bowel syndrome, placebo intervention, psychological treatment, systematic review</p></sec><sec><title>OP157 EFFICACY OF A CARBON DIOXIDE-RELEASING SUPPOSITORY (EDUCTYL®) IN PATIENTS WITH DYSCHEZIA AND TREATED BY ANORECTAL BIOFEEDBACK TRAINING: A DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED CLINICAL TRIAL</title><p><bold>O. Cotelle</bold><sup>1</sup>, G. Cargill<sup>2</sup>, M. Marty<sup>3</sup>, L. Bueno<sup>4</sup>, M.-C. Cappelletti<sup>5</sup> H. Colangeli-Hagège V <sup>6</sup>, Berger<sup>3</sup>, B. Savarieau<sup>7</sup>, P. Ducrotté<sup>8,*</sup></p><p><italic><sup>1</sup>Service de chirurgie viscérale et gynécologique, Groupe hospitalier des Diaconesses Croix St Simon, <sup>2</sup>Cabinet de gastro-entérologie, <sup>3</sup>Département études cliniques, Nukleus, PARIS, <sup>4</sup>Unité de neuro-gastroentérologie, INRA, TOULOUSE, <sup>5</sup>Centre d’Exploration et de Rééducation Périnéale, <sup>6</sup>Centre de soins du Marais, PARIS, <sup>7</sup>Service d’hépato-gastroentérologie, Hôpital Intercommunal, CRETEIL, <sup>8</sup>Service d’hépato-gastroentérologie, Hôpital Charles Nicolle, ROUEN, France</italic></p><p><bold>INTRODUCTION:</bold> Dyschezia is a defecatory disorder with a heavy burden on quality of life. There is a lack of evidence regarding how dyschezia should be managed. Only anorectal biofeedback training has proven effective. This study aims to assess the efficacy and safety of a carbon dioxide-releasing suppository, Eductyl<sup>®</sup>, in patients with dyschezia treated by anorectal biofeedback training.</p><p><bold>AIMS&METHODS:</bold> A randomized, double-blind, placebo-controlled study was conducted in patients (18-75 years) with dyschezia defined according to modified Rome III criteria. Patients were randomly assigned to once-a-day carbon dioxide-releasing suppository or placebo for 21 days. At least 5 sessions of biofeedback training was performed during the study. The primary endpoint was the change from D0 to D21 in intensity of symptoms related to dyschezia self-assessed using a VAS (0 -100). Analyses were performed using intent-to-treat principles.</p><p><bold>RESULTS:</bold> 122 patients were randomized (62 intervention group and 60 placebo group). A greater reduction from baseline to D21 in symptom VAS score was observed in the intervention group (- 41.3 mm; SEM: 3.1) than in the control group (- 22.3; SEM: 3.3) (p<0.0001). Some secondary efficacy parameters were more improved in the intervention group: percent of patients who improved ≥ 50% (p=0.0014), symptom intensity over 21 days (p<0.001), stools stains on underwear or pads (p=0.0178) and need to practice manual maneuvers to facilitate defecation (p=0.0028). At D21 rectal sensitivity in the interventiongroup (31.4mL (SD 26.4)) was lower than in the control group (39.1 mL (SD 18.3) (p=0.0058).</p><p><bold>CONCLUSION:</bold> The present trial provides evidence of the efficacy of a carbon dioxide-releasing suppository to treat patients with dyschezia during anorectal biofeedback training.</p><p>ClinicalTrial.gov, number NCT00910832</p><p><bold>Contact E-mail Address:</bold><email>v.berger@nukleus.fr</email></p><p><bold>Disclosure of Interest</bold>: O. Cotelle Financial support for research from: Techni Pharma Laboratory, G. Cargill Financial support for research from: Techni Pharma Laboratory, M. Marty Financial support for research from: Techni Pharma Laboratory, L. Bueno Financial support for research from: Techni Pharma Laboratory, M.-C. Cappelletti Financial support for research from: Techni Pharma Laboratory, H. Colangeli-Hagège Financial support for research from: Techni Pharma Laboratory, V. Berger Financial support for research from: Techni Pharma Laboratory, B. Savarieau Financial support for research from: Techni Pharma Laboratory, P. Ducrotté Financial support for research from: Techni Pharma Laboratory</p><p><bold>Keywords:</bold> anorectal biofeedback training, dioxide-releasing suppository, dyschezia</p></sec><sec><title>OP158 ASSESSING ADEQUATE RELIEF-BASED THRESHOLDS FOR ABDOMINAL AND BOWEL SYMPTOMS IN TWO PHASE 3 TRIALS OF LINACLOTIDE FOR IRRITABLE BOWEL SYNDROME WITH CONSTIPATION</title><p><bold>A. Lembo</bold><sup>1</sup>, B. J. Lavins<sup>2</sup>, J. E. MacDougall<sup>2</sup>, S. J. Shiff<sup>3</sup>, X. D. Jia<sup>3</sup>, M. G. Currie<sup>2</sup>, C. B. Kurtz<sup>2</sup>, J. M. Johnston<sup>2,*</sup></p><p><italic><sup>1</sup>Beth Israel Deaconess Medical Center, Boston, <sup>2</sup>Ironwood Pharmaceuticals Inc., Cambridge, <sup>3</sup>Forest Research Institute, Jersey City, United States</italic></p><p><bold>INTRODUCTION:</bold> To assess patient-reported adequate relief (AR)-based thresholds for abdominal and bowel symptoms in patients with irritable bowel syndrome with constipation (IBS-C) and to compare weekly responder rates for AR to FDA IBS-C responder criteria.</p><p><bold>AIMS&METHODS:</bold> Data from two randomised, placebo-controlled Phase 3 trials of linaclotide (LIN) in patients with IBS-C were pooled. Patients reported abdominal symptoms (pain, discomfort, bloating, fullness, cramping) and bowel symptoms (spontaneous bowel movement [SBM] and complete SBM [CSBM] frequency, stool consistency, straining) daily, and AR of IBS-C symptoms (yes/no) weekly. Clinically meaningful thresholds were estimated using AR as an anchor on the pooled 12-week data and were used to define 12-week responders (LIN vs placebo [PBO]). The distribution of the agreement between weekly AR and the FDA weekly responder criteria (≥30% reduction in worst abdominal pain and ≥1 increase in CSBMs/week from baseline) was assessed.</p><p><bold>RESULTS:</bold> The table shows AR-based thresholds for clinically meaningful changes. LIN-treated patients had significantly greater rates of clinically meaningful improvement for all symptoms vs PBO (P<0.001 for all). The numbers needed to treat (NNT) were 5.1–6.4 for abdominal symptoms and 2.4–3.7 for bowel symptoms. Responder rates for AR and FDA criteria were greater for the LIN group vs PBO, with 70% and 76% agreement between AR and FDA weekly responder rates for the LIN and PBO groups, respectively. <bold>AR-based thresholds and 12-week responder rates</bold><table-wrap id="table22-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1"></th><th rowspan="1" colspan="1"></th><th rowspan="1" colspan="1"><bold>Threshold</bold></th><th rowspan="1" colspan="1"><bold>LIN, % (n/N)</bold></th><th rowspan="1" colspan="1"><bold>PBO, % (n/N)</bold></th><th rowspan="1" colspan="1"><bold>NNT</bold></th></tr></thead><tbody align="left"><tr><td rowspan="5" colspan="1">Abdominal symptoms (% improvement from baseline)</td><td rowspan="1" colspan="1">Pain </td><td rowspan="1" colspan="1">30.1%</td><td rowspan="1" colspan="1">55.3%<sup>*</sup> (445/805)</td><td rowspan="1" colspan="1">37.4% (298/797)</td><td rowspan="1" colspan="1">5.6</td></tr><tr><td rowspan="1" colspan="1">Discomfort</td><td rowspan="1" colspan="1">26.7%</td><td rowspan="1" colspan="1">57.5%<sup>*</sup> (463/805)</td><td rowspan="1" colspan="1">39.3% (313/797)</td><td rowspan="1" colspan="1">5.5</td></tr><tr><td rowspan="1" colspan="1">Bloating</td><td rowspan="1" colspan="1">24.5%</td><td rowspan="1" colspan="1">54.7%* (440/804)</td><td rowspan="1" colspan="1">35.3% (281/796)</td><td rowspan="1" colspan="1">5.1</td></tr><tr><td rowspan="1" colspan="1">Fullness</td><td rowspan="1" colspan="1">21.9%</td><td rowspan="1" colspan="1">58.5%* (470/804)</td><td rowspan="1" colspan="1">38.8% (309/797)</td><td rowspan="1" colspan="1">5.1</td></tr><tr><td rowspan="1" colspan="1">Cramping</td><td rowspan="1" colspan="1">33.6%</td><td rowspan="1" colspan="1">50.7%* (408/804)</td><td rowspan="1" colspan="1">35.1% (279/794)</td><td rowspan="1" colspan="1">6.4</td></tr><tr><td rowspan="4" colspan="1">Bowel symptoms (change from baseline)</td><td rowspan="1" colspan="1">SBMs/week</td><td rowspan="1" colspan="1">2.1</td><td rowspan="1" colspan="1">62.2%<sup>*</sup> (501/805)</td><td rowspan="1" colspan="1">26.5% (211/797)</td><td rowspan="1" colspan="1">2.8</td></tr><tr><td rowspan="1" colspan="1">CSBMs/week</td><td rowspan="1" colspan="1">0.7</td><td rowspan="1" colspan="1">58.4%* (470/805)</td><td rowspan="1" colspan="1">31.0% (247/797)</td><td rowspan="1" colspan="1">3.7</td></tr><tr><td rowspan="1" colspan="1">Straining (5-point scale)</td><td rowspan="1" colspan="1">-1.0</td><td rowspan="1" colspan="1">63.6%* (440/692)</td><td rowspan="1" colspan="1">32.1% (215/669)</td><td rowspan="1" colspan="1">3.2</td></tr><tr><td rowspan="1" colspan="1">Stool consistency (7-point scale)</td><td rowspan="1" colspan="1">1.0</td><td rowspan="1" colspan="1">76.0%* (526/692)</td><td rowspan="1" colspan="1">34.5% (231/669)</td><td rowspan="1" colspan="1">2.4</td></tr></tbody></table></table-wrap></p><p><sup>*</sup>P<0.001 for LIN vs PBO.</p><p><bold>CONCLUSION:</bold> Responder endpoint analyses using AR-based thresholds indicate that, compared to PBO, LIN treatment results in more patients with clinically meaningful abdominal and bowel symptom improvements and there is reasonable agreement between the FDA and AR endpoints.</p><p><bold>Contact E-mail Address:</bold><email>alembo@bidmc.harvard.edu</email></p><p><bold>Disclosure of Interest</bold>: A. Lembo Consultancy for: Ironwood Pharmaceuticals and Forest Laboratories, B. Lavins Shareholder of: Ironwood Pharmaceuticals, Other: Employee Ironwood Pharmaceuticals, J. MacDougall Shareholder of: Ironwood Pharmaceuticals, Other: Employee Ironwood Pharmaceuticals, S. Shiff Shareholder of: Forest Research Institute, Other: Employee of Forest Research Institute, X. Jia Shareholder of: Forest Research Institute, Other: Employee of Forest Research Institute, M. Currie Shareholder of: Ironwood Pharmaceuticals, Other: Employee Ironwood Pharmaceuticals, C. Kurtz Shareholder of: Ironwood Pharmaceuticals, Other: Employee Ironwood Pharmaceuticals, J. Johnston Shareholder of: Ironwood Pharmaceuticals, Other: Employee Ironwood Pharmaceuticals</p><p><bold>Keywords:</bold> Abdominal, Bowel, IBS-C, Symptoms, treatment</p></sec><sec><title>OP159 EFFICACY OF AMYTRIPTILINE IN IMPROVING INTESTINAL PERMEABILITY AND QUALITY OF LIFE IN PATIENTS WITH IBS</title><p><bold>G. Gigante</bold><sup>1,*</sup>, G. Caracciolo<sup>1</sup>, M. Campanale<sup>1</sup>, V. Cesario<sup>1</sup>, M. E. Ainora<sup>1</sup>, V. Bove<sup>1</sup>, V. Ojetti<sup>1</sup>, G. Gasbarrini<sup>2</sup>, A. Gasbarrini<sup>1</sup></p><p><italic><sup>1</sup>Internal Medicine and Gastroenterology, Catholic University - Gemelli Hospital, Rome, <sup>2</sup>Fondazione Italiana Ricerca in Medicina, Bologna, Italy</italic></p><p><bold>INTRODUCTION:</bold> Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder (GFD). In the pathogenesis are implicated alterations of GUT microbiota, motility, intestinal immunity and inflammation, and recently was given a major role to changes in intestinal permeability. IBS is a debilitating disease with a great socio-economic impact that lowers the quality of life of patients. For the treatment of IBS we use probiotics, antibiotics and recent studies including meta-analysis have demonstrated the efficacy of tricyclic antidepressant (TCA) in particular amitriptyline.</p><p><bold>AIMS&METHODS: The aim</bold> of our study was to evaluate the efficacy of amitriptyline not only to improve the quality of life of patients but also in improving intestinal permeability.</p><p>We consecutively enrolled, from our Unit, 20 pts (10F, 10M; age mean 38±4yrs) with IBS according to Roma III criteria (negative inflammatory markers, negative stool culture and parasitological, no abdominal surgery, no chronic diseases, no daily drugs, not history of psycotropic drugs, glucose BT negative). All patients underwent to intestinal permeability with chromium EDTA test. Quality of life was analyzed by SF36 test. Then, we administered amytriptiline 10 mg po twice daily for 30 days. At the end of treatment we repeated intestinal permeability with chromium EDTA test and SF36 test.</p><p><bold>RESULTS:</bold> All items analyzed by SF36 were lower compared to the normal values. Mean Mental Health Index (MHI) and Physical Health Index (PHI), the two main scores of SF 36, were both under the normal values: MHI 39.1±11.8 (nv 50, mean difference -10.9, 95% CI -15.0, -6.7; P < 0.001); PHI 45.8±9.0 (nv 50, mean difference -4.2, 95% CI -7.4, -1.1; P = 0.010). All patient had increase of intestinal permeability to chromium EDTA test at baseliChromium EDTA after therapy was: 18 patients within normal limits and 2 upper normal limits. In these 2 patients Sf36 test was altered but slightly improved (MHI from 39 ±2 to 45 ±2, PHI from 45 ±1 to 48±1). In 18 patients in which intestinal permeability was normalized, Sf36 test was in normal limits (MHI e PHI > 50 in all patients).</p><p><bold>CONCLUSION:</bold> Amytriptiline is effective in improving quality of life and intestinal permeability in patients with IBS. This result may demonstrate the role of the GUT brain axis in the pathogenesis of IBS, and how the use of psycotropic drugs can play a role on the bowel functions. Further studies are necessary for dose finding, time of recurrence and biochimical effect of amytriptiline on intestinal permeability.</p><p><bold>Contact E-mail Address:</bold><email>vanni.gigante@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> AMYTRIPTILINE, IBS, intestinal permeability</p></sec><sec><title>OP160 TREATMENT RESPONSE TO TEMPORARY PERCUTANEOUS GASTRIC ELECTRICAL STIMULATION, A DOUBLE BLIND CROSSOVER STUDY</title><p><bold>S. Kilincalp</bold><sup>1,2,*</sup>, M. Simrén<sup>1</sup>, G. Ringström<sup>1</sup>, H. Abrahamsson<sup>1</sup>, H. Törnblom<sup>1</sup></p><p><italic><sup>1</sup>Dept of Internal Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden, <sup>2</sup>Department of gastroenterology, Diskapi Yildirim Beyazit Education Hospital, Ankara, Turkey</italic></p><p><bold>INTRODUCTION:</bold> Gastric electrical stimulation (GES) is a therapeutic alternative for patients with drug-refractory chronic nausea and vomiting secondary to diabetic or idiopathic gastroparesis (GP). A proportion of patients are non-responders to treatment. Temporary percutaneous GES (TPGES) aims to select patients who are treatment responders, and thus candidates to receive permanent GES.</p><p><bold>AIMS&METHODS:</bold> The aim of this study was to evaluate the response rate to TPGES in patients with drug-refractory chronic nausea and vomiting secondary to other diagnoses than diabetic GP in a double blind crossover design. We used the TPGES implantation technique as previously described<sup>1</sup>. In order to be included, the stimulation must not have been possible to sense in the 5-10 mA range. Randomisation to 1-2 weeks with stimulation ON followed by stimulation OFF, or the opposite order, was done by an independent person, thereby blinding both the patient and the physician to the procedure. Gastrointestinal (GI) symptoms were registered daily (vomiting frequency, nausea hours and a 0-3 (none-severe) rating for five other GI symptoms, and a 0-4 (good-worst) rating for general well-being). The last 7 days in each stimulation period was used for analysis. Treatment response was defined as a symptom reduction ≥ 50% during the ON period compared to the OFF period for one or both of weekly nausea hours (WNH) and weekly vomiting frequency (WVF).</p><p><bold>RESULTS:</bold> We included 28 patients (21 females; median age 47 years (range 20-70 years)). Twelve patients (43%) were responders to treatment without any effect of sex (9/21 females vs. 3/7 males; p=.67) or coexisting GP (7/16 normal vs. 5/12 GP; p=.91). The distribution of diagnoses, gastric emptying status and response rate are outlined in Table 1. The responder rate was higher in the group with TPGES ON during period one compared to those with TPGES ON during period two (9/15 vs. 3/13; p=.049). In the responder group, apart from the significant reduction in WVF (p=.005) and WNH (p=.009), reduced rating for fullness (p=.023) and increased general well-being (p=.02) were noted, and a trend for reduced early satiety (p=.08).</p><p>Table 1.
<table-wrap id="table23-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1"></th><th rowspan="1" colspan="1">n</th><th rowspan="1" colspan="1">Gastroparesis (GP)</th><th rowspan="1" colspan="1">Responders (GP)</th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">Functional dyspepsia</td><td rowspan="1" colspan="1">8</td><td rowspan="1" colspan="1">0</td><td rowspan="1" colspan="1">4 (0)</td></tr><tr><td rowspan="1" colspan="1">Diabetes mellitus</td><td rowspan="1" colspan="1">5</td><td rowspan="1" colspan="1">0</td><td rowspan="1" colspan="1">1 (0)</td></tr><tr><td rowspan="1" colspan="1">Postsurgical nausea/vomiting</td><td rowspan="1" colspan="1">8</td><td rowspan="1" colspan="1">6</td><td rowspan="1" colspan="1">4 (3)</td></tr><tr><td rowspan="1" colspan="1">Enteric dysmotility</td><td rowspan="1" colspan="1">4</td><td rowspan="1" colspan="1">3</td><td rowspan="1" colspan="1">2 (1)</td></tr><tr><td rowspan="1" colspan="1">Idiopathic gastroparesis</td><td rowspan="1" colspan="1">3</td><td rowspan="1" colspan="1">3</td><td rowspan="1" colspan="1">1 (1)</td></tr></tbody></table></table-wrap></p><p><bold>CONCLUSION:</bold> This double blind crossover study strengthens our previous results that GES may be effective in a subset of patients with intractable nausea and vomiting, regardless of gastric emptying status and clinical diagnosis. The importance of TPGES and blinded stimulation as a tool for patient selection will be further explored.</p><p><bold>REFERENCES:</bold></p><p>1. Elfvin et al. Neurogastroenterol Motil 2007</p><p><bold>Contact E-mail Address:</bold><email>hans.tornblom@gu.se</email></p><p><bold>Disclosure of Interest</bold>: S. Kilincalp: None Declared, M. Simrén: None Declared, G. Ringström: None Declared, H. Abrahamsson: None Declared, H. Törnblom Lecture fee(s) from: Allmirall, Shire, Danone, Consultancy for: Almirall, Shire</p><p><bold>Keywords:</bold> double blind crossover study, nausea, temporary gastric electrical stimulation, vomiting</p></sec><sec><title>OP161 EFFICACY OF NALOXEGOL IN A SUBPOPULATION OF PATIENTS WITH OPIOID-INDUCED CONSTIPATION AND AN INADEQUATE BASELINE RESPONSE TO LAXATIVES: RESULTS FROM 2 PROSPECTIVE, RANDOMIZED, CONTROLLED TRIALS</title><p><bold>J. Tack</bold><sup>1,*</sup>, W. D. Chey<sup>2</sup>, L. Webster<sup>3</sup>, M. Sostek<sup>4</sup>, P. N. Barker<sup>4</sup>, J. Lappalainen<sup>4</sup></p><p><italic><sup>1</sup>University of Leuven, Leuven, Belgium, <sup>2</sup>Univ. Michigan Health System, Ann Arbor, MI, <sup>3</sup>CRI Lifetree Research, Salt Lake City, UT, <sup>4</sup>AstraZeneca, Wilmington, DE, United States</italic></p><p><bold>INTRODUCTION:</bold> Patients on chronic opioid therapy commonly experience opioid-induced constipation (OIC) that is inadequately treated by laxatives. The objective of this analysis was to examine the efficacy of naloxegol (NGL), an investigative, oral, peripherally acting, µ-opioid receptor antagonist, in OIC patients with an inadequate response to ≥1 or ≥2 laxative classes.</p><p><bold>AIMS&METHODS:</bold> Data were from two phase 3 randomized, double-blind, 12-week studies of NGL (KODIAC-04 [NCT01309841] and KODIAC-05 [NCT01323790]) conducted in outpatients with noncancer pain and OIC receiving NGL 12.5 mg, NGL 25 mg, or placebo once daily. The primary endpoint was spontaneous bowel movement (SBM) response over 12 weeks (≥3 SBMs/wk with ≥1 SBM/wk increase over baseline for ≥9 of the 12 weeks and ≥3 of the last 4 weeks). Both studies were powered for this endpoint in the subgroup of patients at baseline who were considered laxative inadequate responders (LIR). LIR was defined as self-reported moderate, severe, or very severe symptoms in ≥1 of the 4 stool symptom domains (incomplete bowel movement [BM], hard stools, straining, or false alarms) of the Baseline Laxative Response Status Questionnaire in patients taking ≥1 laxative class for ≥4 days prior to screening. LIR patients with inadequate response to ≥2 laxative classes were considered 2X LIR. Within the individual studies, response in the LIR subgroup was included in a multiple-testing procedure and was analyzed via chi-squared tests. Pooled analysis was conducted in the LIR and 2X LIR subgroup.</p><p><bold>RESULTS:</bold> Each of the studies demonstrated statistically significant improvements compared with placebo for the 25-mg group in the overall population (<italic>P</italic>=0.001, <italic>P</italic>=0.021) and LIR subgroup (<italic>P</italic>=0.002, <italic>P</italic>=0.014). For the 12.5-mg dose in the overall population and LIR subgroup, statistical significance was only met in KODIAC-04 (<italic>P</italic>=0.021 and <italic>P</italic>=0.028, respectively). Pooled analyses revealed a consistent treatment effect in the 1X LIR and 2X LIR subgroups (see Table).
<table-wrap id="table24-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th colspan="4" rowspan="1"><hr></hr>Table. Pooled Naloxegol Response Rates for Weeks 1–12 in LIR Patients</th></tr><tr><th rowspan="1" colspan="1">LIR Category</th><th rowspan="1" colspan="1">Treatment Group</th><th rowspan="1" colspan="1">N</th><th rowspan="1" colspan="1">Number (%) of Patients Responding</th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">1X LIR</td><td rowspan="1" colspan="1">Placebo</td><td rowspan="1" colspan="1">239</td><td rowspan="1" colspan="1">72 (30.1)</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">12.5 mg</td><td rowspan="1" colspan="1">240</td><td rowspan="1" colspan="1">102 (42.5)<sup>*</sup></td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">25 mg</td><td rowspan="1" colspan="1">241</td><td rowspan="1" colspan="1">115 (47.7)<sup>†</sup></td></tr><tr><td rowspan="1" colspan="1">2X LIR</td><td rowspan="1" colspan="1">Placebo</td><td rowspan="1" colspan="1">90</td><td rowspan="1" colspan="1">27 (30.0)</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">12.5 mg</td><td rowspan="1" colspan="1">88</td><td rowspan="1" colspan="1">39 (44.3)<sup>‡</sup></td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">25 mg</td><td rowspan="1" colspan="1">99</td><td rowspan="1" colspan="1">44 (44.4)<sup>‡</sup></td></tr></tbody></table></table-wrap></p><p>LIR=laxative-inadequate responder. <sup>*</sup><italic>P</italic>≤0.005; <sup>†</sup><italic>P</italic><0.001; <sup>‡</sup><italic>P</italic>≤0.05 vs placebo.</p><p><bold>CONCLUSION:</bold> NGL was efficacious in OIC patients who had an inadequate response to ≥1 and ≥2 classes of laxatives.</p><p><bold>Contact E-mail Address:</bold><email>jan.tack@med.kuleuven.be</email></p><p><bold>Disclosure of Interest</bold>: J. Tack Lecture fee(s) from: Abbott; Menarini; Movetis; Novartis; Nycomed, Consultancy for: Almirall; AstraZeneca; Danone; Menarini; Novartis; Shire; Takeda; Theravance; Zeria, W. Chey Consultancy for: AstraZeneca, L. Webster Consultancy for: AstraZeneca; Covidien Mallinckrodt; CVS; Jazz Pharmaceuticals; Medtronic; Neura Therapeutik; Theravance, Other: Travel Support; AstraZeneca; Covidien Mallinckrodt; Nektar Therapeutics; Theravance, M. Sostek Shareholder of: AstraZeneca, Other: Employee of AstraZeneca, P. Barker Shareholder of: AstraZeneca, Other: Employee of AstraZeneca, J. Lappalainen Shareholder of: AstraZeneca, Other: employee of AstraZeneca</p><p><bold>Keywords:</bold> laxative response, naloxegol, opioid-induced constipation, opioids, peripherally acting mu-opioid receptor antagonist, responder analysis</p></sec><sec><title>OP162 STRUCTURED PATIENT EDUCATION FOR PATIENTS WITH IRRITABLE BOWEL SYNDROME (IBS-SCHOOL) IMPROVES SYMPTOMS AND QUALITY OF LIFE ALSO IN CLINICAL PRACTICE</title><p><bold>G. Ringstrom</bold><sup>1,*</sup>, P. Jerlstad<sup>1</sup>, S. Storsrud<sup>1</sup>, H. Tornblom<sup>1</sup>, M. Simren<sup>1</sup></p><p><italic><sup>1</sup>Institute of medicine, SAHLGRENSKA ACADEMY, Gothenburg, Sweden</italic></p><p><bold>INTRODUCTION:</bold> Patients with irritable bowel syndrome (IBS) often feel insufficiently informed about their condition. Positive effects of structured patient education on symptoms, quality of life and perceived knowledge of IBS have previously been demonstrated in controlled clinical trials (Ringstrom et al. BMC Gastroenterol. 2009, Eur J Gastroenterol Hepatol. 2010 & Gastroenterol Hepatol. 2012).</p><p><bold>AIMS&METHODS:</bold> The aim was to evaluate the effects of the of educational class in clinical practice.We included 371 patients (mean age 39 (17-80) years; 308 women) referred from primary and secondary care fulfilling Rome III criteria for IBS. The education consisted of three weekly two-hour lessons held by a nurse or a dietician specialized in functional gastrointestinal (GI) disorders with eight to ten patients in each group. All patients completed validated questionnaires before and three months after the start of the education to evaluate GI symptom severity (IBS Severity Scoring System, IBS-SSS), GI symptom-specific anxiety (Visceral Sensitivity Index, VSI) and IBS related Quality of Life (IBSQOL). Short Health Scale (SHS) was used to evaluate symptom burden, daily function, disease-related worry and general well-being. The patients rated their perceived IBS knowledge and satisfaction with that knowledge, as well as the covered topics after the education on a visual analogue scale (VAS), and their satisfaction with the education in general on a seven graded scale.</p><p><bold>RESULTS:</bold> After the education, improvements were seen for GI symptom severity (IBS-SSS) (304±101 vs. 258±106; p<0.001) (mean ± SD)), GI symptom-specific anxiety (VSI) (42±16 vs. 37±16; p<0.001), and six out of nine IBSQOL dimensions compared to before the education. All SHS subscale ratings improved: symptom burden (64±22 vs. 57±23; p<0.001), daily function (62±27 vs. 53±29; p<0.001), disease-related worry (66±26 vs.55±31; p<0.001) and well-being (49±25 vs. 45±25; p=0.01). The patients experienced increased knowledge of IBS (43±24 vs. 74±15; p<0.001), were more satisfied with their knowledge (28±22 vs. 68±23; p<0.001) and expressed satisfaction with the education in general (median value 6 (IQR 5-7)). The four main topics of the education were all rated as highly important issues by the patients; pathophysiology (85±18), treatment options (85±17), dietary advice (87±15) and psychological aspects (86±16).</p><p><bold>CONCLUSION:</bold> Structured education for patients with IBS is associated with high satisfaction ratings, reduced symptom burden and improved QOL. This type of patient care seems to be important in the management of IBS and can easily be included in clinical practice.</p><p><bold>Contact E-mail Address:</bold><email>gisela.ringstrom@vgregion.se</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Patient education, Qality of life, Symptoms</p></sec><sec><title>OP163 PLECANATIDE PRODUCES A DIARRHEA PLATEAU EFFECT IN CHRONIC IDIOPATHIC CONSTIPATION PATIENTS</title><p><bold>R. Fogel</bold><sup>1,*</sup>, L. Barrow<sup>2</sup>, D. Drossman<sup>3</sup>, P. Miner<sup>4</sup>, K. Shailubhai<sup>2</sup>, A. Joslyn<sup>2</sup>, G. Jacob<sup>2</sup></p><p><italic><sup>1</sup>Clinical Research Institute of MI, Chesterfield, <sup>2</sup>Synergy Pharmaeuticials, Inc, New York, <sup>3</sup>Drossman Gastroenterology PLLC, Chapel Hill, <sup>4</sup>Oklahoma Institution for Digestive Research,, Oklahoma City, United States</italic></p><p><bold>INTRODUCTION:</bold> Plecanatide, a new guanylate cyclase-C receptor agonist, restores intestinal fluid balance in CIC patients resulting in increased number of bowel movements (BM). The dose-response relationship of plecanatide on the incidence of diarrhea was explored in a large multicenter study in Chronic Idiopathic Constipation (CIC) patients</p><p><bold>AIMS&METHODS:</bold> The large multicenter study was a randomized, double-blind, placebo-controlled, dose-ranging study in 951 patients. Patients who met modified Rome III criteria for CIC, with < 3 CSBMs/ week were randomized to 0.3, 1.0, or 3.0 mg plecanatide, or placebo for 12 weeks. During the study BMs, associated symptoms, safety and tolerability were assessed. The primary efficacy end point was an overall responder analysis. Adverse events were collected at study visits by standard methods utilized in other large multicenter trials. Duration, severity, whether study drug was interrupted or discontinued and whether other interventions to treat the adverse event were also collected. Bristol Stool Form Scores (BSFS) of 6 or 7 were not considered as an AE of diarrhea in this study.</p><p><bold>RESULTS:</bold><italic>T</italic>here was a dose response in the overall incidence of AEs (with patients counted once for AEs) and in the incidence of diarrhea. For diarrhea, the relative % increase in incidence rates between plecanatide doses occurred with decreasing increments- ie, the difference between 0.3 mg to 1 mg was 35% whereas the difference between 1 mg and 3 mg was 13%. Other measures describing diarrhea including time of onset and duration of event did not establish a dose-response relationship between doses.
<table-wrap id="table25-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1"></th><th rowspan="1" colspan="1">PBO N=236 n (%) </th><th rowspan="1" colspan="1">PLE 0.3 mg N = 237 n(%)</th><th rowspan="1" colspan="1">PLE 1 mg N=238 n (%) </th><th rowspan="1" colspan="1">PLE 3 mg N=237 n (%) </th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">Treatment-emergent AEs </td><td rowspan="1" colspan="1">40.7% </td><td rowspan="1" colspan="1">41.8% </td><td rowspan="1" colspan="1">43.3% </td><td rowspan="1" colspan="1">44.7% </td></tr><tr><td rowspan="1" colspan="1">All Diarrhea TEAEs</td><td rowspan="1" colspan="1">3 (1.3%) </td><td rowspan="1" colspan="1">13 (5.5%) </td><td rowspan="1" colspan="1">20 (8.4%) </td><td rowspan="1" colspan="1">23 (9.7%) </td></tr><tr><td rowspan="1" colspan="1">Severe Diarrhea TEAEs </td><td rowspan="1" colspan="1">0 </td><td rowspan="1" colspan="1">0 </td><td rowspan="1" colspan="1">4(1.7%) </td><td rowspan="1" colspan="1">1 (0.4%) </td></tr><tr><td rowspan="1" colspan="1">Days Duration of Diarrhea (mean)</td><td rowspan="1" colspan="1">19</td><td rowspan="1" colspan="1">29.9</td><td rowspan="1" colspan="1">18.8</td><td rowspan="1" colspan="1">21.9</td></tr><tr><td rowspan="1" colspan="1">Days from first dose to onset of diarrhea (mean)</td><td rowspan="1" colspan="1">45</td><td rowspan="1" colspan="1">18</td><td rowspan="1" colspan="1">21.5</td><td rowspan="1" colspan="1">20.4</td></tr><tr><td rowspan="1" colspan="1">WD due to Diarrhea </td><td rowspan="1" colspan="1"> 1 (0.4%) </td><td rowspan="1" colspan="1">2 (0.8%) </td><td rowspan="1" colspan="1">8 (3.4%) </td><td rowspan="1" colspan="1">7 (3.0%) </td></tr></tbody></table></table-wrap></p><p><bold>CONCLUSION:</bold> Diarrhea incidence increased in a dose-dependent manor, but with decreasingly small increments suggesting there may be a plateau for this effect. Secondary measures such as first dose onset and duration of event suggest a plateau effect beginning at low placanatide doses without a clear dose response. Solicitation of AEs of diarrhea was comparable to methods used in previous CIC clinical trials.</p><p><bold>Contact E-mail Address:</bold><email>ajoslyn@sentinellapharma.com</email></p><p><bold>Disclosure of Interest</bold>: R. Fogel: None Declared, L. Barrow Shareholder of: Synergy Pharma, Other: Employee Synergy Pharma, D. Drossman: None Declared, P. Miner: None Declared, K. Shailubhai Shareholder of: Synergy Pharma, Other: Employee Synergy Pharma, A. Joslyn Consultancy for: Synergy Pharma, G. Jacob Shareholder of: Synergy Pharma, Other: Employee Synergy Pharma</p><p><bold>Keywords:</bold> chronic constipation, constipation, diarrhoea, GC-C, plecanatide</p></sec><sec><title></title><p><bold>TUESDAY, OCTOBER 15, 2013 8:30-10:30</bold></p><p><bold>New tools for IBD diagnosis and monitoring – Hall Oslo</bold></p></sec><sec><title>OP164 DEVELOPMENT OF A NEW TOOL TO ASSESS CROHN'S DISEASE MAGNETIC RESONANCE INFLAMMATION SEVERITY</title><p><bold>Y. BOUHNIK</bold><sup>1,*</sup>, M. ZAPPA<sup>2</sup>, V. ABITBOL<sup>3</sup>, M. LEWIN<sup>4</sup>, M. BOUDIAF<sup>5</sup>, J. COSNES<sup>4</sup>, J. Y. MARY<sup>6</sup> on behalf of GETAID</p><p><italic><sup>1</sup>CHU Beaujon, Clichy, <sup>2</sup>Radiology, hospital Beaujon, PARIS, <sup>3</sup>CHU Cochin, <sup>4</sup>CHU St Antoine, <sup>5</sup>CHU Lariboisière, <sup>6</sup>DBIM, CHU St Louis, Paris, France</italic></p><p><bold>INTRODUCTION:</bold> The degree of inflammation of Crohn’s disease (CD) lesions is a key component of the therapeutic choice as inflammatory lesions may reverse under medical treatment</p><p><bold>AIMS&METHODS:</bold> Aims: to develop a small bowel CD Magnetic Resonance (MR) index of Inflammation Severity (CDMRIS).Thirteen centres participated to this prospective transversal study and selected MR-DVDs from 6 patients with small bowel CD, stratified on inflammation severity, 2 nil-mild, 2 intermediate and 2 severe. The 78 MR-DVDs were sent anonymised to the central unit, and were allocated through balanced incomplete bloc design per stratum of severity to centres for a combined reading by a pair of gastroenterologist and radiologist. Each DVD was read by 4, 9 and 4 pairs and each pair evaluated 8, 18 and 8 DVDs per severity stratum. Globally, each reader-pair had to evaluate 34 MR-DVDs sent in 3 successive sets. Total length and number of 20 cm-diseased segments were noted. In each segment, the following data were recorded: localisation, maximal wall thickness, minimal luminal diameter, presence of T2 wall hypersignal, deep ulceration without fistula, comb sign, abscess, sclerolipomatosis, lymph nodes, T1 degree of intensity enhancement (mild or moderate, severe) and pattern (homogeneous, layered), type of fatty proliferation (blurred wall or inflammatory mass) and fistula (blind, internal cutaneous). For each MR examination, global inflammation severity (GIS) was evaluated qualitatively between zero and 100 using a visual analog scale.To construct the CDMRIS, multivariate linear mixed model was used with backward selection through likelihood ratio test. The dependent variable was the GIS and the independent variables were the number of segments in which each sign was observed at a given level or above, the maximal wall thickness and the minimal luminal diameter. Reader pair and examinations were considered as random factors.</p><p><bold>RESULTS:</bold> Up to now, 421 readings are available. Mean ± SD of GIS was 21.6 ± 19.7. Spearman correlation values between the later and the various predictors varied between 0.05 and 0.59. The independent predictors of the GIS were maximal wall thickness over 8 mm, deep ulceration without fistula, comb sign, abscess > 5 mm, T1 intensity of enhancement (mild or moderate, severe) and layered pattern, any fistula. These predictors explained 78% of the GIS variance.</p><p><bold>CONCLUSION:</bold> The CDMRIS is a standardized index to evaluate the severity of inflammation in patients with small bowel CD.</p><p><bold>Contact E-mail Address:</bold><email>yoram.bouhnik@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Crohn`s disease, inflammation-based prognostic score, magnetic resonance imaging, scoring system</p></sec><sec><title>OP165 ENDOSCOPIC ULTRASOUND OF THE COLON AS A MARKER FOR EARLY THERAPY RESPONSE IN PATIENTS WITH ULCERATIVE COLITIS – FIRST RESULTS OF A PILOT STUDY.</title><p><bold>M. Ellrichmann</bold><sup>1,*</sup>, J. Bethge<sup>1</sup>, A. Arlt<sup>1</sup>, S. Nikolaus<sup>2</sup>, T. Kuehbacher<sup>2</sup>, S. Schreiber<sup>2</sup>, A. Fritscher-Ravens<sup>1</sup></p><p><italic><sup>1</sup>Medical Department I, Interdisciplinary Endoscopy, <sup>2</sup>Medical Department I, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany</italic></p><p><bold>INTRODUCTION:</bold> The activity of ulcerative colitis (UC) is based on a combination of clinical, endoscopic and histological activity indices. The evaluation of disease severity solely on the basis of these findings exhibits a high interobserver variability and therefore often fails to evaluate response to medical treatment. Endoscopic ultrasound of the colonic wall allows exact quantification of the total wall thickness (TWT) and differentiation of the different layers and can therefore quantify the grade of inflammation more accurately.</p><p><bold>AIMS&METHODS:</bold> Aim:</p><p>To evaluate EUS of the gastrointestinal wall and it’s layers in patients with acute UC undergoing treatment with the Anti-TNF-alpha antibody adalimumab (TNF-Ab) for possible detection of early therapy response.</p><p><bold>Methods: </bold> After IRB approval consecutive patients with acute UC were examined using a forward-viewing radial echoendoscope (Pentax, Japan). Mucosal, submucosal and total wall-thickness (TWT) were investigated by EUS in the mid sigmoid colon before and 1, 4 and 12 weeks after initiation of therapy with TNF-Ab. Results were compared to healthy controls (HC) undergoing screening colonoscopy. The examiners were blinded to the macroscopic inflammation scores. EUS results were correlated to macroscopic Mayo score. Microscopic inflammation scores served as reference.</p><p><bold>RESULTS:</bold> TWT in HC was 1.71±0.02 mm (n=10) with clear differentiation of the different layers. Patients with an acute UC (n=11) had a TWT of 3.4±0.87mm (p<.0.001). In patients with clinical response to therapy with TNF-Ab (n=10) TWT was reduced by 27.9% (TWT<sub>7d</sub>=2.5±0.2mm; p=0.01) compared to baseline levels. In contrast, Mayo scores (2.1) did not show a reduction in this interval (Mayo<sub>baseline</sub>=2.2). After 4 weeks of therapy a further reduction of the TWT (TWT<sub>28d</sub>=2.2±0.2mm) was observed, accompanied by significant reduction of the Mayo score (Mayo<sub>28d</sub>=1.2±0.2). Prior to therapy there was a strong correlation of TWT and Mayo score. In contrast, no correlation was observed 1 and 4 weeks after TNF-Ab therapy (p>0.05). During the whole course of therapy, there was a positive relation between TWT and histological activity scores (r=0.65; p<0.001).</p><p>In one patient no reduction of the TWT was observed within 1 week of therapy. This patient turned out to be a non-responder to TNF-Ab therapy 6 weeks later.</p><p><bold>CONCLUSION:</bold> Measurement of TWT had a high positive predictive value to quantify the level of inflammation in patients with acute UC. Therefore, EUS of the colonic wall could become an important marker to early predict therapy response in patients with acute UC.</p><p><bold>Contact E-mail Address:</bold><email>mark.ellrochmann@uk-sh.de</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> endoscopic ultrasound, inflammation, ulcerative colitis</p></sec><sec><title>OP166 MAGNETIC RESONANCE ENTEROGRAPHY, SMALL INTESTINE CONTRAST ULTRASONOGRAPHY AND CAPSULE ENDOSCOPY TO EVALUATE SMALL BOWEL IN PEDIATRIC CROHN’S DISEASE: A PROSPECTIVE, BLINDED, COMPARISON TRIAL.</title><p><bold>M. Aloi</bold><sup>1,*</sup>, G. Di Nardo<sup>1</sup>, G. Romano<sup>1</sup>, E. Casciani<sup>2</sup>, F. Civitelli<sup>1</sup>, S. Oliva<sup>1</sup>, F. Viola<sup>1</sup>, G. Gualdi<sup>2</sup>, S. Cucchiara<sup>1</sup></p><p><italic><sup>1</sup>Pediatric Gastroenterology And Liver Unit, <sup>2</sup>Radiology DEA, SAPIENZA UNIVERSITY OF ROME, Rome, Italy</italic></p><p><bold>INTRODUCTION:</bold> Small bowel (SB) disease is a distinct clinical entity within the heterogeneous phenotypes of Crohn’s disease (CD), determining a huge impact on child’s growth and pubertal development. Despite advances in imaging tools, the role of each method for evaluating the entire SB it is still unsettled.</p><p><bold>AIMS&METHODS:</bold> To assess sensitivity, specificity and accuracy of magnetic resonance enterography (MRE), small-bowel contrast ultrasonography (SICUS), and capsule endoscopy (CE) in evaluating involvement of SB in 34 patients (pts) referred for suspected or known CD to our Pediatric Gastroenterology Unit (mean age: 12.24±4.6 years; range 8.3-18.1). Twenty-eight (84%) pts with a previous CD diagnosis and 6 (16%) with suspected CD underwent ileocolonoscopy, MRE and SICUS in a 4-days period; 25 (77%) without stenosis also underwent CE. For imaging evaluation, SB was conventionally divided into 5 segments: proximal and distal jejunum, proximal, medium and distal ileum. For each of the three methods evaluated (MRE, CE, SICUS) sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV) and accuracy were determined comparing the results to a Consensus reference standard used as a gold standard for the SB<sup>1</sup> and to ileocolonoscopy for terminal ileum.</p><p><bold>RESULTS:</bold> In both proximal and distal jejunum sensitivity of SICUS in detecting active CD was 83%, not significantly higher than CE (83%), and MRE (70%); however, the specificity of CE (58%) was significantly lower than both imaging techniques (p: 0.002). In the proximal and medium ileum, MRE had the highest sensitivity and specificity (100% and 95%, respectively), compared to SICUS (80% and 93%, respectively) and CE (70% and 75%, respectively). At the terminal ileum, SICUS had the highest sensitivity (100%) compared to ileocolonoscopy, not significantly higher than MRE (93%) and CE (79%); however, CE had higher specificity (89%) compared to SICUS (60%) and MRE (70%). CE obtained its best performance in the central SB (distal jejunum and proximal ileum) with a sensitivity of 100% and a NPV of 100%.</p><p><bold>CONCLUSION:</bold> MRE and SICUS had higher sensitivity and specificity compared to CE in detecting active CD of SB, except in distal jejunum and proximal ileum. In the evaluation of the terminal ileum, SICUS had the best sensitivity, with a high negative predictive value. An integrated use of different imaging tools could be required to achieve a complete and accurate assessment of the entire SB in children with suspected or confirmed CD of the SB.</p><p><bold>REFERENCES:</bold></p><p>1. Solem CA, Loftus EV, Fletcher JG, et al. Small-bowel imaging in Crohn’s disease: a prospective, blinded, 4-way comparison trial. Gastrointest Endosc 2008;68:255-66</p><p><bold>Contact E-mail Address:</bold><email>marina.aloi@uniroma1.it</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> capsule endoscopy, crohn's disease, Diagnosis, magnetic resonance imaging enterography, Small Bowel, ultrasonography</p></sec><sec><title>OP167 CONFOCAL LASER ENDOMICROSCOPY FOR THE ASSESSMENT OF MUCOSAL HEALING IN CROHN’S COLITIS AND ULCERATIVE COLITIS.</title><p><bold>G. Hundorfean</bold><sup>1,*</sup>, M. T. Chiriac<sup>1</sup>, M. Neurath<sup>2</sup>, J. Mudter<sup>1</sup></p><p><italic><sup>1</sup>Medical Clinic 1, University of Erlangen-Nuremberg, <sup>2</sup>Medical Clinic 1, University of Erlangen-Nuremberg, Department of Internal Medicine 1, Erlangen, Erlangen, Germany</italic></p><p><bold>INTRODUCTION:</bold> Mucosal healing (MH) is the main goal in the treatment of IBD. Monitoring of MH is important in evaluating the therapy response and the course of disease. By contrast to the macroscopic scores provided by conventional endoscopy in MH assessment, the analysis of the mucosal microstructure using confocal laser endomicroscopy (CLE) might give new insights into MH during therapy and define more precisely MH in Crohn’s colitis (CC) and ulcerative colitis (UC).</p><p><bold>AIMS&METHODS:</bold> The aim was to investigate the utility of CLE for assessing microscopic mucosal changes before and after the start of anti-TNF alpha therapy in CC and UC. The morphological criteria of crypt number and architectural changes (distortion, crypt erosions/ulcerations) were evaluated for a MH score for IBD (IBD-MH score). Consecutive active UC patients (17; Mayo>6) and CC patients (18; CDAI >220) were prospectively included and underwent colonoscopy with CLE before and after 3 infliximab (IFX) infusions. Based on the Mayo-score and CDAI score, 2 groups i.e. therapy responders (Mayo<3; CDAI< 150) and nonresponders (Mayo>3; CDAI>150) were defined. A total of 3.500 random endomicrographs from 35 patients (17 UC and 18 CC) were analyzed in a blinded fashion by 2 endoscopists (50 random micrographs/patient taken before and 50 after IFX therapy)- based on the IBD-MH score ranging from 0 to 9.</p><p><bold>RESULTS:</bold> Post-IFX, responder group IBD patients showed an increase in crypt number and a decrease of IBD-MH score. The differences between these two parameters were statistically significant in the responder group (p<0,05). In the non-responder group, the differences between the pre- and post-treatment scores were not statistical significant (P>0,05). MH was defined as IBD-MH score=0. </p><p><bold>CONCLUSION:</bold> Our new IBD-MH-score showed excellent accuracy with the therapy response assessed by clinical scores. Furthermore, microscopic aspects allow a more precise assessment of MH. CLE can accurately assess MH in vivo based on the newly developed and statistically validated IBD-MH-score for UC and CC.</p><p><bold>REFERENCES:</bold></p><p>1. <sup>1</sup>Solem CA, Loftus EV, Fletcher JG, et al. Small-bowel imaging in Crohn’s disease: a prospective, blinded, 4-way comparison trial. Gastrointest Endosc 2008;68:255-66</p><p><bold>Contact E-mail Address:</bold><email>gheorghe.hundorfean@uk-erlangen.de</email></p><p><bold>Disclosure of Interest</bold>: G. Hundorfean Financial support for research from: MSD/ Essex, M. Chiriac: None Declared, M. Neurath Consultancy for: MSD/ Essex, J. Mudter Financial support for research from: MSD/ Essex</p><p><bold>Keywords:</bold> crohn's disease, endomicroscopy, mucosal healing, ulcerative colitis</p></sec><sec><title>OP168 DEVELOPMENT OF MRE BASED MULTI ITEM MEASURES OF INFLAMMATION AND INTESTINAL DAMAGE IN PAEDIATRIC CROHN’S DISEASE: THE IMAGEKIDS STUDY</title><p><bold>P. Church</bold><sup>1</sup>, M.-L. Greer<sup>2</sup>, A. Griffiths<sup>1</sup>, M. M. Amitai<sup>3</sup>, T. Walters<sup>1</sup>, R. Cytter<sup>2</sup>, G. Focht<sup>4</sup>, D. Turner<sup>4,*</sup></p><p><italic><sup>1</sup>Gastroenterology, Hepatology and Nutrition, <sup>2</sup>Diagnostic Imaging, The Hospital for Sick Children, University of Toronto, Toronto, Canada, <sup>3</sup>Diagnostic Imaging, Sheba Medical Center, Tel Aviv, <sup>4</sup>Pediatric Gastroenterology and Nutrition Unit, The Hebrew University of Jerusalem, Shaare Zedek Medical Center, Jerusalem, Israel</italic></p><p><bold>INTRODUCTION:</bold> Treatment goals in paediatric Crohn’s disease (CD) have moved beyond symptom control to intestinal healing. Magnetic resonance enterography (MRE) has become the modality of choice for sequentially imaging small bowel, but description and interpretation of MRE findings must be standardized so that impact of therapies can be assessed.</p><p><bold>AIMS&METHODS:</bold> We undertook to develop 2 multi-item MRE-based measures in children with CD; one of inflammation, (Pediatric MRE-based Crohn’s Activity Index, P-MECAI) and one of structural change, (Pediatric Crohn’s Disease Intestinal Damage, PECDID) through a rigorous process of item generation and reduction. First, comprehensive lists of MRE parameters reflecting inflammation and structural change were prepared by systematically reviewing the literature. In an iterative process over email, a Delphi group of 30 expert radiologists contributed items to the lists which were reviewed and consolidated by the steering committee. Items were scored and rank-ordered by the group according to importance and frequency. The highest ranked items were retained and judgmentally formatted in a face to face meeting.</p><p><bold>RESULTS:</bold> The literature review yielded 80 relevant manuscripts which contributed 35 items; the Delphi process added a further 15 items totaling 33 items reflecting inflammation and 17 reflecting damage. Item reduction trimmed this to 6 items reflecting inflammation and 7 reflecting structural change. Some variables were common to inflammation and damage, while others were specific (table). Motility (normal/impaired), wall enhancement pattern (mucosal, striated, transmural) and fibrofatty proliferation (present/absent) will be considered separately by data-driven analysis of the ongoing prospective cohorts.
<table-wrap id="table26-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th colspan="2" rowspan="1">Common Items</th><th colspan="2" rowspan="1">Categories</th></tr></thead><tbody align="left"><tr><td colspan="2" rowspan="1">Wall thickness</td><td colspan="2" rowspan="1">(Continuous)</td></tr><tr><td colspan="2" rowspan="1">Wall T2- hyperintensity</td><td colspan="2" rowspan="1">None, Mild, Marked</td></tr><tr><td colspan="2" rowspan="1">Wall enhancement</td><td colspan="2" rowspan="1">None, Mild, Marked</td></tr><tr><td colspan="2" rowspan="1">Wall restricted diffusion</td><td colspan="2" rowspan="1">None, Mild, Marked</td></tr><tr><td colspan="2" rowspan="1">Lumen calibre</td><td colspan="2" rowspan="1">Normal, Narrow, Narrow with prestenotic dilation</td></tr><tr><td rowspan="1" colspan="1"><bold>Inflammation Items</bold></td><td rowspan="1" colspan="1"><bold>Categories</bold></td><td rowspan="1" colspan="1"><bold>Damage Items</bold></td><td rowspan="1" colspan="1"><bold>Categories</bold></td></tr><tr><td rowspan="1" colspan="1">Comb sign</td><td rowspan="1" colspan="1">None, Mild, Marked</td><td rowspan="1" colspan="1">Pseudosacculation</td><td rowspan="1" colspan="1">Present, Absent</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">Penetrating lesions</td><td rowspan="1" colspan="1">None, Sinus/phlegmon, Fistula/abscess</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">History of surgical intervention</td><td rowspan="1" colspan="1">None, Endoscopic dilation, Stricturoplasty, Resection</td></tr></tbody></table></table-wrap></p><p><bold>CONCLUSION:</bold> The formatted indices are being prospectively validated in the ongoing multi-centre international ImageKids study. These measures could be used to assess the effect of therapies on the control of inflammation and the progression of bowel damage in pediatric Crohn’s disease.</p><p><bold>Contact E-mail Address:</bold><email>peter.church@sickkids.ca</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> crohn's disease, inflammatory bowel disease, inflammatory index, intestinal damage, MR enterography</p></sec><sec><title>OP169 BLOOD BACTERIAL DNA AS AN INDEPENDENT RISK FACTOR OF FLARE IN THE SHORT-TERM IN PATIENTS WITH CROHN’S DISEASE. PRELIMINARY RESULTS ON ADATHEC STUDY</title><p><bold>A. Gutiérrez</bold><sup>1</sup>, L. Sempere<sup>1</sup>, P. Zapater<sup>1,2</sup>, M. García<sup>3</sup>, R. Laveda<sup>4</sup>, I. Almenta<sup>1</sup>, A. Martínez<sup>4</sup>, P. Giménez<sup>2</sup>, J. M. González-Navajas<sup>1,2</sup>, J. Such<sup>1,2</sup>, R. Francés<sup>1,2,*</sup></p><p><italic><sup>1</sup>Hospital General Universitario de Alicante, Alicante, <sup>2</sup>CIBERehd, Madrid, <sup>3</sup>Hospital General de Elche, Elche, <sup>4</sup>Hospital Clínico Universitario de San Juan, Alicante, Spain</italic></p><p><bold>INTRODUCTION:</bold> Bacterial DNA (bactDNA) translocation into blood has been reported to increase systemic inflammatory markers in patients with Crohn’s disease and affect the efficacy of anti-TNF therapies, with a suspected impact on the risk of relapse in the short-term in these patients. We aimed at evaluating the presence of bactDNA in blood as an independent risk factor of flare at six months in patients with Crohn’s Disease.</p><p><bold>AIMS&METHODS:</bold> Patients with Crohn’s disease who were on remission at inclusion, as determined by CDAI<150, were admitted in the study. Clinical and analytical characteristics of all patients were recorded. BactDNA translocation into blood was evaluated by 16SrRNA broad-range PCR and partial sequencing analysis.</p><p><bold>RESULTS:</bold> 151 patients were included in the study. One hundred and twenty-two patients were bactDNA- (80.8%) vs 29 bactDNA+ (19.2%). Flare at six months (12.3% bactDNA- <italic>vs</italic> 34.5% bactDNA+, <italic>p</italic>=0.004) and the mean number of hospitalizations in the following 6 months (1.0 ±0.0 bactDNA- <italic>vs</italic> 1.67±0.58 bactDNA+, <italic>p</italic>=0.015) were significantly different between both groups. Montreal classification, therapy at inclusion, previous surgery, PCR and the rest of clinical and anlytical variables studied were not different between bactDNA-based groups. In a second analysis, patients were distributed by their therapy in 4 groups: mesalazine, immunesuppresors (non-biologic), anti-TNF-alpha on monotherapy and anti-TNF-alpha on combined therapy. Number of flares was significantly higher in groups on biologics, either alone or combined with immunesupressors. A multivariate analysis revealed that the established therapy and the presence of bactDNA remained as independent risk factors of flare at six months (bactDNA; odds ratio (OR) 8.34 95% CI 2.40-29.0, p=0.001; therapy, OR 3.50 95% CI 1.30-9.40, p=0.013).</p><p><bold>CONCLUSION:</bold> The presence of bactDNA in the blood of patients with Crohn’s disease identifies a subgroup of patients with an increased risk of flare at six months independent of their established therapy.</p><p><bold>REFERENCES:</bold></p><p>1. Gutiérrez A, Scharl M, Sempera L, Holler E, Zapater P, et al. Genetic susceptibility to increased bacterial translocation influences the response to biological therapy in patients with Crohn's disease. Gut 2013 (in press).</p><p><bold>Contact E-mail Address:</bold><email>frances_rub@gva.es</email></p><p><bold>Disclosure of Interest</bold>: A. Gutiérrez: None Declared, L. Sempere: None Declared, P. Zapater: None Declared, M. García: None Declared, R. Laveda: None Declared, I. Almenta: None Declared, A. Martínez: None Declared, P. Giménez: None Declared, J. González-Navajas: None Declared, J. Such: None Declared, R. Francés Financial support for research from: Abbvie</p><p><bold>Keywords:</bold> bacterial translocation, Crohn’ disease , flare up, therapy</p></sec><sec><title>OP170 ASYMPTOMATIC WHITE MATTER LESIONS IN BRAIN SUSPICIOUS OF DEMYELINATION IN PATIENTS WITH CROHN´S DISEASE</title><p><bold>J. Stovicek</bold><sup>1,*</sup>, P. Liskova<sup>2</sup>, S. Hlava<sup>1</sup>, R. Keil<sup>1</sup></p><p><italic><sup>1</sup>Clinic of Internal Medicine, Gastroenterology, <sup>2</sup>Neurology, UNIVERSITY HOSPITAL MOTOL PRAGUE, Prague, Czech Republic</italic></p><p><bold>INTRODUCTION:</bold> Extraintestinal manifestaions of inflamantory bowel disease (IBD) involve several organs. Neurologic complications are not rare, but are underdiagnosed. Some of neurologic complications are probably immune-mediated. Several studies had suggested higher incidence of demyelinating diseases in IBD patients, such as multiple scleroses (MS). Demyelinating disorders in these patients can be rarely caused or worsen by anti-TNF therapy. Some studies confirmed higher occurance of T2 focal white matter lesions of CNS on MRI in IBD patients.</p><p><bold>AIMS&METHODS:</bold> In our single center prospective observational study we focused on presence of T2 focal white matter lesions of CNS on magntetic resonance investigation (MRI) in patiens with IBD, that may by suspicious of demyelination. We examined 68 patients with Crohn´s disease before inducing anti-TNF alfa therapy. These patients were treated with azathioprine, mesalazine or both. Patients were examined by neurologist with the concern of possible signs of demyelinating disease and underwent MRI examination of brain (native T1, T2, FLAIR sequences).</p><p><bold>RESULTS:</bold> 68 patients with Crohn´s disease underwent both – MRI and neurological examination. 38 patients (51%) had some abnormalities in neurological examination. In 26 patients (38%) there were described some abnormalities on MRI. In 7 cases these MRI abnormalities (periventricular lesions) were suspicious of demyelination. In all of these patients we provided lumbal puncture including polyclonal bands examination. Results were completely negative in 5 cases, in one case the finding was evaluated as borderline, but in one case MS was confirmed. Pathological MRI findings in other 19 patients were found clinically nonsignificant. Most of these pathologies were nonspecific sporadic lesions in white matter or mild atrophy.</p><p><bold>CONCLUSION:</bold> Our results support the previous data that frequency of neurological findings in IBD patients is generally underestimated. With the extension of biological anti-TNF alfa treatment for IBD, possible influence on higher risk of developing MS should be considered. We suggest that the patients should undergo MRI brain examination before initiation of antiTNF treatment.</p><p><bold>REFERENCES:</bold></p><p>1. Liu J.: TNF is a potent anti-inflammatory cytokine in autoimmune-mediated demyelination, Nature Medicine 1998, 4: 78-83</p><p>2. Mohan N.: Demyelination Occurring During Anti–Tumor Necrosis Factor Therapy for Inflammatory Arthritides, ARTHRITIS & RHEUMATISM, 2001, 44 (12): 2862–2869</p><p>3. Hoejtnen F.: Safety of anti-tumor necrosis factor therapy in inflammatory bowel disease, World J Gastroenterol 2009 May 7; 15 (17): 2067-2073</p><p>4. Cohen R.: Autoimmune Disease Concomitance Among Inflammatory Bowel disease Patiens in the United States 2001-2002, Inflamm Bowel Dis, Jun 2008, 14: 738-743</p><p>5. Elsehety A.: Neurologic and Neuropsychiatric Complications of Crohn´s disease, SMJJ, June 1997, 90(6): 606-610</p><p>6. Henderson R.D.: The Occurrence of Autoimmune Diseases in Patients with Multiple Sclerosis and Their Families, Journal of Clinical Neuroscience 2000, 7(5): 434–437</p><p><bold>Contact E-mail Address:</bold><email>jan.stovicek@fnmotol.cz</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> biologics, Crohn´s disease, demyelination</p></sec><sec><title>OP171 DIAGNOSTIC ACCURACY OF ZINC PROTOPORPHYRIN/HEME RATIO FOR SCREENING IN IRON DEFICIENCY ANAEMIA IN IBD PATIENTS</title><p><bold>M. Wiesenthal</bold><sup>1,2,*</sup>, D. Jacobsen<sup>1,2</sup>, F. Hartmann<sup>1</sup>, A. Dignass<sup>3</sup>, J. Stein<sup>2,4</sup></p><p><italic><sup>1</sup>Marien Hospital, <sup>2</sup>interdisziplinary Crohn-Colitis-Center Rhein-Main, <sup>3</sup>Apaglesion Markus Hospital, <sup>4</sup>Hospital of Sachsenhausen, Frankfurt a.M., Germany</italic></p><p><bold>INTRODUCTION:</bold> In the absence of a feasible, non-invasive gold standard, iron deficiency anaemia (IDA) is best measured by the use of multiple indicators. However, the choice of an appropriate single iron biomarker to replace the multiple-criteria model for screening for IDA at the population level continues to be debated.</p><p><bold>AIMS&METHODS:</bold> Zinc protoporphyrin (ZPP) has been shown to be a sensitive and specific screening marker for functional iron deficiency. This study evaluated for the first time the diagnostic value of ZPP in the diagnosis of IDA and differential diagnosis of IDA and anaemia of chronic disease. The study population consisted of 116 patients with IBD (age, 36.40 ± 13.14 years, 59 % female), who consecutively attended the Crohn Colitis Centre Frankfurt for routine evaluation between October 2009 and October 2012. Blood count, transferrin saturation (TSAT), serum ferritin (SF), C-reactive protein and ZPP were determined by routine assays. Anemia was defined, according to the World Health Organization criteria, as a hemoglobin concentration of < 13 g/dl for men and 12 g/dl for women. For the multiple-criteria model, ID was considered present if individuals had ≥ 2 abnormal values from SF (< 30 µg/l), TSAT (< 20%), and ZPP (< 40 µmol/mol Hb)<sup>1</sup>.Patients with anemia were classified as having iron deficiency anaemia (IDA), anaemia of chronic disease (ACD) or according to<sup>2</sup>.</p><p><bold>RESULTS:</bold> In contrast to SF, ZPP significantly correlated with hemoglobin. The receiver operating characteristic (ROC) curves for the various iron indicators used to diagnose IDA as defined by the multiple-criteria model indicated that the diagnostic accuracy of ZPP was superior to that of the other iron status indicators. As the most important finding of our study, ZPP has been shown to be elevated even in the case of ACD, indicating iron-deficient erythropoesis (fig. 1)</p><p><bold>CONCLUSION:</bold> ZPP is not a simple parameter of iron deficiency, but rather a screening parameter of iron-deficient erythropoesis. These results clearly demonstrate the potential utility of ZPP in the detection of iron deficiency in IBD patients with inflammation and anaemia, even in the presence of ACD. Our findings indicate that ZPP can provide added value in diagnosing iron deficiency in anaemic IBD patients.</p><p><bold>REFERENCES:</bold></p><p>1. Grant KE et al. Comparison of indicators of iron deficiency in Kenyan children. Am J Clin Nutr. 2012;95:1231–7</p><p>2. Weiss G, Goodnough LT. Anemia of chronic disease. N EnglJ Med 2005;352:1011–23</p><p><bold>Contact E-mail Address:</bold><email>j.stein@em.uni-frankfurt.de</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Iron Deficiency Anaemia, Screening Marker </p></sec><sec><title>OP172 THE UKS FIRST INTERNET BASED REMOTE MANAGEMENT SYSTEM FOR MONITORING STABLE IBD PATIENTS IN THE COMMUNITY, IBD SSHAMP (SUPPORTED SELF HELP AND MANAGEMENT PROGRAMME)</title><p>T. Price<sup>1</sup>, K. Lithgow<sup>1</sup>, <bold>M. W. Johnson</bold><sup>1,*</sup></p><p><italic><sup>1</sup>Gastroenterology, Luton and Dunstable University Hospital, Luton, United Kingdom</italic></p><p><bold>INTRODUCTION:</bold> The Luton & Dunstable University Hospital became the first hospital in UK to commence a remote management programme for stable inflammatory bowel disease (IBD) patients. The project,entitled IBD-SSHAMP (Supported, Self Help And Management Programme) was funded by an Innovation Award presented by the East of England Primary Care Trust (PCT) Innovation Team. The aim was to discharge patients from routine clinic visits, whilst maintaining an efficient remote monitoring system that could be co-ordinated through our specialist nurses.</p><p><bold>AIMS&METHODS:</bold> A retrospective 10 year review we identified a total of 2790 IBD patients. Using Patient Knows Best we developed individualise websites to offer a communication portal between patients and specialist care, through which we could monitor their symptoms and offer management advice through a traffic light system. An alert is sent out to the IBD nursesand clinician involved if any patients symptom indices deteriorate markedly. Periodic faecal calprotectin and inflammatory markers will also be used to support the monitoring process. Virtual clinics will be held for these patients twice a year. If necessary patients can be seen in hospital clinics usually within 24-48hrs</p><p><bold>RESULTS:</bold> We have successfully discharged 400 onto the first wave of IBD-SSHAMP, with a further 300 due to follow shortly in the second wave. With confidence in the system building amongst the relevant clinicians the second wave will primarily contain patients stable on immunosuppressants eg. azathioprine. With most patients being seen at 6 monthly intervals, and follow up clinic appointments costing our PCT £85, this project could potentially save them £119,000 per year, whilst still providing a patient friendly and efficient management system.</p><p><bold>CONCLUSION:</bold> IBD-SSHAMP is the UK’s first internet based remote management system for managing stable IBD patients. It aims to reduce cost and free up NHS outpatient time, whilst providing an efficient monitoring and management programme.</p><p><bold>Contact E-mail Address:</bold><email>tracey.price@ldh.nhs.uk</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> IBD Monitoring, MANAGEMENT SAVINGS</p></sec><sec><title></title><p><bold>TUESDAY, OCTOBER 15, 2013 8:30-10:30</bold></p><p><bold>Treatment of rectal cancer in 2013 – Roof Garden</bold></p></sec><sec><title>OP173 SHOULD COLON AND RECTAL T1 CANCER BE CONSIDERED AS A SINGLE ENTITY?</title><p><bold>K. Ichimasa</bold><sup>1,*</sup>, S.-E. Kudo<sup>1</sup>, H. Miyachi<sup>1</sup>, T. Hisayuki<sup>1</sup>, H. Oikawa<sup>1</sup>, S. Matsudaira<sup>1</sup>, M. Misawa<sup>1</sup>, Y. Mori<sup>1</sup>, Y. Sugihara<sup>1</sup>, T. Kudo<sup>1</sup>, K. Kodama<sup>1</sup>, K. Wakamura<sup>1</sup>, T. Hayashi<sup>1</sup>, S. Ohkoshi<sup>1</sup>, S. Hamatani<sup>1</sup>, S. Mukai<sup>1</sup>, E. Hidaka<sup>1</sup>, F. Ishida<sup>1</sup></p><p><italic><sup>1</sup>Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama city, Japan</italic></p><p><bold>INTRODUCTION:</bold> Previous reports suggested that the biology of colorectal cancers differed according to the location. Although the investigation of clinicopathological diversities between colon and rectal cancers could provide useful information for more effective clinical management, there is little evidence of the differences. Furthermore, the issue of whether these cancers should be considered as a single entity or two distinct entities is still debated.</p><p><bold>AIMS&METHODS:</bold> The aim is to clarify the clinicopathological features of rectal T1 cancers in comparison to colon ones.</p><p> A total of 19452 colorectal neoplasms were resected endoscopically or surgically at our institution between April 2001 and December 2012. Of these, 806 T1 cancers (661 colon and 145 rectal) were eligible for analysis. To evaluate the clinical significance of tumor location, we performed a detailed clinicopathological review of colon and rectal T1 cancers as follows: age, gender, lesion size, recurrence, invasion rate, wel or mod/ por or muc component, vessel permeation, tumor budding and lymph node metastasis.</p><p><bold>RESULTS:</bold> Rectal T1 cancers were detected at younger age (colon 66.2±11.4 vs. rectum 64.0±12.0, p<0.05), in larger size (19.8mm±11.4mm vs. 24.3mm±15.6mm, p<0.05) and with massive invasion (72.9% vs. 82.5%, p<0.05). In addition, rectal T1 cancers showed significantly higher incidence of venous permeation (22.6% vs. 36.6%, p<0.05) and recurrence (0.30% vs. 2.82%, p<0.05). No significant differences were observed in the other clinicopathological factors.</p><p><bold>CONCLUSION:</bold> Colon and rectal T1 cancer could be considered as two different diseases requiring different forms of treatment.</p><p><bold>Contact E-mail Address:</bold><email>ichitommy14@yahoo.co.jp</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> clinical characteristics, pathological characteristics, T1 colorectal carcinoma</p></sec><sec><title>OP174 OPTIMAL TIMING OF SURGERY AFTER NEOADJUVANT TREATMENT IN LOCALLY ADVANCED RECTAL CANCER</title><p><bold>C. Späth</bold><sup>1,*</sup>, U. Nitsche<sup>1</sup>, M. Maak<sup>1</sup>, T. Müller<sup>1</sup>, J. Kleeff<sup>1</sup>, F. G. Bader<sup>1</sup></p><p><italic><sup>1</sup>Surgery, Klinikum rechts der Isar, Technical University Munich, Munich, Germany</italic></p><p><bold>INTRODUCTION:</bold> Preoperative chemoradiotherapy (CRT) in locally advanced rectal cancers reduces the risk of local recurrence and increases the number of R0 resections. The optimal interval between end of CRT and time of surgery is still unclear. Accumulating data suggest that the number of pathologic complete responses (pCR) increase with a longer time interval between CRT and surgery.</p><p><bold>AIMS&METHODS:</bold> A systematic review and meta analysis was performed according to the PRISMA statement. Trials were identified by searching PubMed, MEDLINE and EMBASE from 1995 to September 2012. Retrospective and prospective articles comparing at least two time intervals were included in this study. Single-arm studies were excluded. Odds ratios and 95% confidence intervals were calculated using random-effects models.</p><p><bold>RESULTS:</bold> Systematic literature search revealed a total of 15 retrospective and prospective studies meeting inclusion criteria. Of the identified articles five retrospective and two prospective studies (n=768) compared time periods of <8 and >8 weeks and were included in the meta analysis. A total of 388 patients (51 %) were operated later than 8 weeks after completion of CRT. In these patients a significantly higher rate of pCR was observed (OR 0.52, 95% CI 0.34-0.80). Postoperative morbidity (rate of anastomotic leaks, intraabdominal abscesses etc.) was similar in both groups (OR 1.23, 95% CI 0.61-2.46). Also the rate of sphincter preserving resections did not differ (OR 1.14 , 95% CI 0.75-1.75).</p><p><bold>CONCLUSION:</bold> Although current data are limited due to lack of randomized controlled trials and heterogeneous study designs the rate of pathologic complete responses seems to be increased in patients with a time interval of more than 8 weeks after end of CRT. There were no significant differences of morbidity rates in both groups. A time interval of more than 8 weeks between CRT and resection should be considered. High quality randomized controlled trials are required to predict the optimal time interval.</p><p><bold>Contact E-mail Address:</bold><email>christoph.spaeth@tum.de</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Neoadjuvant therapy, Rectal cancer</p></sec><sec><title></title><p><bold>TUESDAY, OCTOBER 15, 2013 8:30-10:30</bold></p><p><bold>Management of pancreatic cancer – Hall Helsinki</bold></p></sec><sec><title>OP175 DISCOVERY OF NEW METABOLIC BIOMARKERS FOR THE DIAGNOSIS OF PANCREATIC DUCTAL ADENOCARCINOMA (PDAC)</title><p><bold>J. Mayerle</bold><sup>1,*</sup>, H. Kalthoff<sup>2</sup>, R. Reszka<sup>3</sup>, B. Kamlage<sup>4</sup>, C. Pilarsky<sup>5</sup>, R. Grützmann<sup>5</sup>, F.-U. Weiss<sup>1</sup>, M. M. Lerch<sup>1</sup></p><p><italic><sup>1</sup>Department of Medicine A, University Medicine Greifswald, Ernst-Moritz-Arndt-University, Greifswald, <sup>2</sup>Institut für Experimentelle Tumorforschung (IET), UKSH, Campus Kiel, Kiel, <sup>3</sup>Metanomics Health GmbH, <sup>4</sup>metanomics GmbH, Berlin, <sup>5</sup>Clinic and Outpatient Clinic for Visceral-, Thorax- and Vascular Surgery, University Hospital Carl Gustav Carus, Dresden, Germany</italic></p><p><bold>INTRODUCTION:</bold> Early symptoms of pancreatic cancer (PDAC) are rare and nonspecific and this burdenes PDCA with a especially dismail prognosis. Although modern imaging techniques have pushed the detection limit combination of diagnostic imaging and lab-based biomarkers can, under the best of circumstances, distinguish between pancreatic cancer and chronic pancreatitis in only 67%. We have therefore conducted discovery and confirmation studies to identify metabolite plasma biomarkers for the detection of pancreatic cancer and the differentiation from chronic pancreatitis.</p><p><bold>AIMS&METHODS:</bold> The study was conducted in three phases: An initial pilot study on plasma samples was followed by analysis of a second plasma sample collection and a serum sample collection from pancreatic cancer, chronic pancreatitis and liver cirrhosis patients as well as matched healthy blood donors. Metabolomic profiles of plasma and serum samples were generated applying high quality polar and lipid GC-MS and LC-MS/MS technology (MxP™ Broad Profiling). In addition, targeted platforms for steroids and lipids (MxP™ Steroid, MxP™ Lipids) were applied. Up to 477 metabolites were analyzed semi-quantitatively or quantitatively. Statistical data analysis was done by linear models (ANOVA) on log10 transformed data considering age, gender, BMI and sample storage time as fixed effects. A selection of 10 metabolites was done via classification by using the Random Forest (RF) algorithm with forward feature selection. The predictive ability of the biomarker was evaluated through the estimation of ROC characteristics and AUC values from Bootstrap-based Cross-Validation.</p><p><bold>RESULTS:</bold> Within the three consecutive studies, a multimarker panel identified by Random Forest consisted of 10 metabolites and provided an AUC=0.85 when discriminating between pancreatic cancer and pancreatitis. When CA19-9 serum levels (AUC=0.82) were included in the analysis, an AUC of 0.94 was reached.</p><p><bold>CONCLUSION:</bold> The results indicate that a plasma metabolite biomarker panel may be used to distinguish between pancreatic cancer and chronic pancreatitis with a high degree of accuracy. The most discriminating metabolites showed robustness with respect to transferability of their diagnostic potential from plasma to serum. A diagnostic assay based on this biomarker would help in guiding suspected PDCA patients and chronic pancreatitis patients burdened with an increased PDCA risk towards more or less invasive diagnostic procedures.</p><p><bold>Contact E-mail Address:</bold><email>mayerle@uni-greifswald.de</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Metabolom, Pancreatic Cancer, prognostic value</p></sec><sec><title></title><p><bold>TUESDAY, OCTOBER 15, 2013 8:30-10:30</bold></p><p><bold>Upper GI interventions and advanced endoscopy: Top late breaking abstracts – Hall 7</bold></p></sec><sec><title>OP175-LB1 RADIOFREQUENCY ABLATION IN BARRETT’S ESOPHAGUS WITH CONFIRMED LOW-GRADE DYSPLASIA REDUCES NEOPLASTIC PROGRESSION: RESULTS OF THE SURF RANDOMIZED TRIAL</title><p><bold>K. N. Phoa</bold><sup>1,*</sup>, F. van Vilsteren<sup>1</sup>, B. Weusten<sup>2</sup>, R. Bisschops<sup>3</sup>, E. Schoon<sup>4</sup>, K. Ragunath<sup>5</sup>, G. Fullarton<sup>6</sup>, M. Di Pietro<sup>7</sup>, N. Ravi<sup>8</sup>, M. Visser<sup>1</sup>, G. J. Offerhaus<sup>1</sup>, C. Seldenrijk<sup>2</sup>, S. L. Meijer<sup>1</sup>, F. J. Ten Kate<sup>1</sup>, J. Tijssen<sup>1</sup>, J. J. Bergman<sup>1</sup></p><p><italic><sup>1</sup>ACADEMIC MEDICAL CENTER AMSTERDAM, Amsterdam, <sup>2</sup>St Antonius Hospital, Nieuwegein, Netherlands, <sup>3</sup>UZ Gasthuisberg, Leuven, Belgium, <sup>4</sup>Catharinaziekenhuis, Eindhoven, Netherlands, <sup>5</sup>Queens Medical Centre, Nottingham, <sup>6</sup>Royal Infirmary, Glasgow, <sup>7</sup>Addenbrookes Hospital, Cambridge, United Kingdom, <sup>8</sup>St James Hospital, Dublin, Ireland</italic></p><p><bold>INTRODUCTION:</bold> Barrett’s esophagus (BE) with confirmed low-grade dysplasia (LGD) is associated with an increased risk of neoplastic progression to high-grade dysplasia (HGD) and/or esophageal adenocarcinoma (EAC). We assessed whether radiofrequency ablation (RFA) could decrease the rate of neoplastic progression.</p><p><bold>AIMS & METHODS:</bold> In a multicenter randomized trial we randomly assigned 136 patients with BE-LGD to either RFA+surveillance or surveillance alone (control). 68 patients underwent RFA every 2-3 months (max 5 sessions) and subsequent surveillance with 4Q/2cm biopsy at 12-24-36 mo follow-up (FU). 68 controls underwent endoscopic surveillance with 4Q/2cm biopsy at 6-12-24-36 mo. A central expert GI pathology panel confirmed baseline pathology and primary outcome. The primary outcome was neoplastic progression (HGD or EAC) during 3 year FU. After review at 2 years the data safety monitoring board recommended early termination of the study protocol due to superiority of RFA.</p><p><bold>RESULTS:</bold> Randomization resulted in similar sex, age and BE length between the two groups. One RFA patient died of unrelated cause during treatment. 63 of the remaining 67 RFA patients (94%) reached complete eradication of dysplasia (CE-D), 60/67 patients (90%) reached CE-intestinal metaplasia (CE-IM). CE-D and CE-IM occurred in 19 (28%) and 0 (0%) controls, respectively.</p><p>Primary outcome: Patients in the RFA group had less overall neoplastic progression to HGD/EAC (1.5% vs. 26.5%, p<0.001) and less progression to EAC (1.5% vs. 8.8%,p=0.026) as compared to controls. The single progressor in RFA (EAC) reached CE-D and CE-IM after endoscopic resection. Of the 18 progressors in control (12 HGD, 6 EAC); 1 had esophagectomy (T1bN0M0), 17 underwent endoscopic treatment or surveillance. Treatment related adverse events (AE) occurred in 13 RFA patients (19%) and 4 controls (6%, all progressors who underwent therapy). The most common AE was stenosis; 12% in RFA (n=8) and 3% in control (n=2). There were no study related deaths.</p><p><bold>CONCLUSION:</bold> In patients with Barrett’s esophagus with confirmed LGD, radiofrequency ablation was associated with a reduced risk of disease progression as compared to control. Preventive RFA treatment is therefore beneficial for BE-LGD patients in whom the histological diagnosis is confirmed.</p><p><bold>Disclosure of Interest</bold>: K. Phoa: None Declared, F. van Vilsteren: None Declared, B. Weusten: None Declared, R. Bisschops: None Declared, E. Schoon: None Declared, K. Ragunath: None Declared, G. Fullarton: None Declared, M. Di Pietro: None Declared, N. Ravi: None Declared, M. Visser: None Declared, G. Offerhaus: None Declared, C. Seldenrijk: None Declared, S. Meijer: None Declared, F. Ten Kate: None Declared, J. Tijssen: None Declared, J. Bergman Financial Support from: AstraZeneca, BARRX medical</p><p><bold>Keywords:</bold> Barrett’s esophageal cancer, Low-grade dysplasia, radiofrequency ablation, randomized controlled trial</p></sec><sec><title>OP175-LB2 LIGATION-ASSISTED ENDOSCOPIC ENUCLEATION FOR TREATMENT OF ESOPHAGEAL SUBEPITHELIAL LESIONS ORIGINATING FROM THE MUSCULARIS PROPRIA: A PRELIMINARY STUDY</title><p><bold>J. Guo</bold><sup>1,*</sup>, S. Sun<sup>1</sup>, Z. Liu<sup>2</sup>, Z. Liu<sup>1</sup>, S. Sun<sup>1</sup></p><p><italic><sup>1</sup>Endoscopy Center, <sup>2</sup>Shengjing Hospital of China Medical University, Shenyang, China</italic></p><p><bold>INTRODUCTION:</bold> An innovative ligation-assisted endoscopic enucleation (EEL) technique was developed for the diagnosis and treatment of esophageal subepithelial lesions originating from muscularis propria, by combing endoscopic band ligation and endoscopic enucleation techniques.</p><p><bold>AIMS & METHODS:</bold> The aim of the study was to evaluate efficacy and safety of EEL technique in the treatment of esophageal subepithelial lesions originating from muscularis propria.</p><p>47 esophageal subepithelial lesions originating from the muscularis propria in 44 patients were treated with EEL between September 2010 and September 2012. Endoscopic ligation was first performed to force the tumor to assume a polypoid form with a pseudostalk, endoscopic enucleation was then performed until the tumor was completely enucleated from muscularis propria using a Hook knife and forcep.</p><p><bold>RESULTS:</bold> All tumors were enucleated completely. The mean time of the EEL procedure was 12.5±4.6 minutes. No perforation, massive hemorrhage, or peritonitis requiring further endoscopic or surgical intervention occurred. There were no recurrences during the 6-24 month follow-up period.</p><p><bold>CONCLUSION:</bold> EEL offers the option of localized treatment of esophageal muscularis propria tumors with relatively few complications and low mortality, and provides the advantage of allowing a histopathological diagnosis.</p><p><bold>Contact E-mail Address:</bold><email>guojt@sj-hospital.org</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Enucleation, Ligation, Muscularis Propria Layer, subepithelial lesions</p></sec><sec><title>OP175-LB3 PROPHYLACTIC SOMATOSTATIN CAN REDUCE INCIDENCE OF POST-ERCP PANCREATITIS: A MULTICENTER RANDOMIZED CONTROLLED TRIAL</title><p><bold>B. Yu</bold><sup>1,*</sup>, X.-F. Zhang<sup>2</sup>, X.-G. Guo<sup>3</sup>, X.-J. Wan<sup>4</sup>, Z.-G. Nie<sup>5</sup>, S.-T. Han<sup>6</sup>, P. Bie<sup>7</sup>, D.-A. Tian<sup>8</sup>, M. Ji<sup>9</sup>, X. Ren<sup>10</sup>, N.-H. Lv<sup>11</sup>, Z.-S. Li<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology, Changhai Hospital, Shanghai, <sup>2</sup>Gastroenterology, First People's Hospital of Hangzhou, Hangzhou, <sup>3</sup>Gastroenterology, Xijing Hospital of Digestive Diseases, Xi'An, <sup>4</sup>Gastroenterology, First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai , <sup>5</sup>Gastroenterology, Urumchi General Hospital, Urumchi , <sup>6</sup>Gastrointestinal Endoscopy Center, Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing, <sup>7</sup>Gastroenterology, Southwest Hospital, Chongqing, <sup>8</sup>Gastroenterology, Tongji Hospital, Wuhan, <sup>9</sup>Gastroenterology, Beijing Friendship Hospital, Beijing , <sup>10</sup>Gastroenterology, Heilongjiang Province Hospital, Harbin, <sup>11</sup>Gastroenterology, The First Affiliated Hospital, Nan Chang, China</italic></p><p><bold>INTRODUCTION:</bold> Post-ERCP pancreatitis is the most common complication of ERCP. Somatostatin can inhibit pancreatic secretion and has been tested for post-ERCP pancreatitis prophylaxis, but the results of previous studies are inconsistent or even contradictory. This present study investigated whether somatostatin could reduce the incidence of post-ERCP pancreatitis.</p><p><bold>AIMS & METHODS:</bold> Nine hundreds patients undergoing ERCP were randomized: 445 received a somatostatin 250ug bolus injection started before ERCP and 250ug/h intravenous infusion continued for 11 hours after ERCP, and 455 patients randomized to no somatostatin. The frequencies of post-ERCP pancreatitis and hyperamylasemia in the two groups were compared.</p><p><bold>RESULTS:</bold> In the control group, post-ERCP pancreatitis developed in 34 (7.5%) patients, while post-ERCP pancreatitis developed in 18 (4.0%) patients in the somatostatin group (p = 0.03). The incidence of hyperamylasemia was 10.1% in the control group and 6.1% in the somatostatin group (p = 0.026). No perforation or death occurred in this study.</p><p><bold>CONCLUSION:</bold> The results of this study indicate that somatostatin prophylaxis can reduce the incidence of post-ERCP pancreatitis and hyperamylasemia.</p><p><bold>Contact E-mail Address:</bold> Correspondence to: Professor Zhao-Shen Li, Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China. Email:
<email>li.zhaoshen@hotmail.com</email></p><p>Professor Xu Ren, Department of Gastroenterology, Heilongjiang Province Hospital, Harbin, China. Email: xhhospital@126.com</p><p>Professor Nong-Hua Lv, Department of Gastroenterology, The first affiliated Hospital, Nan Chang University, Jiangxi, China. Email: lunonghua@163.com</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> ERCP complications, pancreatitis</p></sec><sec><title></title><p><bold>TUESDAY, OCTOBER 15, 2013 8:30-10:30</bold></p><p><bold><italic>H. pylori</italic> and gastric cancer risk – Hall 9</bold></p></sec><sec><title>OP176 HISTOLOGICAL CHARACTERISTICS OF GASTRIC MUCOSA PRIOR TO HELICOBACTER PYLORI ERADICATION MAY PREDICT GASTRIC CANCER</title><p><bold>K. Murakami</bold><sup>1,*</sup>, M. Kodama<sup>1</sup>, T. Okimoto<sup>1</sup>, Y. Nakagawa<sup>1</sup>, T. Fujioka<sup>1</sup></p><p><italic><sup>1</sup>Department of Gastroenterology, OITA UNIVERSITY, Yuhu, Japan</italic></p><p><bold>INTRODUCTION:</bold> Although <italic>Helicobacter pylori</italic> eradication has been shown to inhibit gastric cancer, it does not completely suppress it. In our previous study, significant improvement of atrophy was observed during a ten-year follow-up period following eradication. However, intestinal metaplasia(IM) did not show a similar improvement, except for IM at the lesser curvature of the corpus (1). Therefore risk factors associated with gastric cancer development following <italic>H. pylori</italic> eradication were examined.</p><p><bold>AIMS&METHODS:</bold> A total of 2355 patients (1501 males, 824 females) underwent successful eradication of <italic>H. pylori</italic>. Endoscopical atrophy, serum pepsinogen, and histological gastritis were evaluated after eradication.</p><p><bold>RESULTS:</bold> Following <italic>H. pylori </italic>eradication, 33/2355 patients (25 males, 8 females) developed gastric cancer. When a non-gastric cancer group was matched according to gender and age of the gastric cancer group, the incidence of endoscopic atrophy (3.52 ± 1.45 vs. 4.71 ± 1.31, <italic>P </italic>< 0.001), histological atrophy (1.42 ± 0.80 vs. 2.00 ± 0.87, <italic>P </italic>= 0.0028) at the greater curvature of the antrum, inflammation (2.05 ± 0.59 vs. 2.32 ± 0.65, <italic>P </italic>= 0.036), and intestinal metaplasia (IM) (0.06 ± 0.30 vs. 0.23 ± 0.53, <italic>P </italic>= 0.034) at the greater curvature of the corpus for the gastric cancer group was significantly higher than for the non-gastric cancer group. Multivariate analysis also showed that the odds ratio and 95% confidence interval (CI) for these categories were 2.20 (1.36–3.55) (<italic>P </italic>= 0.001), 3.26 (1.45–7.34) (<italic>P </italic>= 0.004), 2.69 (1.01–7.26) (<italic>P </italic>= 0.05), and 5.98 (1.27–28.10) (<italic>P </italic>= 0.023), respectively.</p><p><bold>CONCLUSION:</bold> Severe endoscopical atrophy, histological atrophy at the antrum, inflammation, and particularly IM at the corpus, were identified as risk factors for gastric cancer development following <italic>H. pylori</italic> eradication. Therefore, eradication should be performed before these predictors develop.</p><p><bold>REFERENCES:</bold></p><p>1. Kodama M, Murakami K,Okimoto T, Sato R, Uchida M, Abe T, et al.Ten-year prospective follow-up of histological changes at 5 points on the gastric mucosa as recommended by the updated Sydney system after <italic>Helicobacter pylori</italic> eradication. J Gastroenterol. 2012;47:394-403</p><p><bold>Contact E-mail Address:</bold><email>murakam@oita-u.ac.jp</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> updated Sydney system, atrophic gastritis, Gastric cancer, Helicobacter pylori, intestinal metaplasia</p></sec><sec><title>OP177 INVESTIGATION ABOUT THE RISK OF GASTRIC CANCER AFTER SUCCESSFUL ERADICATION OF <italic>H. PYLORI</italic></title><p><bold>M. Kato</bold><sup>1,*</sup>, K. Mabe<sup>1</sup>, M. Ohno<sup>2</sup>, S. Ohmori<sup>2</sup>, M. Suzuki<sup>2</sup>, M. Takahashi<sup>2</sup>, T. Yoshida<sup>2</sup>, S. Ono<sup>1</sup>, Y. Shimizu<sup>2</sup>, N. Sakamoto<sup>2</sup></p><p><italic><sup>1</sup>Endoscopy, Hokkaido University Hospital, <sup>2</sup>Gastroenterology, Hokkaido University, Graduate School of Medicine, Sapporo, Japan</italic></p><p><bold>INTRODUCTION:</bold> Although successful eradication of <italic>H. pylori</italic> reduced the incidence of gastric cancer, the risk of post-eradication gastric cancer continues for long-term. Therefore, the periodic surveillance of gastric cancer is necessary after eradication of <italic>H. pylori</italic> in Japan. The aim of this study is to clarify the incident risk of post-eradication.</p><p><bold>AIMS&METHODS:</bold> Retrospective multicenter survey about the patients who received periodic follow-up using endoscopic examination after successful eradication of<italic> H. pylori</italic> was conducted in Japan. Successful eradication was dined as continually negative results of more than two diagnostic tests of<italic> H. pylori</italic>.</p><p><bold>RESULTS:</bold> A total 6225 eradicated patients from 38 institutions (mean age: 56.1 male-female ratio: 2.2:1 mean follow up period: 47 months) were registered. 186 gastric cancers were detected from registered patients. Follow-up period of cases who detected gastric cancer ranged from 3.2 months to 170.0 month, while 14 gastric cancers were detected 10 years or more after eradication. The incidence of post-eradication gastric cancer in each pre-existing gastric lesion was 10.0% in early gastric cancer that were removed by endoscopic resection, 8.3% in adenoma, 3.1% in hyperplastic polyp, 2.4% in gastric ulcer, 2.2% in MALT lymphoma, 1.6% in gastroduodenal ulcer, 1.6% in chronic gastritis, 0.3% in duodenal ulcer and 0.0% in nodular gastritis.</p><p><bold>CONCLUSION:</bold> Gastric cancer was detected even after 10 years or more after successful <italic>H. pylori </italic>eradication. The incident risk of post-eradication gastric cancer depended on background of gastric lesions.</p><p><bold>Contact E-mail Address:</bold><email>m-kato@med.hokudai.ac.jp</email></p><p><bold>Disclosure of Interest</bold>: M. Kato Financial support for research from: Eisai Co. Ltd., Lecture fee(s) from: Takeda Pharmaceutical Co. Ltd, K. Mabe: None Declared, M. Ohno: None Declared, S. Ohmori: None Declared, M. Suzuki: None Declared, M. Takahashi: None Declared, T. Yoshida: None Declared, S. Ono: None Declared, Y. Shimizu: None Declared, N. Sakamoto: None Declared</p><p><bold>Keywords:</bold> Gastric cancer, post-eradication, risk of cancer</p></sec><sec><title>OP178 EVALUATION OF GASTROPANEL IN GASTRIC CANCER PATIENTS, FIRST-DEGREE RELATIVES AND AUTOIMMUNE CHRONIC ATROPHIC GASTRITIS (ACAG)</title><p><bold>E. Orzes</bold><sup>1</sup>, R. Cannizzaro<sup>1</sup>, S. Maiero<sup>1</sup>, M. Tabuso<sup>1,*</sup> M. Fornasarig V <sup>1</sup>, De Re<sup>2</sup>, A. Steffan<sup>3</sup>, S. Cervo<sup>3</sup>, V. Canzonieri<sup>4</sup></p><p><italic><sup>1</sup>SOC Gastroenterology, <sup>2</sup>Pharmacology, <sup>3</sup>Clinical Pathology, <sup>4</sup>Pathology, CENTRO RIFERIMENTO ONCOLOGICO, Aviano, Italy</italic></p><p><bold>INTRODUCTION:</bold> Due to short survival in advanced gastric cancer (GC), the early detection of GC in high-risk selected patients is important also in low incidence areas. In the absence of well-founded biomarkers for the detection of GC, a program to identify individuals at high risk would include the evaluation of markers such as serum pepsinogens and the detection of <italic>H. pylori</italic>.</p><p><bold>AIMS&METHODS:</bold> To examine if the serological differences of the gastric mucosa in first-degree relatives (FDRs) of GC patients, patients with autoimmune chronic atrophic gastritis (ACAG) and GC patients can select very high risk patients.</p><p>A total of 182 consecutive patients (85M, 97F) were enrolled in the study since 2009. In 66 patients with GC (mean age: 63), 44 with ACAG (mean age: 55) and 72 FDRs (mean age: 46) serum levels of PG I, PG II, G-17 and PGI/II ratio were assessed. GCs have been classified by localisation and Laurèn type, while OLGA classification system has been applied for staging chronic gastritis. In every histological sample the presence of intestinal metaplasia and the <italic>H. pylori </italic>status was investigated and the association of clinicopathologic characteristics with serological values were statistically analyzed.</p><p><bold>RESULTS:</bold> 16.7% of patients with confirmed GC had a positive family history of GC. There was a statistically significant difference in PGI median levels in cancer group, ACAG group and FDRs group (respectively 179.0, 14.6, 105.9 ng/mL, p = 0.0003); in particular, patients with diffuse type GC had 1.51-fold higher PGI levels compared to those with intestinal type (237.2 vs. 157.3 ng/mL) and also PGI/II ratio resulted higher (7.6 vs. 6.7). In patients affected with cancer and intestinal metaplasia in the stomach both PGI and PGI/II levels resulted lower than patients with cancer without metaplasia (125.2 vs. 214.0 ng/mL). Furthermore, patients with ACAG and intestinal metaplasia had significantly lower PGI (12.8 vs. 51.7 ng/mL) and PGI/II ratio (2.1 vs. 4.9) than patients without intestinal metaplasia. 38.9% of FDRs had an active <italic>H. pylori</italic> infection and 9.7% demonstrated to have intestinal metaplasia in the stomach.</p><p><bold>CONCLUSION:</bold> Our data showed a high prevalence of positive family history of GC in cancer group. PGI level was significantly higher in cancer group than ACAG group and it also resulted higher in diffuse type compared to intestinal type GC. The combinatorial approach of Gastropanel and risk factors may be helpful to identify very high-risk patients for GC.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> autoimmune atrophic gastritis, gastric cancer, pepsinogens</p></sec><sec><title>OP179 CHARACTERIZATION OF THE GASTRIC MICROBIOTA IN PATIENTS WITH CHRONIC GASTRITIS AND GASTRIC CARCINOMA</title><p><bold>R. M. Ferreira</bold><sup>1,*</sup>, J. L. Costa<sup>1</sup>, C. Figueiredo<sup>1,2</sup>, J. C. Machado<sup>1,2</sup></p><p><italic><sup>1</sup>IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, <sup>2</sup>Dept. Pathology and Oncology, Faculty of Medicine of the University of Porto, Porto, Portugal</italic></p><p><bold>INTRODUCTION:</bold> Gastric carcinoma is the second cause of cancer death worldwide. The majority of gastric carcinoma cases are related to <italic>Helicobacter pylori </italic>infection. This infection induces chronic inflammation that, depending on the strain virulence, host susceptibility factors, and other environmental factors, increases the risk of progression towards carcinoma. During gastric carcinogenesis other bacteria may grow in the stomach as a result of the profound changes in gastric physiology induced by<italic> H. pylori</italic>. The new bacterial growth that competes for the gastric niche may have the potential to enhance inflammation, contributing to gastric carcinogenesis.</p><p><bold>AIMS&METHODS:</bold> The aim of this study is to characterize the gastric microbiota present in individuals with chronic gastritis and gastric carcinoma. To date we have analysed data from ten chronic gastritis and seven gastric carcinoma patients. The next generation sequencing platform Ion PGM was used to sequence part of the bacterial 16S rRNA gene. This gene contains highly variable regions that provide discriminatory power for the characterization of microbiota. The data resulting from mass parallel sequencing was analysed in Qiime pipeline. Clustering of samples was evaluated by Principal Coordinate Analysis (PCoA).</p><p><bold>RESULTS:</bold> So far we have obtained 1,715,309 high quality sequences representing on average 90,279 reads per individual, which were converted in 17,971 operational taxonomic units. A complex and diverse gastric microbiota was identified, which varied considerably between individuals. The majority of the gastric microbiota could be distributed in five main <italic>phyla</italic>, <italic>Proteobacteria</italic>, <italic>Firmicutes</italic>, <italic>Actinobacteria</italic>, <italic>Bacteroidetes</italic>, and <italic>Fusobacteria</italic>. In patients with chronic gastritis and with gastric carcinoma the most representative <italic>phylum</italic> was the <italic>Proteobacteria</italic> with 69.5% and 84.2% reads, respectively. The remaining four <italic>phyla</italic> were always less represented in patients with gastric carcinoma than in patients with chronic gastritis. Interestingly, the abundance of <italic>Helicobacter sp.</italic> was significantly lower in patients with gastric carcinoma (15.8%) than in patients with chronic gastritis (63.9%). Analysis of the diversity between groups of individuals by PCoA, revealed clustering based on the type of disease, meaning that distinct profiles of microbiota distinguish the two patient groups.</p><p><bold>CONCLUSION:</bold> Apart from the complex and diverse gastric microbiota found within individuals, we were able to identify gastric microbiota profiles that distinguish between patients with chronic gastritis and gastric carcinoma. The microbiota profiles identified may have an important role in <italic>H. pylori</italic>-associated gastric carcinogenesis.</p><p><bold>Contact E-mail Address:</bold><email>josem@ipatimup.pt</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Gastric adenocarcinoma, microbiota</p></sec><sec><title>OP180 GASTROKINE-2 RESTRAINS PRENEOPLASTIC PROGRESSION BY MODULATING GASTRIC MUCOSAL IMMUNITY TO HELICOBACTER PYLORI</title><p><bold>T. R. Menheniott</bold><sup>1,*</sup>, Y.-T. Chionh<sup>1</sup>, L. O'Connor<sup>1</sup>, J. Däbritz<sup>1</sup>, P. Sutton<sup>1</sup>, L. M. Judd<sup>1</sup>, A. S. Giraud<sup>1</sup></p><p><italic><sup>1</sup>Murdoch Childrens Research Institute, Melbourne, Australia</italic></p><p><bold>INTRODUCTION:</bold> Gastrokine (GKN)2 belongs to a family of proteins exclusively expressed in the gastric mucosa. While tumor suppressor and/or mucosal immune/homeostatic roles are suspected, functions of GKN2 in <italic>H. pylori</italic> infection and related neoplasias have not been elucidated.</p><p><bold>AIMS&METHODS:</bold><italic>GKN2</italic> expression was assessed in human gastric tissues collected from patients with <italic>H. pylori</italic> infection, intestinal metaplasia (IM), gastric cancers and disease-free controls by quantitative RT-PCR. <italic>Gkn2</italic> expression was also investigated in mouse models of gastric pathology. <italic>Gkn2 </italic>knockout (-/-) mice were created by standard gene targeting. Functional impact of GKN2 loss on preneoplastic progression was investigated in <italic>Gkn2</italic>-/- mice infected with mouse adapted <italic>H. pylori</italic> SS1 for 1-week and 2-months. Effects of GKN2 loss on mucosal immunity were studied in primary gastric epithelial cells derived from <italic>Gkn2</italic>-/- mice.</p><p><bold>RESULTS:</bold><italic>GKN2</italic> mRNA expression was progressively lost in human <italic>H. pylori</italic> infection, IM and adenocarcinoma. <italic>Gkn2</italic> mRNA was also suppressed in mouse models of <italic>H. pylori</italic> infection, autoimmune gastritis, mucous metaplasia, fundic hypertrophy and gastric tumourigenesis. In functional studies, <italic>Gkn2</italic>-/- mice showed perturbed epithelial homeostasis in the gastric fundus characterised by increased cell proliferation and reduced parietal/zymogenic cell numbers. After 1-week <italic>H. pylori</italic> infection, Gkn2 -/- mice showed elevated gastric NF-kB activation and cytokine/chemokine release compared with WT controls. After 2-months <italic>H. pylori</italic> infection <italic>Gkn2</italic>-/- mice showed accelerated development of atrophic gastritis and mucous metaplasia in the fundus. Molecular studies of 2-month <italic>H. pylori</italic> infected <italic>Gkn2</italic>-/- mice revealed increased fundic expression of T-helper (Th)-type1 cytokines and chemokines, but Th-17 immunity was not differentially activated. 2-month <italic>H. pylori</italic> infected <italic>Gkn2</italic>-/- mice showed significantly reduced <italic>H. pylori</italic> colonisation levels in the fundus suggesting increased bacterial clearance. Surprisingly, <italic>H. pylori</italic> colonisation was also reduced in the antrum and fundus of 1-week infected and in the antrum of 2-month infected <italic>Gkn2</italic>-/- mice, independently of gastritis. Primary gastric epithelial cells derived from <italic>Gkn2</italic>-/- mice showed enhanced release of interleukin (IL)-1β and IL-6 after co-incubation with <italic>H. pylori</italic> for 24h suggesting that GKN2 may suppress formative mucosal innate immune responses.</p><p><bold>CONCLUSION:</bold> We show that GKN2 restrains inflammation and related preneoplastic progression in the stomach by attenuating mucosal immune responses to <italic>H. pylori</italic>. We further propose that GKN2 regulates <italic>H. pylori</italic> colonisation via immune dependent and independent mechanisms.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Gastric cancer, Gastrokine, Helicobacter pylori, Innate Immunity, Stomach Neoplasms</p></sec><sec><title>OP181 SERUM TREFOIL FACTOR 3 IS A VALID NON-ENDOSCOPIC BIOMARKER FOR GASTRIC CANCER RISK –INFLUENCE OF HELICOBACTER PYLORI STATUS AND ERADICATION</title><p><bold>A. Yamada</bold><sup>1,*</sup>, S. hoteya<sup>1</sup>, T. iizuka<sup>1</sup>, D. kikuchi<sup>1</sup>, T. furuhata<sup>1</sup>, M. kaise<sup>1</sup></p><p><italic><sup>1</sup>toranomon hospital, tokyo, Japan</italic></p><p><bold>INTRODUCTION:</bold> We have shown that trefoil factors 3 (TFF3) is a valid predictor of gastric cancer (GCA) at 66.1 % of sensitivity and 91.7 % specificity in a cohort of limited numbers of patients and controls. We aimed to confirm the level of predictive value using a large number of cases and to evaluate influence of <italic>H. pylori</italic> eradication on the serum TFF3 in GCA patients.</p><p><bold>AIMS&METHODS:</bold> Healthy individuals who underwent a thorough medical checkup and GCA patients who underwent endoscopic workup were sequentially recruited. Enrolled GCA patients were divided into those with and without the history of successful <italic>H. pylori</italic> eradication. Serum levels of TFF1, TFF2, TFF3, <italic>H. pylori</italic> antibody, PG 1 and PG2 were examined.</p><p><bold>RESULTS:</bold> We recruited 1410 healthy individuals aged 52.3±12.4 and 429 GCA patients aged 67.6±10.0. The serum levels of TFF3 were 5.6 ± 3.1 ng/ml in healthy individuals and 9.3 ± 6.2 ng/ml in GCA (p<0.0001). The sensitivity (60.8%) of TFF3 (≧7 ng/ml) for predicting GCA presence was comparable to that (57.2%) of PG test (PG I<50, PG I/II ratio<3), whereas the sensitivity (70.9%) of the combination of TFF3 (≧7 ng/ml) and PG test (PG I<30, PG I/II ratio<2) was higher. The areas under the receiver-operation characteristic curve for predicting GCA presence were comparably high for all factors (0.847) and the combination of TFF3 and PG test (0.846), but was significantly (p<0.0001) lower for PG test alone (0.772).</p><p>Serum TFF3 levels were 7.8 ± 4.3 ng/ml and 9.4 ± 6.4 ng/ml in early GCA patients with (n=49) and without <italic>H. pylori</italic> eradication history (n=380), respectively(p<0.001). In 49 <italic>H. pylori</italic>-eradicated patients, the sensitivity (44.9%) of TFF3 for predicting GCA presence was significantly superior to that of a positive PG test (30.6%). However, the sensitivity of TFF3 was significantly (p<0.05) lower in <italic>H. pylori</italic>-eradicated patients than in none-eradicated patients (62.3 %).</p><p><bold>CONCLUSION:</bold> This study using a large number of GCA cased has confirmed the validity of serum TFF3 as a GCA predictor in the combination of PG test. Serum TFF3 may be a stable biomarker for GCA risk even after <italic>H. pylori</italic> eradication in contrast with PG test, but<italic> H.pylori</italic> eradication may partially decrease the sensitivity of serum TFF3.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> trefoil factor 3, gastric cancer, Helicobacter pylori eradication</p></sec><sec><title>OP182 HELICOBACTER PYLORI COLONIZATION RATE IN CHILDREN IS HIGHLY VARIABLE AMONG DIFFERENT ETHNIC GROUPS IN WESTERN POPULATIONS: THE GENERATION R STUDY</title><p><bold>W. J. den Hollander I</bold><sup>1,1,*</sup>, L. Holster<sup>1</sup>, B. van Gilst<sup>1</sup> A. J. van Vuuren V <sup>1</sup>, W. Jaddoe<sup>2,3</sup>, G. I. Perez-Perez<sup>4</sup>, M. J. Blaser<sup>4</sup>, E. J. Kuipers<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology and Hepatology, <sup>2</sup>Pediatrics, <sup>3</sup>Generation R, Erasmus MC University Medical Center, Rotterdam, Netherlands, <sup>4</sup>Medicine and Microbiology, New York Langone Medicine Center, New York, United States</italic></p><p><bold>INTRODUCTION:</bold><italic>Helicobacter pylori (H. pylori) </italic>is usually acquired during childhood. Although colonization rates have been declining in Western countries, less is known about <italic>H. pylori</italic> prevalence and risk factors among children living in a multi-ethnic Western city.</p><p><bold>AIMS&METHODS:</bold> We therefore aimed to identify <italic>H. pylori </italic>and CagA status and <italic>H. pylori-</italic>related risk factors in young children living in Rotterdam, a large European city. IgG anti-<italic>H. pylori</italic> and CagA-antibodies were measured in serum of children participating in the Generation R study, a population-based prospective cohort study. Information on demographics and maternal characteristics was collected by questionnaires. Chi-square tests and logistic regression were used. Odds ratios (OR) for <italic>H. pylori</italic> colonization were adjusted for children’s age, gender, ethnicity, day care attendance and maternal parity and education level.</p><p><bold>RESULTS:</bold> Serum of 4467 children was analysed (mean age 6.2 years ± 0.48 SD), of which 2164 were female (48%). Overall, 438 children were <italic>H. pylori </italic>positive (10%), and 142 of them were CagA-positive (32%). The highest colonization rate was found in children of Moroccan ethnicity (27%), followed by children originating from Cape Verde (23%), Dutch Antilles (15%), Turkey (13%), other non-western countries (12%), Surinam (10%), other western countries (10%), and the Netherlands (6%) respectively (p<0.001). The colonization rate if all non-Dutch children were pooled together was 15% compared with 6% of the Dutch children (p<0.001). Multivariate regression analyses revealed the following associations with childhood <italic>H. pylori </italic>colonization: non-Dutch ethnicity (OR 2.30; 95% confidence interval 1.82-2.90), male gender (0.69; 0.56-0.84), and day care attendance (0.60; 0.41-0.88). <italic>H. pylori-</italic>positive Dutch children were CagA-positive in 15% of the cases compared with 39% of the non-Dutch subjects (p<0.001).</p><p><bold>CONCLUSION:</bold> We identified large differences in colonization rates among children living in a multi-ethnic population. Highest <italic>H. pylori</italic> and CagA prevalence was found in children from non-Western countries, implying that in coming decades <italic>H. pylori </italic>and related diseases will be prevalent in this multi-ethnic population.</p><p><bold>Contact E-mail Address:</bold><email>w.denhollander@erasmusmc.nl</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Child, epidemiology, Ethnic Groups, Helicobacter pylori</p></sec><sec><title>OP183 HELICOBACTER PYLORI ERADICATION AND SERUM LEVELS OF GHRELIN AND LEPTIN: IS THERE A CONNECTION?</title><p><bold>S. M. D. Giestas</bold><sup>1,*</sup>, D. Marado<sup>1</sup>, A. Coelho<sup>1</sup>, C. Agostinho<sup>1</sup>, C. Sofia<sup>1</sup></p><p><italic><sup>1</sup>Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal</italic></p><p><bold>INTRODUCTION:</bold> Obesity is a rising public health problem in industrialized countries. Recent studies suggest that colonization of the stomach with Helicobacter pylori (Hp) can affect gastric synthesis of hormones related to energy homeostasis. Some studies have shown that Hp eradication significantly increases the body mass index (BMI) due to elevated plasma levels of ghrelin and lower leptin levels. However, the relationship between obesity and Hp eradication is still controversial.</p><p><bold>AIMS&METHODS:</bold> To evaluate the effect of Hp eradication on plasma ghrelin and leptin concentrations and body composition.</p><p>Patients and methods: included prospectively 89 obese colonized with Hp (confirmed in gastric biopsy) underwent successful eradication triple therapy (Amoxicillin 1g/2i.d., Clarithromycin 500mg/2i.d., Omeprazole 20mg / 2i.d for 14 days). Eradication was determined by urease breath test 34 ± 5.4 days after completing treatment regimen. The bioimpedance and plasma levels of leptin and ghrelin (assessed by radioimmunoassay after 12h overnight fast) were determined before and 3 months after eradication.</p><p><bold>RESULTS:</bold> The serum ghrelin levels increased significantly after 3 months eradication of Hp (3.1 ± 1.3 vs. 4.9 ± 1.7 ng / dl, p <0.05). However, leptin levels did not decrease significantly after eradication (34.4 ± 17.1 vs 33.6 ± 14.2 ng / dl, p> .05). The BMI did not increase significantly after Hp eradication (43.8 ± 4.3 vs 44.1 ± 4.6 kg/m2, p> 0.05), but there was a significant increase in fat mass and percentage of fat mass (37.6 ± 6.2 vs 41.3 ± 7.9 kg, 43.9 ± 2.7 vs 47.3 ± 4.7%, respectively, p <0,05).</p><p><bold>CONCLUSION:</bold> This study showed that Hp eradication is associated with a significant increase in fat mass presumably due to elevated plasma levels of ghrelin. The results of this study seem to indicate that Hp plays a role in the regulation of energy homeostasis.</p><p><bold>REFERENCES:</bold></p><p>1. Papamichael KX, et all. Helicobacter pylori infection and endocrine disorders: Is there a link? Worl J of Gastroenterology 2009; 15(22): 2701-2707</p><p><bold>Contact E-mail Address:</bold><email>silviagiestas@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> ghrelin, Helicobacter pylori eradication, leptin</p></sec><sec><title>OP184 SUSCEPTIBILITY TO HELICOBACTER PYLORI INFECTION: RESULTS OF AN EPIDEMIOLOGICAL INVESTIGATION AMONG GASTRIC CANCER PATIENTS</title><p><bold>N. Panic</bold><sup>1,*</sup>, E. Mastrostefano<sup>1</sup>, E. Leoncini<sup>1</sup>, R. Persiani<sup>2</sup>, D. Arzani<sup>1</sup>, R. Amore<sup>1</sup>, R. Ricci<sup>3</sup>, F. Sicoli<sup>2</sup>, S. Sioletic<sup>4</sup>, M. Bulajic<sup>5</sup>, D. D'Ugo<sup>6</sup>, W. Ricciardi<sup>1</sup>, S. Boccia<sup>1</sup></p><p><italic><sup>1</sup>Department of Public Health, <sup>2</sup>Department of Surgery, <sup>3</sup>Pathology Department, Università Cattolica del Sacro Cuore, Rome, Italy, <sup>4</sup>The Ludwig Center, Dana-Farber/Harvard Cancer Center, Boston, United States, <sup>5</sup>University Clinical Hospital “Santa Maria della Misericordia”, Udine, <sup>6</sup>Università Cattolica del Sacro Cuore, Rome, Italy</italic></p><p><bold>INTRODUCTION:</bold><italic>Helicobacter pylori </italic>(<italic>H. pylori</italic>) is proven to be group 1 carcinogen for gastric cancer. Prevention of <italic>H. pylori</italic> infection and <italic>H. pylori</italic> eradication are the most effective way to prevent gastric cancer.</p><p><bold>AIMS&METHODS:</bold> The aim of this study is to identify the clinical, demographic, environmental factors and selected genetic polymorphisms that might affect the susceptibility towards <italic>H.pylori </italic>infection. Histological confirmed gastric adenocarcinoma cases that underwent curative gastrectomy between 2002-2012 were included. Gastric biopsy samples were obtained to determine the <italic>H. pylori </italic>status. If <italic>H.pylori</italic> was present, <italic>cagA</italic> and <italic>vacA</italic> genotypes were identified using polymerase chain reaction. Patients were interviewed with structured questionnaires. Proportions were compared in univariate analysis, while the relation between <italic>H. pylori</italic> positivity and putative risk factors were measured using logistic regression analysis.</p><p><bold>RESULTS:</bold> One hundred forty-nine gastric cancer patients were included in the study, of which 78,5% were HP+, 50% <italic>cagA</italic>+, 72,5% <italic>vacA</italic> m1, 80,7 % <italic>vacA</italic> s1. The presence of <italic>cagA</italic> was determined less frequent among <italic>vacA</italic> m1 (p=0.031) and <italic>vacA</italic> s1 (p=0.052) subtypes. The presence of father history for any cancer was a significant risk factor for <italic>H.pylori </italic>infection [adjusted odds ratio (OR): 8.18, 95% confidence interval (CI): 1.04-64.55]. <italic>EPHX1 </italic>exon 3 T>C (OR: 0.35, CI 95%: 0.13-0.94), IL1B-511 T>C (OR: 0.38, CI 95%: 0.15-0.97) and <italic>IL1-RN VNTR</italic> (OR: 0.19, CI 95%: 0.06-0.58) polymorphisms were protective for <italic>H.pylori</italic> infection in the univariate analysis. Wine consumption was associated with higher risk of carrying the <italic>H.pylori vacA</italic> m1 virulent subtype (p=0.034). Lastly, cardiovascular diseases were less common among <italic>cagA</italic> positive subjects (p=0.023).</p><p><bold>CONCLUSION:</bold> Father history of any cancer appears to be a risk factor for <italic>H.pylori</italic> infection. Additional larger studies are needed to confirm our results.</p><p><bold>Contact E-mail Address:</bold><email>nikola.panicmail@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Family history, Gastric cancer, Gene polymorphism, Helicobacter pylori</p></sec><sec><title></title><p><bold>TUESDAY, OCTOBER 15, 2013 8:30-10:30</bold></p><p><bold>Beneficial and detrimental effects of bacteria in the GI tract – Hall 10</bold></p></sec><sec><title>OP185 RUMINOCOCCUS GNAVUS, BACTERIODES VULGATES AND CLOSTRIDIUM PERFRINGENS PREDICT POUCHITIS FOLLOWING COLECTOMY AND IPAA IN ULCERATIVE COLITIS</title><p><bold>K. Machiels</bold><sup>1,*</sup>, L. Vandermosten<sup>1</sup>, M. Joossens<sup>2</sup>, I. Arijs<sup>1</sup>, I. Terrasson<sup>1</sup>, V. Ballet<sup>1</sup>, M. Ferrante<sup>1</sup>, J. Verhaegen<sup>1</sup>, A. De Buck Van Overstraeten<sup>1</sup>, A. Wolthuis<sup>1</sup>, A. D'Hoore<sup>1</sup>, P. Rutgeerts<sup>1</sup>, S. Vermeire<sup>1</sup></p><p><italic><sup>1</sup>University Hospital Leuven, Leuven, <sup>2</sup>VIB-Vrije Universiteit Brussel, Brussels, Belgium</italic></p><p><bold>INTRODUCTION:</bold> Pouchitis is the most common complication after colectomy with ileal pouch anal anastomosis (IPAA) for ulcerative colitis (UC). The cumulative risk to develop pouchitis is approximately 50% and is the highest within the first year after surgery. The pathogenesis of pouchitis is not completely understood but altered gut microbiota has been proposed to play a dominant role.</p><p><bold>AIMS&METHODS:</bold> We hypothesized that the risk for pouchitis following IPAA can be predicted based on differences in the fecal microbial composition before colectomy. 17 fecal samples before colectomy were obtained from patients who are included in a prospective study with clinical and endoscopic assessment at predefined time points: at month 1 (N<sub>pouchitis</sub>=2; N<sub>normal pouch</sub>=15), month 3 (N resp 4;12), month 6 (N=3;9) and month 12 (N=3;5). After bacterial DNA extraction, the predominant microbiota was analyzed using denaturing gradient gel electrophoresis (DGGE) analysis. Sequencing of purified bands was done to identify species. Kaplan–Meier log-rank testing was performed to study occurrence of pouchitis with respect to presence and absence of the identified species and Partial Least Squares Discriminant Analysis (PLS-DA) to cluster microbial profiles.</p><p><bold>RESULTS:</bold> PLS-DA showed clustering of patients with pouchitis and with normal pouches during the first year of follow up, based on similar microbial profiles before colectomy. DGGE analysis identified an increase of <italic>Rumminococcus gnavus </italic>(p=0.017)<italic>, Bacteroides vulgates</italic> (p=0.027) and <italic>Clostridium perfringens</italic> (p=0.012) before colectomy in patients developing pouchitis compared to patients with normal pouches. The cumulative risk for pouchitis one year following IPAA was clearly increased in patients where <italic>R. gnavus</italic>, <italic>B. vulgates</italic>, <italic>C. perfringens </italic>were present before colectomy (75%, 67%, and 100% resp) in contrast to absence of the species (0%, 40%, 38% resp; p=0.011, p=0.086, p=0.003). A combination of 2 or more species increased the risks even to 100%.</p><p><bold>CONCLUSION:</bold> Predominant presence of <italic>R. gnavus, B. vulgates </italic>and <italic>C. perfringens </italic>in fecal samples of UC patients before surgery is associated with a higher risk of pouchitis within the first year after IPAA. <italic>R. gnavus</italic> is a dominant commensal species expressing β-glucuronidase activity. Both <italic>B. vulgates</italic>, an inducer of experimental colitis and <italic>C. perfringens</italic> have been associated with inflammatory bowel disease. Our findings shed new light on the etiology of pouchitis and may lead to new predictive and therapeutic strategies.</p><p><bold>Contact E-mail Address:</bold><email>kathleen.machiels@med.kuleuven.be</email></p><p><bold>Disclosure of Interest</bold>: K. Machiels: None Declared, L. Vandermosten: None Declared, M. Joossens: None Declared, I. Arijs: None Declared, I. Terrasson: None Declared, V. Ballet: None Declared, M. Ferrante Financial support for research from: Janssen Biologics, Lecture fee(s) from: Merck, Tilotts, Ferring, Abbvie, Consultancy for: Abbvie, Merck, Janssen Biologics, J. Verhaegen: None Declared, A. De Buck Van Overstraeten: None Declared, A. Wolthuis: None Declared, A. D'Hoore: None Declared, P. Rutgeerts Financial support for research from: UCB Pharma, Abbvie, Janssen Biologics, Merck, Prometheus, Lecture fee(s) from: Abbvie, Merck, Consultancy for: Amgen, Merck, UCB Pharma, Genentech, BMS, Abbvie, Janssen Biologics, Millenium, Neovacs, Actogenics, Prometheus, S. Vermeire Financial support for research from: UCB Pharma, MSD, Abbvie, Lecture fee(s) from: Abbvie, Merck, Ferring, UCB Pharma, Centocor, Consultancy for: UCB Pharma, AstraZeneca, Ferring, Abbvie, Merck, Ferring, Shire, Pfizer</p><p><bold>Keywords:</bold> Bacteroides vulgates, Clostridium perfringens, Pouchitis, Ruminococcus gnavus</p></sec><sec><title>OP186 FECAL MICROBIOTA TRANSPLANTATION (FMT) ERADICATES CLOSTRIDIUM DIFFICILE INFECTION (CDI) IN INFLAMMATORY BOWEL DISEASE (IBD)</title><p><bold>T. J. Borody</bold><sup>1,*</sup>, A. Wettstein<sup>1</sup>, A. Nowak<sup>1</sup>, S. Finlayson<sup>1</sup>, S. Leis<sup>1</sup></p><p><italic><sup>1</sup>Department of Research and Innovation, Centre for Digestive Diseases, Sydney, Australia</italic></p><p><bold>INTRODUCTION:</bold> The incidence of CDI has doubled in recent years, with an estimated 500,000 new cases per year in the US<sup>1</sup>. IBD patients are particularly susceptible to superimposed CDI and associated complications, with over 50% of infections resulting in hospitalisation and 20% in colectomy<sup>2</sup>. With traditional antibiotic therapies increasingly recognised as ineffective<sup>3</sup>, FMT has emerged as a safe and effective therapy for non-IBD CDI, with an eradication rate of 90-100%<sup>4</sup>, however there are only few reports of FMT use in IBD CDI.</p><p><bold>AIMS&METHODS:</bold> This study aimed to determine the safety and efficacy of FMT for CDI in IBD patients, and to examine the effect of successful eradication on IBD disease state.</p><p>A retrospective review was conducted of 28 patients (11F, m 36±18.1 yrs; 17M, m 31±16 yrs) with diagnosed IBD who had undergone FMT for CDI eradication. At time of FMT, 12 patients had Crohn’s disease (CD) and 16 had ulcerative colitis (UC), with two UC patients subsequently deemed CD. Infusion regimes varied between single infusions (36%), two-day infusions (18%) and regimens of more than 2 days duration (46%). Patients were not required to cease immunosuppressive medications. Initial post-FMT ‘remission’ was defined as >3 months improvement in disease state with stable or reducing medication. Prolonged remission was defined as the absence of active disease for ≥3 years for UC and ≥5 years for CD.</p><p><bold>RESULTS:</bold> CDI was successfully eradicated in 89.3% (25/28) of cases. No adverse effects of FMT were recorded and no patients required hospitalisation as a result of any FMT complications. Initial ‘remission’ of IBD was noted in 60.7% (17/28) of cases, with prolonged remission achieved in 23.5% of these (4/17). There was no improvement of IBD symptoms in 9/28 patients.</p><p><bold>CONCLUSION:</bold> FMT eradicates CDI in almost 90% of IBD patients, equivalent to eradication rates for FMT in non-IBD patients and notably higher than those of standard antibiotic therapy. FMT is also safe for use in this vulnerable and frequently immunosuppressed IBD population. CDI eradication was associated with improved disease state in 60.7% of cases, with the longest cases of remission lasting up to 3-5 years.</p><p><bold>REFERENCES:</bold></p><p>1. Bakken JS <italic>et al</italic>. <italic>Clin Gastroenterol Hepatol</italic> 2011; 9:1044-9</p><p>2. Issa M <italic>et al</italic>. <italic>Inflamm Bowel Dis</italic> 2008; 14:1432-42</p><p>3. van Nood E <italic>et al. NEJM</italic> 2013; 368:407-415</p><p>4. Brandt LJ <italic>et al</italic>. <italic>J Clin Gastroenterol</italic> 45(8):655-657</p><p><bold>Contact E-mail Address:</bold><email>anna.nowak@cdd.com.au</email></p><p><bold>Disclosure of Interest</bold>: T. Borody Directorship(s) for: Professor Borody has a pecuniary interest in the Centre for Digestive Diseases, where fecal microbiota transplantation is a treatment option, Other: Professor Borody holds patents in the field of fecal microbiota transplantation, A. Wettstein : n/a, A. Nowak : n/a, S. Finlayson : n/a, S. Leis : n/a</p><p><bold>Keywords:</bold> Clostridium difficile infection, crohn's disease, Fecal microbiota transplantation, Inflammatory bowel disease (IBD), ulcerative colitis</p></sec><sec><title>OP187 PRELIMINARY CLINICAL RESULTS OF REPEATEDLY FECAL MICROBIOTA TRANSPLANTATION (FMT) IN CHRONIC ACTIVE ULCERATIVE COLITIS.</title><p><bold>P. K. Kump</bold><sup>1,*</sup>, H. P. Gröchenig<sup>2</sup>, W. Spindelböck<sup>1</sup>, C. M. Hoffmann<sup>3</sup>, G. Gorkiewicz<sup>4</sup>, H. Wenzl<sup>1</sup>, W. Petritsch<sup>1</sup>, G. Reicht<sup>5</sup>, C. Hoegenauer<sup>1</sup></p><p><italic><sup>1</sup>Clinical Department of Gastroenterology, UNIVERSITY HOSPITAL GRAZ, Graz, <sup>2</sup>Dept. of Internal Medicine, Convent Hospital , St. Veith, <sup>3</sup>Dept. of Pediatrics, UNIVERSITY HOSPITAL GRAZ, <sup>4</sup>Institute of Pathology, University Graz, <sup>5</sup>Dept. of Internal Medicine, Convent Hospital, Graz, Austria</italic></p><p><bold>INTRODUCTION:</bold> As dysbiosis plays a pivotal role in the pathogenesis of IBD, fecal microbiota transplantation (FMT) has been investigated to be a therapeutic tool in chronic active ulcerative colitis (UC). In a previous pilot study we demonstrated that FMT by a protocol with a single endoscopic application of donor stool in the right colon without prior antibiotic therapy, revealed disappointing clinical results in patient with therapy refractory UC. The aim of this study was to investigate if a protocol using repeated FMT after prior antibiotic therapy is more effective in the treatment of chronic active UC.</p><p><bold>AIMS&METHODS:</bold> 9 patients with chronic active UC were included in the study for repeated FMT. After antibiotic triple therapy for 10 days, patients received filtered and diluted stool of a healthy volunteer in the right colon via colonoscope. FMT was repeated in 14 days intervals for a total of 5 applications. The repeated applications were performed by sigmoidoscopy in the left colon. Clinical efficacy was assesses by the mayo score. Furthermore disease activity was also measured by fecal calprotectin, and by endoscopy. The follow up of the patients were 90 days.</p><p><bold>RESULTS:</bold> 5/9 patients showed a reduction of the Mayo score for <italic>></italic> 3 points 90 days after the first FMT. One patient demonstrated a sustained mucosal healing at day 90. 4/9 failed a sustained clinical improvement, however, 2 of them missed one of the 5 FMTs. None of the patients suffered any severe adverse events.</p><p><bold>CONCLUSION:</bold> These preliminary clinical data show a positive effect of repeated FMT after antibiotic pretreatment in chronic active UC. In contrast to recurrent <italic>C. difficile</italic> colitis repeated administration of FMT seems to be superior to a single FMT in the case of treatment of chronic active UC.</p><p><bold>Contact E-mail Address:</bold><email>patrizia.kump@medunigraz.at</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Clinical efficacy, Fecal microbiota transplantation, stool transplantation, ulcerative colitis</p></sec><sec><title>OP188 EFFICACY OF PROFERMIN® IN PATIENTS WITH ACTIVE ULCERATIVE COLITIS – A RANDOMISED CONTROLLED TRIAL</title><p><bold>A. Krag</bold><sup>1,*</sup>, P. Munkholm<sup>2</sup>, H. Israelsen<sup>3</sup>, B. V. Ryberg<sup>3</sup>, K. K. Andersen<sup>4</sup>, F. Bendtsen<sup>5</sup></p><p><italic><sup>1</sup>Odense University Hospital, Odense, <sup>2</sup>Gastroenterology Unit, Medical Section,, Herlev University Hospital, Copenhagen, <sup>3</sup>Nordisk Rebalance, Allerød, <sup>4</sup>Danish Cancer Society Research Center, <sup>5</sup>Hvidovre University Hospital, Copenhagen, Denmark</italic></p><p><bold>INTRODUCTION:</bold> Profermin® is developed for the dietary management of ulcerative colitis (UC), it consists of water, fermented oats, barley malt, lecithin and Lactobacillus plantarum 299v. In a previous study (CUPE-1), Profermin® was safe and showed a promising clinical effect in patients with active UC.</p><p><bold>AIMS&METHODS:</bold> The aim of this study was in a randomized trial to assess the clinical efficacy of Profermin®. The study included 74 patients who were randomly assigned to Profermin® (n=32) or Fresubin® (n=41), a comparator with a similar nutritional content. Patients with a flare-up of UC (defined as SCCAI score <italic>></italic>5 and <italic><</italic> 11) were followed for 8 weeks with daily Simple Clinical Colitis Activity Index (SCCAI). SSCAI was reported on a daily basis observer blinded via the Internet. The primary end point of the study was to assess, whether addition of Profermin® in UC to patients who were already under treatment with 5-aminosalicylic acid (ASA) and / or immunosuppressant’s at stable doses or in tapering of systemic corticosteroids, significantly could reduce SCCAI in comparison with Fresubin®.</p><p><bold>RESULTS:</bold> After 8 weeks treatment, the primary endpoint, the difference in SCCAI score was lower in the Profermin® group, mean difference -1.77 SCCAI, 95% confidence interval (CI) (-2.97;-0.55), p<0.005, in intention to treat analyses. Remission defined as (SCCAI≤ 2.5) was achieved in 10/32 (31 %) in the Profermin® group and in 6/41 (15 %) in the Fresubin® group, p=0.048. The decrease in SCCAI scores of 50% or more was higher in the Profermin® group 17/32 (53%) vs. 11/41 (27%), p=0.04. The risk of dropping out due to treatment failure/lack of effect was higher in the Fresubin® group 18/41 (44%) vs. 2/32 (6%), p<0.01. The overall risk of dropping out when treated with Fresubin® was higher, Hazard Ratio 4.48 95% CI (1.51-13.28), p<0.01.</p><p><bold>CONCLUSION:</bold> Supplementation with Profermin® is safe, palatable and able to reduce SCCAI scores at a clinically significant level in patients with mild-to-moderate UC with a flare-up.</p><p><bold>Contact E-mail Address:</bold><email>aleksander.krag@rsyd.dk</email></p><p><bold>Disclosure of Interest</bold>: A. Krag Consultancy for: Nordisk Rebalance, P. Munkholm: None Declared, H. Israelsen Shareholder of: Nordisk Rebalance, Other: Employee, B. Ryberg Shareholder of: Nordisk Rebalance, Other: Employee, K. Andersen: None Declared, F. Bendtsen: None Declared</p><p><bold>Keywords:</bold> dietary management, probiotic, Ulcerative colitis</p></sec><sec><title>OP189 THE BENEFICIAL EFFECT OF MULTIPROBIOTIC “SYMBITHER ACIDOPHILIC” ON CEFTRIAXONE-INDUCED INFLAMMATION IN RAT COLON</title><p><bold>A. Putnikov</bold><sup>1</sup>, T. Furzikova<sup>1</sup>, I. Vareniuk<sup>1</sup>, M. Rudyk<sup>1</sup>, V. Pozur<sup>1</sup>, V. Svyatetska<sup>1</sup>, N. Roslova<sup>1</sup>, T. Dovbynchuk<sup>1</sup>, L. Zakordonets<sup>2</sup>, L. Skivka<sup>1</sup>, M. Dzerzhynsky<sup>1</sup>, T. Beregova<sup>1</sup>, L. Ostapchenko<sup>1</sup>, G. Tolstanova<sup>1,*</sup></p><p><italic><sup>1</sup>Educational-Scietific Center "Institute of Biology, Kiev National Taras Shevchenko University, <sup>2</sup>Bogomolets National Medical University, Kiev, Ukraine</italic></p><p><bold>INTRODUCTION:</bold> Accordingly recent epidemiological studies antibiotic treatment can increase susceptibility to inflammatory bowel disease development [1, 2].</p><p><bold>AIMS&METHODS:</bold> In present study we tested the hypothesis that antibiotic-treatment may result in intestinal barrier disruption and inflammation development, while treatment with multiprobiotic may prevent these changes. Study was done on male Wistar rats (180-230 g). The broad-spectrum cephalosporin antibiotic ceftriaxone (Cf) (50 mg/kg, i.m.) were injected daily for 14 days. Symbiter (0.16 ml/kg, per os) was injected daily via 4 hr after Cf administration. Rats were euthanized in 1 day after Cf withdrawal. The parietal microflora was analyzed by bacteriological culture methods. Histologic changes of colonic epithelial was assessed by morthometric analysis, mucus secretion – by Alcian blue staining. Oxidative metabolism, arginine metabolism by NO-production (Griess reaction) and arginase activity by colorimetric method were measured in peritoneal macrophages.</p><p><bold>RESULTS:</bold> Cf treatment induced appearing of <italic>Clostridium spp</italic>. (lg 0.5±0.1 CFU/cm<sup>2</sup>) in parietal microflora and increased number of lactose(-) <italic>E.coli</italic> (from lg 0.5±0.1 to lg 3.0±0.1 CFU/cm<sup>2</sup>). These changes were accompanied by increase number (p<0.05) and hypertrophy of Goblet cells, edema and leukocyte infiltration in the colonic mucosa. Moreover, Cf increased the oxidative metabolism by 64%, decreased NO production and arginase activity levels in peritoneal macrophages. It resulted in depletion of macrophages functional reserve. Combined administration of Symbiter with Cf prevented the colonization of colonic parietal mucosa by <italic>Clostridium spp.</italic> It was also accompanied by decrease in Goblet cells hypertrophy and hyperplasia, attenuation of edema and prevention of leukocyte infiltration in colonic mucosa. The level of spontaneous macrophages oxidative metabolism was 48%. The cells were characterized by the presence of functional reserve and recovered arginine metabolism.</p><p><bold>CONCLUSION:</bold> Systemic administration of ceftriaxone induced pro-inflammatory changes in rat colon. Administration of multiprobiotic “Symbiter acidophilic” along with Cf prevented the antibiotic-induced intestinal barrier disruption, colonic inflammation and peritoneal macrophages activation.</p><p><bold>REFERENCES:</bold></p><p>1. Kronman MP, Zaoutis TE, Haynes K, Feng R, Coffin SE. Antibiotic exposure and IBD development among children: a population-based cohort study. Pediatrics. 2012;130(4):e794-803.</p><p>2. Shaw SY, Blanchard JF, Bernstein CN. Association between the use of antibiotics in the first year of life and pediatric inflammatory bowel disease. Am J Gastroenterol. 2010;105(12):2687-92.</p><p><bold>Contact E-mail Address:</bold><email>gtolstanova@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> ceftriaxone, colon, inflammation, probiotics</p></sec><sec><title>OP190 SPECIFIC CLUSTERING OF KLEBSIELLA OXYTOCA ISOLATES CAUSING ANTIBIOTIC-ASSOCIATED HEMORRHAGIC COLITIS DETECTED BY A NOVEL MULTILOCUS SEQUENCE TYPING SCHEME</title><p><bold>K. A. T. Herzog</bold><sup>1,2,*</sup>, G. Schneditz<sup>2</sup>, G. Gorkiewicz<sup>3</sup>, R. Krause<sup>1</sup>, E. Leitner<sup>4</sup>, G. Feierl<sup>4</sup>, K. M. Hoffmann<sup>5</sup>, E. L. Zechner<sup>2</sup>, C. Högenauer<sup>1</sup></p><p><italic><sup>1</sup>Department of Internal Medicine, Medical University of Graz, <sup>2</sup>Institute of Molecular Biosciences, University of Graz, <sup>3</sup>Institute of Pathology, <sup>4</sup>Institute of Microbiology and Environmental Medicine, <sup>5</sup>Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria</italic></p><p><bold>INTRODUCTION:</bold><italic>Klebsiella oxytoca </italic>is an opportunistic pathogen and causes diseases like antibiotic-associated hemorrhagic colitis (AAHC) and nosocomial pneumonia. The latter is thought to be caused by strains originating from the intestine. A subgroup of <italic>K. oxytoca </italic>isolates produces a non-ribosomal cytotoxic peptide, which induces colitis in AAHC and is absent from other <italic>Klebsiella spp</italic>. Previous attempts to assess the genetic relatedness of K. oxytoca isolates using typing methods such as pulsed field gel electrophoresis were not successful in discriminating different subtypes. To move forward we established a novel multilocus sequence typing (MLST) for <italic>K. oxytoca</italic>.</p><p><bold>AIMS&METHODS:</bold> 56 clinical <italic>K. oxytoca</italic> isolates - obtained predominantly from patients with AAHC and pneumonia - were analyzed with the here developed MLST scheme. The sequences of seven loci were compared and a new sequence type (ST) was assigned to each distinct allelic profile.</p><p><bold>RESULTS:</bold> The MLST scheme successfully typed all clinical isolates yielding 42 STs. 6 of the 42 STs were represented by more than one isolate and different toxigenicity within one ST was observed. Consistent with that finding, no clustering of toxin-positive isolates in the phylogeny could be seen. Instead, <italic>K. oxytoca </italic>isolates clustered according to habitat (intestinal vs. respiratory tracts) and to disease state (AAHC vs. other infections).</p><p><bold>CONCLUSION:</bold> Our findings indicate that the <italic>K. oxytoca </italic>cytotoxin has polyphyletic origin. Indeed, organization of the toxin producing genes suggests lateral acquisition. In summary, AAHC isolates share a common genetic background, which could be caused by a niche adaptation to the intestinal tract. Interestingly, <italic>K. oxytoca </italic>isolates from pneumonia patients showed a different genetic clustering, suggesting that these strains have special adaptation for respiratory tract colonization or do not originate from the intestine.</p><p><bold>Contact E-mail Address:</bold><email>christoph.hoegenauer@medunigraz.at</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> colitis, horizontal gene transfer, klebsiella oxytoca, multilocus sequence typing, nosocomial infection, phylogenetic</p></sec><sec><title>OP191 STAT3 ACTIVATION IN CD4+ T CELLS, BUT NOT CD4+ ILCS PREVENTS FROM BACTERIAL SPREAD DURING INFECTIOUS COLITIS</title><p><bold>I. Backert</bold><sup>1</sup>, S. Wirtz<sup>1</sup>, K. Hildner<sup>1</sup>, K. Floh<sup>1</sup>, M. F. Neurath<sup>1</sup>, C. Becker<sup>1</sup>, C. Neufert<sup>1,*</sup></p><p><italic><sup>1</sup>First Department of Medicine, FRIEDRICH-ALEXANDER-UNIVERSITÄT ERLANGEN-NÜRNBERG, Erlangen, Germany</italic></p><p><bold>INTRODUCTION:</bold> Compromised intestinal barrier function renders individuals susceptible to enteropathogenic bacteria, and genome wide association studies have linked STAT3 to intestinal inflammation. The <italic>Citrobacter rodentium </italic>model mimics the pathogenesis of colonic inflammation by enteropathogenic bacteria and the clearance of <italic>C. rodentium </italic>requires contributions from different immune cell populations including innate lymphoid cells (ILCs, during the early phase) and T cells (during the late phase).</p><p><bold>AIMS&METHODS:</bold> The role of STAT3 activation in CD4+ innate and adaptive immune cells during host defense against enteropathogenic bacteria has not been clarified yet. To address that topic, we have studied the course of infection with <italic>C. rodentium</italic> with different genetically modified mice and serial in vivo analyses by bioluminescence imaging and mini-endoscopy as well as immunomonitoring by flow cytometry. In addition, a novel minicircle-vector based expression system was applied for investigations into differential contributions of STAT3 dependent effector functions mediated by CD4+ cells.</p><p><bold>RESULTS:</bold> Defective STAT3 signaling in CD4+ cells caused high susceptibility to <italic>C. rodentium</italic> including increased bacterial transmission across the colon mucosa and systemic distribution suggesting a marked loss of intestinal barrier function. Interestingly, the molecular mechanisms could be attributed to functionally defective T cells which were unable to initiate sufficient crosstalk to IECs. Moreover, mice with constitutive activation of STAT3 in CD4+ cells induced high levels of numerous antimicrobial effector molecules in IECs and were strongly protected from enteropathogenic bacteria. In contrast, STAT3 was dispensable for the host defense against <italic>C. rodentium</italic> by CD4+ innate lymphoid cells during the early phase.</p><p><bold>CONCLUSION:</bold> Our work indicates a crucial contribution of STAT3 activation in CD4+ T cells, but not CD4+ ILCs for the host protection and colonic barrier function during infectious colitis. Thus, our data suggest approaches specifically elevating STAT3 activation in CD4+ T cells may serve as future therapeutic options for infections with enteropathogenic bacteria.</p><p><bold>Contact E-mail Address:</bold><email>clemens.neufert@uk-erlangen.de</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> infectious colitis, STAT3</p></sec><sec><title>OP192 MUCOSAL PHOSPHTIDYLCHOLINE AND LYSOPHOSPHATIDYLCHOLINE CONCENTRATIONS ARE REDUCED IN SEPSIS INDUCED MUCOSAL BARRIER DYSFUNCTION</title><p><bold>C. Schmidt</bold><sup>1,2,*</sup>, C. Lautenschläger<sup>1</sup>, A. Gauss<sup>3</sup>, O. Huber<sup>4</sup>, W. Stremmel<sup>3</sup>, A. Stallmach<sup>1</sup></p><p><italic><sup>1</sup>Clinic of Internal Medicine IV, <sup>2</sup>Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), UNIVERSITY Hospital JENA, Jena, <sup>3</sup>Clinic of Internal Medicine IV, University Clinic Heidelberg, Heidelberg, <sup>4</sup>Institute of biochemistry II, UNIVERSITY Hospital JENA, Jena, Germany</italic></p><p><bold>INTRODUCTION:</bold> Disturbances of microcirculation of the gastrointestinal tract give rise to bacterial translocation and are one of the main causes of sepsis. Intestinal mucus overlying epithelial cells is one of the main components of intestinal barrier integrity. We speculate that during sepsis a degradation of the extracellular protective phospholipid layer is associated with an increased GI permeability.</p><p><bold>AIMS&METHODS:</bold> Sepsis in mice was induced by peritoneal contamination and infection. Animals were sacrificed 6 and 24 h after induction of sepsis, resp. Nano-electrospray ionization tandem mass spectrometry (ESI-MS/MS) was used to determine phosphtidylcholine <bold>(</bold>PC) and lysophosphtidylcholine (LPC) in lipid extracts of colonic mucus specimens. Mucosal barrier function was evaluated in miniaturized Ussing chambers by quantification of translocation of nanoparticles and microparticles across the colonic wall. Using Western-Blot analysis we quantified concentrations of different colonic tight junctions (TJ)-proteins.</p><p><bold>RESULTS:</bold> Six and 24 hours after induction of sepsis the disease score increased significantly. PC and lyso-PC concentrations were significantly reduced in sepsis compared to healthy controls (PC: 6094 +/- 2112 pmol/100 µg protein vs. 17650 +/- 3382 pmol/100 µg protein; p=0,0125; lyso-PC: 765 +/- 259 pmol/100 µg protein vs. 1725 +/- 337 pmol/100 µg protein; p=0,0266; combined data). In Ussing chamber experiments we observed a significantly increased translocation of FITC dextrane 4kDa and FITC dextrane 70kDa, corresponding to 1 and 4 nm size, resp., while translocation of nanoparticles (300nm) and microparticles (3 µm) was unchanged. Moreover, after 24 h we observed a significantly increased translocation of LPS after sepsis induction. Concentrations of claudin-4 and occludin were significantly reduced in septic animals (by 50% and 55%, resp.; p<0,05).
<table-wrap id="table27-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1"></th><th rowspan="1" colspan="1">Time [h]</th><th rowspan="1" colspan="1">Sham</th><th rowspan="1" colspan="1">Sepsis</th><th rowspan="1" colspan="1">p</th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">FITC dextrane 4kDa</td><td rowspan="1" colspan="1">6</td><td rowspan="1" colspan="1">23.2 +/- 4.6</td><td rowspan="1" colspan="1">44.3 +/- 10.3</td><td rowspan="1" colspan="1">< 0.001</td></tr><tr><td rowspan="1" colspan="1">FITC dextrane 4kDa</td><td rowspan="1" colspan="1">24</td><td rowspan="1" colspan="1">20.4 +/- 34.9</td><td rowspan="1" colspan="1">321.6 +/- 56.7</td><td rowspan="1" colspan="1">< 0.001</td></tr><tr><td rowspan="1" colspan="1">FITC dextrane 70kDa</td><td rowspan="1" colspan="1">6</td><td rowspan="1" colspan="1">0.4 +/- 0.1</td><td rowspan="1" colspan="1">0.5 +/- 0.2</td><td rowspan="1" colspan="1">0.016</td></tr><tr><td rowspan="1" colspan="1">FITC dextrane 70kDa</td><td rowspan="1" colspan="1">24</td><td rowspan="1" colspan="1">0.7 +/- 0.2</td><td rowspan="1" colspan="1">6.4 +/- 3.4</td><td rowspan="1" colspan="1">0.019</td></tr></tbody></table></table-wrap></p><p><bold>CONCLUSION:</bold> Reductions of mucosal PC and lyso-PC content are associated with a disturbance of mucosal barrier function in the early phase of sepsis. We speculate that these alterations of innate immunity may contribute to bacterial translocation. Studies using oral phosphatidylcholine gavage will be performed to evaluate the potential of PC to prevent or restore sepsis-induced mucosal damage and to potentially reduce translocation of intestinal pathogens.</p><p><bold>Contact E-mail Address:</bold><email>carsten.schmidt@med.uni-jena.de</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> mucosal barrier dysfunction, phosphatidylcholine, sepsis</p></sec><sec><title>OP193 ROLE OF MILK FAT GLOBULE-EPIDERMAL GROWTH FACTOR 8 DURING CITROBACTER RODENTIUM-INDUCED COLITIS IN MICE</title><p><bold>N. Oshima</bold><sup>1,*</sup>, S. Ishihara<sup>1</sup>, H. Sonoyama<sup>1</sup>, Y. Tada<sup>1</sup>, A. Oka<sup>1</sup>, R. Kusunoki<sup>1</sup>, N. Fukuba<sup>1</sup>, I. Moriyama<sup>1</sup>, T. Yuki<sup>2</sup>, K. Kawashima<sup>1</sup>, Y. Kinoshita<sup>1</sup></p><p><italic><sup>1</sup>Second Department of Internal Medicine, Shimane University School of Medicine, <sup>2</sup>Division of Gastrointestinal Endoscopy, Shimane University Hospital, Izumo, Japan</italic></p><p><bold>INTRODUCTION:</bold> Milk fat globule-epidermal growth factor-8 (MFG-E8) promotes phagocytic clearance of apoptotic cells to maintain normal tissue homeostasis and modulate immune responses. We recently reported that MFG-E8 also has protective and regenerating roles in colonic inflammation. However, its role in murine infectious colitis remains to be elucidated.</p><p><bold>AIMS&METHODS:</bold> We investigated the role of MFG-E8 in mice with infectious colitis. <italic>Citrobacter rodentium</italic> is a murine model pathogen for enteropathogenic <italic>Escherichia coli</italic> (EPEC), which colonizes the surface of intestinal epithelial cells and causes mucosal inflammation in the colon. <italic>C. rodentium</italic> was orally administered to induce colitis in 8-week-old female C57BL/6N wild type (WT) and MFG-E8 knockout (KO) mice. Colitis activity parameters (body weight, colon length, histological score) were determined in inflamed colon tissues obtained from the mice, while cytokine expression in colonic tissues was determined using real-time PCR, and levels of IL-17, IFN-γ, and IL-22 secreted by lamina propria mononuclear cells (LPMCs) or mesenteric lymph node (MLN) cells were determined with ELISA. Phagocytosis and bacterial killing assays were performed using bone marrow derived macrophages (BMMPhs) infected with <italic>C. rodentium</italic>.</p><p><bold>RESULTS:</bold> MFG-E8 KO mice were not protected against infection by <italic>C. rodentium</italic> as compared to the WT controls. MFG-E8 KO mice infected with <italic>C. rodentium</italic> had a higher bacterial burden in the intestine, and showed body weight loss and developed severe intestinal inflammation. Furthermore, LPMCs in those mice secreted higher levels of IL-22, IL-17, and IFN-γ as compared to LPMCs in the WT mice. MFG-E8-deficient BMMPhs were also less efficient in phagocytosis of <italic>C. rodentium</italic> and showed a lower bacterial load at 4 hours after infection.</p><p><bold>CONCLUSION:</bold> MFG-E8 protects mice from <italic>C. rodentium</italic> infection and may play an important role in defense against gut bacterial pathogens.</p><p><bold>Contact E-mail Address:</bold><email>n-oshima@med.shimane-u.ac.jp</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Citrobacter rodentium, milk fat globule-epidermal growth factor 8</p></sec><sec><title></title><p><bold>TUESDAY, OCTOBER 15, 2013 8:30-10:30</bold></p><p><bold>Nutrients, gut function and obesity – Hall 8</bold></p></sec><sec><title>OP194 INTRAGASTRIC GLUCOSE AND FRUCTOSE HAVE OPPOSING EFFECTS ON HUMAN BRAIN ACTIVITY</title><p><bold>L. Wasse</bold><sup>1</sup>, C. Bryant<sup>1</sup>, S. McKie<sup>2</sup>, J. McLaughlin<sup>3,*</sup></p><p><italic><sup>1</sup>GI Centre, <sup>2</sup>Neuroscience and Psychiatry Unit, University of Manchester, Manchester, <sup>3</sup>GI Centre, University of Manchester, Salford, United Kingdom</italic></p><p><bold>INTRODUCTION:</bold> Recent advances in physiological magnetic resonance imaging (physMRI) have made it possible to map activity in the areas of the brain that receive vagal inputs from the gut. We initially characterised the spatiotemporal responses to intragastric lipid using, showing significant CCK<sub>1</sub> receptor dependent increases in the blood oxygen level dependent (BOLD) signal in the anticipated brain regions such as the brain stem and hypothalamus (1,2). We recently found that unlike lipid, intragastric glucose decreases BOLD signal in the identical brain areas. It is unknown whether fructose, another monosaccharide, acts similarly to glucose (inhibition of BOLD) or more like lipid (stimulation of BOLD). This may be of key importance in understanding the effects of different nutrients on appetite and satiety, particularly since fructose is now a major contributor to the caloric excess driving the obesity epidemic.</p><p><bold>AIMS&METHODS:</bold> The aim was to assess the response of the human brain to glucose or fructose. 8 healthy human volunteers completed visits in randomised order. They attended after an overnight fast and underwent 30 minutes of physMRI acquisition (3.0T Philips scanner). After a 5 min baseline, participants received 250 mL of test solution (0.5M glucose, 0.5M fructose or a saline control) via nasogastric tube. Data were analysed using the p-block method with 2 min time-bins. Two one-way repeated measures ANOVAs were used to investigate regions within the brainstem and hypothalamus that showed significant differences for glucose 0.5M <italic>vs</italic> fructose 0.5M.</p><p><bold>RESULTS:</bold> There was a significant difference between 0.5M glucose and 0.5M fructose observed in key brain areas including the hypothalamus (P<0.05). The BOLD responses were similar until approximately 8 min. They diverged thereafter, with a progressive decrease in BOLD evident with 0.5M glucose, but a progressive increase following fructose, in a manner very similar to that observed following lipid.</p><p><bold>CONCLUSION:</bold> The results demonstrate that despite glucose and fructose being chemically similar, administration of a 0.5M dose of glucose or fructose elicits divergent BOLD responses in the brain areas controlling appetite and satiety. The precise mechanism is unknown but neurons may respond directly to glucose as the brain’s primary fuel (unlike fructose and lipid). Furthermore, fructose does not elicit the same glycaemic and neuroendocrine responses as glucose, so differential changes in blood glucose, insulin or gut hormones could partly explain the different response seen. Further work is required to understand the implications for appetite control in health and disease.</p><p><bold>REFERENCES:</bold></p><p>1. Lassman DJ <italic>et al</italic>. (2010). <italic>Gastroenterology</italic><bold>138</bold>, 1514 – 1524.</p><p>2. Jones RB <italic>et al</italic>. (2012) <italic>Gut</italic><bold>61</bold>, 1435 – 1551.</p><p>3. This work was funded by BBSRC.</p><p><bold>Contact E-mail Address:</bold><email>john.mclaughlin@manchester.ac.uk</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Brain Imaging, Gut-brain, Nutrient</p></sec><sec><title>OP195 ADIPONECTIN ANTAGONIZES LEPTIN-INDUCED HEPCIDIN EXPRESSION IN HUMAN LIVER CELLS. NEW INSIGHTS IN OBESITY ASSOCIATED IRON DEFICIENCY</title><p><bold>B. Fischer</bold><sup>1</sup>, D. Steinhilber<sup>2</sup>, S. Ulrich<sup>2</sup>, J. Stein<sup>3,*</sup></p><p><italic><sup>1</sup>University of Giessen, Giessen, <sup>2</sup>University of Frankfurt, <sup>3</sup>INTERDISZIPLINÄRES CROHN-COLITIS-CENTRUM RHEIN-MAIN, Frankfurt a.M., Germany</italic></p><p><bold>INTRODUCTION:</bold> Obesity is rapidly becoming a pandemic and is associated with increased prevalence of iron deficiency anemia (IDA). Obese populations have higher circulating levels of leptin in contrast to low concentrations of adiponectin. Hence, it is important to evaluate the dynamic role between adiponectin and leptin in obesity-related IDA.</p><p><bold>AIMS&METHODS:</bold> Since leptin shares a number of common biological features with IL-6, a major factor in the development of the anemia of chronic disease (ACD), we speculated that leptin and its metabolic counter part adiponectin might play a role in regulating iron metabolism in the overweight population.The human hepatoma cells HuH7 and Hep G2 were exposed to IL-6 [10-50ng/ml], Leptin [0,1-10µg/ml] and adiponectin [5µg/ml] for 16h. mRNA expression was determined using real-time quantitative RT-PCR, protein levels were detected by western blot analysis. Both cell lines were also transfected with a hepcidin promoter–luciferase reporter gene construct to investigate transcriptional regulation of hepcidin.</p><p><bold>RESULTS:</bold> Similar to IL-6 (***p<0.001), Leptin leads to a significant dose-dependent increase of Hepcidin promoter activity (***p<0.001) in both cell lines, which further resulted in elevated mRNA-levels. The activation of transcription factor STAT3 thereby seems to be a crucial event which was further confirmed with specific STAT3-Inhibitor S3I201 [50µM] (***p<0.001). Furthermore we could show for the first time, that adiponectin completely abolished leptin effects on hepcidin promoter activation (***p<0.001 in HepG2, *p<0.05 in Huh7).</p><p><bold>CONCLUSION:</bold> Collectively, these data provide a novel insight into the molecular linkage between obesity and IDA and further demonstrate that adiponectin has the molecular potential to inhibit the leptin induced hepcidin expression.</p><p><bold>Contact E-mail Address:</bold><email>j.stein@em.uni-frankfurt.de</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> adiponectin, iron deficiency, OBESITY</p></sec><sec><title>OP196 VARIOUS HIGH-FRUCTOSE DIETS AS MODEL OF NASH AND INSULINO RESISTANCE IN WISTAR RATS: 60% OR 20% FRUCTOSE INDUCES SOME SIMILAR EARLY CHANGES. A LIVER STUDY BY SPECTROSCOPIC NMR.</title><p><bold>M.-C. Beauvieux</bold><sup>1,*</sup>, J. Naulin<sup>1</sup>, A.-K. Bouzier-Sorre<sup>1</sup>, T. Sumessur<sup>1</sup>, D. El Hamrani<sup>1</sup>, H. Gin<sup>2</sup>, J.-L. Gallis<sup>1</sup></p><p><italic><sup>1</sup>RMSB UMR5536, CNRS-UNIVERSITÉ BORDEAUX2, <sup>2</sup>Nutrition, CHU Bordeaux, BORDEAUX, France</italic></p><p><bold>INTRODUCTION:</bold> High-fructose diet (HF) is used in rodents to induce insulin resistance (IR) and offers a NASH model [1]. Half of the publications reported a 60% HF diet in contrast to a 10-20% one in the other half, this later being closer to a Western diet. Much diets inducing obesity (“high-fat”) include both lipids and sucrose (glucose+fructose). The increased human consumption of high-fructose corn syrup is linked with the prevalence of overweight [2]. Non-alcoholic fatty liver disease patients often have high fructose supply (soft drinks) [3]. Some disparate findings concern the stimulation of liver lipogenesis by fructose [4]. Liver metabolic profile was studied by <sup>1</sup>H HRMAS NMR in rat fed with 60% or 20% HF, besides morphometric and blood measurements.</p><p><bold>AIMS&METHODS:</bold> 7wks-old male Wistar rats were pair-fed (6wks) with isocaloric diets. Control (Ct): standard chow; HF60: 60% fructose instead of starch (SAFE) in solid diet + drinking water; HF20: 20% fructose (Sigma) in drinking water + a standard solid chow. Body weight (BW), consumed food and beverage, were measured. Before sacrifice, blood was withdrawal. A piece for histology was removed before livers freeze-clamping (N<sub>2</sub>). Intraabdominal (IA) fat was weighted. <sup>1</sup>H HRMAS was performed on 20mg liver (Brucker AVANCE500 11.7T; 6min acquisition).</p><p><bold>RESULTS:</bold> Pair-feeding was chosen to induce IR without obesity. Surprisingly, for a similar caloric intake, fructose induced a lower BW <italic>vs</italic> Ct (-14% HF60, -10% HF20), whereas the percentage of IA fat tended to increased. HF60 induced IR (normoglycaemia + hyperinsulinemia) from 3wks, and a macro- and microsteatosis and liver inflammation at 6wks, these impairments being lesser in HF20. In all groups, ALAT remained normal. By HRMAS, the content of fatty acids increased both in HF60 (+42±5.3%) and HF20 (+44±6%) <italic>vs</italic> Ct. Choline/Pcholine ratio was higher <italic>vs</italic> Ct (+46% in HF60 and +33% in HF20).</p><p><bold>CONCLUSION:</bold> For a similar caloric intake, a lower BW besides a higher IA adiposity evidenced a different metabolic yield even with only HF20 during a short period. The increase in the liver fatty acids content occurred whatever the dose. Moreover, whereas morphological or histological changes are less marked in HF20, the Chol/Pchol ratio was modified in the same proportion than in HF60, and should be an early metabolic marker. Chol and Pchol measured by HRMAS represent free fractions in dynamic exchange with membranes and their variations depict early membranes changes which could explain later functional impairments occurring in a Western diet. IREB Grants.</p><p><bold>REFERENCES:</bold></p><p>1. Basciato H. <italic>NutrMetab</italic>, 2005</p><p>2. Bray GA. <italic>AmJClinNutr</italic>, 2004</p><p>3. Abid A. <italic>JHepatol</italic>, 2009</p><p>4. Rippe JM. <italic>AdvNutr</italic>, 2013</p><p><bold>Contact E-mail Address:</bold><email>jean.louis.gallis@free.fr</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Choline, Fructose, Liver, NMR, steatosis</p></sec><sec><title>OP197 ALKALINE-SPHINGOMYELINASE PROMOTES CHOLESTEROL ABSORPTION THROUGH REGULATING SPHINGOMYELIN LEVELS IN THE INTESTINAL TRACT</title><p><bold>R.-D. Duan</bold><sup>1,*</sup>, P. Zhang<sup>1</sup>, Y. Cheng<sup>1</sup>, L. Ohlsson<sup>1</sup>, E. Hertervig<sup>1</sup>, Å. Nilsson<sup>1</sup></p><p><italic><sup>1</sup>Institution of clinical sciences, , UNIVERSITY HOSPITAL OF LUND, Lund, Sweden</italic></p><p><bold>INTRODUCTION:</bold> Previous studies have shown that milk sphingomyelin (SM) in the intestinal tract inhibits cholesterol absorption. Under physiological conditions, digestion of dietary SM is not complete and the SM levels in the gut is mainly affected by the activities of alkaline sphingomyelinase (alk-SMase), which is a new member of nucleotide pyrophosphatase /phosphodiesterase (NPP) family, and is therefore also called NPP7. Alk-SMase is highly expressed in the small intestine where cholesterol absorption occurs. The physiological role of the enzyme in cholesterol absorption has not been established. The present study addresses the question in alk-SMase knockout (KO) mice.</p><p><bold>AIMS&METHODS:</bold> Alk-SMase KO mice were generated by Cre-Loxp recombination. Neither alk-SMase activity nor the enzyme protein was identified in these KO mice. After feeding the KO and the wild type (WT) mice with radio labelled SM, the non-digested SM was 90% higher in the small intestine in the KO mice than in the WT mice, indicating a fundamental effect of the enzyme on the levels of SM. Upon experiment, these mice were then fed a mixture of 0.1 microCi <sup>14</sup>C-cholesterol which can be absorbed and 0.5 microCi <sup>3</sup>H-sitosterol which cannot be absorbed by gavage, and the feces were collected 4, 8 and 24 h thereafter. The total lipids in the feces collected were extracted and the radio activities were analyzed by TLC and liquid scintillation. Expression of NPC1L1 in the small intestine was examined by qPCR and Western blot.</p><p><bold>RESULTS:</bold> The amounts of the feces collected at each time points did not differ significantly between the KO and the WT mice. The recovery of <sup>14</sup>C-cholesterol in the feces was higher at all time points in the KO mice than in the WT mice, maximal increase being by 107% (p<0.05) over that of the WT mice 8 h after administration of the cholesterol. The <sup>14</sup>C-cholesterol in the serum 4 h after feeding was decreased by 35% in the KO mice compared to the WT mice. No significant change was found for the recovery of <sup>3</sup>H-sitosterol in the feces between the KO and the WT mice, and the ratio of <sup>14</sup>C-cholesterol/<sup>3</sup>H-sitosterol in the KO mice were 133% and 75% higher than those in the WT mice at 8 and 24 h after feeding, respectively (p<0.05). Studies on the expression of NPC1L1, the transporter of cholesterol in the intestinal mucosa did not show significant changes between the KO and WT mice.</p><p><bold>CONCLUSION:</bold> Intestinal alk-SMase is a gut factor that enhances cholesterol absorption by decreasing SM, without affecting the expression of cholesterol transporter NPC1L1. Inhibition of alk-SMase may reduce the cholesterol absorption.</p><p><bold>Contact E-mail Address:</bold><email>Rui-dong.duan@med.lu.se</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Alkaline sphingomyelinase, Cholesterol absorption, Sphingomyelin</p></sec><sec><title>OP198 PHYSICAL PROPERTIES OF LIPID EMULSIONS IMPACT ON VISCERAL PERCEPTION, BLOOD TRIGLYCERIDES AND GI PEPTIDES</title><p><bold>S. Buetikofer</bold><sup>1,*</sup>, T. Radovic<sup>1</sup>, T. J. Wooster<sup>2</sup>, M. Arnold<sup>3</sup>, O. Goetze<sup>1</sup>, W. Langhans<sup>3</sup>, M. Fried<sup>1</sup>, W. Schwizer<sup>1</sup>, A. Steingoetter<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland, <sup>2</sup>Preventative Health Flagship, CSIRO, Werribee, Australia, <sup>3</sup>Institute of Food, Nutrition and Health, ETH Zurich, Zurich, Switzerland</italic></p><p><bold>INTRODUCTION:</bold> The rising consumption of processed foods with high amounts of emulsified lipids is frequently cited as a leading cause of the increasing prevalence of overweight/obesity. Therefore, understanding how the physical properties of lipid emulsions (LE) affect fat digestion and satiation responses is of central interest. Intraduodenal infusion of LE of different physical properties has been shown to affect GI peptide release and appetite, but little is known about their impact after regular oral intake and gastric processing.</p><p><bold>AIMS&METHODS:</bold> This randomized, double-blind, 4-way crossover study assessed the influence of four LE of different physical properties (Table) on <italic>hunger</italic>, <italic>fullness</italic>, GI peptides (active Ghrelin [aGhr] and peptide tyrosine tyrosine [PYY]), and blood triglycerides (TG). 17 healthy volunteers (6 m, age 25 ±7, BMI 22 ±1) orally ingested the LE on separate occasions. Visceral perception scores (scale from 0-10) and blood samples were acquired in the fasted state and at 10, 20, 30, 40, 60, 85, 135, 180, and 240 min after LE ingestion. Hunger/fullness scores and temporal changes in concentration of TG and GI peptides were compared by ordinal and linear mixed models, respectively.</p><p><bold>RESULTS:</bold> Emulsion acid and shear stability, droplet size and redispersibility had a significant impact on all assessed parameters (Table). LE1 (acid stable, 0.6 µm) resulted in lowest <italic>hunger</italic> (p<0.003) and highest <italic>fullness</italic> scores (p<0.05). Plasma profiles of aGhr reflected the differences in <italic>hunger</italic> with LE1 inducing the most pronounced decrease. Similarly, PYY profiles reflected differences in <italic>fullness</italic> with LE1 producing the greatest increases. LE3 (acid unstable/not redispersible, 0.6 µm) resulted in lowest TG levels and, in general, showed the most distinct differences to LE1.
<table-wrap id="table28-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1"></th><th rowspan="1" colspan="1">LE1</th><th rowspan="1" colspan="1">LE2</th><th rowspan="1" colspan="1">LE3</th><th rowspan="1" colspan="1">LE4</th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">Physical properties</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"> Acid-stable</td><td rowspan="1" colspan="1">Y</td><td rowspan="1" colspan="1">Y</td><td rowspan="1" colspan="1">N</td><td rowspan="1" colspan="1">N</td></tr><tr><td rowspan="1" colspan="1"> Shear-stable</td><td rowspan="1" colspan="1">N</td><td rowspan="1" colspan="1">N</td><td rowspan="1" colspan="1">Y</td><td rowspan="1" colspan="1">N</td></tr><tr><td rowspan="1" colspan="1"> Redispersible</td><td rowspan="1" colspan="1">Y</td><td rowspan="1" colspan="1">Y</td><td rowspan="1" colspan="1">N</td><td rowspan="1" colspan="1">Y</td></tr><tr><td rowspan="1" colspan="1"> Initial droplet size [µm]</td><td rowspan="1" colspan="1">0.6</td><td rowspan="1" colspan="1">30</td><td rowspan="1" colspan="1">0.6</td><td rowspan="1" colspan="1">0.6</td></tr><tr><td rowspan="2" colspan="1">Blood samples aGhr [pg/ml/min] PYY [pg/ml/min] TG [µmol/L/min]</td><td rowspan="2" colspan="1">-0.23±0.03 0.31±0.03 1.6±0.3</td><td colspan="3" rowspan="1">Difference to LE1</td></tr><tr><td rowspan="1" colspan="1">0.07±0.04* -0.13±0.04<sup>#</sup> 0.2±0.4</td><td rowspan="1" colspan="1">0.16±0.04<sup>#</sup> -0.23±0.04<sup>#</sup> -1.5±0.4<sup>#</sup></td><td rowspan="1" colspan="1">0.06±0.04 -0.25±0.04<sup>#</sup> 0.5±0.4</td></tr></tbody></table></table-wrap></p><p>Table: Physical properties of LE, reference values of LE1 and corresponding differences in TG and GI peptide levels compared to LE1 (estimate±SE). *p<0.05; <sup>#</sup>p<0.001.</p><p><bold>CONCLUSION:</bold> These findings confirm that visceral perception and GI peptides can be modulated by systematic modification of physical properties of LE. Therefore, functional foods including tailored LE are a promising target to modulate energy intake in patients with obesity and related co-morbidities.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Food intake, Gut Hormones, Lipid Emulsion, Satiation</p></sec><sec><title>OP199 MOSAPRIDE CITRATE INCREASES LEVELS OF POSTPRANDIAL PLASMA-ACTIVE GLUCAGON-LIKE PEPTIDE-1 AND SERUM INSULIN</title><p><bold>D. Maruoka</bold><sup>1,*</sup>, M. Arai<sup>1</sup>, A. Oyamada<sup>1</sup>, S. Minemura<sup>1</sup>, T. Matsumura<sup>1</sup>, T. Nakagawa<sup>1</sup>, T. Katsuno<sup>1</sup>, O. Yokosuka<sup>1</sup></p><p><italic><sup>1</sup>Department of Gastroenterology and Nephrology, GRADUATE SCHOOL OF MEDICINE, CHIBA UNIVRSITY, Chiba City, Japan</italic></p><p><bold>INTRODUCTION:</bold> Mosapride citrate is a gastrointestinal prokinetic agent that is widely used in East Asia. Studies have indicated that mosapride citrate can reduce the levels of haemoglobin A1c (HbA1c) in patients with type 2 diabetes [1, 2]. Other reports have demonstrated that it increases sugar utilisation by enhancing insulin sensitivity within the muscles [1] and increases the mobilisation of glucose transporters from intracellular pools in muscles [3]; however, the causative mechanisms for these actions are unclear. L-cells in the gastrointestinal tract, which are enteroendocrine cells, secrete glucagon-like peptide-1 (GLP-1), which stimulates insulin secretion from beta cells of the pancreas and enhances insulin sensitivity within the muscles. Thus, we hypothesised that the effect of mosapride citrate on glucose metabolism was mediated through GLP-1 and tested this hypothesis in the present study.</p><p><bold>AIMS&METHODS:</bold> Twelve healthy men (mean age, 31.9 ± 7.8) consumed a test meal (460 kcal). Their levels of serum insulin, plasma glucose, glucagon, and active GLP-1, as well as the blood chemistry results in the pre- and postprandial (90 min after the test meal) states were measured. After the oral administration of 5 mg of mosapride citrate 3 times per day for 14 days, blood samples were again drawn for analysis before and after subjects consumed the test meal. This study was approved by the medical ethics board of our institution.</p><p><bold>RESULTS:</bold> None of the subjects developed side effects or demonstrated a change in body weight. Postprandial plasma-active GLP-1 concentrations were significantly higher after the 14-day administration of mosapride citrate (4.8 ± 2.2 pmol/L) than those before administration (3.7 ± 1.2 pmol/L, p < 0.05, paired <italic>t</italic>-test). In addition, postprandial serum insulin concentrations were significantly higher after administration (45.6 ± 41.6 μIU/mL) than those before administration (34.1 ± 28.4 μIU/mL, p < 0.05, paired <italic>t</italic>-test). In contrast, the concentrations of preprandial plasma-active GLP-1 and serum insulin did not change after the 14-day administration of mosapride citrate.</p><p><bold>CONCLUSION:</bold> Administration of a conventional dose of mosapride citrate increases postprandial concentrations of plasma-active GLP-1 and serum insulin in healthy men.</p><p><bold>REFERENCES:</bold></p><p>1. Ueno N, et al. Diabetologia. 2002; 45: 792-7</p><p>2. Koshiyama H, et al. Diabetes Care. 2000; 23: 1198-9</p><p>3. Nam JS, et al. Diabetes Res Clin Pract. 2010; 87: 329-34</p><p><bold>Contact E-mail Address:</bold><email>d-maruoka@chiba-u.jp</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> glucagon-like peptide-1 (GLP-1), incretin, L-cell, mosapride citrate</p></sec><sec><title>OP200 ESCHERICHIA COLI NISSLE 1917 PRODUCING PREBIOTIC (FRUCTOSE OLIGOSACCHARIDE (FOS)) AND SECRETING PYRROLOQUINOLINE QUINONE ALLEVIATES SUCROSE INDUCED METABOLIC EFFECT</title><p><bold>S. K. Pandey</bold><sup>1,*</sup>, A. K. Singh<sup>1</sup>, G. Kumar<sup>1</sup></p><p><italic><sup>1</sup>Biochemistry, The Maharaja Sayajirao University Of Baroda, Vadodara, India</italic></p><p><bold>INTRODUCTION:</bold> High levels of simple carbohydrates (sucrose) consumption and presence of high level of reactive oxygen species (ROS) are associated with several metabolic disorders including obesity in humans. These metabolic disorders have been implicated in cardiovascular risk factors, hypertriglyceridemia and oxidative stress. Amongst Probiotics, <italic>E. coli </italic>Nissle 1917 is unique without endotoximia and beneficial antimicrobial activity which is considered as the most suitable therapeutic agent against enteroathogens.</p><p><bold>AIMS&METHODS:</bold> To develop <italic>E. coli </italic>Nissle 1917 for alleviating dietary effect of sucrose induced metabolic syndrome. Tn7 mediated genomic integration was carried out to integrate <italic>vgb </italic>(Vitreoscilla Hemoglobin) and<italic> gfp</italic> (Green fluorescent protein) gene. Pyrroloquinoline quinone (<italic>pqq</italic>) and inulosucrase (<italic>inuJ</italic>) was sub-cloned in pMALP2 vector. Charles foster rat weighing 200-250 grams were fed with 20% sucrose in drinking water for six month. Probiotic treatment (<italic>E. coli </italic>Nissle 1917) was given once per week 10<sup>9</sup> cells and fecal cell count was monitored by FACS. Antioxidant enzyme activity, lipid profile, Short chain fatty acid (SCFA) analysis and liver oil red staining was carried out.</p><p><bold>RESULTS:</bold><italic>E. coli </italic>Nissle 1917 <italic>vgb-gfp </italic>genomic integrant were confirmed by loss of ampicillin resistance and PCR. Rat fed with 20% sucrose in drinking water developed clinical characteristics of the metabolic syndrome including increased plasma glucose, triglycerides, total cholesterol and oxidative stress (Blood and Hepatic) in comparison to control group. In addition, they showed increased liver lipid accumulation, compared to chow fed controls. <italic>E. coli </italic>Nissle <italic>vgb-gfp-pqq-inuJ</italic> treatment restored clinical characteristics of metabolic syndrome to almost normal levels. In addition, <italic>E. coli </italic>Nissle <italic>vgb-gfp-pqq-inuJ </italic>showed significant increase in colonic SCFA (Acetic acid, propionic acid and butyric acid) on comparison with all other groups.</p><p><bold>CONCLUSION:</bold> Genetically engineered Probiotic <italic>E. coli </italic>Nissle (<italic>vgb-gfp-pqq-inuJ</italic>) showed improved colonization potential and suppressed clinical characteristics of sucrose induced metabolic syndrome, therefore, may provide a natural alternative for the treatment of diet-induced metabolic syndrome.</p><p><bold>REFERENCES:</bold></p><p>1. McKenzie GJ and Craig NL. Fast, easy and efficient: site-specific insertion of transgenes into Enterobacterial chromosomes using Tn<italic>7</italic> without need for selection of the insertion event. <italic>BMC Microbiology</italic> 2006, 6:39.</p><p>2. Lindqvist A. Effects of sucrose, glucose and fructose on peripheral and central appetite signals. Regulatory Peptides 2006, 150: 26–32.</p><p>3. Backhed F, Ley RE, Sonnenburg JL. Host-bacterial mutualism in the human intestine. <italic>Science</italic> 2005, 307: 1915–1920.</p><p>4. Sonnenborn U, Schulze J (2009) The non-pathogenic <italic>Escherichia coli</italic> strain Nissle 1917 – features of a versatile probiotic. <italic>Microb Ecol Hlth Dis.</italic></p><p><bold>Contact E-mail Address:</bold><email>sumitkumarpandey2@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> hypertriglyceridemia, oxidative stress, prebiotic, probiotic, pyrroloquinoline quinone</p></sec><sec><title>OP201 COFFEE RESTORES INTESTINAL TIGHT JUNCTION BARRIER INTEGRITY IN A RAT MODEL OF NASH</title><p><bold>G. Mazzone</bold><sup>1,*</sup>, G. D'Argenio<sup>1,2</sup>, V. Lembo<sup>1</sup>, P. Vitaglione<sup>3</sup>, C. Ferraiuoli<sup>1</sup>, E. Clery<sup>1</sup>, V. Fogliano<sup>3</sup>, F. Morisco<sup>1</sup>, N. Caporaso<sup>1</sup></p><p><italic><sup>1</sup>Clinical Medicine and Surgery, <sup>2</sup>Università of Naples Federico II, Naples , Italy, <sup>3</sup>Agricolture, Università of Naples Federico II, Naples , Italy</italic></p><p><bold>INTRODUCTION:</bold> Exposure to bacterial products of intestinal origin, most notably endotoxin, including LPS, leads to liver inflammation, hepatocyte injury and hepatic fibrosis . Impaired gut epithelial integrity due to alterations in tight junction (TJ) proteins may be the pathological mechanism underlying bacterial translocation. It is well known that gut permeability plays a crucial role in the pathogenesis of non-alcoholic steatohepatitis (NASH) and that some nutrients and food components may modulate intestinal TJ. Many epidemiological, experimental and clinical studies demonstrate that coffee beverage reduces liver damage caused by high fat diet (HFD) .</p><p><bold>AIMS&METHODS:</bold> Aims of the study were to evaluate the effect of coffee on the HFD-induced damage of intestinal mucosal barrier and on pro-inflammatory TLR-4 in a rat model of NASH.</p><p>Methods: Male Wistar rats were fed with a HFD for 5 months and divided in two groups: one group drunk simple water while the other group had drinking water added with 1.2 mL decaffeinated coffee per die starting from the 4<sup>th</sup> month. Contemporarily, another group fed a standard diet and was used as control. Protein and mRNA expression levels of TLR-4, Occludin and ZO-1 were examined from proximal jejunum of rats fed with standard diet, HFD + water and HFD + coffee.</p><p><bold>RESULTS:</bold> Results: A significant reduction of TJ proteins Occludin and Zo-1 in HFD fed rats was observed; it was partially reverted by the addition of coffee to the HFD (0.83±0.27 vs 0.14±0.07, p<0.05 and 0.85±0.12 vs 0.57±0.14, p<0.05 respectively). Coffee also reduced TLR-4 expression up-regulated in the HFD + water group.</p><p><bold>CONCLUSION:</bold> Conclusion:</p><p>These preliminary data confirmed that HFD impairs the intestinal TJ barrier integrity and that coffee is able to partially revert it by increasing ZO-1 and Occludin and reducing TLR4 expression.</p><p><bold>Contact E-mail Address:</bold><email>giovanna.mazzone@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> coffee, Intestinal epithelial barrier</p></sec><sec><title>OP202 LONG-TERM EFFECTS OF AN INTERDISCIPLINARY 52-WEEK WEIGHT LOSS PROGRAM ON ADIPOKINES AND NONALCOHOLIC FATTY LIVER DISEASE IN OBESE PATIENTS – A PROSPECTIVE EVALUATION.</title><p><bold>J. Martin</bold><sup>1,*</sup>, A. Mueller<sup>2</sup>, A. Waechtershaeuser<sup>3</sup>, I. Blumenstein<sup>3</sup>, J. Stein<sup>1</sup></p><p><italic><sup>1</sup>INTERDISZIPLINÄRES CROHN-COLITIS-CENTRUM RHEIN-MAIN, Frankfurt a.M., <sup>2</sup>University of Giessen, Giessen, <sup>3</sup>Krankenhaus Sachsenhausen, Frankfurt a.M., Germany</italic></p><p><bold>INTRODUCTION:</bold> Nonalcoholic fatty liver disease (NAFLD) is considered to be the most common liver disorder in western countries, with a rising prevalence. NAFLD is strongly associated with the presence and severity of obesity, but there is to date no convincing medical therapy. Thus, weight reduction is still the first-line therapy for NAFLD patients.</p><p><bold>AIMS&METHODS:</bold> The aim of this study was to evaluate the efficacy of Optifast 52, a commercial interdisciplinary weight loss program, with special emphasis on the adipokines leptin and adiponectin in NAFLD patients. A total of 72 participants with a BMI of > 30 kg/m<sup>2 </sup>were included. Participants attended weekly over the course of 52 weeks for medical assessment, physical activity, dietary counseling and psychological support. Laboratory values were determined and bioelectrical impedance analyses (BIA) of body composition performed at baseline, and after 26 and 49 weeks. Assessment of NAFLD was carried out using non-invasive parameters: the NAFLD fibrosis score and the BARD score.</p><p><bold>RESULTS:</bold> Of the 72 participants, 42 completed the Optifast program. Initial weight was reduced significantly from 121.1(± 24)kg to 96.3(± 21.9)kg (p<0.0005). Thus, BMI fell from 41.3(± 6.9)kg/m<sup>2</sup> to 32.8(± 6.5)kg/m<sup>2</sup> and fat mass was reduced from an initial 54.5(± 13.3)kg to 35(± 13.2)kg. The AST/ALT ratio improved with weight loss from 1.17(± 0.5) to 0.83(± 0.26). At baseline, 69% of patients were found to have a pathological AST/ALT ratio, compared to only 24.1% at week 49. The NAFLD score improved from -0.11(± 1.3) to -1.1(± 1.3) on study completion, where a score of -1,455 indicates that liver fibrosis can be excluded. Thus, at the beginning of the study, 14.3% of participants were at low risk of fibrosis, while 28.6% were at high risk. This changed to 39.3% and 3.6% at week 49, respectively. The BARD score improved significantly from 3.5(± 0.87) (baseline) to 2.6(± 1.1) (week 49), coincidentally with an improvement of the leptin/adiponectin ratio from initial 1.16(±0.96) to 0.31(±0.25) (p<0.0005).</p><p><bold>CONCLUSION:</bold> These data clearly demonstrate the Optifast 52 interdisciplinary weight reduction program to effectively reduce not only liver parameters, but also scores for estimating NAFLD in obese patients. A combination of diet and activity has a particularly positive impact on the leptin/adiponectin ratio. As long as no medication is available, weight reduction in the form of an interdisciplinary weight management program is therefore a suitable therapy for NAFLD.</p><p><bold>Contact E-mail Address:</bold><email>martin.julia@gmx.de</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> nonalcoholic fatty liver disease, weight loss</p></sec><sec><title></title><p><bold>TUESDAY, OCTOBER 15, 2013 8:30-10:30</bold></p><p><bold>Endoscopic interventions in pancreatic diseases – Salon 11/12</bold></p></sec><sec><title>OP203 THE INCREMENTAL ROLE OF THE CONTRAST ENHANCED ENDOSCOPIC ULTRASOUND IN GUIDING FINE NEEDLE ASPIRATION FOR PANCREATIC MASSES</title><p><bold>A. Seicean</bold><sup>1,*</sup>, A. Moldovan-Pop<sup>1</sup>, S. Vultur<sup>1</sup>, C. Tefas<sup>1</sup>, E. Botan<sup>1</sup>, T. Zaharia<sup>1</sup>, R. Seicean<sup>1</sup>, C. Iancu<sup>1</sup>, R. Badea<sup>1</sup>, M. Tantau<sup>1</sup></p><p><italic><sup>1</sup>Third Medical Clinic, UNIVERSITY OF MEDICINE AND PHARMACY IULIU HATIEGAN, CLUJ-NAPOCA, Romania</italic></p><p><bold>INTRODUCTION:</bold> The global accuracy of fine needle aspiration endoscopic ultrasound (EUS-FNA) for pancreatic adenocarcinoma is about 85%. The contrast agents during EUS may highlight the vessels and the necrotic parts of the pancreatic masses, but their incremental role in diagnosis is not known.</p><p><bold>AIMS&METHODS:</bold> To evaluate whether the guidance of FNA during harmonic contrast-enhanced pancreatic endoscopic ultrasound (CEH-EUS) would increase the diagnostic accuracy of EUS- FNA in the same pancreatic masses.</p><p>In each of the 54 prospectively examined patients with pancreatic masses on CT scan, EUS- FNA was performed using a 22 G needle, followed by CEH-EUS using Sonovue. A second cluster of EUS-FNA was performed on contrast image, avoiding vessels and the regions inside the mass considered as necrosis. The final diagnosis was based on the results of EUS-FNA and surgery, or 6 months of follow-up in benign lesions. The pairs of samples obtained during conventional EUS-FNA and CEH-EUS-FNA, were assessed blindely by two pathologists. Perfusion analysis of the contrast image was performed by post-processing of the raw data.</p><p><bold>RESULTS:</bold> The final diagnosis was adenocarcinoma (n=40), chronic pancreatitis (n=6),pancreatic metastasis (n= 3) or another (n=5).The contrast hypoenhanced homogenous aspect was seen in 92.5% of pancreatic adenocarcinoma, while necrotic area inside mass was seen in 10% of the patients. No complications appeared during procedures.</p><p> Macroscopically , the cell blocks obtained during CEH-EUS-FNA were significantly larger than those obtained in the conventional EUS-FNA guided group (p<0.01). Microscopically, the diagnostic accuracy increased with 10%. The combination of the quantitative assessment of the contrast image with pathologic results significantly improved the diagnostic accuracy.</p><p><bold>CONCLUSION:</bold> Although necrotic regions inside pancreatic mass were seen less frequently, the CEH-EUS allows a better orientation of the needle inside the pancreatic lesion and increases the yield of diagnostic, especially in combination with the quantitative CEH-EUS analysis.</p><p><bold>Contact E-mail Address:</bold><email>andradaseicean@yahoo.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Contrast enhanced ultrasound, Endoscopic ultrasound , fine needle aspiration biopsy, pancreatic mass</p></sec><sec><title>OP204 QUANTITATIVE ENDOSCOPIC ULTRASOUND ELASTOGRAPHY (Q-EUS-E) FOR THE DIFFERENTIAL DIAGNOSIS OF SOLID PANCREATIC MASSES: A VALIDATION STUDY</title><p><bold>J. Iglesias-García</bold><sup>1,2,*</sup>, J. E. Dominguez-Muñoz<sup>1,2</sup>, J. Lariño-Noia<sup>1,2</sup></p><p><italic><sup>1</sup>Gastroenterology, University Hospital of Santiago de Compostela, <sup>2</sup>Foundation for Research in Digestive Diseases, Santiago de Compostela, Spain</italic></p><p><bold>INTRODUCTION:</bold> Quantitative endoscopic ultrasound elastography (Q-EUS-E) is considered as a useful tool for the differential diagnosis of solid pancreatic masses (SPM). However there are certain drawbacks concerning the methodology of performing the elastographic evaluation.</p><p><bold>AIMS&METHODS: Aim</bold> of the study was to validate and determine the accuracy of Q-EUS-E in the differential diagnosis of SPM, performed according to a well-established protocol, in a large series of patients. <bold>Methods:</bold> Prospective study including consecutive patients who underwent EUS for the evaluation of SPM. EUS-elastography was performed under conscious sedation with the linear Pentax EUS (EG-3870-UTK) and the Hitachi-PREIRUS processor. Two different areas (A and B) were selected for quantitative elastographic analysis: Area A is a representative area of the mass and B refers to a soft peripancreatic reference area. The quotient B/A (strain ratio) was considered as the result of the elastographic evaluation. Final diagnosis was based on surgical histopathology or, in non-operated cases, on imaging assessment; EUS-guided fine needle biopsy and clinical follow-up. Data are shown as median and 95%CI. Diagnostic accuracy of Q-EUS-E for detecting malignancy was calculated after drawing the corresponding ROC curves.</p><p><bold>RESULTS: :</bold> 199 patients (mean age 64 years, 17-90 years, 121 male) were included in the study. Size of SPM was 34.88±17.4 mm (mean±SD). Tumors were located in the head of the pancreas in 133 patients, in the body in 53 patients and in the tail in 13 patients. Final diagnoses and strain ratio levels in different pancreatic solid lesions are show in table. The strain ratio was significantly higher among patients with pancreatic malignant tumors compared with those with benign lesions.</p><p>ROC curve showed, for a cut-off point of 9.5 (AUC=0.951), a sensitivity, specificity, PPV, NPV and overall accuracy in detecting malignancy of 100%, 91%, 97%, 100% and 98%, respectively.</p><p><bold>CONCLUSION:</bold> Q-EUS-E is a very useful tool for the differential diagnosis of SPM, performed under a well-established protocol, confirming previous results
<table-wrap id="table29-2050640613502899" position="float"><label>Table</label><caption><p>OP204</p></caption><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1">Diagnosis</th><th rowspan="1" colspan="1">Pancreatic cancer (n=135)</th><th rowspan="1" colspan="1">Inflammatory mass (n=38)</th><th rowspan="1" colspan="1">Malignant NET (n=11)</th><th rowspan="1" colspan="1">Benign NET (n=4)</th><th rowspan="1" colspan="1">AIP (n=2)</th><th rowspan="1" colspan="1">Lymphoma (n=3)</th><th rowspan="1" colspan="1">Mesenchy-mal tumor (n=2)</th><th rowspan="1" colspan="1">Metastasis (n=4)</th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">Strain ratio (mean; 95%CI)</td><td rowspan="1" colspan="1">38.05 (34.3-41.7)</td><td rowspan="1" colspan="1">7.23 (5.1-9.3)</td><td rowspan="1" colspan="1">99.4 (52.9-145.9)</td><td rowspan="1" colspan="1">4.29 (2.66-5.9)</td><td rowspan="1" colspan="1">44.22 (31.5-56.9)</td><td rowspan="1" colspan="1">41.1 (0-98.3)</td><td rowspan="1" colspan="1">73.75 (16.80-130.70)</td><td rowspan="1" colspan="1">55.04 (16-94)</td></tr></tbody></table></table-wrap></p><p><bold>Disclosure of Interest</bold>: J. Iglesias-García Lecture fee(s) from: Cook-Medical, Consultancy for: Cook-Medical, J. E. Dominguez-Muñoz Consultancy for: Pentax Medical, J. Lariño-Noia: None Declared</p><p><bold>Keywords:</bold> Endoscopic Ultrasound, Pancreatic Cancer, quantitative elastography</p></sec><sec><title>OP205 NEEDLE-BASED CONFOCAL LASER ENDOMICROSCOPY (NCLE) FOR THE DIAGNOSIS OF PANCREATIC MASSES : PRELIMINARY CRITERIA (CONTACT STUDY)</title><p><bold>M. Giovannini</bold><sup>1,*</sup>, F. Caillol<sup>1</sup>, B. Napoléon<sup>2</sup>, B. Pujol<sup>2</sup>, A.-I. Lemaistre<sup>3</sup></p><p><italic><sup>1</sup>Gastroenterology and Hepatology, Institut Paoli Calmettes, Marseille, <sup>2</sup>Gastroenterology and Hepatology, Hôpital privé Jean Mermoz, <sup>3</sup>Pathology, Centre Léon Bérard, Lyon, France</italic></p><p><bold>INTRODUCTION:</bold> Needle-based Confocal Laser Endomicroscopy (nCLE) is an imaging technique , which enables microscopic observation of solid organs, <italic>in vivo</italic> and in real-time, during an EUSFNA procedure.</p><p><bold>AIMS&METHODS:</bold> This study aims at building an image atlas, and define interpretation criteria for nCLE images in the pancreatic masses. 3 centres in France (7 investigators) took part in this prospective study. Any pancreatic mass (but only one) studied by EUSFNA could be imaged by nCLE. The definition of the preliminary interpretation criteria was done by consensus, with 5 investigators, including one pathologist. 35 patients with a pancreatic mass were included prospectively during the study (June 2012 to March 2013) and the corresponding nCLE recordings were reviewed. For each case, the investigators had the following data: patient's clinical history, information on the EUS procedure preceding nCLE imaging, cytology, histology findings, nCLE sequences, and, in certain cases, histological images. When reviewing the video sequences, they were asked to identify characteristic descriptive criteria, and correlate them with a final diagnosis if possible. The localization of the pancreatic masses was : head (17 cases), body (12 cases), tail (6 cases). There were 17 men, and 16 women (2 na), mean age 66 years, (extreme : 32-87 years old). The puncture of the mass was done in all cases with a 19G puncture needle. Mean size is 30mm (+/- 9mm).</p><p><bold>RESULTS:</bold> No complication occured during the nCLE procedure or the puncture. A definitive histological diagnosis was obtained in 31/35 patients. It was the following : adenocarcinoma (21 cases), fibrous stroma adenocarcinoma (1 case), neuroendocrine tumor (4 cases), pseudopapillary tumor (1), chronic pancreatitis (3). During this review, all exocrine adenocarcinomas showed 2 signs, dark cells aggregates with pseudo-glandular aspects, and straight hyperdense elements more or less thick corresponding to tumoral fibrosis. This last element was preposterous in the fibrous stroma tumor. However, both signs were absent in the tumor with acini cells and neuroendocrine tumor. This one showed a very dense network of small vessels on a dark background. Moreover, normal pancreas shows an aspect of coffee beans corresponding to acinis.</p><p><bold>CONCLUSION:</bold> This preliminary classification of nCLE images obtained in pancreatic masses could help in the differentiation of adenocarcinomas and neuroendocrine tumors, and between malignant tumors from normal pancreatic tissue. nCLE could therefore facilitate the diagnosis of these lesions, by bringing <italic>in vivo</italic> microscopic information, in real-time.</p><p><bold>Contact E-mail Address:</bold><email>alexandras@maunakeatech.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> endocrine, endomicroscopy, masses </p></sec><sec><title>OP206 EUS-GUIDED TRANSDUODENAL BILIARY DRAINAGE USING A NOVEL, LUMEN-APPOSING SEMS AFTER FAILED TRANSPAPILLARY STENTING.</title><p><bold>R. Kunda</bold><sup>1,*</sup>, D. Brenke<sup>2</sup>, A. Larghi<sup>3</sup>, M. Perez-Miranda<sup>4</sup>, M. Faehndrich<sup>5</sup>, T. Desimio<sup>6</sup>, S. Ullrich<sup>7</sup>, F. Hagenmueller<sup>8</sup>, K. Binmoeller<sup>9</sup></p><p><italic><sup>1</sup>Surgical Gastroenterology, Aarhus University Hospital, Aarhus, Denmark, <sup>2</sup>Gastroenterology, Stadtisches Klinikum Karlsruhe, Karlsruhe, Germany, <sup>3</sup>Digestive Endoscopy Unit , Università Cattolica del Sacro Cuore , Rome, Italy, <sup>4</sup>Department of Endoscopy, Hospital Universiario Rio Hortega, Valladolid, Spain, <sup>5</sup>Department of Interventional Endoscopy, Klinikum Dortmund, Dortmund, Germany, <sup>6</sup>Xlumena, Inc, Mountain View, United States, <sup>7</sup>Department of Medicine I (Gastroenterology), , <sup>8</sup>Department of Medicine I (Gastroenterology), Asklepios Klinik Altona, Hamburg, Germany, <sup>9</sup>Interventional Endoscopy Service, California Pacific Medical Center, San Francisco, United States</italic></p><p><bold>INTRODUCTION:</bold> Endoscopic trans papillary stenting by ERCP is widely practiced as first-line treatment of malignant obstructive jaundice. If ERCP fails, percutaneous drainage is an alternative approach, but often considered less desirable by the patient. As an alternative, we investigated the efficacy of a newly developed lumen-aopposing stent system for EUS-guided internal biliary drainage.</p><p><bold>AIMS&METHODS:</bold> 16 patients with biliary obstruction due to malignancy and failed trans papillary drainage were treated with EUS-guided placement of a dual-flanged lumen-opposing stent (AXIOS, Xlumena, Inc. Mountain View, CA) between the duodenal bulb and the extra hepatic bile duct following needle puncture and guide wire placement. Two stent sizes were used: 6mm x 8mm and 10mm x 10mm (inside diameter x working length). Fluoroscopy was used for cholangiography.</p><p><bold>RESULTS:</bold> Technical success rate was 94% (15/16). In all cases biliary drainage was achieved at the first attempt. Drainage was effective on follow up (mean=48 days, range= 4-101) in 93% of patients (14/15). Stent-related complications (2/16, 12.5%) were one perforation of the duodenum due to stent maldeployment that required stent removal (defect closed with clips) and one case of cholangitis due to sump syndrome (resolved with duct sweep through the AXIOS). One patient had intraductal bleeding from tumour infiltration, treated by coil embolization prior to endoscopic intervention, but later died of sepsis due to bile duct obstruction from blood clots. The majority of patients reported an improvement of general condition.</p><p><bold>CONCLUSION:</bold> EUS guided trans duodenal biliary drainage with a novel lumen-apposing stent is effective for the treatment of malignant obstructive jaundice in patients who have failed trans papillary drainage. Further study is warranted to establish safety and long-term patency.</p><p><bold>Contact E-mail Address:</bold><email>tdesimio@xlumena.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> EUS guided biliary drainage, lumen apposing stent, transluminal technique</p></sec><sec><title>OP207 NATURAL HISTORY OF FLUID COLLECTIONS IN ACUTE PANCREATITIS CLASSIFIED AS PER 2012 ATLANTA REVISION</title><p><bold>M. Manrai</bold><sup>1,*</sup>, P. K. Siddappa<sup>1</sup>, J. B. Medarapalem<sup>1</sup>, S. Appasani<sup>1</sup>, T. D. Yadav<sup>2</sup>, N. Khandelwal<sup>3</sup>, K. Singh<sup>1</sup>, R. Kochhar<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology, <sup>2</sup>Surgery, <sup>3</sup>Radiology, Postgraduate Institute of Medical Education and Research(PGIMER), Chandigarh, India</italic></p><p><bold>INTRODUCTION:</bold> Acute pancreatitis (AP) is a significant medical and surgical problem. Acute fluid collections in acute pancreatitis are a marker of severity and have been used in imaging severity scoring systems. There is paucity of data on the natural history of acute fluid collections in acute pancreatitis.</p><p><bold>AIMS&METHODS:</bold> To study the course and outcome of pancreatic and extra pancreatic acute fluid collections in patients of acute pancreatitis.</p><p>Consecutive patients of acute pancreatitis >12 yrs of age were subjected to complete demographic profile, clinical and laboratory evaluation. Details of acute fluid collections i.e acute peripancreatic fluid collections (APFCs) and acute necrotic collections (ANCs) based on CECT findings were noted. Patients were followed up for short term (up to 3 months) and long term (>3 months) for for development of walled off necrosis(WON) or pseudocyst, development of infection, requirement of intervention and mortality.</p><p><bold>RESULTS:</bold> 189 patients (mean age 38.85(13-90)years, 70%males) of AP were studied. Alcohol was the major cause(n=80(42.3%)). Necrotizing pancreatitis was seen in 153(80.9%) patients with ANC in 143, interstitial edematous pancreatitis in 36 and APFC in 8 of them. No fluid collections were seen in 38(20.1%)patients. Collections were located in pancreas in 5(3.31%), peripancreatic tissue in 52(34.43%), distant areas in 5(3.31%), peripancreatic and distant in 52(34.43%), and pancreatic, peripancreatic and distant in 38(25.1%). ANCs were associated with pancreatic and extra/peripancreatic necrosis in 135(94.4%) patients. 142(75.13%)patients were followed up for 3 months and 64 beyond 3 months. 105 ANCs were followed up, of whom 21(20%) resolved and 83(79%) developed WON and one patient had WON+pseudocyst. All APFCs resolved except one which evolved into pseudocyst. Infections were seen in 56.7% of ANCs and none of APFCs. 54 patients required percutaneous drainage; 30 of them resolved, 16 had resolving WON and 8 had persistent WON, expired. Endoscopic drainage was done in 16 patients; 2 resolved, 11 had resolving WON and 2 had persistent WON. 24 patients required surgery in total and 12 patients expired.</p><p><bold>CONCLUSION:</bold> Fluid collections developed in 80% of AP and most were peripancreatic or distant or a combination of the two. ANCs occurred in 93.4% of patients with necrotizing pancreatitis, of whom 20% resolved and rest developed WON. APFCs developed in 22.2% of interstitial pancreatitis and all of them resolved except 1 who developed a pseudocyst.</p><p><bold>Contact E-mail Address:</bold><email>dr_kochhar@hotmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Acute Fluid Collection, Acute Necrotic Collection, Acute Pancreatitis</p></sec><sec><title>OP208 INFECTED WALLED-OFF PANCREATIC NECROSIS IS ASSOCIATED WITH ORGAN FAILURE AND MORTALITY</title><p><bold>S. Roug</bold><sup>1,2,*</sup>, S. Novovic<sup>1</sup>, E. Feldager<sup>1</sup>, J. D. Knudsen<sup>3</sup>, P. N. Schmidt<sup>1</sup></p><p><italic><sup>1</sup>Department of Gastroenterology and Gastrointestinal Surgery, Copenhagen University Hospital Hvidovre, <sup>2</sup>Department of Internal Medicine I, Copenhagen University Hospital Bispebjerg, <sup>3</sup>Department of Clinical Microbiology, Copenhagen University Hospital Hvidovre, Copenhagen, Denmark</italic></p><p><bold>INTRODUCTION:</bold> Data on the microbial spectrum in infected pancreatic necrosis are scarce, and only few studies have addressed this in a larger, consecutive group of patients. Further, few studies have related the microbial findings to the use of antibiotics and external drainage.</p><p><bold>AIMS&METHODS:</bold> To evaluate the microbial spectrum of infected pancreatic necrosis and possible relationship between the occurrence of infected necrosis, organ failure and in-hospital mortality in patients treated with endoscopic, transmural drainage and necrosectomy (ETDN). Furthermore to investigate whether aetiology, previous external drainage, and previous antibiotic treatment influenced the microbial findings.</p><p>A retrospective analysis of medical charts on 78 patients who underwent ETDN in our tertiary referral centre between November 2005 and November 2011.</p><p><bold>RESULTS:</bold> The prevailing microbial aetiologies on index endoscopy were <italic>Enterococci</italic> (32%), <italic>Enterobacteriaceae</italic> (29%), and yeasts (15%). When comparing findings on second to index endoscopy, there was a significant increase of polymicrobial findings at the second endoscopy (74% vs. 51%, p=0.02), as was the case for yeasts (31% vs. 15%, p=0.04). There was a significant difference in in-hospital mortality, development of organ failure, and the need for treatment in an intensive-care unit between patients with infected necrosis as compared to patients with sterile necrosis (table). Findings of <italic>Enterococci</italic> and yeasts at the index endoscopy were significantly associated with negative outcome. Neither the aetiology of pancreatitis, the use of external drainage nor antibiotic treatment prior to the index endoscopy influenced the occurrence of infected necrosis. However, <italic>Enterococci </italic>were found more often in the group treated with antibiotics before the index endoscopy than in the group not treated with antibiotics (41% vs. 13%, p=0.01).</p><p>Table. Association between infected necrosis at index endoscopy and outcome.
<table-wrap id="table30-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1"></th><th rowspan="1" colspan="1">Infected necrosis</th><th rowspan="1" colspan="1">Sterile necrosis</th><th rowspan="1" colspan="1"><italic>p-value</italic></th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1"><bold>In-hospital mortality</bold></td><td rowspan="1" colspan="1">9/55</td><td rowspan="1" colspan="1">0/23</td><td rowspan="1" colspan="1"><bold><italic>0.039</italic></bold></td></tr><tr><td rowspan="1" colspan="1"><bold>Organ failure<italic>*</italic></bold></td><td rowspan="1" colspan="1">24/54</td><td rowspan="1" colspan="1">2/22</td><td rowspan="1" colspan="1"><bold><italic>0.003</italic></bold></td></tr><tr><td rowspan="1" colspan="1"><bold>Need for ICU<italic>*</italic></bold></td><td rowspan="1" colspan="1">28/54</td><td rowspan="1" colspan="1">1/22</td><td rowspan="1" colspan="1"><bold><italic>< 0.001</italic></bold></td></tr></tbody></table></table-wrap></p><p><italic>* In two patients it was not possible to find data on organ failure and need for ICU treatment</italic></p><p><bold>CONCLUSION:</bold></p><p>We have documented the influence of infected pancreatic necrosis and fungal infection on organ failure and mortality in necrotizing pancreatitis, and showed that <italic>Enterococcus</italic> spp and yeasts were especially associated with a poor outcome. Antibiotic prophylaxis had no effect on the occurrence of infected necrosis and external drainage prior to endoscopy did not increase the rate of infected pancreatic necrosis.</p><p><bold>Contact E-mail Address:</bold><email>stineroug@dadlnet.dk</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> antibiotics, organ failure, pancreatic necrosis, infection, microbial findings, mortality</p></sec><sec><title>OP209 NONSTEROIDAL ANTIINFLAMMATORY DRUIGS (NSAIDS) IN THE PREVENTION OF POST-ERCP PANCREATITIS: A META-ANALYSIS</title><p><bold>J. M. Libuit</bold><sup>1,*</sup>, A. R. B. Lomboy<sup>1</sup>, M. A. A. de Lusong<sup>1</sup>, J. P. Ong<sup>1</sup></p><p><italic><sup>1</sup>Medicine, Philippine General Hospital, Manila, Philippines</italic></p><p><bold>INTRODUCTION:</bold> Acute pancreatitis is considered the most common complication of ERCP occurring in approximately 1-10% of cases, sometimes even as high as 30% depending on the presence of risk factors<sup>1-2</sup>. It may cause significant morbidity and additional health expenditure that amounts to approximately US$ 150 million annually in the US. Death from post-ERCP pancreatitis occurs in 0.2-0.6% of cases<sup>3-4</sup>.</p><p>Post-ERCP pancreatitis (PEP) is defined as having typical symptoms of pancreatic-type abdominal pain associated with at least a three-fold elevation in serum amylase or lipase occurring within 24 hours of ERCP that is severe enough to require admission to a hospital or to prolong hospital stay of patients who are already hospitalized<sup>5</sup>.</p><p>Several well-designed studies that used different prophylactic agents have been conducted to determine their chemopreventive efficacy. To date, no agent has proven to be consistently effective in minimizing the incidence of acute post-ERCP pancreatitis.</p><p>NSAIDs are nonselective inhibitors of the cyclooxygenase enzyme thereby preventing the formation of chemokines involved in the pathogenesis of acute pancreatitis. By blocking the formation of these cytokines, it is postulated that the incidence of acute post-ERCP pancreatitis will be decreased with prophylactic administration of these agents. The use of NSAIDs as prophylaxis against acute post-ERCP pancreatitis appears to be attractive because of its availability and cheap cost.</p><p><bold>AIMS&METHODS:</bold> The role of prophylactic NSAIDs in the prevention of post-ERCP pancreatitis is still unclear. This meta-analysis was performed to determine the efficacy of NSAIDs in the prevention of post-ERCP pancreatitis. It also determined if the use of NSAIDs for this purpoase was associated with any adverse effect.</p><p>Searches were conducted using online database: EMBASE, PubMed, Google Scholar, Cochrane Library, and clinicaltrials.gov. Nine eligible studies were included in this meta-analysis. Data were extracted by three independent investigators based on predetermined criteria. Data were encoded and tabulated using RevMan 5.</p><p><bold>RESULTS:</bold> The risk of pancreatitis was lower in the experimental group which used either Diclofenac or Indomethacin compared to placebo (OR: 0.47, 95% CI: 0.35 to 0.62). There were no adverse events reported in all the RCTs.</p><p><bold>CONCLUSION:</bold> Prophylactic administration of either Diclofenac or Indomethacin may reduce the incidence of post-ERCP pancreatitis. Rectal administration of these NSAIDs showed more consistent effect in preventing the incidence of post-ERCP pancreatitis. Larger studies must still be undertaken in order to recommend its routine use in clinical practice.</p><p><bold>REFERENCES:</bold></p><p>1. Freeman ML, DiSario JA, Nelson DB, Fennerty MB, Lee JG, Bjorkman DJ, et al. Risk factors for post-ERCP pancreatitis: a prospective, multicenter study. Gastrointest Endosc. 2001;54:425–34.</p><p>2. Masci E, Toti G, Mariani A, Curioni S, Lomazzi A, Dinelli M, et al. Complications of diagnostic and therapeutic ERCP: a prospective multicenter study. Am J Gastroenterol. 2001;96:417–23.</p><p>3. Freeman ML, Nelson DB, Sherman S, et al. Complications of endoscopic biliary sphincterotomy. N Engl J Med 1996;335:909-18.</p><p>4. National inpatient sample — Healthcare Cost and Utilization Project. Rockville, MD: Agency for Healthcare Research and Quality (<ext-link ext-link-type="uri" xlink:href="http://hcupnet.ahrq.gov">http://hcupnet.ahrq.gov</ext-link>).</p><p>5. Cotton PB, Lehman G, Vennes J, Geenen JE, Russell RC, Meyers WC, Liguory C, Nickl N. Endoscopic sphincterotomy complications and their management: an attempt at consensus. Gastrointest Endosc 1991; 37: 383-393.</p><p>6. Cheon Y, Cho K, Watkins J, et al. Efficacy of diclofenac in the prevention of post- ERCP pancreatitis in predominantly high risk patients: a randomized double-blind prospective trial. Gastrointest Endosc 2007;66:1126–32.</p><p>7. Döbrönte Z, Erzsébet T, et al. Az indometacin szerepe az endoszkópos retrograde cholangiopancreatographiát követő akut pancreatitis prevenciójában. Orv Hetil 153:990-6. 2012.</p><p>8. Elmunzer BJ, Scheiman JM, et al. A Randomized Trial of Rectal Indomethacin to Prevent Post-ERCP Pancreatitis. N Engl J Med 2012; 366(15): 1414-1422.</p><p>9. Khoshbaten M, Khorram H, Madad L, et al. Role of diclofenac in reducing postendoscopic retrograde cholangiopancreatography pancreatitis. J Gastroenetrol Hepatol 2007.</p><p>10. Montano Loza A, Rodriguez Lomeli X, Garcia Correa J, et al. Effect of rectal administration of indomethacin on amylase serum levels after endoscopic retrograde cholangiopancreatography, and its impact on the development of secondary pancreatitis episodes. Rev Esp Enferm Dig 2007;99:330–6.</p><p>11. Murray B, Carter R, Imrie C, et al. Diclofenac reduces the incidence of acute pancreatitis after endoscopic retrograde cholangiopancreatography. Gastroenterology 2003;124:1786–91.</p><p>12. Otsuka T, Kawazoe S, Nakashita S, et al. Low-dose rectal diclofenac for prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: a randomized control trial. J Gastroenterol online publication 18 February 2012.</p><p>13. Senol A, Saritas U, and Demirkan H. Efficacy of intramuscular diclofenac and fluid replacemen in prevention of post-ERCP pancreatitis. World J Gastroenterol 2009 August 28; 15(32): 3999-4004.</p><p>14. Sotoudehmanesh R, Khatibian M, Kolahdoozan S, et al. Indomethacin may reduce the incidence and severity of acute pancreatitis after ERCP. Am J Gastroenetrol 2007;102:978–83.</p><p><bold>Contact E-mail Address:</bold><email>jefflibuitmd@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> ERCP, NSAIDs, Pancreatitis, Prophylaxis</p></sec><sec><title>OP210 A NEW FULLY COVERED LARGE BORE WIDE FLARE METAL STENT FOR DRAINAGE OF PANCREATIC FLUID COLLECTIONS (PFC) – RESULTS OF A MULTICENTER STUDY</title><p><bold>A. Bapaye</bold><sup>1,*</sup>, T. Itoi<sup>2</sup>, P. Kongkam<sup>3</sup>, N. A. Dubale<sup>1</sup>, F. Itokawa<sup>2</sup></p><p><italic><sup>1</sup>Department of Digestive Diseases and Endoscopy, Deenanath Mangeshkar Hospital and Research Center, Pune, India, <sup>2</sup>Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan, <sup>3</sup>Department of Internal Medicine, Chulalongkorn University, Bangkok, Thailand</italic></p><p><bold>INTRODUCTION:</bold> Endoscopic ultrasonography guided transmural drainage (EUTMD) of pancreatic fluid collections (PFC’s) is currently the standard treatment modality. Conventional multiple double pigtail plastic stents (DPT’s) have limitations of adequate drainage, whereas conventional fully covered self-expandable metallic stents (FCSEMS), although they can provide optimal drainage, are more prone to migrate.</p><p><bold>AIMS&METHODS:</bold> A new specially designed large bore wide flare FCSEMS has been recently developed (Nagi stent™, Niti-S, Taewoong Medical, South Korea) to accomplish this purpose with fewer disadvantages. This study aimed to evaluate the efficacy of this FCSEMS for PFC drainage.</p><p>During a 22-month period (May 2011 – February 2013), 19 patients with 21 PFC’s underwent EUTMD using FCSEMS in 3 centers, 16 males & 3 females. Mean age was 46.9 years (range 23 - 80). Etiology of pancreatitis was alcohol in 12 (63%), gall stone in 3 (16%), idiopathic in 3 (16%) and pancreas divisum in 1 (5%) patients. Mean longest diameter of PFC was 107mm (range 46 - 206). Types of PFC's drained were - acute fluid collection (AFC) - 1, pseudocyst (PPC) - 8, infected pseudocyst - 1, walled off pancreatic necrosis (WOPN) - 11. PFC was located in body/tail region - 18, head region - 2 and perihepatic - 1. Solid debris was seen in 12 / 21 (57%) PFC's. Indication for drainage was sepsis - 12 (63%) and pain - 7 patients (37%).</p><p>Assessment parameters included – resolution of symptoms and resolution of PFC on imaging, ability to perform necrosectomy (when required) and incidence of complications.</p><p><bold>RESULTS:</bold><table-wrap id="table31-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th colspan="2" rowspan="1"><hr></hr>Details </th><th rowspan="1" colspan="1">N (total = 21) </th><th rowspan="1" colspan="1">Percent </th></tr><tr><th rowspan="1" colspan="1">Puncture site</th><th rowspan="1" colspan="1">Esophagus / Stomach / Duodenum</th><th rowspan="1" colspan="1">1 / 18 / 2</th><th rowspan="1" colspan="1">5 / 86 / 9</th></tr></thead><tbody align="left"><tr><td colspan="2" rowspan="1">Access – 19G FNA needle</td><td rowspan="1" colspan="1">21</td><td rowspan="1" colspan="1">100</td></tr><tr><td rowspan="1" colspan="1">Balloon dilatation of track</td><td rowspan="1" colspan="1">4 / 6 / 8 / 15mm</td><td rowspan="1" colspan="1">9 / 3 / 8 / 1</td><td rowspan="1" colspan="1">43 / 14 / 38 / 5</td></tr><tr><td rowspan="1" colspan="1">Concurrent drainage</td><td rowspan="1" colspan="1">DPT / Nasocystic drain</td><td rowspan="1" colspan="1">10 / 7</td><td rowspan="1" colspan="1">48 / 33</td></tr><tr><td colspan="2" rowspan="1">Necrosectomy</td><td rowspan="1" colspan="1">7</td><td rowspan="1" colspan="1">33</td></tr><tr><td colspan="2" rowspan="1">Stent removal (14 patients, 67%) – Days after insertion, mean (range)</td><td rowspan="1" colspan="1">49.1 (45 – 60)</td><td rowspan="1" colspan="1">67</td></tr><tr><td colspan="2" rowspan="1">Technical success</td><td rowspan="1" colspan="1">21</td><td rowspan="1" colspan="1">100</td></tr><tr><td colspan="2" rowspan="1">Clinical success</td><td rowspan="1" colspan="1">21</td><td rowspan="1" colspan="1">100</td></tr><tr><td colspan="2" rowspan="1">Complications – stent migration</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">5</td></tr></tbody></table></table-wrap></p><p><bold>CONCLUSION:</bold> The Nagi stent™ is effective and safe for EUTMD of PFC’s including infected PPC’s and WOPN. It permits rapid resolution of PFC with 100% technical and clinical success rates. Necrosectomy can be successfully performed through the stent in all needed cases. The stent can be easily extracted at the end of the therapy period. Based on results of this study, stent migration rate was low. The Nagi stent™ should be considered as the first option for patients undergoing EUTMD of PFC’s. Further prospective randomized controlled trials comparing this stent to multiple plastic stents is recommended.</p><p><bold>Contact E-mail Address:</bold><email>amolbapaye@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: A. Bapaye : No conflict of interest, T. Itoi : No conflict of interest, P. Kongkam : No conflict of interest, N. Dubale : No conflict of interest, F. Itokawa : No conflict of interest</p><p><bold>Keywords:</bold> EUS-guided, pseudocyst, SEMS, Walled off pancreatic necrosis</p></sec><sec><title>OP211 IMPACT OF PANCREATIC DUCT STENTING ON THE LONG-TERM ENDOCRINE FUNCTION IN CHRONIC ALCOHOLIC PANCREATITIS</title><p><bold>C. Juergensen</bold><sup>1,*</sup>, U. Gottschalk<sup>2</sup></p><p><italic><sup>1</sup>Gastroenterology, CCM, Charite university Berlin (Germany), <sup>2</sup>Gastroenterology, Caritas-Klinik Pankow, Berlin, Germany</italic></p><p><bold>INTRODUCTION:</bold> Chronic pancreatitis is associated with a substantial risk of new onset diabetes secondary to progressive loss of parenchyma. Clinical facts are indicative for a central role of pancreatic duct obstruction in the development of diabetes. However, an impact of endoscopic pancreatic duct stenting on the outcome of endocrine function has not been established yet.</p><p><bold>AIMS&METHODS:</bold> 108 patients with symptomatic chronic alcoholic pancreatitis treated by endoscopic pancreatic duct stenting (PDS) for a period of 1 year were followed as part of a prospective interventional study. 56 patients suffering from symptomatic jaundice secondary to chronic pancreatitis but without pancreatic duct intervention, who were treated by sole bile duct stenting (BDS), served as control.</p><p><bold>RESULTS:</bold> At inclusion, the incidence of diabetes in both patients group was similar (PDS 36 of 108 (33.3%) vs. 19 of 56 patients (33.9%) in control group). After 5 years of follow-up, the incidence of new onset diabetes was significantly lower in the interventional group compared with sole BDS control (5 of 52 (9.6%) vs. 8 of 22 (36.4%), p <0.01).</p><p><bold>CONCLUSION:</bold> Pancreatic duct decompression by endoscopic stenting seems to be favorable for the preservation of endocrine function. A randomized trial on the impact of pancreatic duct stenting on the prevalence of diabetes is needed.</p><p><bold>Contact E-mail Address:</bold><email>Christian.Juergensen@charite.de</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Chronic Pancreatitis, diabetes mellitus, pancreatic stenting</p></sec><sec><title></title><p><bold>TUESDAY, OCTOBER 15, 2013 11:00-12:30</bold></p><p><bold>IBD therapy: Safety issues – Hall 2</bold></p></sec><sec><title>OP212 THIOGUANINE REMAINS AN ACCEPTABLE ALTERNATIVE IMMUNOSUPPRESSANT IN IBD</title><p><bold>K. Patel</bold><sup>1,*</sup>, R. Goel<sup>1</sup>, V. Kariyawasam<sup>1</sup>, P. Blaker<sup>1</sup>, M. Ward<sup>1</sup>, S. Ray<sup>1</sup>, S. Zaman<sup>1</sup>, S. Anderson<sup>1</sup>, P. Irving<sup>1</sup>, J. Sanderson<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom</italic></p><p><bold>INTRODUCTION:</bold> A significant proportion of inflammatory bowel disease (IBD) patients do not tolerate conventional thiopurines (azathioprine (AZA) and mercaptopurine (MP)). Thioguanine (TG) remains an alternative immunomodulator (IM) and has been in regular use in the IBD clinic at Guy’s & St. Thomas’ for more than 10 years. Concerns remain regarding nodular regenerative hyperplasia (NRH) in long-term use.</p><p><bold>AIMS&METHODS:</bold> We aimed to describe the indications, efficacy, monitoring and sequelae of TG use in IBD patients. Patients prescribed TG from 2008-2012, subsequent to a previously published series, were reviewed.</p><p><bold>RESULTS:</bold> 37 patients were identified (15 male, mean age 43 years). 29 patients had Crohn’s disease with 2 having co-existing orofacial granulomatosis, 6 had ulcerative colitis and 1 had IBD-unclassified. All had previous exposure to AZA and/or MP. The indications for TG were thiopurine intolerance in 23 and thiopurine induced pancreatitis in 13 patients.</p><p>Median duration of exposure was 11 months (IQR: 3-30). Maintenance doses were 20mg or 40mg. 20 patients (54%) were in clinical remission at the end of follow-up period, and 16 (41%) of these were steroid free. Mean TGN levels were 1177 pmol/8x10<sup>8 </sup>RBC (range 70-3182 pmol/8x10<sup>8</sup>). Differences in TGN concentrations in clinical responders and non-responders were not statistically significant.</p><p>Treatment was withdrawn in 7 patients. Withdrawal was for adverse events in 3 patients, which resolved on TG withdrawal (neutropenic sepsis, pancytopenia and AST rise) and treatment failure in further 3 patients. TG was ceased in another after the diagnosis of metastatic breast cancer whilst receiving Adalimumab and concomitant TG for 12 months. 7 patients discontinued TG because of side effects occurring within 2 months of initiation.</p><p>11 patients had long-term exposure (>18 months). Screening with liver biopsy and/or MRI-Liver was performed in 9 patients. All patients were screened with regular platelet counts and liver profile. None were diagnosed with NRH during follow-up.</p><p><bold>CONCLUSION:</bold> TG is a viable second-line IM and appears to be effective with an acceptable safety profile. Side effects are uncommon, occur early and cease upon TG withdrawal. Chief indications are previous failure of immunosuppressant therapy or thiopurine-associated pancreatitis. There were no cases of TG-associated pancreatitis. Concerns regarding hepatotoxicity and NRH were not manifest in this small series of patients in concordance with results from similar recent European series. Dedicated liver MRI screening along with quarterly liver profile and platelet counts to monitor for NRH should be offered to patients on long term therapy.</p><p><bold>Contact E-mail Address:</bold><email>kamal.patel@gstt.nhs.uk</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Immunosuppression, Inflammatory Bowel Diseases </p></sec><sec><title>OP213 LONG-TERM INCREASE OF SERUM CHOLESTEROL LEVEL IN ULCERATIVE COLITIS PATIENTS TREATED WITH CYCLOSPORINE: AN UNDERDIAGNOSED SIDE EFFECT FREQUENTLY ASSOCIATED WITH OTHER DRUG-RELATED COMPLICATIONS</title><p><bold>Z. Szepes</bold><sup>1</sup>, A. Bálint<sup>1</sup>, K. Farkas<sup>1</sup>, M. Szűcs<sup>2</sup>, F. Nagy<sup>1</sup>, T. Wittmann<sup>1</sup>, T. Molnár<sup>1,*</sup></p><p><italic><sup>1</sup>First Department of Medicine, <sup>2</sup>Department of Medical Physics and Informatics, University of Szeged, Szeged, Hungary</italic></p><p><bold>INTRODUCTION:</bold> Cyclosporine is one of the recommended therapeutic choices in severe ulcerative colitis (UC) refractory to steroid therapy, although several serious side effects may limit the use of the drug. Cyclosporine has been reported to increase the total cholesterol level; however, the change in the serum cholesterol levels before and after cyclosporine therapy has not been examined in UC patients.</p><p><bold>AIMS&METHODS:</bold> The aim of this study was to compare the serum cholesterol levels before and after the cyclosporine therapy in patients with refractory UC and to examine the association between serum cholesterol level and other common side effects.We prospectively assessed the serum cholesterol levels of UC patients who had been treated with cyclosporine. Data of 72 patients (39 females, 33 males, mean age at diagnosis 31.8 years, mean disease duration: 13.5 years) were analyzed statistically.</p><p><bold>RESULTS:</bold> The mean age of UC patients at the start of cyclosporine therapy was 40.3 years, and the mean disease duration at the beginning of the therapy was 8.6 years. The median duration of cyclosporine therapy was 9.6 months, and side effects developed in 52 patients. 65% of them developed increased cholesterol levels. The mean levels of serum cholesterol were 4.48, 6.1 and 5.08 mmol/l at the beginning, during and at the end of the therapy. Elevated serum cholesterol levels were detected in 47.2% of the patients. The serum cholesterol level was significantly increased during and after stopping cyclosporine therapy compared to the time before the use of the drug (p<0.001, p<0.004). However, cholesterol levels measured during the therapy were significantly higher compared to the time after stopping cyclosporine (p<0.001). A significant association was found between the increased serum cholesterol levels during (p=0.006) and after the cyclosporine therapy (p=0.003) and the frequency of side effects.</p><p><bold>CONCLUSION:</bold> Our findings suggest that cyclosporine therapy may result in increased serum cholesterol levels even in long-term after stopping the therapy. Considering that increased cholesterol levels were significantly more common in patients developing drug-related complications, the routine measurement of serum cholesterol may increase the safety of the drug.</p><p><bold>Contact E-mail Address:</bold><email>szepes.zoltan@med.u-szeged.hu</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> cholesterol, cyclosporine, ulcerative colitis</p></sec><sec><title>OP214 PYRAMID REGISTRY: AN OBSERVATIONAL STUDY OF ADALIMUMAB IN CROHN’S DISEASE: RESULTS AT YEAR 5</title><p><bold>G. D'Haens</bold><sup>1,2,*</sup>, W. Reinisch<sup>3</sup>, J. Satsangi<sup>4</sup> E. Loftus Jr <sup>5</sup>, R. Panaccione<sup>6</sup>, M. Castillo<sup>7</sup>, N. Kan-Dobrosky<sup>8</sup>, S. Eichner<sup>7</sup>, R. Thakkar<sup>7</sup></p><p><italic><sup>1</sup>Imelda GI Clinical Research Center, Bonheiden, Belgium, <sup>2</sup>Academic Medical Center, Amsterdam, Netherlands, <sup>3</sup>Medical University Vienna, Vienna, Austria, <sup>4</sup>Western General Hospital, Edinburgh, United Kingdom, <sup>5</sup>Mayo Clinic, Rochester, United States, <sup>6</sup>University of Calgary, Calgary, Canada, <sup>7</sup>AbbVie Inc, N Chicago, United States, <sup>8</sup>AbbVie Deutschland, Ludwigshafen, Germany</italic></p><p><bold>INTRODUCTION:</bold> Objective: To evaluate the long-term safety of adalimumab (ADA), up to 5 years (yrs), as it is used in routine clinical practice in patients (pts) with moderately to severely active Crohn’s disease (CD) from the observational registry PYRAMID.</p><p><bold>AIMS&METHODS:</bold> All pts entering the multicenter, non-interventional registry PYRAMID were to be followed for up to 6 yrs. Adverse events (AEs) were collected from the first dose up to 70 days after the last dose of ADA or through the 01 Dec 2012 cut-off. Rates of AEs were assessed per 100 patient-yrs (PY).</p><p><bold>RESULTS:</bold> A total of 5061 pts (57% female, mean age 37.8 yrs, median duration of CD 8.2 yrs) have enrolled in PYRAMID, totaling 13,914.2 PY of exposure, including prior exposure in CD ADA clinical trials. As of 01 Dec 2012, 3197 pts (63.2%) were still participating and 397 pts (7.8%) had up to 5 yrs of ADA exposure. Of the 2600 pts (51%) who received biologic therapy prior to enrollment, 98% were infliximab-experienced. Concomitant corticosteroids (CS), immunosuppressants (IMM) and IMM + CS were used by 30%, 36%, and 12% of pts, respectively. More pts receiving ADA combination therapy with IMM and/or CS experienced serious infections than pts receiving ADA monotherapy (10.7%/10.2% vs 7.3%, p<0.02). Standardized mortality ratios, calculated using the most recent country-specific mortality rates in a general population through 2006, were 0.90 (95% confidence interval [CI] 0.64-1.24) overall, 1.10 (95% CI 0.65-1.74) for females, and 0.77 (95% CI 0.46-1.20) for males. There were 37 treatment-emergent deaths reported; 6 of the 37 were considered possibly related to ADA. The table shows an overview of exposure-adjusted registry treatment-emergent AEs for years 3 and 5.</p><p>Table. Treatment-emergent Adverse Events (AE)
<table-wrap id="table32-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1">AE</th><th rowspan="1" colspan="1">Year 3 8174.7<sup>a</sup> PY Events (E/100PY)</th><th rowspan="1" colspan="1">Year 5 13351.8<sup>a</sup> PY Events (E/100PY)</th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">Any AE</td><td rowspan="1" colspan="1">2301 (28.1)</td><td rowspan="1" colspan="1">4673 (35.0)</td></tr><tr><td rowspan="1" colspan="1">Serious AE</td><td rowspan="1" colspan="1">1827 (22.3)</td><td rowspan="1" colspan="1">3389 (25.4)</td></tr><tr><td rowspan="1" colspan="1">AE leading to discontinuation</td><td rowspan="1" colspan="1">266 (3.3)</td><td rowspan="1" colspan="1">530 (4.0)</td></tr><tr><td rowspan="1" colspan="1">Serious infection</td><td rowspan="1" colspan="1">340 (4.2)</td><td rowspan="1" colspan="1">596 (4.5)</td></tr><tr><td rowspan="1" colspan="1">Opportunistic infection (excluding oral candidiasis and TB)</td><td rowspan="1" colspan="1">4 (<0.1)</td><td rowspan="1" colspan="1">17 (0.1)</td></tr><tr><td rowspan="1" colspan="1">TB</td><td rowspan="1" colspan="1">5 (<0.1)</td><td rowspan="1" colspan="1">15 (0.1)</td></tr><tr><td rowspan="1" colspan="1">Malignancy</td><td rowspan="1" colspan="1">48 (0.6)</td><td rowspan="1" colspan="1">90 (0.7)</td></tr><tr><td rowspan="1" colspan="1">Lymphoma</td><td rowspan="1" colspan="1">3 (<0.1)</td><td rowspan="1" colspan="1">6 (<0.1)</td></tr><tr><td rowspan="1" colspan="1">Demyelinating disorder</td><td rowspan="1" colspan="1">1 (<0.1)</td><td rowspan="1" colspan="1">6 (<0.1)</td></tr></tbody></table></table-wrap></p><p><sup>a</sup>PY refer to exposure in registry only</p><p><bold>CONCLUSION:</bold> At the 5-year timepoint, long-term ADA exposure continues to be well-tolerated in pts with moderately to severely active CD. No new safety signals have been identified. AE rates have remained stable over time.</p><p><bold>Disclosure of Interest</bold>: G. D'Haens Financial support for research from: AbbVie, Jansen Biologics, Given Imaging, MSD, DrFalk Pharma, Photopill, Lecture fee(s) from: AbbVie, Tillotts, Tramedico, Ferring, MSD, UCB, Norgine, Shire, Consultancy for: AbbVie, Actogenix, Boehringer Ingelheim, Janssen, Cosmo Technologies, Elan, Engene, Ferring Pharmaceuticals, Giuliani, GlaxoSmithKline, Merck, MSD, Neovacs, Novonordisk, Otsuka, PDL Biopharma, Pfizer, SetPoint, Shire, Takeda, Teva, UCB, W. Reinisch Consultancy for: AbbVie, Aesca, Amgen, Astellas, Astra Zeneca, Biogen IDEC, Bristol-Myers Squibb, Cellerix, Chemocentryx, Celgene, Janssen, Danone Austria, Elan, Ferring, Genentech, Grünenthal, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, Millenium, Mitsubishi Tanabe Pharma Corporation, MSD, Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer, Procter & Gamble, Prometheus, Robarts Clinical Trial, Schering-Plough, Setpointmedical, Shire, Takeda, Therakos, Tigenix, UCB, Vifor, Yakult, Zyngenia, Austria and 4SC., J. Satsangi: None Declared, E. Loftus, Jr Financial support for research from: AbbVie, UCB, Janssen Biotech, Millenium (now Takeda), GlaxoSmithKline, Amgen, Pfizer, Santarus, Braintree, Genentech, Bristol-Myers Squibb, Shire, Consultancy for: AbbVie, UCB, Janssen Biotech, Elan, Hospira, Eisai, Given, R. Panaccione Consultancy for: AbbVie, Amgen, AstraZeneca, Axcan Pharma (now Aptalis), Biogen Idec, Bristol-Myers Squibb, Centocor, ChemoCentryx, Eisai Medical Research Inc, Elan Pharmaceuticals, Ferring, Genentch, GlaxoSmithKline, Janssen, Merck Sharp and Dohme Corp, Millenium Pharmaceuticals Inc (now Takeda), Ocera Therapeutics Inc, Otsuka America Pharmaceutical, Pfizer, Shire Pharmaceuticals, Prometheus Labs, Schering-Plough, Synta Pharmaceuticals Corp, Teva, UCB Pharma, and Warner Chilcott, M. Castillo Shareholder of: AbbVie, Other: AbbVie employee, N. Kan-Dobrosky Shareholder of: AbbVie, Other: AbbVie employee, S. Eichner Shareholder of: AbbVie, Other: AbbVie employee, R. Thakkar Shareholder of: AbbVie, Other: AbbVie employee</p><p><bold>Keywords:</bold> adalimumab, Crohn’s disease, Safety</p></sec><sec><title>OP215 PREGNANCY OUTCOMES IN PATIENTS WITH CROHN’S DISEASE TREATED WITH INFLIXIMAB: RESULTS FROM THE TREAT™ REGISTRY</title><p><bold>G. R. Lichtenstein</bold><sup>1,*</sup>, B. G. Feagan<sup>2</sup>, R. D. Cohen<sup>3</sup>, B. A. Salzberg<sup>4</sup>, W. Langholff<sup>5</sup>, J. Morgan<sup>6</sup>, R. Nissinen<sup>6</sup>, S. R. Yerram<sup>6</sup>, F. Taillard<sup>6</sup>, W. J. Sandborn<sup>7</sup></p><p><italic><sup>1</sup>U Pennsylvania School of Medicine, Philadelphia, United States, <sup>2</sup>Robarts Research Institute, London, Canada, <sup>3</sup>University of Chicago Medical Center, Chicago, <sup>4</sup>Atlanta Gastroenterology Associates, Atlanta, <sup>5</sup>Janssen R&D, LLC, Spring House, <sup>6</sup>Janssen Services, LLC., Horsham, <sup>7</sup>University of California San Diego, La Jolla, United States</italic></p><p><bold>INTRODUCTION:</bold> Knowledge of pregnancy outcomes in pts with CD receiving anti-TNF therapy remains limited.</p><p><bold>AIMS&METHODS:</bold> TREAT is an observational registry which evaluates clinical safety outcomes in CD pts treated with IFX and other standards of care in North America. Pregnancy outcomes between July 1999-February 2012 are reported.</p><p><bold>RESULTS:</bold> 6273 pts were enrolled, 3440 received IFX. At enrollment, IFX-treated pts had a disease duration of 8.4yrs, had more severe disease, were more often smokers and were using more concomitant medication(s) vs pts on other CD treatments. A total of 348 pregnancies have been reported. Of these, 273 were maternal pregnancies, and 105 occurred in mothers treated with IFX. IFX-treated mothers had higher disease activity during pregnancy: 17.3% had moderate-to-severe disease, 48.0% had mild-to-moderate disease, and 34.7% were in remission vs 3.4%, 37.5% and 58% of the mothers on other CD treatments, respectively. Of the IFX-treated mothers 33.7% were on AZA/6-MP and 26.5% were on prednisone during pregnancy vs 36.4% and 11.4% of the mothers in the other-treatment-only group. Through an average of 6yrs of pt follow-up, 81.6% (80/98) of pregnancies with known outcome in IFX-exposed mothers and 91.0% (81/89) in other-treatments-only exposed mothers resulted in live births (p=0.064). Spontaneous abortions were reported in 16.3% of IFX-treated and 9.0% of the other-treatment-only treated mothers (p=0.134). 92.5% of IFX exposed and 87.7% of other–treatment-only live births resulted in healthy babies with no defect or other AE. One (1.3%) congenital malformation (an ectrodactyly in a familial context) was reported in the IFX-exposed infants and 3 (3.7%) (a heart murmur associated with a suspicion of cystic fibrosis, a Down’s syndrome, and a cortical vision delay) in the other-treatment-only exposed infants. 5 (4.8%) IFX-exposed infants were reported to have a prolonged hospital stay vs 12 (11.5%) in the other-treatment-only exposed infants.</p><p><bold>CONCLUSION:</bold> Data from TREAT show that the clinical condition of infants born to women with prenatal exposure to IFX is comparable to those exposed to other CD treatments. A trend for a lower rate of live birth was reported among IFX-exposed mothers as compared to mothers not exposed to IFX. The confirmation of these results and the role of potential confounding factors such as high disease activity before or during pregnancy, smoking and concomitant medication use, will require further study.</p><p><bold>Contact E-mail Address:</bold><email>rnissine@its.jnj.com</email></p><p><bold>Disclosure of Interest</bold>: G. Lichtenstein Financial support for research from: Janssen , B. Feagan Financial support for research from: Janssen, R. Cohen Financial support for research from: Janssen , B. Salzberg Financial support for research from: Janssen , W. Langholff Other: Janssen R&D employee, J. Morgan Other: Janssen Services, LLC. employee, R. Nissinen Other: Janssen Services, LLC. employee, S. Yerram Other: Janssen Services, LLC. employee, F. Taillard Other: Janssen Services, LLC. employee, W. Sandborn Financial support for research from: Janssen</p><p><bold>Keywords:</bold> Crohn's disease, Infliximab, TREAT Registry</p></sec><sec><title>OP216 ADALIMUMAB (ADA) AND INFLIXIMAB (IFX) THERAPY DURING PREGNANCY IN IBD: A PROSPECTIVE ASSESSMENT OF OUTCOME, SAFETY, ANTI-TNFΑ CORD BLOOD AND FOLLOW UP BLOOD LEVELS IN NEWBORNS</title><p><bold>S. Traussnigg</bold><sup>1,*</sup>, A. Eser<sup>1</sup>, C. Primas<sup>1</sup>, P. Papay<sup>1</sup>, C. Gratzer<sup>1</sup>, A. Mikulits<sup>2</sup>, S. Angelberger<sup>1</sup>, W. Reinisch<sup>1</sup>, M. Trauner<sup>1</sup>, H. Vogelsang<sup>1</sup>, G. Novacek<sup>1</sup>, C. Dejaco<sup>1</sup> Austrian Working Group on IBD</p><p><italic><sup>1</sup>Department of Internal Medicine III - Division of Gastroenterology and Hepatology, <sup>2</sup>Gastroenterology and Hepatology, Medical University Vienna, Vienna, Austria</italic></p><p><bold>INTRODUCTION:</bold> Reports on anti-TNFα therapy during pregnancy have not shown serious adverse events, although data are still scare. Cord blood levels have been assessed in few newborns revealing significant placental transfer of anti-TNFα antibodies. Therefore discontinuation of treatment prior to the third trimester of pregnancy is recommended. First data about drug levels detectable up to 6 months of age indicate a careful handling of life vaccinations.</p><p><bold>AIMS&METHODS:</bold> We aimed to evaluate the safety and impact of anti-TNFα therapy on fetal development and pregnancy outcome, and to assess cord blood as well as drug levels in the newborns at three and six months follow-up (FU). All women with Crohn’s disease (CD) or ulcerative colitis (UC) at our tertiary referral center treated with anti-TNFα therapy during pregnancy were included from Aug 2003 to April 2013 including drug levels since 2011.</p><p><bold>RESULTS:</bold> A total of 14 pregnancies in 13 women with IBD were included (median age 26 years; 13 CD, 1 UC). Patients received either ADA (n=9) or IFX (n=5). At time of conception all women received anti-TNFα treatment. Therapy was discontinued at median gestational week (GW) 24 (2-37). Seven patients remained in remission during the whole pregnancy. Three out of four new flares developed after cessation of anti-TNFα. Four women experienced new flares within one week after birth. All completed pregnancies (n=14; 5 IFX, 9 ADA) ended in live births at median GW 40 (36-42). Median birth weight was 3180g (1960-4530g). No perinatal complications or congenital malformations occurred. After discontinuation of ADA in median GW 27 (24-30) cord blood levels (n=5) of median 1.10 μg/mL (0.36-3.05) were detectable, which all were higher than the available maternal levels at median 0.83 μg/ml (0.33-1.25). At 3 months FU (n=3) levels were still detectable (median 0.7; 0.45-1.1) whereas at 6 months FU (n=1) a value of 0.29 µg/ml was interpreted as negative. During FU of median 12 months no clinical signs of immunodeficiency were observed.</p><p><bold>CONCLUSION:</bold> Anti-TNFα therapy during pregnancy in women with IBD appears to be safe. However, data on ADA cord blood levels in newborns emphasize neonatal antibody exposure, suggesting a similar early cessation of ADA therapy, as recommended for IFX. ADA levels at 3 months FU were still detectable supporting a very cautious handling of life vaccines especially in the first 12 months of age.</p><p><bold>Contact E-mail Address:</bold><email>stefan.traussnigg@meduniwien.ac.at</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> adalimumab, anti TNF therapy, crohn disease, IBD, infliximab, Pregnancy</p></sec><sec><title>OP217 EFFICACY AND SAFETY OF ANTI-TNF THERAPY IN ELDERLY PATIENTS WITH INFLAMMATORY BOWEL DISEASE</title><p><bold>T. Lobatón</bold><sup>1,*</sup>, M. Ferrante<sup>1</sup>, V. Ballet<sup>1</sup>, P. Rutgeerts<sup>1</sup>, S. Vermeire<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology, University Hospital Leuven, LEUVEN, Belgium</italic></p><p><bold>INTRODUCTION:</bold> The general increased life expectancy is reflected in the age of patients with inflammatory bowel disease (IBD). The knowledge about efficacy and safety of anti-tumor necrosis factor (TNF) therapy is scarce and conflicting.</p><p><bold>AIMS&METHODS:</bold> Our objectives were to assess the efficacy and safety of anti-TNF therapy in elderly patients taking into account eventual comorbidity. <bold>Methods: </bold>We performed a retrospective single-centre study where 64 IBD patients initiating anti-TNF treatment at age ≥65 years (cases) were compared to 104 IBD patients initiating anti-TNF at age <65 years (control 1) and 70 anti-TNF naïve IBD patients treated with azathioprine (AZA) and/or corticosteroids (CS) ≥65 years (control 2). Both control groups were matched to the case-group for type of IBD (Crohn’s disease or ulcerative colitis), follow up (FU) and type of anti-TNF (adalimumab or infliximab) in the case of control 1. Comorbidity was assessed using the Charlson Comorbidity Index (ChCI). Both efficacy and safety of treatment were analyzed.</p><p><bold>RESULTS:</bold><table-wrap id="table33-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1"></th><th rowspan="1" colspan="1">Cases (n=64)</th><th rowspan="1" colspan="1">Control 1 (n=104)</th><th rowspan="1" colspan="1">Control 2 (n=70)</th></tr></thead><tbody align="left"><tr><td colspan="4" rowspan="1"><bold>Baseline characteristics</bold></td></tr><tr><td rowspan="1" colspan="1">Age (mean, (range))</td><td rowspan="1" colspan="1">70 (65-92) </td><td rowspan="1" colspan="1">38 (15-63) </td><td rowspan="1" colspan="1">67 (65-84) </td></tr><tr><td rowspan="1" colspan="1">Disease duration in years (mean ± SD)</td><td rowspan="1" colspan="1">13.7 ±14.3 </td><td rowspan="1" colspan="1">8.8 ± 8.7 </td><td rowspan="1" colspan="1">9.7 ± 12.7</td></tr><tr><td rowspan="1" colspan="1">FU period in months (mean ± SD)</td><td rowspan="1" colspan="1">54.1 ± 41.7</td><td rowspan="1" colspan="1">65.6 ± 35.3</td><td rowspan="1" colspan="1">72.1 ± 62.1</td></tr><tr><td colspan="4" rowspan="1"><bold>Adverse events</bold></td></tr><tr><td rowspan="1" colspan="1">Infections</td><td rowspan="1" colspan="1">8 (13%)</td><td rowspan="1" colspan="1">9 (9%) <italic>P</italic>= 0.44</td><td rowspan="1" colspan="1">18 (26%) <italic>P</italic>= 0.44</td></tr><tr><td rowspan="1" colspan="1">Malignancy</td><td rowspan="1" colspan="1">6 (9%)</td><td rowspan="1" colspan="1">5 (5%) <italic>P</italic>= 0.34</td><td rowspan="1" colspan="1">13 (19%) <italic>P</italic>= 0.14</td></tr><tr><td rowspan="1" colspan="1">Hospitalizations</td><td rowspan="1" colspan="1">27 (42%)</td><td rowspan="1" colspan="1">29 (28%) <italic>P</italic>= 0.07</td><td rowspan="1" colspan="1">34 (49%) <italic>P</italic>= 0.30</td></tr><tr><td rowspan="1" colspan="1">Death</td><td rowspan="1" colspan="1">5 (8%)</td><td rowspan="1" colspan="1">2 (2%) <italic>P</italic>= 0.11</td><td rowspan="1" colspan="1">7 (10%) <italic>P</italic>= 1.</td></tr></tbody></table></table-wrap></p><p>Mean age, disease duration, FU and adverse events for each group are collected in Table 1. The clinical response to anti-TNF at short term (4-10 weeks) and long term (at least 6 months) was significantly lower in the elderly population than in younger patients (67% vs. 89%; <italic>P</italic>=0.001 and 50% vs. 76%; <italic>P</italic><0.001 respectively). These results were confirmed after adjusting for disease duration in multivariate analysis (<italic>P</italic>=0.001). When considering all patients with a ChCI =0, the age of ≥ 65 years remained a significant risk factor for lower short and long term clinical response (67% vs. 88%; <italic>P</italic>=0.016 and 52% vs. 76%; <italic>P</italic>=0.014). Elderly patients treated with anti-TNF with a ChCI>0 had a higher risk for malignancy and death than patients with a ChCI=0 (19% vs. 0%; <italic>P</italic>=0.01 and 16% vs.0%; <italic>P</italic>=0.02 respectively).</p><p><bold>CONCLUSION:</bold> Elderly patients treated with anti-TNF have a lower rate of clinical response (regardless of their comorbidity). The rate of adverse events is higher in elderly patients but especially in those with a higher comorbidity. Comorbidity is an important factor to take into account when starting anti-TNF therapy in elderly patients.</p><p><bold>REFERENCES:</bold></p><p>1. Cottone M, Kohn A, Daperno M, et al. Advanced age is an independent risk factor for severe infections and mortality in patients givenanti-tumor necrosis factor therapy for inflammatory bowel disease. Clin Gastroenterol Hepatol. 2011;9:30–35.</p><p>2. Bhushan A, Pardi DS, Loftus EV, et al. Association of age with adverse events from biologic therapy in patients with inflammatory bowel disease. Gastroenterology. 2010;138:Supplement (Abstract 413).</p><p>3. Desai A, Zator ZA, de Silva P et al. Older age is associated with higher rate of discontinuation of anti-TNF therapy in patients with inflammatory bowel disease.Inflamm Bowel Dis. 2013 Feb;19(2):309-15.</p><p><bold>Contact E-mail Address:</bold><email>tlobaton@bellvitgehospital.com</email></p><p><bold>Disclosure of Interest</bold>: T. Lobatón: None Declared, M. Ferrante Financial support for research from: Janssen Biologics , Lecture fee(s) from: Merck, Tillotts, Ferring, Abbvie, Consultancy for: Abbvie, Merck, Janssen Biologics , V. Ballet: None Declared, P. Rutgeerts Financial support for research from: UCB Pharma, Abbvie, Janssen Biologics, Merck, Prometheus, Lecture fee(s) from: Abbvie, Merck, Consultancy for: Amgen, Merck, UCB Pharma, Genentech, BMS, Abbvie, Janssen Biologics, Millenium, Neovacs, Actogenics, Prometheus,, S. Vermeire Financial support for research from: UCB Pharma, MSD, Abbvie, Lecture fee(s) from: Abbvie, Merck, Ferring, UCB Pharma, Centocor, Consultancy for: UCB Pharma, AstraZeneca, Ferring, Abbvie, Merck, Ferring, Shire, Pfizer</p><p><bold>Keywords:</bold> anti TNF therapy, elderly patients</p></sec><sec><title></title><p><bold>TUESDAY, OCTOBER 15, 2013 11:00-12:30</bold></p><p><bold>Non-invasive diagnosis and staging of liver disease – Hall Stockholm</bold></p></sec><sec><title>OP221 META-ANALYSIS OF ACOUSTIC RADIATION FORCE IMPULSE IMAGING FOR THE STAGING OF LIVER FIBROSIS</title><p><bold>M. Friedrich-Rust</bold><sup>1,*</sup>, J. Nierhoff<sup>2</sup>, A. Chávez Ortis<sup>1</sup>, S. Zeuzem<sup>1</sup>, E. Herrmann<sup>2</sup></p><p><italic><sup>1</sup>Department of Internal Medicine 1, J.W.Goether University Hospital, <sup>2</sup>Institute of Biostatistics and Mathematical Modelling , Faculty of Medicine, J.W. Goethe-University, Frankfurt, Germany</italic></p><p><bold>INTRODUCTION:</bold> Acoustic Radiation Force Impulse (ARFI) imaging is an ultrasound-based elastography method which is integrated in a conventional ultrasound machine enabling the exact localization of measurement site. Many single studies have reported promising results.</p><p><bold>AIMS&METHODS:</bold> The aim of the present meta-analysis based on original and abstract publications was to evaluate the overall performance of ARFI for the diagnosis of liver fibrosis.</p><p>Literature databases and conference abstracts were searched from January 2007 up to February 2012. Studies were included if they evaluate the performance of ARFI of the liver using liver biopsy as reference standard. A random effects meta-analysis of the area under the receiver operating characteristics curve (AUROC) was performed as well as summary receiver operating curve techniques. Quality analyses were conducted to assess sources of heterogeneity.</p><p><bold>RESULTS:</bold> The systematic literature search revealed 37 studies with overall 3983 patients. The mean diagnostic accuracy of ARFI expressed as AUROC was 0.84 for the diagnosis of significant fibrosis (F≥2), 0.89 for the diagnosis of severe fibrosis (F≥3) and 0.92 for the diagnosis of liver cirrhosis (F=4). Subgroup analyses revealed sources of heterogeneity between the different underlying liver diseases for the diagnosis of severe fibrosis (F≥3) and liver cirrhosis. In addition, AUROC for the diagnosis of severe fibrosis (F≥3) was significantly lower in studies examining patients with chronic hepatitis B only as compared to patients with mixed chronic liver disease (0.87 vs 0.92, p=0.017). Further, analysing quantitative factors showed a significant influence of the mean BMI on the AUROC for the diagnosis of significant fibrosis (F≥2) with a reduction of the AUROC with increasing BMI (p=0.0062).</p><p><bold>CONCLUSION:</bold> The meta-analysis revealed a good diagnostic accuracy of the ARFI-imaging for the staging of significant and severe fibrosis and an excellent diagnostic accuracy for the diagnosis of liver cirrhosis.</p><p><bold>Contact E-mail Address:</bold><email>Mireen.Friedrich-Rust@kgu.de</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> ARFI, elastography, liver fibrosis, metaanalysis</p></sec><sec><title></title><p><bold>TUESDAY, OCTOBER 15, 2013 11:00-12:30</bold></p><p><bold>Faecal calprotection as a diagnostic tool in IBS and IBD – Hall Oslo</bold></p></sec><sec><title>OP222 DIAGNOSTIC ACCURACY AND CLINICAL APPLICATION OF FAECAL CALPROTECTIN IN ADULT PATIENTS PRESENTING WITH GASTROINTESTINAL SYMPTOMS IN PRIMARY CARE</title><p><bold>P. Pavlidis</bold><sup>1,*</sup>, F. Chedgy<sup>1</sup>, B. Davies<sup>1</sup>, J. Tibble<sup>1</sup></p><p><italic><sup>1</sup>Digestive Diseases Centre, Brighton and Sussex University Hospitals, Brighton, United Kingdom</italic></p><p><bold>INTRODUCTION:</bold> General practitioners (GPs) are often consulted for symptoms related to the gastrointestinal tract. Irritable bowel syndrome (IBS) is a non organic chronic condition characterised by chronic abdominal pain, diarrhoea, constipation and/ or alternating bowel habit and accounts for almost 12% of GP consultations and 28% of referrals to gastroenterologists. Endoscopic procedures do not reveal any significant abnormalities in 70% of these patients.</p><p>Faecal calprotectin (FCLP), a protein found in the cytosol of neutrophils, is a sensitive and specific marker of intestinal inflammation and is used widely in secondary care to differentiate between organic and non organic disease. The use of FCLP in primary care in order to reduce referrals to secondary care and invasive endoscopic procedures bookings is appealing although direct evidence to support this practice is limited.</p><p><bold>AIMS&METHODS:</bold> Assessment of FCLP test performance in primary care within an irritable bowel syndrome (IBS) diagnostic pathway. Retrospective study based on consecutively collected FCLP data from 962 patients, aged 18-45, presenting to their general practitioner (GP) with persistent gastrointestinal symptoms (>3 months).</p><p><bold>RESULTS:</bold> 686 (71%) had a negative (<50 μg/g) FCLP test and 276 (29%) patients had a positive (>50 μg/g) FCLP. 28% (77/276) of the patients testing positive and 3% (17/686) of those testing negative had an organic diagnosis, only 5 of whom were diagnosed with IBD (proctitis). 181 (26%) of the 686 patients with negative FCLP were referred to secondary care. At 50mcg/g the sensitivity of the FCLP test for organic disease was 82%, (95% CI 73-89) whilst the specificity for organic disease was 77% (95% CI 74-80). The odds ratio for organic disease with a positive FCLP is 16 (95% CI 9-26), with NPV and PPV of 98% and 28% respectively. A cut off increase to 150μg/g reduces the NPV by 1% whilst increasing the PPV to 71%. This would reduce colonoscopy and flexible sigmoidoscopy bookings by 10% and secondary care referrals by 35% at the cost of 4 missed cases of inflammatory bowel disease.</p><p><bold>CONCLUSION:</bold> This study provides the first evidence on the use of FCLP testing in primary care. The low prevalence of organic disease in this setting has a significant impact on test performance. This suggests a need for change in cut off value, to improve PPV whilst accepting a reduction in test sensitivity, if it is to be used as part of the pathway for management of patients with suspected IBS.</p><p><bold>REFERENCES:</bold></p><p>1. Hatlebakk JG, et al. Diagnostic approach to suspected irritable bowel syndrome. Best Practice and Reseaerch in Clin Gastroenterology 2004;18(4):735-746</p><p>2. Dolwani S, et al. Diagnostic accuracy of faecal calprotectin estimation in prediction of abnormal small bowel radiology. Alim Pharm & Ther 2004;20(6):615-21</p><p>3. Tibble JA, et al. Use of Surrogate Markers of Inflammation and Rome Criteria to Distinguish Organic From Nonorganic Intestinal Disease. Gastroenterology 2002;123:450–460</p><p>4. Van Rheenen PF, Van de Vijver E, Fidler V, Faecal calprotectin for screening of patients with suspected inflammatory bowel disease: diagnostic meta-analysis BMJ 2010;341:c3369 doi:10.1136/bmj.c3369</p><p><bold>Contact E-mail Address:</bold><email>Jeremy.Tibble@bsuh.nhs.uk</email></p><p><bold>Disclosure of Interest</bold>: P. Pavlidis: None Declared, F. Chedgy: None Declared, B. Davies: None Declared, J. Tibble Financial support for research from: Janssen and Roche, Other: Advisory board member for Janssen</p><p><bold>Keywords:</bold> diagnostic accuracy, faecal calprotectin, irritable bowel syndrome, primary care </p></sec><sec><title>OP223 THE IMPACT OF VARIABILITY OF FAECAL CALPROTECTIN (F-CP) ENZYME-LINKED IMMUNOSORBENT ASSAY (ELISA) KITS RESULTS IN CLINICAL PRACTICE.</title><p><bold>S. Whitehead</bold><sup>1,*</sup>, C. Morgese<sup>2</sup>, P. Banerjee<sup>2</sup>, A. Ali<sup>2</sup>, B. McKaig<sup>2</sup>, C. Ford<sup>1</sup>, J. French<sup>3</sup>, R. Gamma<sup>1</sup>, M. J. Brookes<sup>2</sup></p><p><italic><sup>1</sup>Clinical Chemistry, <sup>2</sup>Gastroenterology Unit, WOLVERHAMPTON HOSPITAL, Wolverhampton, <sup>3</sup>University of Birmingham, Birmingham, United Kingdom</italic></p><p><bold>INTRODUCTION:</bold> Faecal calprotectin (f-Cp), a marker of intestinal inflammation; (i) distinguishes irritable bowel syndrome (IBS) from inflammatory bowel disease (IBD), (ii) monitors disease activity in IBD and (iii) predicts relapse in IBD. We have reported a greater than threefold between-assay variability in f-Cp values with different commercially available ELISA assays. We now report on whether between-assay variability of f-cp results may influence clinical decision making. We measured f-cp in patients with IBS and IBD using four commercially available ELISA assays; Immunodiagnostik, Bühlmann Laboratories, Phadia and Calprest f-Cp ELISA assays.</p><p><bold>AIMS&METHODS:</bold> We prospectively evaluated patients. At the time of stool donation the following were collected to define clinical activity of IBD: (i) demographic data, (ii) clinical activity indices (Harvey-Bradshaw index or Mayo score), (iii) serum and whole blood samples for inflammatory markers, (iv) radiological imaging (MRI or CT enterography) and/or (v) endoscopic evaluation. F-Cp, following extraction, was measured with Immunodiagnostik, Bühlmann Laboratories, Phadia and Calprest f-Cp ELISA assays. These assays all recommend a f-Cp cut-of of <50 ug/g as normal</p><p><bold>RESULTS:</bold> 70 patients were invited to participate; 12.8% (n=9) failed to provide a sample and 1 sample was inadequate. The remaining patients (n=60) had clinically established diagnoses of IBS (28.3%; n=17), Crohns (25%; n= 15) and Ulcerative colitis (UC: 46.7%; n=28). f-Cp was significantly higher in patients with severe UC than patients with mild or moderate disease activity (Mayo activity score). There was no correlation between f-Cp and disease activity in Crohns disease (Harvey-Bradshaw index). Inter-assay variability of up to 3-fold was seen in the reporting ranges between the three ELISA kits. This variability means that there are obvious differences between the sensitivity and specificity at different cut-off values (Table 1).</p><p>Table1
<table-wrap id="table34-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="2" colspan="1"></th><th colspan="2" rowspan="1"><hr></hr><bold>50 ug/g cut-off</bold></th><th colspan="2" rowspan="1"><hr></hr><bold>100 ug/g cut-off</bold></th></tr><tr><th rowspan="1" colspan="1"><bold>Sens </bold></th><th rowspan="1" colspan="1"><bold>Spec</bold></th><th rowspan="1" colspan="1"><bold>Sens</bold></th><th rowspan="1" colspan="1"><bold>Spec</bold></th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1"><bold>Buhlmann</bold></td><td rowspan="1" colspan="1">97.7%</td><td rowspan="1" colspan="1">82.3%</td><td rowspan="1" colspan="1">95.3%</td><td rowspan="1" colspan="1">100%</td></tr><tr><td rowspan="1" colspan="1"><bold>Immunodiagnostik</bold></td><td rowspan="1" colspan="1">100%</td><td rowspan="1" colspan="1">94.1%</td><td rowspan="1" colspan="1">95.3%</td><td rowspan="1" colspan="1">100%</td></tr><tr><td rowspan="1" colspan="1"><bold>Phadia</bold></td><td rowspan="1" colspan="1">84.6%</td><td rowspan="1" colspan="1">100%</td><td rowspan="1" colspan="1">69.2%</td><td rowspan="1" colspan="1">100%</td></tr><tr><td rowspan="1" colspan="1"><bold>Calprest</bold></td><td rowspan="1" colspan="1">95.3%</td><td rowspan="1" colspan="1">94.1%</td><td rowspan="1" colspan="1">81.4%</td><td rowspan="1" colspan="1">100%</td></tr></tbody></table></table-wrap></p><p><bold>CONCLUSION:</bold> f-Cp is an established technique used to distinguish between IBS and IBD. We demonstrate a good correlation between f-cp levels with the disease activity in UC but not in Crohns disease. In the absence of assay standardization, the reported inter-assay variability indicates that cut-off values for f-cp should be assay specific to maximize diagnostic efficiency.</p><p><bold>Contact E-mail Address:</bold><email>m.j.brookes@bham.ac.uk</email></p><p><bold>Disclosure of Interest</bold>: S. Whitehead: None Declared, C. Morgese: None Declared, P. Banerjee: None Declared, A. Ali: None Declared, B. McKaig: None Declared, C. Ford: None Declared, J. French: None Declared, R. Gamma: None Declared, M. Brookes Financial support for research from: Vifor International</p><p><bold>Keywords:</bold> calprotectin, inflammatory bowel disease</p></sec><sec><title>OP224 FECAL CALPROTECTIN LEVELS IN IBS PATIENTS: RESULTS FROM PROSPECTIVE STUDY</title><p><bold>C. Melchior</bold><sup>1,2,*</sup>, T. Aubry<sup>1</sup>, G. Gourcerol<sup>2,3</sup>, M. Coeffier<sup>2</sup>, A.-M. Leroi<sup>2,3</sup>, P. Ducrotté<sup>1,2</sup></p><p><italic><sup>1</sup>Gastroenterology, Rouen University Hospital, <sup>2</sup>INSERM U1073, Rouen University, <sup>3</sup>Physiology, Rouen University Hospital, ROUEN, France</italic></p><p><bold>INTRODUCTION:</bold> Low-grade inflammation is considered one of the underlying mechanisms of irritable bowel syndrome (IBS). How often stigmata of low-grade inflammation are present in IBS patients remains unclear. Calprotectin is one of the faecal markers for the detection of an intestinal inflammation.</p><p><bold>AIMS&METHODS:</bold></p><p>a) To assess the percentage of Rome III IBS patients with elevated faecal calprotectin levels, b) to look for a relationship between high calprotectin levels and IBS phenotype, an history of post-infectious IBS (PI-IBS), the existence of a small intestinal bacterial overgrowth (SIBO), histological stigmata of inflammation on mucosal biopsies or the clinical response to an anti-inflammatory treatment.</p><p>Calprotectin levels were determined by an ELISA technique (Bühlmann Labs) on at least 50 mg of recent stools in any new IBS patient. In case of elevated levels (≥ 50µg/g), both normal ANCA/ASCA levels and normal small bowel examination by CT-scan, MRI or wireless capsule were required to consider that the patient was an IBS patient. A glucose breath-test was discussed in any patient to detect SIBO.</p><p><bold>RESULTS:</bold> 45 consecutive patients (F/M ratio : 2.5), mean aged 40, were included. In 80 % of the cases, IBS was an IBS-D. Mean pain intensity was scored 6.5 on a 0-10 VAS. Among these 45 patients, 15 (31.1%) exhibited faecal calprotectin levels higher than 50 µg/g (range : 53-155). Calprotectin levels were correlated neither with IBS severity nor an history of PI-IBS. An histological mucosal infiltrate by lymphocytes or leukocytes was found in 18/45 patients (40 %) but was associated with elevated calprotectin levels in only 6 out of 18 (33 %). SIBO was detected in 3 of the 29 patients who accepted to perform the glucose breath test. In these 3 patients, calprotectin levels were normal. A 2-month anti-inflammatory treatment by budesonide or mesalasine was indicated in 16 patients. The treatment was clinically effective in 100 % des 9 cases with high and in only 57 % of the 7 cases with normal calprotectin levels (p=0.0625).</p><p><bold>CONCLUSION:</bold> In this series mainly of IBS-D, 1/3 of the patients had elevated calprotectin levels. Such an increase was correlated neither with histological stigmata of inflammation, nor a PI-IBS history nor IBS severity. Therefore, the interpretation of high calprotectin levels remains unclear. However, a trend for better clinical results with budesonide or mesalasine was observed in patients with high calprotectin levels.</p><p><bold>Contact E-mail Address:</bold><email>chloe.melchior@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> fecal calprotectin, IBS</p></sec><sec><title>OP225 DISEASE LOCALIZATION DETERMINES FECAL CALPROTECTIN LEVELS IN CROHN’S DISEASE</title><p><bold>K. Gecse</bold><sup>1,*</sup>, S. van Wilpe<sup>1</sup>, H. Brandse<sup>1</sup>, M. Lowenberg<sup>1</sup>, C. Ponsioen<sup>1</sup>, G. van den Brink<sup>1</sup>, G. D'Haens<sup>1</sup></p><p><italic><sup>1</sup>Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, Netherlands</italic></p><p><bold>INTRODUCTION:</bold> The correlation between Simple Endoscopic Index for Crohn’s Disease (SES-CD) and fecal calprotectin is well established in (ileo)colonic Crohn’s disease (CD). However, existing data are conflicting with regard to fecal calprotectin and endoscopic mucosal damage in ileal CD.</p><p><bold>AIMS&METHODS:</bold> The objective of this study was to evaluate the correlation between mucosal ulcerations and fecal as well as serum biomarkers and to examine possible differences between biomarker profiles of patients with ileal and (ileo)colonic CD. A retrospective search was carried out to identify CD patients seen between 2011 and 2013, where ileocolonoscopy, fecal calprotectin (CALPRO; Buhlmann Calprotectin ELISA), serum C-reactive protein (CRP) and serum leukocyte (LEU) were measured within four weeks of interval during which no change in medication occurred. Ileocolonoscopies were scored for the presence of ulcers in each segment as none (0), aphthous (1), large (2) and very large (3), as defined by the SES-CD. The sum of segment scores resulted in a partial SES-CD (pSES-CD). Statistical tests were performed with GraphPad Prism 5.01, including Spearman correlation and unpaired t-test.</p><p><bold>RESULTS:</bold> 44 patients (19 male, age (mean ± SEM) 36.5 ± 2.0 years) were identified, of which 9 patients were characterized as ileal (L1), 20 as colonic (L2) and 15 as ileocolonic (L3) according to the Montreal classification. In the total population CALPRO correlated best with pSES-CD (r=0.76, p<0,0001), followed by LEU (r=0.54, p=0.0004) and CRP (r=0.45, p=0.0026). Patients with L1 CD had a significantly lower CALPRO level than those with L2 and L3 disease in the presence of large and/or very large ulcers (mean ± SEM: 297 ± 81μg/g vs. 1523 ± 97μg/g, p<0,0001). LEU was also significantly lower in the presence of large and/or very large ulcers in L1 CD compared to those with L2 and L3 disease (mean± SEM: 6,7 ± 0,9 G/l vs. 10,6 ± 0,8G/l, p=0.02). Similar trend was identified regarding CRP levels (mean ± SEM: 5,3 ± 2,2 mg/l vs. 39,9 ± 13,4mg/l, p=0,17, ns.).</p><p><bold>CONCLUSION:</bold> Patients with ileal CD may have large or very large ulcers in the absence of markedly elevated fecal calprotectin levels. Consequently, cut-off values for ileal CD may differ from those with (ileo)colonic disease. A possible explanation may lie in less extensive ulcerated surface in the ileum, resulting in lower mucosal and systematic inflammatory load.</p><p><bold>Contact E-mail Address:</bold><email>krisztina.gecse@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> biomarker, calprotectin, C-reactive protein, Crohn's disease</p></sec><sec><title>OP226 THE PATHOPHYSIOLOGY AND SEVERITY OF SYMPTOMS IN IBS PATIENTS ARE NOT ASSOCIATED WITH MUCOSAL IMMUNE ACTIVITY AS DETERMINED BY FECAL CALPROTECTIN</title><p><bold>L. Öhman</bold><sup>1,*</sup>, H. Törnblom<sup>1</sup>, B. Le Neve<sup>2</sup>, D. Guyonnet<sup>2</sup>, S. Isaksson<sup>1</sup>, M. Simrén<sup>1</sup></p><p><italic><sup>1</sup>Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden, <sup>2</sup>Danone research, PALAISEAU, France</italic></p><p><bold>INTRODUCTION:</bold> Subgroups of patients with irritable bowel syndrome (IBS) may have low grade mucosal immune activity. Fecal calprotectin (f-calprotectin) is a marker for mucosal neutrophil inflammation. IBS patients are reported to have normal levels of calprotectin, but the levels may vary within the patient group, and it is not known whether this variation within or slightly above the normal range may reflect pathophysiology or symptoms of the patients.</p><p><bold>AIMS&METHODS:</bold> The aim was to determine if levels of f-calprotectin reflect the clinical and pathophysiological phenotype of IBS patients. Analyses of f-calprotectin in stool samples of 98 IBS patients and 35 healthy controls were performed with Buhlmann ELISA (lower detection limit 10 ug/g). All IBS subjects completed Bristol stool form (BSF) scale and IBS symptom severity scale (IBS-SSS) questionnaire. Patients also underwent a rectal barostat test with ballon distentions and colonic transit time measurement with ingestion of radiopaque rings.</p><p><bold>RESULTS:</bold> IBS patients had comparable levels of f-calprotectin to controls (17.5 (10-47.0) vs. 11(10-44.0) (median (25-75%) percentiles) ug/g; p=0.21)). Among IBS patients, 13 subjects (13.2%) had f-calprotectin levels above the 90<sup>th</sup> percentile in the controls (98.8ug/g). There was no difference in IBS subgroup according to Rome III (IBS-C, IBS-D, IBS-M, IBS-U) in patients with high as compared to normal f-calprotectin. Also the disease duration was comparable in the two groups (9.5 (2-15) vs. 10 (5-15.3) years; p=0.46). There was no difference between IBS patients with high vs. normal levels of f-calprotectin regarding intensity or frequency of pain, bloating severity, bowel habit dissatisfaction, or daily life as estimated by IBS-SSS (p> 0.5). Also, total IBS-SSS score was comparable in the two groups (306(243-350) vs. 331(250-384); p=0.36). The average stool form according to BSF (3.7 (2.9-4.4) vs. 4.1 (3.3-4.9); p=0.2) and stool frequency (1.5 (0.75-1.9) vs. 1.6 (1.2-2.3); p=0.29) were similar in patients with high respective normal calprotectin levels. The pain threshold in rectal barostat test was comparable in IBS patients with high respective normal levels of f-calprotectin (24 (24-28) vs. 24 (20-32) mmHg; p=0.65). Oroanal transit time (OATT) was comparable in the two groups (1.5 (0.5-1.9) vs. 1.2(0.7-1.9) days; p=0.95)</p><p><bold>CONCLUSION:</bold> Fecal calprotectin within the normal range is not associated with the severity of IBS symptoms or key pathophysiological factors. Our data do not support that mucosal neutrophil inflammation is of major importance for symptom generation in IBS.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> calprotectin, pathophysiology, symptoms</p></sec><sec><title></title><p><bold>TUESDAY, OCTOBER 15, 2013 11:00-12:30</bold></p><p><bold>Role of gut microbiota in GI diseases – Hall Helsinki</bold></p></sec><sec><title>OP227 DECIPHERING MICROBIOTA-DRIVEN CELL SIGNALING MODULATION IN THE HUMAN GUT USING A FUNCTIONAL METAGENOMIC APPROACH</title><p><bold>M. Nepelska</bold><sup>1</sup>, S. Guglietta<sup>2</sup>, N. Lapaque<sup>1</sup>, D. Brunelli<sup>2</sup>, A. Jamet<sup>1</sup>, T. de Wouters<sup>1</sup>, O. Berteau<sup>1</sup>, A. Benjdia<sup>1</sup>, A. Cultrone<sup>1</sup>, M. Rhimi<sup>1</sup>, F. Ledue<sup>1</sup>, F. Dumetz<sup>1,3</sup>, S. D. Ehrlich<sup>3</sup>, E. Maguin<sup>1</sup>, J. Doré<sup>1</sup>, M. Rescigno<sup>4</sup>, H. M. Blottière<sup>1,3,*</sup></p><p><italic><sup>1</sup>UMR 1319 Micalis, INRA, Jouy en Josas, France, <sup>2</sup>European Institute of Oncology, Milan, Italy, <sup>3</sup>US 1367 MetaGenoPolis, INRA, Jouy en Josas, <sup>4</sup>European Institute of Oncology, Milan, France</italic></p><p><bold>INTRODUCTION:</bold> The intestinal microbiota is a complex community, which exerts functions often associated with beneficial effects for its host, including contribution to mucosal homeostasis and maturation of the immune system. The microbiota complexity associated to the inability to culture the vast majority of these microbes lead to the development of new and powerful approaches namely metagenomics.</p><p><bold>AIMS&METHODS:</bold> To study the interactions between intestinal epithelial cells (IECs) and commensal bacteria, a high throughput cell-based functional metagenomic approach was established (Lakhdari <italic>et al.</italic>, PLoS one, 2010).</p><p>Stably transfected human IECs bearing the luciferase reporter gene under the control of promoter of key genes or binding element of key signaling pathways (NF-κB, PPARγ, AP1) were obtained and used to screen metagenomic libraries bearing large DNA fragments (∼40 kb) derived from human fecal microbiota. To do so, a high throughput screening (HTS) platform was established.</p><p><bold>RESULTS:</bold> HTS led to the identification of bioactive metagenomic clones modulating key pathways in IEC. Sequencing, annotation and transposon mutagenesis allowed the identification of putative genes implicated. For one stimulatory clones derived from a <italic>Bacteroides</italic>-related strain, we identified 2 loci involved in the NF-κB stimulatory effect. Another clone, derived from a Firmicutes, was selected for its stimulation of NF-κB, AP1 and TSLP reporter systems. It also stimulated IL-8 expression and secretion. Biochemical characterization indicated that a small heat resistant compound was secreted and transposon mutagenesis in an ABC transporter system abolished this effect. In a co-culture system, this clone indirectly activated dendritic cells through IEC stimulation and further modulated T cell activity. Furthermore, in a new ex-vivo set up of human organ culture (Tsilingiri <italic>et al</italic>. Gut, 2012), it protected the intestinal mucosa from the destructive effect of a <italic>Salmonella</italic> strain. Finally, this clone displayed a protective effect in a preventive set up DSS colitis model.</p><p><bold>CONCLUSION:</bold> Our Functional Metagenomic approach allowed the identification of new bacterial genes involved in the cross-talk with gut epithelium.</p><p><bold>REFERENCES:</bold></p><p>1. Lakhdari O, Cultrone A, Tap J, Gloux K, Bernard F, Ehrlich SD, Lefèvre F, Doré J, Blottière HM. Functional metagenomics: a high throughput screening method to decipher microbiota-driven NF-κB modulation in the human gut. PLoS One. 2010; 5: e13092.</p><p>2. Tsilingiri K, Barbosa T, Penna G, Caprioli F, Sonzogni A, Viale G, Rescigno M.Probiotic and postbiotic activity in health and disease: comparison on a novel polarised ex-vivo organ culture model. Gut. 2012; 61:1007-15.</p><p><bold>Contact E-mail Address:</bold><email>herve.blottiere@jouy.inra.fr</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> inflamatory pathways, metagenomic, microbial findings, Microbiota, NF-kappaB</p></sec><sec><title>OP228 ESCALATING INCIDENCE OF IBD IN THE EAST AND WEST – IS THE MICROBIOTA THE KEY? IMPACT OF ETHNICITY, GEOGRAPHY, AND DISEASE ON THE MICROBIOTA. THE ENIGMA STUDY.</title><p><bold>L. Prideaux</bold><sup>1,*</sup>, S. Kang<sup>2</sup>, J. Wagner<sup>3</sup>, M. Buckley<sup>2</sup>, J. E. Mahar<sup>3</sup>, P. De Cruz<sup>1</sup>, Z. Wen<sup>4</sup>, L. Chen<sup>5</sup>, B. Xia<sup>5</sup>, D. R. van Langenberg<sup>6</sup>, T. Lockett<sup>2</sup>, S. C. Ng<sup>7</sup>, J. J. Sung<sup>7</sup>, P. Desmond<sup>1</sup>, C. McSweeney<sup>2</sup>, M. Morrison<sup>2</sup>, C. D. Kirkwood<sup>3</sup>, M. A. Kamm<sup>1</sup></p><p><italic><sup>1</sup>Department of Gastroenterology, St Vincent's Hospital, and The University of Melbourne, <sup>2</sup>Commonwealth Scientific and Industrial Research Organisation (CSIRO), Australia, <sup>3</sup>Enteric Virus Group, Murdoch Childrens Research Institute, Parkville, Australia, <sup>4</sup>West China Hospital, Sichuan University, Chengdu, <sup>5</sup>Zhongnan Hospital, Wuhan University School of Medicine, Wuhan, China, <sup>6</sup>Department of Gastroenterology, Box Hill Hospital, Melbourne, Australia, <sup>7</sup>Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Li Ka Shing Institute of Health Sciences, Hong Kong, Hong Kong</italic></p><p><bold>INTRODUCTION:</bold> The gut microbiota is central to health and plays a central pathophysiological role in inflammatory bowel disease (IBD). Differences in microbiota related to geography and ethnicity may hold the key to recent changes in incidence of inflammatory bowel disease. We therefore studied healthy subjects, IBD patients and healthy IBD relatives in the East (Hong Kong) and West (Australia), and surveyed their dietary history.</p><p><bold>AIMS&METHODS:</bold> In this Eastern Inflammatory Bowel Disease Gut Microbiota (“ENIGMA”) study gut mucosal microbiota (ileum, caecum and/or rectum biopsies) was analysed in 190 samples from 87 Caucasian and Chinese subjects, from Australia and Hong Kong, comprising: 22 Crohn’s disease (CD) patients, 30 ulcerative colitis (UC) patients, 29 healthy controls, and 6 healthy relatives of CD patients. Bacterial 16S rRNA microarray and 454 pyrosequencing were performed.</p><p><bold>RESULTS:</bold> The microbiota was diverse in health, regardless of ethnicity or geography [Operational Taxonomic Unit number and Shannon diversity index]. Ethnicity (p=0.017) and geography (p=0.015), however, did significantly affect microbial composition. CD resulted in substantially reduced bacterial diversity, regardless of ethnicity or geography, and was the strongest determinant of composition (p=0.0001). In UC, diversity was significantly reduced in Chinese subjects only (p<0.0004), suggesting that ethnicity is a determinant of bacterial diversity, while composition was determined by disease (p=0.002) and ethnicity (p=0.003). Specific phylotypes were different between health and disease. Chinese IBD patients more often than healthy Chinese tended to have had a Western diet in childhood, in the East and West.</p><p><bold>CONCLUSION:</bold> The healthy microbiota is diverse but composition is affected by geographical and ethnic factors. The microbiota is substantially altered in IBD, but ethnicity may also play an important role. This may be key to the changing epidemiology in developing countries, and emigrants to the West. Diet may be one of the important factors underlying these differences.</p><p>Supported by the Broad Foundation.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> ethnicity, inflammatory bowel disease, microbiota</p></sec><sec><title></title><p><bold>TUESDAY, OCTOBER 15, 2013 11:00-12:30</bold></p><p><bold>Colonoscopic screening: Top late breaking abstracts – Hall 7</bold></p></sec><sec><title>OP228-LB1 EFFECT OF FLEXIBLE SIGMOIDOSCOPY ON INCIDENCE AND MORTALITY FROM COLORECTAL CANCER; FIRST LARGE-SCALE POPULATON-BASED TRIAL</title><p><bold>O. Holme</bold><sup>1,2,*</sup>, M. Loberg<sup>2,3</sup>, M. Kalager<sup>2,4</sup>, M. Bretthauer<sup>2,3</sup>, E. Aas<sup>2</sup>, G. Hoff<sup>4,5</sup> the NORCCAP working group</p><p><italic><sup>1</sup>Dpt of medicine, Sorlandet Hospital Kristiansand, Kristiansand, <sup>2</sup>Insitute of Health and Society, University of Oslo, <sup>3</sup>Department of Transplantation Medicine, Oslo university Hospital, Oslo, <sup>4</sup>Dpt of Research, Telemark Hospital Skien, Skien, <sup>5</sup>Cancer Registry of Norway, Oslo, Norway</italic></p><p><bold>INTRODUCTION:</bold> Recently, three randomised controlled trials (PLCO, US; FlexiScope, UK; SCORE, Italy) have investigated the effect of flexible sigmoidoscopy in colorectal cancer screening. However, the generalizability of the results from these trials is uncertain because the study populations may not be representative for the general population (only volunteers were eligible for randomisation). We report the results after 11-year follow-up of the first large population-based randomised trial on flexible sigmoidoscopy screening.</p><p><bold>AIMS & METHODS:</bold> The Norwegian Colorectal CAncer Prevention (NORCCAP) trial enrolled individuals aged 55-64 years between January 1999 and December 2000. Individuals were randomised directly from the Population Register, mimicking a population-based screening programme. Individuals randomised to the screening group were offered a once-only flexible sigmoidoscopy. Participants with a positive screening test, defined as identification of any adenoma or a polyp 10 mm or larger at flexible sigmoidoscopy, were offered colonoscopy. The control group did not receive any intervention and were never contacted throughout the trial. End-points were acquired from the Cancer Registry and the Cause of Death Registry through December 31<sup>st</sup> 2011.</p><p><bold>RESULTS:</bold> A total of 13,823 individuals were randomised to the screening group, and 41,913 to the control group. Overall compliance with screening was 64.8%. After median 10.9 years of follow up , the incidence rate of colorectal cancer was 141.0 cases per 100,000 person-years in the screening group, compared to 170.8 cases per 100,000 person-years in the control group, hazard ratio [HR] 0.83 (95% confidence Interval [CI] 0.71-0.96). The colorectal cancer mortality rate was 38.6 deaths per 100,000 person-years in the screening group and 54.1 deaths per 100,000 person-years in the control group, HR 0.71 (95% CI 0.54-0.95). There was no serious adverse events in the 8,846 screening procedures.</p><p><bold>CONCLUSION:</bold> Once-only flexible sigmoidoscopy reduces incidence and mortality from colorectal cancer. The design of the NORCCAP trial makes the results generalizable to a public screening programme.</p><p><bold>Contact E-mail Address:</bold><email>oyvind.holme@sshf.no</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> colorectal cancer screening, flexible sigmoidoscopy, mortality</p></sec><sec><title>OP228-LB2 RATES OF POST COLONOSCOPY COLORECTAL CANCER ARE SIGNIFICANTLY AFFECTED BY METHODOLOGY, BUT ARE NEVERTHELESS DECLINING STEADILY IN THE ENGLISH NATIONAL HEALTH SERVICE (NHS)</title><p><bold>R. Valori</bold><sup>1,*</sup>, M. Rutter<sup>2</sup>, E. Morris<sup>3</sup>, J. Thomas<sup>3</sup></p><p><italic><sup>1</sup>Gloucestershire Hospitals, Cheltenham, <sup>2</sup>University Hospital of North Tees, Stockton, <sup>3</sup>Leeds University, Leeds, United Kingdom</italic></p><p><bold>INTRODUCTION:</bold> It is recognised that post-colonoscopy colorectal cancer (PCCRC) can be due to missed cancer, or cancer arising from missed or incompletely removed polyps. Thus the rate of post-colonoscopy colorectal cancer (PCCRC) could become a key quality indicator of colonoscopy. A quality indicator should be relevant to patients, clearly defined, standardised, measurable over time and have a target to aim for. This study compares methods for defining PCCRC rates, proposes a method that best meets these criteria and explores rates over time.</p><p><bold>AIMS & METHODS:</bold> Information on all individuals with a primary colorectal cancer and prior colonoscopic investigations in England between 2001 and 2010 was extracted from the National Cancer Data Repository. Previously published methods (Bressler, Cooper, Singh and leClerc) for deriving PCCRC rates were applied to these data to investigate the effect on the rate. A new method, based on the year of the colonoscopy, not CRC diagnosis, is proposed.</p><p><bold>RESULTS:</bold> Of 259,741 individuals diagnosed with colorectal cancer in the study period a total of 89,735 underwent a colonoscopy in the 3 years prior to their diagnosis. The application of the published methods and exclusion criteria to the dataset produced significantly different PCCRC rates from 2.2 to 7.5%:
<table-wrap id="table35-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="2" colspan="1">Exclusion criteria</th><th colspan="4" rowspan="1"><hr></hr>Method</th></tr><tr><th rowspan="1" colspan="1">Bressler</th><th rowspan="1" colspan="1">Cooper</th><th rowspan="1" colspan="1">Singh</th><th rowspan="1" colspan="1">leClerc</th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">None</td><td rowspan="1" colspan="1">4.2</td><td rowspan="1" colspan="1">7.5</td><td rowspan="1" colspan="1">7.2</td><td rowspan="1" colspan="1">2.2</td></tr><tr><td rowspan="1" colspan="1">Bressler</td><td rowspan="1" colspan="1">3.4</td><td rowspan="1" colspan="1">6.2</td><td rowspan="1" colspan="1">6.0</td><td rowspan="1" colspan="1">6.1</td></tr><tr><td rowspan="1" colspan="1">Cooper</td><td rowspan="1" colspan="1">4.4</td><td rowspan="1" colspan="1">7.5</td><td rowspan="1" colspan="1">7.3</td><td rowspan="1" colspan="1">2.2</td></tr><tr><td rowspan="1" colspan="1">Singh</td><td rowspan="1" colspan="1">3.6</td><td rowspan="1" colspan="1">6.8</td><td rowspan="1" colspan="1">6.6</td><td rowspan="1" colspan="1">2.2</td></tr><tr><td rowspan="1" colspan="1">leClerc</td><td rowspan="1" colspan="1">4.1</td><td rowspan="1" colspan="1">7.4</td><td rowspan="1" colspan="1">5.2</td><td rowspan="1" colspan="1">2.2</td></tr></tbody></table></table-wrap></p><p>The PCCRC rate of 7.2% produced by the Singh method best fulfils the proposed criteria for a quality indicator but it is not suitable for annual reporting: the rate reflects colonoscopy performance in the years <italic>preceding</italic> the year of reporting. Amending this method to look forward from the time of colonoscopy, rather than backward from the time of diagnosis of cancer, provides a rate <italic>related to the year</italic> of reporting. This new method demonstrates that PCCRC rates within 3 years of colonoscopy (without exclusions) decreased in the English NHS over 8 years by 36%: from 10.6% to 6.8% for colonoscopies performed in 2001 and 2008 respectively.</p><p><bold>CONCLUSION:</bold> PCCRC rates in England are improving over time and comparable to those in other countries. The method used to determine rates significantly affects findings, thus international benchmarking requires an agreed method for defining PCCRC. The Singh and suggested new method provide a PCCRC rate most relevant to patients. It is proposed that on the basis of current evidence, and improvements evident over time in this study, a reasonable target for a national rate of PCCRC up to 3 years following a colonoscopy is <5%.</p><p><bold>Contact E-mail Address:</bold><email>roland.valori@nhs.net</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> colon cancer, Colonoscopy, colonoscopy performance, quality assurance, quality control</p></sec><sec><title>OP228-LB4 A COMPOSITE MEASURE OF COLONIC INTUBATION IS BETTER ABLE TO DISTINGUISH PERFORMANCE OF COLONOSCOPY AND IS ASSOCIATED WITH HIGHER POLYP DETECTION RATES</title><p><bold>R. Valori</bold><sup>1,*</sup>, S. Damery<sup>2</sup>, D. Gavin<sup>1</sup>, E. Swarbrick<sup>3</sup></p><p><italic><sup>1</sup>Gloucestershire NHS Foundation Trust, Cheltenham, <sup>2</sup>Primary Care Clinical Sciences, Birmingham University, Birmingham, <sup>3</sup>Royal Hospital, Wolverhampton, United Kingdom</italic></p><p><bold>INTRODUCTION:</bold> Caecal intubation rate (CIR) is a key performance indicator of colonic intubation. CIR with acceptable tolerance is only achieved in some patients with more sedation. As most colonoscopists achieve >90% intubation, CIR alone cannot determine excellent performance. This study proposes a new composite measure of colonoscopy intubation (CIR<sup>C</sup>) that combines caecal intubation, patient comfort and sedation. Characteristics of patient, unit, equipment and colonoscopist associated with CIR<sup>C</sup> and the relation of CIR<sup>C</sup> to pathology detection are reported.</p><p><bold>AIMS & METHODS:</bold> Data from 20085 colonoscopies reported in a UK national audit (Gut 2013;62:242-249) were used for this analysis. The CIR<sup>C</sup> was defined as percentage of procedures achieving caecal intubation (adjusted for obstruction), <= median dose of midazolam (2mg) and nurse assessed comfort score 1-3 (max 5). Multivariate analysis using binary logistic regression assessed patient, unit and colonoscopist factors in order to derive Odds Ratios (ORs) and 95% confidence intervals (CIs) for factors independently associated with CIR<sup>c</sup> after controlling for effects of all model variables. ORs have significance of <0.001 unless stated.</p><p><bold>RESULTS:</bold> Overall achievement of CIR<sup>C</sup> was 54.1% (n=10865 procedures). The CIR<sup>C</sup> was better able to distinguish differences in performance than single measures (CIR and polyp detection). Older age, male sex (OR 1.40; CI:1.32-1.49), adequate/excellent bowel prep and FOBT screen positivity were all associated with a higher chance of achieving CIR<sup>C</sup>. Unit (JAG) accreditation (OR 1.26; CI 1.16-1.35) and the presence of >=1 magnetic imagers in the unit (OR 1.29; 1.19-1.40) were associated with higher CIR<sup>C</sup>. Greater annual volume, fewer years’ experience and course participation were associated with higher CIR<sup>C</sup>. Course faculty had higher CIR<sup>C</sup> (OR 1.74;1.57-1.92). Achieving CIR<sup>C</sup> was associated with significantly higher polyp detection rates (OR 1.12; 1.04-1.20) and higher cancer detection rates (OR 1.14; 0.98-1.32, p=0.10).</p><p><bold>CONCLUSION:</bold> The CIR<sup>C</sup> provides a richer picture of colonoscopic intubation than CIR alone and is better able to distinguish factors associated with intubation competence in relation to patients, units and colonoscopists. Unit (JAG) accreditation was associated with higher CIR<sup>C</sup>. Colonoscopists who perform more procedures, have more experience of training or being trained and have practised fewer years had significantly higher rates of CIR<sup>C</sup>. The CIR<sup>C</sup>was associated with a significantly higher polyp detection rate. It is proposed that CIR<sup>C</sup> replaces CIR as the key performance indicator for intubation of the colon.</p><p><bold>Contact E-mail Address:</bold><email>roland.valori@nhs.net</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Patient comfort, Quality of colonoscopy, sedation</p></sec><sec><title>OP228-LB5 FUSE™ COLONOSCOPY SIGNIFICANTLY IMPACTS ADENOMA SURVEILLANCE RECOMMENDATIONS – DATA FROM A PROSPECTIVE MULTICENTER RANDOMIZED TANDEM COLONOSCOPY STUDY</title><p><bold>I. M. Gralnek</bold><sup>1,*</sup>, P. D. Siersema<sup>2</sup>, D. K. Rex<sup>3</sup>, O. Segol<sup>4</sup>, Z. Halpern<sup>5</sup>, R. D'Agostino<sup>6</sup>, B. S. Lewis<sup>7</sup></p><p><italic><sup>1</sup>RAMBAM HEALTH CARE CAMPUS, Haifa, Israel, <sup>2</sup>Utrecht University Medical Center, Utrecht, Netherlands, <sup>3</sup>Indiana University, Indianapolis, United States, <sup>4</sup>Carmel Medical Center, Haifa, <sup>5</sup>Tel Aviv Medical Center, Tel Aviv, Israel, <sup>6</sup>Wake Forest University, Winston-Salem, <sup>7</sup>Mount Sinai Medical Center, New York City, United States</italic></p><p><bold>INTRODUCTION:</bold> Fuse colonoscopy (EndoChoice, Alpharetta, GA, USA) utilizes unique imaging technology providing a 330<sup>o</sup> field of view while maintaining identical colonoscope technical features. We previously reported that Fuse colonoscopy significantly increased the adenoma find rate by 71% (p<0.0001) & significantly reduced the adenoma miss rate (p<0.0001) [1].</p><p><bold>AIMS & METHODS:</bold> To compare Traditional Forward Viewing (TFV) colonoscopy with Fuse colonoscopy & evaluate the impact of Fuse on colonoscopy surveillance recommendations based on current U.S. guidelines [2]. In a multicenter international study (3 sites Israel, 1 site The Netherlands, 2 sites USA), subjects (ages 18-70 years) were randomly assigned (concealed allocation) to undergo same day, tandem, back-to-back colonoscopy starting with either TFV colonoscopy or Fuse colonoscopy. All identified polyps were removed. Patient level data including adenoma quantity, size, and histology type were captured.</p><p><bold>RESULTS:</bold> From 1/12 to 3/13, 197 subjects were enrolled, 12 subjects were excluded due to inability to reach the cecum, poor prep, or protocol violation. In total, 185 subjects (101 F (54.6%); mean age 55.8 ± 9.7 yrs) completed same day tandem colonoscopies and are included for analysis. Indications for colonoscopy: CRC screening n=103 (55.7%), polyp surveillance n=36 (19.5%), and diagnostic evaluation n=46 (24.9%). TFV colonoscopy missed 20 adenomas in 15 subjects. The detection of these additional adenomas led to 9/15 (60%) subjects having a change in their surveillance colonoscopy recommendations. In 4/15 (26.7%) the colonoscopy surveillance interval was shortened from 5-10 yrs to 3 yrs, in 4/15 (26.7%) it was shortened from 10 yrs to 5-10 yrs due to finding an adenoma in patients in whom nothing was found on TFV colonoscopy, and in 1/15 (6.7%) the colonoscopy surveillance interval was shortened from 10 yrs to 3 yrs due to finding a large size (>10mm) adenoma only at Fuse colonoscopy.</p><p><bold>CONCLUSION:</bold> Fuse colonoscopy shortened adenoma surveillance recommendations in 60% of the examinations where TFV colonoscopy missed adenomas. TFV colonoscopy did not alter any adenoma surveillance recommendation. Due to finding missed adenomas, Fuse colonoscopy significantly impacts colonoscopy surveillance recommendations and therefore could lead to improved protection against interval colorectal cancers.</p><p><bold>Contact E-mail Address:</bold> Prof Ian M. Gralnek, MD, MSHS, FASGE</p><p>i_gralnek@rambam.health.gov.il</p><p><bold>Disclosure of Interest</bold>: I. Gralnek Consultancy for: EndoChoice, P. Siersema Consultancy for: EndoChoice, D. Rex Consultancy for: EndoChoice, O. Segol Consultancy for: PeerMedical, Z. Halpern Consultancy for: PeerMedical, R. D'Agostino Consultancy for: EndoChoice, B. Lewis Consultancy for: EndoChoice</p><p><bold>Keywords:</bold> adenoma detection, adenoma detection rate, colonoscopy, Colonoscopy surveillance, technology</p></sec><sec><title></title><p><bold>TUESDAY, OCTOBER 15, 2013 11:00-12:30</bold></p><p><bold>Viral hepatitis B – Hall 6</bold></p></sec><sec><title>OP229 CLINICAL CHARACTERISTICS OF PATIENTS WITH CHRONIC HEPATITIS B WHO DEVELOPED GENOTYPIC RESISTANCE TO ENTECAVIR</title><p><bold>D. S. Lee</bold><sup>1,*</sup>, Y. S. Jung<sup>1</sup>, C. M. Moon<sup>1</sup>, J. H. Park<sup>1</sup>, D. I. Park<sup>1</sup>, Y. K. Cho<sup>1</sup>, C. I. Sohn<sup>1</sup>, W. K. Jeon<sup>1</sup>, B. I. Kim<sup>1</sup>, H. J. Kim<sup>1</sup></p><p><italic><sup>1</sup>Internal Medicine, SUNGKYUNKWAN UNIVERSITY KANGBUK SAMSUNG HOSPITAL, Seoul, Korea, Republic Of</italic></p><p><bold>INTRODUCTION:</bold> It has been reported that the development of entecavir resistance in nucleoside-naïve patients is very rare, even after 5 years of treatment. Most cases of entecavir resistance were reported in patients with prior use of lamivudine.</p><p><bold>AIMS&METHODS:</bold> Here, the authors present the clinical characteristics of patients with CHB who developed genotypic resistance to entecavir compared to those who did not develop resistance. One hundred twelve patients with CHB who underwent entecavir treatment in our institution from July 2007 to July 2011 were included in the current study. We included the nucleoside-naïve patients (n=74, 66.1%) as well as those who had prior nucleoside treatment (total n=38, 33.9%; lamivudine n=33, 29.5%; clevudine n=4, 3,6%; telbivudine n=1, 0.9%) who had underwent hepatitis B virus (HBV) mutation test at least once during the follow-up period (Drug Resistance Pyrosequencing Assay).</p><p><bold>RESULTS:</bold> Eight (7.1%) patients developed genotypic resistance to entecavir during the follow-up period. The patterns of genotypic resistance to entecavir were as follows: L180M + M204V + S202G (n=3); M204I + V173M (n=1); I169V + V173M (n=1); L180M + M204V + V173L (n=1); L180M + M204V + V173L + M250V (n=1); M204I + V214A + P237H (n=1). Mean ± standard deviation time to develop genotypic resistance to entecavir was 27.1 ± 11.6 months. Prior nucleoside treatment and drug compliance were not significant contributors to the development of entecavir resistance. Older age, higher baseline log<sub>10</sub>HBV-DNA (copies/ml), non-complete responder (more than 300 copies/ml of HBV DNA at 24 weeks of entecvir treatment by real-time PCR), and nonresponder (less than 2log<sub>10</sub> decrease of HBV-DNA at 24 weeks of entecvir treatment) were significant contributors to the development of genotypic resistance to entecavir. By Kaplan-Meier analysis with log rank comparison, negative conversion of HBeAg was significantly lower in patients with CHB who developed entecavir resistance (P=0.019).</p><p><bold>CONCLUSION:</bold> Clinical characteristics of patients who developed genotypic resistance to entecavir were older age, higher baseline log<sub>10</sub>HBV-DNA, non-complete responder and nonresponder during the entecavir treatment. Adding potent another antiviral drug, such as tenofovir may be needed for patients with CHB who have above-mentioned characteristics before and during the entecavir treatment.</p><p><bold>Contact E-mail Address:</bold><email>hongjoo3.kim@samsung.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Entecavir, Genotypic resistance, HBeAg, HBV DNA, negative conversion</p></sec><sec><title>OP230 IDENTIFICATION OF HBX TARGET MIRNAS THAT REGULATE HBV REPLICATION BY CHIP-SEQ</title><p><bold>F. Guerrieri</bold><sup>1,*</sup>, L. Belloni , , D. D’Andrea , , A. Tramontano , , M. Levrero</p><p><italic><sup>1</sup>Dept Internal Medicine, Sapienza University of Rome, Rome, Italy</italic></p><p><bold>INTRODUCTION:</bold> HBx regulatory protein is required for HBV cccDNA transcription/viral replication and contributes to HBV oncogenicity. Recent evidence indicates that HBx affects the epigenetic control of HBV viral chromatin, by preventing HDACs recruitment onto the cccDNA, as well as of cellular chromatin, by favouring the recruitment of CBP acetyl-transferase on CREB-activated target genes and of the de novo methyl-transferase DNMT3a on repressed genes.</p><p><bold>AIMS&METHODS:</bold> Aim of this study was to use a broad chromatin immunoprecipitation approach to define the HBx - miRNAs transcriptome. High-throughput sequencing of anti-HBx ChIP-enriched DNA fragments (ChIPSeq) was performed on an Illumina GAIIx. Chromatin immunoprecipitated from mock, wt and HBx-mt monomeric linear full lenght HBV DNA cells was analysed by TaqMan real-time PCR using gene (promoter) specific primers. HBx target miRNAs levels were assessed by real-time RT-PCR.</p><p><bold>RESULTS:</bold> ChIPSeq analysis of HBx chromatin recruitment revealed a specific binding to a large number of new and known target sequences. In 4 independent ChIP-seq experiments ∼16000 HBx binding sites were identified, 12.8% located within 10 kb of a transcription start site. Several peaks were validated by quantitative PCR (qPCR). Sistematic integrative analysis of the ∼ 7000 genes potentially regulated by HBx shows an enrichment in gene invoved in cell metabolism, chromatin dynamics and cancer but also HBV replication (Ras, calcium transport, endocytosis, MAPK/WNT pathways, Src, the EGF/HGF family). HBx also binds to 233 potential miRNAs [99 putative miRNA promoters and 133 mirtrons], including mir224, mir21 and several miRNA deregulated in cancer. ∼ 230 miRNAs are potentially regulated by HBx. Functional analysis shows that: a) HBx can both upregulate and repress the expression of miRNAs that affect HBV replication and define new regulatory loops (i.e, miR224, miR138, miR596 and others) and the control of cellular functions (i.e. miR21, miR26b, miR-502); b) multiple transcription factors mediate HBx binding to its target genomic sequences (NFkB, E2F1, b-catenin, ….); c) HBx binding to miRNAs regulatory regions is accompanied reshuffling of chromatin modyfying enzymes binding and histones epigenetic changes.</p><p><bold>CONCLUSION:</bold> HBx is recruited to several genomic loci to modulate the epigenetic control of target genes and miRNA transcription</p><p><bold>REFERENCES:</bold></p><p>1. Nuclear HBx binds the HBV minichromosome and modifies the epigenetic regulation of cccDNA function. Belloni L, Pollicino T, De Nicola F, Guerrieri F, Raffa G, Fanciulli M, Raimondo G, Levrero M.Proc Natl Acad Sci U S A. 2009</p><p>2. Epigenetic modification induced by hepatitis B virus X protein via interaction with de novo DNA methyltransferase DNMT3A. Zheng DL, Zhang L, Cheng N, Xu X, Deng Q, Teng XM, Wang KS, Zhang X, Huang J, Han ZG. J Hepatol. 2009</p><p>3. Hepatitis B virus X protein sensitizes cells to starvation-induced autophagy via up-regulation of beclin 1 expression Tang H et al. Hepatology. 2009</p><p>4. The hepatitis B virus X protein functionally interacts with CREB-binding protein/p300 in the regulation of CREB-mediated transcription. Cougot D, Wu Y, Cairo S, Caramel J, Renard CA, Lévy L, Buendia MA, Neuveut C. J Biol Chem. 2007</p><p>5. Activation of ERAD pathway by human hepatitis B virus modulates viral and subviral particle production. Lazar C et al. PLoS One. 2012</p><p><bold>Contact E-mail Address:</bold><email>fraguerrieri@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> CHIP-SEQ, ENDOCYTOSIS, HBV DNA, HBX, microRNA</p></sec><sec><title>OP231 A 10-YEAR PROSPECTIVE STUDY OF 673 PATIENTS WITH CHRONIC HEPATITIS B (CHB) INFECTION – BASELINE DETERMINANTS AND RATE OF DEVELOPMENT OF CIRRHOSIS AND HEPATOCELLULAR CARCINOMA (HCC)</title><p><bold>Z. Poh</bold><sup>1,*</sup>, B. B. G. Goh<sup>1</sup>, P. E. J. Chang<sup>1</sup>, C. K. Tan<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology & Hepatology, Singapore General Hospital, Singapore, Singapore</italic></p><p><bold>INTRODUCTION:</bold> Our department has a physician-driven HCC surveillance programme for CHB outpatients using recommended surveillance parameters of liver biochemistry, serum alfafetoprotein (AFP) level and abdominal ultrasonography. As cirrhosis and HCC are significant progression events, it is useful to identify patients at risk using surveillance blood tests and demography at presentation. We have now followed up a cohort of 673 CHB patients prospectively for 10 years in our HCC surveillance programme.</p><p><bold>AIMS&METHODS:</bold> Aims:To determine the rate and risk factors for development of cirrhosis and HCC in CHB patients using baseline screening parameters.</p><p>Methods:Singapore General Hospital Department of Gastroenterology & Hepatology outpatients with CHB between 1st March 2003-1st March 2004 were enrolled in a physician driven HCC surveillance programme. They were reviewed 3-6 monthly with liver biochemistries and serum alfafetoprotein (AFP). Cirrhosis/HCC surveillance imaging was done 6-12 monthly. Cirrhosis was diagnosed on histology or imaging with supportive clinical evidence. HCC was diagnosed on dynamic CT/MRI scan. Census for events (cirrhosis/HCC) was done 10 years later on 1st March 2013.</p><p><bold>RESULTS:</bold> There were 673 patients with 545 (81%) still on follow-up after 10 years. There were 421 (62.6%) males. Mean age was 56.4 years old (<italic>±</italic>12.7). Using Kaplan-Meier (KM) analysis, cirrhosis development was 2.1%, 8.7%, 12.9% and 17.8% at 1, 5, 8 and 10 years respectively (about 1.8%/year). HCC developed in 43 patients. By KM analysis, risk of HCC in cirrhotics was 8.1%, 13.9%, 23.1% and 29.8% at 1, 5, 8 and 10 years respectively (about 3.0%/year after the 1st year). Cirrhotics with alanine transaminase (ALT) >upper limit of normal (ULN, 36U/L) had significant risk of developing HCC (49.5% vs 31.0%, p=0.04). On univariate analysis, male gender, baseline age, serum AFP, ALT and alkaline phosphatase (ALP) were significantly higher, and serum albumin was significantly lower in patients who developed events. On Cox regression analysis, male gender (OR 1.68; p=0.023), age>55 years old (OR 1.73; p=0.015), albumin<38g/L (OR 1.61;p=0.039) and AFP>4.1ug/L (OR 1.77; p=0.001) were independent risk factors.</p><p><bold>CONCLUSION:</bold> The rate of development of cirrhosis is 1.8%/year, with a 10-year risk of HCC in cirrhotics of 30%. The rate of HCC in cirrhotics is highest in the 1st year and drops to a consistent annual rate thereafter. Patient demography, serum albumin and AFP can independently predict the development of significant events of cirrhosis and/or HCC in CHB patients.</p><p><bold>Contact E-mail Address:</bold><email>poh.zhongxian@sgh.com.sg</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Cirrhosis, HCC, Hepatitis B virus</p></sec><sec><title>OP232 HIGH TREATMENT MODIFICATION RATES UNDER LAMIVUDINE THERAPY IN HBV MONOINFECTED PATIENTS WITH LOW BASELINE VIREMIA AND EARLY VIROLOGIC RESPONSE: A MULTICENTER STUDY</title><p><bold>C. Gonen</bold><sup>1,*</sup>, F. Gunduz<sup>1</sup>, L. Doganay<sup>2</sup>, F. Enc<sup>3</sup>, E. Gunes<sup>4</sup>, E. Ahıshalı<sup>5</sup>, E. Erdem<sup>1</sup>, M. Sokmen<sup>2</sup>, I. Tuncer<sup>3</sup>, O. Ozdogan<sup>4</sup></p><p><italic><sup>1</sup>Gastroenterology, Haydarpasa Numune Training and Research Hospital, <sup>2</sup>Umraniye Training and Research Hospital, <sup>3</sup>Medeniyet University, <sup>4</sup>Marmara University, <sup>5</sup>Kartal Training and Research Hospital, Istanbul, Turkey</italic></p><p><bold>INTRODUCTION:</bold> Suppression of hepatitis B virus (HBV) replication with antiviral therapy has been linked to reduced risk of liver failure and hepatocellular carcinoma. The HBV roadmap concept proposes that patients with complete virological response under low genetic barrier drugs at week 24 should remain on treatment with regular monitoring.</p><p><bold>AIMS&METHODS:</bold> According to our countries reimbursement protocol; all patients with HBV DNA < 7 log copies/ml must initially receive lamivudine (LAM) or telbivudine. Treatment can be modified if HBV DNA greater than 300 copies/ml at week 24, or re-emergence of detectable viremia thereafter. The aim of this study is to assess the effectiveness of this concept in LAM treated patients. HBV monoinfected patients with low initial viral load (HBV DNA < 7 log copies/ml) and early virologic response (< 300 copies/ml at week 24) to LAM treatment were included in this multicenter, retrospective, real-life setting study. HBV DNA levels and laboratory asessments were repeated with an interval of at least 6 months. Treatment modification was allowed if at least 1 log increase in HBV DNA level or re-emergence of detectable viremia have occured during follow-up (treatment failure group –TF).</p><p><bold>RESULTS:</bold> Of 111 patients, 72% were male, mean (±SD) age 50±13 years, median ALT 56,5 IU/ml, median HBV DNA 170130,2 copies/ml and 93% HBeAg (-). 61 patients underwent biopsy (median HAI 7, mean fibrosis 2,5±1,7). Treatment failure had occured in 29% of patients during a median follow-up period of 35 months (10-156 months). TF rates were 6%, 12%, 24%, 32%, and 39% at years 1,2,3,4 and 5. After 33 patients with cirrhosis and advanced fibrosis were excluded; remaining population was %68 male, mean age 48±12 years, median HBV DNA 201500 copies/ml, median ALT 58, and 94% HBeAg (-). Treatment failure had occured in 31% of patients during a median follow-up period of 33 months (10-156 months). TF rates were 7%, 14%, 31%, 40%, and 43% at years 1,2,3,4 and 5.</p><p><bold>CONCLUSION:</bold> Even in patients with low baseline viremia, and early virologic response under LAM treatment, follow-up indicate high treatment failure and treatment modification requirement in a large patient population, under real-life setting. Unlike telbivudine, roadmap management strategy with lamivudine should be cautiously reviewed.</p><p><bold>Contact E-mail Address:</bold><email>drcgnn@yahoo.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> HBV, Lamivudine, Roadmap, Therapy</p></sec><sec><title>OP233 ENHANCED HMGB1 EXPRESSION REGULATES DISEASE PROGRESSION OF CHRONIC HEPATITIS B VIA THE AXIS OF TLR-4-IL-6-TREG/TH17 BALANCE</title><p><bold>J. Li</bold><sup>1,*</sup>, W. Jiang<sup>2</sup>, C.-Q. Yang<sup>1</sup>, F.-P. Wang<sup>2</sup></p><p><italic><sup>1</sup>gastroenterology, Tongji Hospital, <sup>2</sup>gastroenterology, Zhongshan Hospital, Shanghai, China</italic></p><p><bold>INTRODUCTION:</bold> HMGB1, as a potent pro-inflammatory cytokine, is substantially up-regulated in chronic hepatitis; howbeit its immunopathogenic role remains elusive. Accumulating evidence indicate its possible association with Treg/Th17 balance.</p><p><bold>AIMS&METHODS:</bold> This study aimed to determine the involvement of HMGB1-Treg/Th17 balance in chronic hepatitis B (CHB). Blood and liver specimens were collected from 36 CHB patients. Peripheral and intra-hepatic HMGB1 expression and Treg/Th17 balance were evaluated by ELISA, flowcytometry and immunohistochemistry. Sera were freshly prepared from CHB at advanced stages while PBMC from those at earlier stages. To determine the effects of HMGB1 on Treg/Th17 balance, CHB-PBMC was incubated with CHB-sera, with or without blocking of HMGB1, TLR2, TLR4, IL-6, TGFβ1, or IL-1β. Besides, purified CHB-CD4<sup>+ </sup>and non-CD4<sup>+</sup> (the residual PBMC after CD4 purification) were co-cultured in both contact and non-contact manners, stimulated by recombinant HMGB1 at different concentrations. The changes of TLR4, IL-6, Foxp3 and RORγt expression in total PBMC, CD4<sup>+</sup> cells and non-CD4<sup>+</sup> cells after incubations or co-cultures were detected by real-time PCR and western blot. Finally, using ConA-induced mouse liver fibrosis models, we intra-peritoneally blocked HMGB1 signal by neutralizing antibody or exacerbated it using rHMGB1 with or without simultaneous TLR4 or IL-6 blockade, and monitored intra-hepatic Treg/Th17 balance and collagen deposition by flowcytometry and immuohistochemistry.</p><p><bold>RESULTS:</bold> Serum HMGB1 were enriched in CHB patients and correlated with exacerbated liver injury, inflammation and fibrosis. Notably, HMGB1 increased with decreased peripheral and intra-hepatic Treg/Th17 ratios, suggesting HMGB1 might favor Th17 however inhibit Treg response. HMGB1 in CHB-sera significantly enhanced RORγt whereas inhibited Foxp3 expression of CHB-PBMC, which could be reversed by TLR4 or IL-6 blocking. Besides, rHMGB1 up-regulated RORγt and down-regulated Foxp3 expression of CHB-CD4<sup>+</sup> in a dose-dependent manner, which required non-contact interactions between CD4 and non-CD4 cells for it only enhanced TLR4 and IL-6 expression in non-CD4<sup>+</sup> rather than CD4<sup>+</sup> cells. Moreover, in mouse livers, HMGB1 blocking increased the Treg/Th17 ratios; decreased Th17 cytokine profile: IL-17, IL-21 and IL-22; increased CTLA-4 expression on Treg cells; and attenuated fibrosis progression. In addition, rHMGB1 showed the opposite effects to anti-HMGB1, which could be reversed by either TLR4 or IL-6 blockade.</p><p><bold>CONCLUSION:</bold> Enhanced HMGB1 expression shifts Treg/Th17 balance to Th17 dominance via the TLR4-IL-6 pathway, which exacerbates fibrosis progression of chronic hepatitis B.</p><p><bold>Contact E-mail Address:</bold><email>lijingshengping@163.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> chronic hepatitis B , high-mobility group box 1, interleukin-6, regulatory T cells (Treg)/T helper 17 (Th17) balance, toll-like receptor-4</p></sec><sec><title>OP234 DETERMINANTS OF HEPATOCELLULAR CARCINOMA IN CHRONIC HEPATITIS B PATIENTS WITH CIRRHOSIS UNDER CONTINUOUS NUCLEOS(T)IDE ANALOGUES</title><p><bold>Y.-C. Hsu</bold><sup>1,*</sup>, C.-Y. Wu<sup>2</sup>, C.-Y. Chang<sup>1</sup>, L.-R. Mo<sup>1</sup>, J.-T. Lin<sup>3</sup></p><p><italic><sup>1</sup>Department of Internal Medicine, E-DA HOSPITAL/I-SHOU UNIVERSITY , Kaohsiung, <sup>2</sup>School of Medicine, National Yang-Ming University,, Taipei, <sup>3</sup>School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan, Province of China</italic></p><p><bold>INTRODUCTION:</bold> Risk stratification for hepatocellular carcinoma (HCC) has been extensively investigated in the natural history of chronic hepatitis B (CHB), but little is known regarding patients who receive antiviral regimens.</p><p><bold>AIMS&METHODS:</bold> We aimed to identify risk factors for HCC in CHB patients with cirrhosis under nucleos(t)ide analogue therapy. After screening 1,559 patients who received nucleos(t)ide analogues for CHB between July, 2007 and February, 2013 in the E-Da Hospital (Kaohsiung, Taiwan), this retrospective cohort study enrolled 195 subjects with cirrhosis, all of whom were viremic with a pretreatment viral load greater than 2,000 IU/mL, continuously treated, and free of HCC within 3 months of treatment. The primary outcome was HCC occurrence, for which the incidence and risk factors were analyzed by the Kaplan Meyer method and the Cox proportional hazard model, respectively.</p><p><bold>RESULTS:</bold> Twenty-eight (14.4%) patients developed HCC during the observation period for as long as 52.9 months (median, 19.3 months; mean ± standard deviation, 20.9 ± 12.1 months), with an annual incidence of 8.24% (95% confidence interval [CI], 5.69-11.93%) and a cumulative incidence of 23.9% (95% CI, 16.5-33.8%) at 4 years. Univariate analyses identified diabetes mellitus, ascites, and model for end-stage liver disease (MELD) score as significant risk factors. Multivariate analysis revealed that diabetes (adjusted hazard ratio, 2.37; 95% CI, 1.12-5.01; <italic>P </italic>= 0.024) and higher MELD scores (adjusted hazard ratio, 1.07 per point; 95% CI, 1.01-1.13; <italic>P</italic> = 0.027) were significantly and independently associated with risk of HCC.</p><p><bold>CONCLUSION:</bold> Comorbidity with diabetes mellitus and severity of hepatic dysfunction were major determinants of HCC in CHB patients with cirrhosis under nucleos(t)ide analogues.</p><p><bold>Contact E-mail Address:</bold><email>jawtown@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> chronic hepatitis b, diabetes mellitus, hepatocellular carcinoma, risk factor</p></sec><sec><title></title><p><bold>TUESDAY, OCTOBER 15, 2013 11:00-12:30</bold></p><p><bold>Gastro-oesophageal cancer: The science behind the medicine – Hall 9</bold></p></sec><sec><title>OP235 INVOLVEMENT OF MAST CELL TRYPTASE AND PROTEINASE-ACTIVATED RECEPTOR-2 IN STRESS-INDUCED EPITHELIAL BARRIER DYNFUNCTION IN ESOPHAGUS</title><p><bold>C.-J. Zhong</bold><sup>1,*</sup>, K. Wang<sup>1</sup>, L.-P. Duan<sup>1</sup></p><p><italic><sup>1</sup>Department of Gastroenterology, Peking University Third Hospital, Beijing, China</italic></p><p><bold>INTRODUCTION:</bold> It has been reported that chronic stress can increase esophageal mucosa permeability and epithelial intercellular spaces (ICS), which is accompanied by an increasing number in mucosal mast cells.</p><p><bold>AIMS&METHODS:</bold> Regarding numerous previous researches having been discussed on how mast cells could involve in the process of stress-induced barrier function in gut, we try to explore whether mast cell plays a role in stress-induced esophageal barrier function and the possible underlying mechanism.</p><p> Mast cell intact wildtype Brown Norway rats (+/+) and mast cell deficient gene-mutant rats (Ws/Ws) were both subjected to chronic restraint stress (CRS) for 7 days. All rats were sacrificed at the 8<sup>th</sup> day and tissue/blood was harvested. Stress state was confirmed by weight loss and analysis of serum stress-related hormones. ICSs were measured bytransmission electron microscope (TEM) and tight junction proteins were alsoaccessed to evaluate the epithelial barrier dysfuntion after stress. Mast cells were counted by alcian blue staining and their activation status was evaluated as well. Alterations of tryptase and proteinase-activated receptor-2 (PAR2) were analyzed by western blot.</p><p><bold>RESULTS:</bold> CRS induced significantly changes in several parameters that are typically affected by stress. The body weight of all stressed rats dropped continuously during this 7-day period. Serum corticotropin-releasing hormone (CRH) increased nearly 45% in stressed +/+ rats and 25% in stressed Ws/Ws rats. An approximate 50% increase of epithelial ICS with a significant decrease in tight junction protein of Occludin and ZO-1 were observedin stressed +/+ rats, but not in stressed Ws/Ws rats. In these stressed +/+ rats, there was a mast cell hyperplasia by about 30% and an obvious mast cell activation compared with respective controls (38.3% vs 16.7%) confirmed by TEM. Mast cell derived tryptase increased nearly two folds in parallel with mast cell hyperplasia/activation in these stressed +/+ rats, and epithelial PAR2 expression also increased concordantly with its ligand tryptase.</p><p><bold>CONCLUSION:</bold> Chronic stress can induced a mast cell-dependent esophageal epithelial barrier dysfunction which is characterized by increasing epithelial ICS and decreasing tight junction proteins. Mast cells may regulate epithelial barrier dysfunction through tryptase, which can interact with epithelial PAR2and consequently results in tight junction alteration and dilated intercellular spaces.</p><p><bold>Contact E-mail Address:</bold><email>duanlp@bjmu.edu.cn</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> epithelial barrier dynfunction, mast cell deficient gene-mutant rats , mast cell tryptase, proteinase-activated receptor-2</p></sec><sec><title>OP236 INDUCTION OF ER STRESS IDENTIFIES POTENTIAL ESOPHAGEAL STEM CELL MARKERS</title><p><bold>S. Rosekrans</bold><sup>1,*</sup>, J. Heijmans<sup>1</sup>, C. Puylaert<sup>1</sup>, J. Westerlund<sup>1</sup>, V. Muncan<sup>1</sup>, G. van den Brink<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology, Academic Medical Center, Amsterdam, Netherlands</italic></p><p><bold>INTRODUCTION:</bold> The squamous epithelium of the esophagus is a rapidly renewing tissue. The esophageal epithelium is hierarchically organized with rapidly proliferating cells, which maintain cellular renewal, localized in the basal layer. To date, no specific markers have been identified that distinguish stem cells from non stem cell proliferating cells in the basal layer. In the intestinal epithelium, long lived stem cells and transcripts that mark stemness are rapidly depleted upon induction of endoplasmic reticulum (ER) stress (Heijmans et al.). We hypothesize that esophageal stem cell markers exhibit a similar sensitivity to ER stress.</p><p><bold>AIMS&METHODS:</bold> We aim to identify stem cell genes that mark a hierarchically distinct population of cells in the basal layer cells by analysis of a gene signature that is lost upon induction of ER stress. Sensitivity of esophageal precursor cells to ER stress was examined <italic>in vivo</italic> and <italic>in vitro.</italic> For proof of principle experiments <italic>in vivo</italic>, we chemically induced ER stress in mice, by injections with thapsigargin. For <italic>in vitro</italic> experiments, ER stress was induced in vitro in TE7 and OE21 esophageal squamous cell carcinoma (SCC) cell lines using SubAB, a cytotoxin that induces ER stress by depleting the major ER chaperone GRP78. From <italic>in vitro</italic> experiments, we next performed gene arrays to identify those transcripts that were significantly down regulated in both cell lines upon induction of ER stress. Next, we localized mRNA of all these genes in wild type mouse esophagus by Dig labeled <italic>in situ</italic> hybridization.</p><p><bold>RESULTS:</bold> Induction of ER stress in mice resulted in rapid depletion of esophageal precursor cells and accelerated differentiation, thus showing that in analogy to the intestine, esophageal stemness is lost. Using RNA micro-arrays, we identified a gene signature of 47 genes that were lost in both individual cell lines upon induction of ER stress. Of these genes, we found 29 genes to be restricted to the basal layer of the mouse esophagus. Out of these 29, nine genes show expression in only a small proportion of the basal cells, potentially marking stem cells.</p><p><bold>CONCLUSION:</bold> ER stress depletes esophageal precursor cells. Our in vitro screen combined with <italic>in situ</italic> hybridization identified nine genes that are specifically expressed in a subset of proliferating genes, thereby potentially marking esophageal stem cells.</p><p><bold>Contact E-mail Address:</bold><email>s.l.rosekrans@amc.uva.nl</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> ER stress, ESOPHAGUS,STOMACH DUODENUM, stem cell</p></sec><sec><title>OP237 TUMOR MICROENVIRONMENT IN ESOPHAGEAL ADENOCARCINOMA: INNATE AND ADAPTIVE IMMUNITY ACTIVATION IN NEOPLASTIC MUCOSA</title><p><bold>M. Scarpa</bold><sup>1</sup>, M. Scarpa<sup>1,*</sup>, A. Kotsafti<sup>1</sup>, B. Filip<sup>1</sup>, M. Cagol<sup>1</sup>, R. Alfieri<sup>1</sup>, M. Bortolami<sup>2</sup>, A. Porzionato<sup>2</sup>, I. Castagliuolo<sup>2</sup>, C. Castoro<sup>1</sup></p><p><italic><sup>1</sup>Veneto Institute of Oncology (IOV-IRCCS), <sup>2</sup>University of Padova, Padova, Italy</italic></p><p><bold>INTRODUCTION:</bold> Esophageal adenocarcinoma is an increasingly common cancer with a poor prognosis. Esophageal adenocarcinoma microenvironment is characterized by lack of cytokines with anti-cancer effect, such as IFN-gamma, and by high expression of several immuno-suppressive factors, such as COX-2, VEGF and IL-8 [1]. Moreover, the expression of costimulatory molecules such as CD80 and CD86 in he esophageal cancer tissue is significantly lower than in the normal mucosa of healthy patients and it is inversely correlated to the expression of TGF-beta1 and IL-10 [2]. This may be one of the mechanisms of immune escape of cancer cells in the esophageal cancer.</p><p><bold>AIMS&METHODS:</bold> The aim of the study is to characterize the immune environment of esophageal adenocarcinoma. Mucosa samples from cancer and from healthy esophagus were obtained during esophagectomy from 44 patients affected by esophageal adenocarcinoma and 13 patients affected by squamous cell cancer. Frozen samples were analysed with Real Time qPCR for TLR4, MyD88, CD80, CD86, CD38 and CD69 mRNA expression. Immunohistochemistry for T cell cytolytic activity (CD107a) of tumor infiltrating lymphocytes and for CD80 was performed. Non parametrical statistics was performed.</p><p><bold>RESULTS:</bold> In patients with adenocarcinoma, mRNA levels of TLR4, MyD88, CD80, CD86, CD38 and CD69 resulted significantly more expressed in the neoplastic mucosa compared to respective healthy mucosa. TLR4, MyD88, CD80 mRNA levels and CD80+ epithelial cells, CD80+ lamina propria mononucleate cells and CD107a+ T cells were significantly higher in ulcerated cancer than in no ulcerated cancer. CD80 mRNA in cancer mucosa was significantly higher in patients with nodal invasion (p=0.03). CD80 expression on neoplastic epithelium surface was increased in patients who had taxane chemotherapy (p=0.04). In neoplastic mucosa of patient having had radiotherapy CD38, TLR4 and MyD88 mRNA levels were reduced (p=0.04, p<0.01 and p<0.01, respectively).</p><p><bold>CONCLUSION:</bold> Differently from what observed by Yang et al [2] CD80 mRNA expression resulted higher in neoplastic tissue compared to normal tissue. Similarly, innate immunity (TLR4 and MyD88) and adaptive immunity (CD38 and CDd69) resulted up regulated in cancer tissue. The activation was peculiarly observed in ulcerated cancer. These results suggest that esophageal adenocarcinoma elicit an adaptive immunologic response even though it does not prevent nodal invasion. Chemotherapy with taxane seems to enhance neoplastic immunogenicity while radiotherapy seems to decrease innate immune response and lymphocytic activation.</p><p><bold>REFERENCES:</bold></p><p>1. Milano F, et al Scand J Immunol. 2008 Dec;68(6):616-23.</p><p>2. Yang W, et al Eur J Surg Oncol. 2010 May;36(5):501-6.</p><p><bold>Contact E-mail Address:</bold><email>marcoscarpa73@yahoo.it</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> CD107, CD80, esophageal adenocarcinoma, TLR4</p></sec><sec><title>OP238 IDENTIFICATION OF GENES SPECIFICALLY METHYLATED IN EPSTEIN-BARR VIRUS ASSOCIATED GASTRIC CARCINOMAS</title><p><bold>J. Nishikawa</bold><sup>1,*</sup>, M. Nakamura<sup>1</sup>, K. Sakai<sup>2</sup>, A. Goto<sup>1</sup>, J. Nishimura<sup>1</sup>, T. Okamoto<sup>1</sup>, Y. Suehiro<sup>2</sup>, I. Sakaida<sup>1</sup></p><p><italic><sup>1</sup>Department of Gastroenterology and Hepatology, <sup>2</sup>Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Ube, Japan</italic></p><p><bold>INTRODUCTION:</bold> Epstein-Barr virus (EBV) is associated with a variety of tumors such as Burkitt lymphoma, nasopharyngeal carcinoma and gastric carcinoma. The precise role of EBV in the carcinogenic progress is not fully understood. It has been reported that hypermethylation of tumor-related genes might be involved in the development of EBV-associated gastric carcinomas.</p><p><bold>AIMS&METHODS:</bold> We studied comprehensive DNA methylation status in naturally derived gastric adenocarcinoma cell line SNU-719, which is infected with EBV, by methylated CpG island recovery on chip (MIRA-chip) assay. To identify genes specifically methylated in EBV-associated gastric carcinomas, we focused on 7 genes, <italic>TP73</italic>, <italic>BLU</italic>, <italic>FSD1</italic>, <italic>BCL7a</italic>, <italic>MARK-1</italic>, <italic>SCRN-1</italic>, and <italic>NKX3.1</italic> based on the results of MIRA-chip assay. DNA methylation of the genes was confirmed by methylation-specific PCR (MSP) in SNU-719. SNU-719 was treated with DAC and/or TSA, and change of mRNA expression of the 7 genes was evaluated by quantitative RT-PCR. Then, we verified DNA methylation of the genes in 75 primary gastric cancer tissues from 25 patients with EBV-associated gastric carcinomas and 50 EBV-negative gastric carcinoma patients as controls.</p><p><bold>RESULTS:</bold> MIRA-chip analysis of SNU-719 showed that 1071 spots were determined as hypermethylated with log ratio of >0.25. Of genes on the spots, 69 genes were known as methylated in cancer, and 29 genes were chosen for further examination. Methylation status of the 29 genes was confirmed by MSP in SNU-719. Coincidence by MIRA-chip analysis and MSP was observed in 22 of 29 (78.3%) genes. To identify genes specifically methylated in EBV-associated gastric carcinomas, we focused on 7 genes, <italic>TP73</italic>, <italic>BLU</italic>, <italic>FSD1</italic>, <italic>BCL7a</italic>, <italic>MARK-1</italic>, <italic>SCRN-1</italic>, and <italic>NKX3.1</italic> because their MSP primers were available in clinical tissues. Expression of the genes, except for <italic>BCL-7a</italic>, was up-regulated by combination of DAC and TSA treatment in SNU-719. After the treatment, unmethylated DNA became detectable in all 7 genes by MSP in SNU-719. We verified DNA methylation of the genes in 75 primary gastric cancer tissues. Methylation frequencies of <italic>TP73, BLU, FSD1, BCL7a, MARK1, SCRN1</italic>, and <italic>NKX3.1</italic> were significantly higher in EBV-associated gastric carcinomas than in EBV-negative GC.</p><p><bold>CONCLUSION:</bold> We identified 7 genes whose promoter regions were specifically methylated in EBV-associated gastric carcinomas. Inactivation of these genes may suppress their function as tumor suppressor genes or tumor-associated antigen to develop and maintain EBV-associated gastric carcinomas.</p><p><bold>REFERENCES:</bold></p><p>1. Role of DNA methylation in the development of Epstein-Barr virus-associated gastric carcinoma. Saito M, Nishikawa J, Okada T, Morishige A, Sakai K, Nakamura M, Kiyotoki S, Hamabe K, Okamoto T, Oga A, Sasaki K, Suehiro Y, Hinoda Y, Sakaida I. J Med Virol. 85(1):121-7. 2013.</p><p><bold>Contact E-mail Address:</bold><email>junnis@yamaguchi-u.ac.jp</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> DAN methylation, Epstein-Barr virus, Gastric cancer</p></sec><sec><title>OP239 TUMOR-RELATED PROTEIN AND PHENOTYPIC EXPRESSION IN EARLY GASTRIC NEOPLASMS AND BACKGROUND MUCOSA</title><p><bold>S. Kawata</bold><sup>1,*</sup>, K. Yashima<sup>1</sup>, S. Sasaki<sup>1</sup>, K. Kawaguchi<sup>1</sup>, K. Harada<sup>1</sup>, Y. Murawaki<sup>1</sup></p><p><italic><sup>1</sup>Division of Medicine and Clinical Science, Faculty of Medicine, Tottori University, Yonago, Japan</italic></p><p><bold>INTRODUCTION:</bold> Recently, several tumor-related genes in association with the development of gastric cancers have been reported. In this study, the differences in tumor-related proteins and phenotypic expression among early gastric neoplasms and their background mucosa were evaluated.</p><p><bold>AIMS&METHODS:</bold> Immunohistochemistry was used to examine activation-induced cytidine deaminase (AID) , P53, and Mlh1 expression in 151 early gastric neoplasias (male109:female42, average age69.7) obtained by endoscopic or surgical resection and comprising 22 gastric adenomas, 92 intramucosal carcinomas (MCs) , and 37 submucosal invasive carcinomas (SMCs) , and compared them to corresponding the surrounding mucosal condition classified by the updated Sydney system. In addition, the cellular phenotypes of neoplasms and background mucosa(intestinal metaplasia;IM) were classified into three categories (gastric-,intestinal- and mixed-phenotypes) based on the combination of expression of CD10, MUC2, and MUC5AC.</p><p><bold>RESULTS:</bold> The mean scores of gastritis surrounding adenomas, MCs, and SMCs were as follows: glandular atrophy, 2.23, 1.83, and 1.89; chronic inflammation, 1.77, 1.89, and 2.24; and IM, 2.27, 1.90, and 1.78, respectively. The mean scores of glandular atrophy and IM surrounding adenomas was significantly higher than those surrounding MCs and SMCs (p<0.01), and the mean score of chronic inflammation surrounding SMCs was higher than those of surrounding adenomas and MCs (p<0.01). The rates of aberrant AID, P53, and Mlh1 expression were 36.3%, 0%, and 0% in the adenomas, 35.9%, 32.6%, and 16.3% in the MCs, and 56.8%, 62.2%, and 21.6% in the SMCs, showing progressive increases during tumor progression (p<0.01). The mean score of chronic inflammation surrounding AID positive neoplasms, was significantly higher than that surrounding AID negative neoplasms, especially in SMC cases (p<0.05). Moreover, that surrounding Mlh1 negative neoplasms was low (p<0.05). Therefore, AID and Mlh1 expression was associated with the severity of mononuclear cell activity in the non-cancerous mucosa adjacent to the tumor (p<0.01). The rate of gastric phenotype was high in MCs (36%) and SMCs (26.7%), and the rate of intestinal phenotype was high in adenomas (50%) (p<0.05). The phenotype of IM surrounding SMCs was highly classified into intestinal type (47.8%), and those surrounding adenomas and MCs were highly classified into mixed type (70%, 76%).</p><p><bold>CONCLUSION:</bold> Our data indicate that adenomas and MCs may arise from similar background mucosa, and P53, Mlh1, and gastric phenotypic expression could be important for carcinogenesis. In addition, chronic inflammation and AID and P53 expression may affect the submucosal invasion.</p><p><bold>Contact E-mail Address:</bold><email>kawataso0527@yahoo.co.jp</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> adenoma, Early gastric cancer, intestinal metaplasia</p></sec><sec><title></title><p><bold>TUESDAY, OCTOBER 15, 2013 11:00-12:30</bold></p><p><bold>Challenges in diagnosis and treatment of colorectal cancer – Hall 10</bold></p></sec><sec><title>OP239-LB1 THE ROLE OF MAINTENANCE TREATMENT WITH CAPECITABINE AND BEVACIZUMAB AFTER INDUCTION TREATMENT WITH CHEMOTHERAPY AND BEVACIZUMAB IN METASTATIC COLORECTAL CANCER (MCRC): UPDATED RESULTS INCLUDING SUBGROUP ANALYSIS AND QUALITY OF LIFE OF THE PHASE III CAIRO3</title><p><bold>C. J. Punt</bold><sup>1,*</sup>, L. Simkens<sup>1</sup>, H. van Tinteren<sup>2</sup>, M. Koopman<sup>3</sup> Dutch Colorectal Cancer Group</p><p><italic><sup>1</sup>Medical Oncology, Academic Medical Center, University of Amsterdam, <sup>2</sup>Biostatistics, Netherlands Cancer Institute, Amsterdam, <sup>3</sup>Medical Oncology, University Medical Center Utrecht, Utrecht, Netherlands</italic></p><p><bold>INTRODUCTION:</bold> The optimal duration of chemotherapy and bevacizumab in mCRC is not well established. The CAIRO3 study investigated the efficacy of maintenance treatment with capecitabine plus bevacizumab versus observation in mCRC patients (pts) not progressing during induction treatment with capecitabine, oxaliplatin and bevacizumab (CAPOX-B).</p><p><bold>AIMS & METHODS:</bold> Previously untreated mCRC pts, PS 0-1, with stable disease or better after 6 cycles of CAPOX-B, were randomized between observation (arm A) or maintenance treatment with capecitabine 625 mg/m2 bid daily continuously and bevacizumab 7.5 mg/kg iv q 3 weeks (arm B). Upon first progression (PFS1), pts in both arms were treated with CAPOX-B until second progression (PFS2, primary endpoint). For pts not able to receive CAPOX-B upon PFS1, PFS2 was considered equal to PFS1. Secondary endpoints were overall survival (OS) and time to second progression (TTP2), which was defined as the time to progression or death on any treatment following PFS1. All endpoints were calculated from the time of randomization. This trial is registered with ClinicalTrials.gov with the number NCT00442637.</p><p><bold>RESULTS:</bold> A total of 558 pts were randomized. Median follow-up is 39 months. The median number of maintenance cycles in arm B was 9 (range 1-54)<italic>. </italic>The median PFS1 in arm A vs B was 4.1 vs 8.5 months (HR 0.44, 95% CI 0.37-0.53, p<0.0001). Upon PFS1, 75% of pts received CAPOX-B in arm A and 47% in arm B. The median PFS2 was 10.5 vs 11.5 months (HR 0.81, 95% CI 0.67-0.98, p=0.03). The median TTP2 and OS in arm A vs B were 14.1 vs 18.7 months (HR 0.67, 95% CI 0.56-0.82, p<0.0001), and 18.0 vs 21.7 months (HR 0.87, 95% CI 0.71-1.06, p=0.16), respectively. When adjusted for imbalances in baseline characteristics, the median OS was significantly better in the maintenance arm (HR 0.80, p=0.035). The overall quality of life (QoL) was not significantly different between the 2 treatment arms.</p><p><bold>CONCLUSION:</bold> Maintenance treatment with capecitabine plus bevacizumab after 6 cycles CAPOX-B significantly prolonged PFS2. The small absolute difference in PFS2 may be due to the low percentage of pts in arm B that received CAPOX-B following PFS1. Maintenance treatment also significantly prolonged PFS1 and TTP2. Data on OS are still immature but show a significant benefit in the adjusted analysis. Our data support the use of maintenance treatment with chemotherapy plus bevacizumab until progression or unacceptable toxicity. Updated and subgroup analyses will be presented.</p><p><bold>Contact E-mail Address:</bold><email>c.punt@amc.uva.nl</email></p><p><bold>Disclosure of Interest</bold>: C. Punt Consultancy for: Roche, Sanofi-Aventis, Bayer, Nordic Pharma, Amgen, L. Simkens: None Declared, H. van Tinteren: None Declared, M. Koopman: None Declared</p><p><bold>Keywords:</bold> bevacizumab, chemotherapy, colorectal cancer, maintenance treatment, phase 3 randomized trial</p></sec><sec><title>OP240 INTERVAL CANCER AFTER NORMAL COLONOSCOPY: PHYSICIAN'S Z SCORE FOR POLYP DETECTION RATE IS THE MOST IMPORTANT FACTOR</title><p><bold>R. Gingold-Belfer</bold><sup>1,*</sup>, A. Geller<sup>1</sup>, A. Vilkin<sup>1</sup>, I. Liphshiz<sup>2</sup>, Y. Niv<sup>1</sup>, Z. Levi<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology Department, Rabin Medical Center, Petah Tikva, <sup>2</sup>Israeli National Cancer Regisrtration, Jerusalem, Israel</italic></p><p><bold>INTRODUCTION:</bold> Interval cancer after normal colonoscopy gains a lot of attention as issues of colonoscopies' quality and health costs are of concern.</p><p><bold>AIMS&METHODS:</bold> Our primary aim was to assess the association between quality indicators of colonoscopy and interval cancer after normal colonoscopy in the context of symptomatic and high risk population in an academic center. Out of a total of 22,466 symptomatic and high risk subjects who underwent colonoscopy with an acceptable preparation, included 13,048 subjects with normal colonoscopy. All colonoscopies were performed by 18 expert gastroenterologists. <italic>Interval cancer</italic> was defined as cancer that was diagnosed between the time of colonoscopy and the next scheduled colonoscopy and up to 5 years. <italic>Z scores</italic> for polyp detection rate (Z score –PDR) as well as cecal intubation rate for individual attending gastroenterologist were prepared. Data about interval cancer was extracted from the Israeli National Cancer Registry. Cox regression analysis was used.</p><p><bold>RESULTS:</bold> During a follow up of 65,073 years (mean 4.9±2.2y) a total of 17 interval cancers were identified (1.3/1,000), the mean time to cancer was 1.65±1.32 y. Z score –PDR of individual gastroenterologist < -1 (PDR ≤22%) was significantly associated with increased hazard risk (HR) for interval cancer [HR 5.0; 95% confidence interval (CI) 1.9-13.1, <0.001]. Gender, family history, FOBT, cecal intubation rate and examination hour were not associated with interval cancer.</p><p><bold>CONCLUSION:</bold> Interval cancer after normal colonoscopy is definitely existent problem. Except for an increasing age, lower Z score for PDR is the most important risk factor for interval cancer among symptomatic/high risk population with normal colonoscopy.</p><p><bold>REFERENCES:</bold></p><p>1. Baxter NN, Sutradhar R, Forbes SS, Paszat LF, Saskin R, Rabeneck L. Analysis of administrative data finds endoscopist quality measures associated with postcolonoscopy colorectal cancer. Gastroenterology. 2011 Jan;140(1):65-72.</p><p>2. Rex DK, Petrini JL, Baron TH, Chak A, Cohen J, Deal SE, Hoffman B, Jacobson BC, Mergener K, Petersen BT, Safdi MA, Faigel DO, Pike IM; ASGE/ACG Taskforce on Quality in Endoscopy. Quality indicators for colonoscopy. Am J Gastroenterol. 2006 Apr;101(4):873-85.</p><p><bold>Contact E-mail Address:</bold><email>rachelgingoldbelfer@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Interval Cancer, Normal colonoscopy, Polyp Detection Rate, Z score</p></sec><sec><title>OP241 THE LONG-TERM OUTCOMES AND RISK FACTORS FOR RECURRENCE AND DISTANT METASTASIS OF SUBMUCOSAL- INVASIVE COLORECTAL CANCERS</title><p><bold>Y. Kouyama</bold><sup>1,*</sup>, S.-E. Kudo<sup>1</sup>, H. Miyachi<sup>1</sup>, S. Matsudaira<sup>1</sup>, K. Icimasa<sup>1</sup>, H. Oikawa<sup>1</sup>, T. Hisayuki<sup>1</sup>, Y. Mori<sup>1</sup>, M. Misawa<sup>1</sup>, T. Kudo<sup>1</sup>, T. Hayashi<sup>1</sup>, K. Wakamura<sup>1</sup>, Y. Kobayashi<sup>1</sup>, E. Hidaka<sup>1</sup>, S. Ohkoshi<sup>1</sup>, F. Ishida<sup>1</sup>, S. Hamatani<sup>1</sup></p><p><italic><sup>1</sup>Digestive Disease Center, SHOWA UNIVERSITY NORTHERN YOKOHAMA HOSPITAL, YOKOHAMA, Japan</italic></p><p><bold>INTRODUCTION:</bold></p><p>There is few evidence for the long-term outcomes of submucosal invasive(SM) colorectal cancers resected endoscopically or surgically.</p><p><bold>AIMS&METHODS:</bold></p><p> The aim is to clarify the long-term outcomes and risk factors for recurrence or distant metastasis.</p><p>A total of 19186 colorectal neoplasms excluding advanced carcinomas were resected endoscopically or surgically at our center from April 2001 to December 2012. Of these, 829 SM colorectal cancers have been included (Male: Female; 532: 297, Age; 67±11.6, tumor size; 18±12.5mm). Excluding synchronous or metachronous advanced cancers<bold>,</bold> we collected data on 742 patients over a median followed-up period of 45.6 months. The criteria for curative endoscopic resection (defined as following pathological factors: horizontal and lateral margin negative, slightly- invasive SM cancers, well or moderately differentiated adenocarcinoma, negative vessel permeation and negative tumor budding grade2 or 3) was met in 159 cases (Group A). Eighty-five cases didn’t meet the curative criteria and were recommended the additional colectomy with lymph node dissection, but were followed up because of their refusal and other reasons (Group B). And surgical colectomy was done in 447 cases (Group C).</p><p> We analyzed their long-term outcomes and risk factors for recurrence or distant metastasis.</p><p><bold>RESULTS:</bold></p><p> The reccurence rate in Group A was 0%(0/159).</p><p> In Group B, that was 2.35%(2/85). Of the 2 patients with reccurence, one had distant metastasis to para-aortic lymph node, and the other to pelvic lymph node and lung.</p><p> In Group C, the rate of reccurence or distant metastasis was 1.26%(6/477). Of the 6 patients, 3 patients had distant metastasis to lung, and 1 patient to pelvic lymph node. The other 2 patients had synchronous liver metastasis. Among the 8 patients with reccurence or distant metastasis in Group B and C, 5 cases(62.5%) were depressed-type lesions and 5 cases(62.5%) located in the rectum.</p><p><bold>CONCLUSION:</bold></p><p> There was no reccurence in the curative resection group, so the validity of the criteria has been confirmed.</p><p>Out of the curative criteria, more carefull assessment would be recommended especially for rectal or depressed-type lesions.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> additional surgery, Colorectal Cancer, Endoscopic resection, long-term outcomes, submucosal invasive colorectal carcinoma</p></sec><sec><title>OP242 THE INDICATION FOR ADDITIONAL SURGICAL COLECTOMY WITH LYMPH NODE DISSECTION IN SUBMUCOSAL-INVASIVE COLORECTAL CARCINOMAS AFTER ENDOSCOPIC TREATMENT</title><p><bold>H. Miyachi</bold><sup>1,*</sup>, S.-E. Kudo<sup>1</sup>, S. Hamatani<sup>1</sup>, K. Ichimasa<sup>1</sup>, S. Matsudaira<sup>1</sup>, H. Oikawa<sup>1</sup>, T. Hisayuki<sup>1</sup>, Y. Mori<sup>1</sup>, M. Misawa<sup>1</sup>, T. Kudo<sup>1</sup>, K. Kodama<sup>1</sup>, S. Mukai<sup>1</sup>, T. Hayashi<sup>1</sup>, K. Wakamura<sup>1</sup>, E. Hidaka<sup>1</sup>, S. Ohkoshi<sup>1</sup>, F. Ishida<sup>1</sup></p><p><italic><sup>1</sup>Digestive Disease Center, SHOWA UNIVERSITY NORTHERN YOKOHAMA HOSPITAL, Yokohama, Japan</italic></p><p><bold>INTRODUCTION:</bold> Recent advance of EMR or ESD technology has enabled easier and safer endoscopic treatment. A lot of submucosal-invasive (SM) colorectal carcinomas are resected endoscopically with negative margins. Therefore, additional surgical colectomy with lymph node dissection should be considered according to the pathological analysis. Although it is critical to determine the criteria for curative endoscopic resection, there is only a few data pursuing a large number of samplings in terms of the indication for additional surgical colectomy.</p><p><bold>AIMS&METHODS:</bold> The aim is to clarify pathological risk factors for lymph node metastasis of SM colorectal carcinomas and to establish the indication for additional surgical colectomy with nodal dissection after endoscopic treatment.</p><p>A total of 18048 colorectal neoplasms excluding advanced cancers have been resected endoscopically or surgically at our unit from April 2001 to June 2012. Of these, 781 SM carcinomas were included. Initial or additional surgical colectomy with nodal dissection was performed in 514 cases, and of which lymph node metastasis was found in 50 cases (9.7%). We analyzed the pathological risk factors as follows: vessel permeation, tumor budding, poorly-differentiated/mucinous carcinoma (POR/MUC) component, desmoplastic reaction (DR) on the superficial layer, and state of muscularis mucosae (MM grade). MM grade was evaluated into two conditions using the desmin immunostaining: MM grade 1 (complete or almost maintenance) and MM grade 2 (fragmentation or disappearance).</p><p><bold>RESULTS:</bold> The existence of vessel permeation, tumor budding, POR/MUC component or MM grade 2 was a significant risk factor. No lesions corresponding to MM grade 1 had lymph node metastases. Among SM carcinomas with MM grade 2, lesions without vessel permeation, tumor budding or POR/MUC component showed low incidence (2/146: 1.4%) of nodal metastases, while 48 (15.1%) of 317 lesions with at least one factor had lymph node involvement.</p><p><bold>CONCLUSION:</bold> The indication for additional surgical colectomy after endoscopic resection has been more clarified: MM grade 1 was suggested to be an anti-risk factor for nodal metastasis (Ultralow-risk group). SM carcinomas with MM grade 2 and without vessel permeation, tumor budding or POR/MUC component may need follow-up (Low-risk group). For SM carcinomas with MM grade 2 and with at least one factor, additional surgical colectomy with lymph node dissection should be recommended (High-risk group).</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> nodal metastasis, additional surgical colectomy, management, MM grade, risk factors, SM colorectal carcinomas</p></sec><sec><title>OP243 MIR-143 AND MIR-145 OVEREXPRESSION IMPROVE THE RESPONSE TO CETUXIMAB IN HCT116 KRAS MUTANT COLON CANCER CELLS</title><p><bold>S. E. Gomes</bold><sup>1,*</sup>, A. E. S. Simões<sup>1</sup>, D. M. Pereira<sup>1</sup>, P. M. Borralho<sup>1,2</sup>, C. M. P. Rodrigues<sup>1,2</sup></p><p><italic><sup>1</sup>iMed.UL, FFUL - Research Institute for Medicines and Pharmaceutical Sciences, Faculty of Pharmacy, University of Lisbon, <sup>2</sup>Department of Biochemistry and Human Biology, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal</italic></p><p><bold>INTRODUCTION:</bold> MicroRNAs (miRs) play important roles in cancer onset and progression, and have been shown to modulate cell sensitivity to chemotherapeutic agents. miR-143 and miR-145 are widely reported as downregulated in cancer, including colon cancer (CC). We have previously demonstrated that miR-143 overexpression reduces tumour growth and proliferation, increases apoptosis and sensitizes to 5-fluorouracil (5-FU). Importantly, the mutational status of the <italic>KRAS</italic> gene in colon tumours has been strongly associated with clinical response to the anti-EGFR monoclonal antibody cetuximab in CC, with <italic>KRAS</italic> mutations being a strong negative predictor of response to cetuximab treatment.</p><p><bold>AIMS&METHODS:</bold> In this study, we aimed to evaluate the effects of miR-143 and/or miR-145 overexpression in the sensitization of KRAS mutant CC cells to cetuximab. We produced miR-overexpressing cell lines by transducing HCT116 CC cells with retroviruses containing constructs, expressing miR-143, -145 or -143/145, and empty-vector (control), followed by G418 selection. miR-overexpression was confirmed by RT-PCR Taqman. Viability and proliferation of cells exposed to serial dilutions of cetuximab up to 1600 mg/ml (or vehicle) were assessed in real-time, using the xCELLigence system, and by MTS assay, after up to 72 h of exposure. Steady-state expression of key miRs targets was determined by immunoblot analysis. In addition, HCT116 cells were also transfected with RREB1 siRNA or scramble siRNA, and exposed to cetuximab for 72 h, to evaluate its role in cetuximab response.</p><p><bold>RESULTS:</bold> Our results show that miR-145 and miR-143/145 overexpression significantly decreases cell proliferation, resulting in increased doubling times, as evaluated in xCELLigence. Importantly, miR-143 and/or miR-145 significantly sensitized KRAS mutant colon cancer cells to cetuximab, translated by up to 40% reduction in cetuximab IC<sub>50</sub> for cells overexpressing these miRNAs, compared to control (<italic>p </italic>< 0.05). In addition our data showed that miR-143 overexpression reduced RREB1, ERK5 and Bcl-2 protein levels (<italic>p</italic> < 0.05). Moreover, RREB1 silencing enhanced the sensitivity of KRAS mutant colon cancer cells to cetuximab.</p><p><bold>CONCLUSION:</bold> Collectively, our data indicates that miR-143 and miR-145 overexpression, alone or in combination, may provide a potential novel therapeutic approach for re-sensitizing KRAS mutant colon cancer cells to cetuximab. However, further studies are required to elucidate the molecular mechanisms involved.</p><p><bold>Contact E-mail Address:</bold><email>segomes@ff.ul.pt</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Cetuximab, Colon Cancer, miR-143, miR-145, Mutant KRAS </p></sec><sec><title>OP244 SIGNIFICANT EFFECT OF VEGF POLYMORPHISMS ON CLINICAL OUTCOMES OF THE COMBINATION CETUXIMAB-FOLFIRI FOR METASTATIC COLORECTAL CANCER PATIENTS</title><p><bold>P. Audrey</bold><sup>1,2,*</sup>, J. Rollin<sup>1,3</sup>, V. Gouilleux<sup>1,4</sup>, M. Boisdron-Celle<sup>5</sup>, N. Azzopardi<sup>1</sup>, A. Morel<sup>5</sup>, Y. Gruel<sup>1,3</sup>, G. Paintaud<sup>1,6</sup>, E. Gamelin<sup>5</sup>, H. Watier<sup>1,4</sup>, T. Lecomte<sup>1,2</sup></p><p><italic><sup>1</sup>CNRS UMR 7292, GICC and University Francois Rabelais, <sup>2</sup>Hepatogastroenterology, <sup>3</sup>Hematology Hemostatis, <sup>4</sup>Immunology, Hospital of Tours, Tours, <sup>5</sup>Hospital of Angers, Angers, <sup>6</sup>Pharmacology Toxicology, Hospital of Tours, Tours, France</italic></p><p><bold>INTRODUCTION:</bold> Modulation of vascular endothelial growth factor (VEGF) expression by anti–epidermal growth factor receptor (anti-EGFR) antibodies in metastatic colorectal cancer (mCRC) has been previously demonstrated. In addition, single nucleotide polymorphisms (SNPs) in the <italic>VEGFA</italic> gene influence expression of VEGF. We evaluated the association of VEGF genotype and circulating level of VEGF with efficacy in a phase II multicenter study evaluating a cetuximab-based regimen for metastatic colorectal cancer.</p><p><bold>AIMS&METHODS:</bold> We analysed the effects of 5 polymorphisms of the <italic>VEGFA</italic> gene (-2549 C/A, -1154 G/A, -460 T/C, +405 G/C and +936C/T) on the outcome of 98 mCRC patients treated with FOLFIRI plus cetuximab. The associations of VEGF serum level with these polymorphisms and patient outcomes were also examined. <italic>KRAS</italic> mutation analysis was performed retrospectively on 61 patients.</p><p><bold>RESULTS:</bold> Tumorale response rate was 61,2 % and progression free survival (PFS) was about 6,5 months. Kras mutation was detected in 58,4 % of analysed tumors. Genotype analysis demonstrated that patients homozygous for the -2549D and -460T alleles had higher response rates to treatment (p=0.02) as well as longer progression free survival (p=0.03) than patient carriers of the -2549I or -460C alleles. In addition, patient homozygous for the -1154G allele were significantly more frequently found in the “responder” group (p=0.015) and had higher PFS (p=0.007). Haplotypes analysis demonstrated that DTGGC and ICGGC haplotypes were significantly associated with a lower risk of disease progression, more so than the major haplotype ICAGC (p=0.003 and p=0.004, respectively). Association of -1154GG genotype and haplotype DTGGC with better PFS was confirmed in a subgroup of patients non-mutated<italic> KRAS</italic>. On the other hand, no relationship was found between SNPs and circulation concentration of VEGF. However, evolution of serum concentration of VEGF mesured for each patient at day 60 and at the initiation of cetuximab-based regimen was associated with tumor response but not with PFS.</p><p><bold>CONCLUSION:</bold> These data support that the VEGF genetic variability, particularly polymorphism -1154G/A, could be a key determinant of an increased efficacy to cetuximab-based chemotherapy for KRAS wild-type colorectal cancer patients.</p><p><bold>Contact E-mail Address:</bold><email>audrey.payance@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> biomarkers, cetuximab, colorectal cancer, VEGF polymorphism</p></sec><sec><title>OP245 MEK5/ERK5 SIGNALLING MODULATES CELL PROLIFERATION AND SURVIVAL AND INFLUENCES SENSITIVITY TO 5-FLUOROURACIL IN COLON CANCER CELLS</title><p><bold>D. M. Pereira</bold><sup>1,*</sup>, A. E. S. Simões<sup>1</sup>, S. E. Gomes<sup>1</sup>, R. E. Castro<sup>1,2</sup>, P. M. Borralho<sup>1,2</sup>, C. M. P. Rodrigues<sup>1,2</sup></p><p><italic><sup>1</sup>Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), <sup>2</sup>Department of Biochemistry and Human Biology, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal</italic></p><p><bold>INTRODUCTION:</bold> Aberrant MEK5/ERK5-mediated signalling has been demonstrated as a poor prognostic marker in breast and prostate cancer, increasing cell proliferation and chemoresistance. In colon cancer (CC) MEK5 overactivation has been correlated with CC stage progression. Moreover, recent data from our group demonstrated that ERK5 and MEK5 expression is increased in human colon adenomas and adenocarcinomas, suggesting that MEK5/ERK5 overactivation may contribute to CC initiation and progression. Additionally, we have previously shown that ERK5 siRNA-mediated silencing induces apoptosis, and enhances cell sensitivity to 5-fluorouracil (5-FU), the most widely used chemotherapeutic for CC treatment.</p><p><bold>AIMS&METHODS:</bold> In the present study, we produced a cell line model with differential activation of the MEK5/ERK5 pathway to investigate its role in cell proliferation, cell death and 5-FU sensitivity. For this purpose, HCT116 and SW620 stable cell lines expressing a constitutively active or a dominant negative form of MEK5, MEK5DD and MEK5AA, respectively, were generated by GFP-lentiviral vector transduction, followed by fluorescence-activated cell sorting (FACS). Cells were treated with 5-FU (8-200 µM) for up to 72 h, and cytotoxicity was evaluated by LDH release. Steady-state expression of MEK5, ERK5 and downstream signalling mediators was evaluated by immunoblotting.</p><p><bold>RESULTS:</bold> Constitutive activation of MEK5/ERK5 signalling decreased p53 and p21 expression (<italic>p</italic><0.05) in HCT116 cells, while inducing KRAS expression (<italic>p</italic><0.05) in both HCT116 and SW620 cells. Importantly, in HCT116 cells, ERK5 overactivation decreased sensitivity to 5-FU, reducing cell death (<italic>p</italic><0.05). In turn, ERK5 loss of function increased cell death (<italic>p</italic><0.01), enhancing cell sensitivity to 5-FU. Furthermore, 5-FU exposure markedly decreased the levels of endogenous ERK5 and MEK5 expression (<italic>p</italic><0.05), while inducing p53 and p21 expression (<italic>p</italic><0.05).</p><p><bold>CONCLUSION:</bold> Overall, our results indicate that overactivation of MEK5/ERK5 pathway may contribute to CC aggressiveness and chemoresistance, suggesting that ERK5-targeted inhibition, via siRNA, miRNA or small-molecule inhibitors, may provide a promising therapeutic approach for CC treatment, warranting further investigation.</p><p>(Supported by PTDC/SAU-ORG/119842/2010, PEstOE/SAU/UI4013/2011, Sociedade Portuguesa de Gastrenterologia, SFRH/BD/88619/2012 and SFRH/BD/79356/2011. The authors thank Dr. Robert Doebele for the kind gift of pWPI-MEK5AA and pWPI-MEK5DD constructs.)</p><p><bold>Contact E-mail Address:</bold><email>dampereira@ff.ul.pt</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> 5-Fluorouracil, Chemosensitization, Colon Cancer, MEK5/ERK5 Signalling</p></sec><sec><title></title><p><bold>TUESDAY, OCTOBER 15, 2013 11:00-12:30</bold></p><p><bold>Nutrition and gut function – Hall 8</bold></p></sec><sec><title>OP246 PPARGAMMA IS A MASTER REGULATOR OF LACTASE PRODUCTION BY INTESTINAL EPITHELIAL CELLS</title><p><bold>M. Fumery</bold><sup>1</sup>, A. Langlois<sup>1</sup>, S. Speca<sup>1</sup>, C. Dubuquoy<sup>1</sup>, M. Figeac<sup>2</sup>, R. Christel<sup>3</sup>, L. Dubuquoy<sup>1</sup>, S. Bellinvia<sup>4</sup>, P. Desreumaux<sup>1</sup>, B. Bertin<sup>1,*</sup></p><p><italic><sup>1</sup>Inserm U995, <sup>2</sup>Genomic platform IFR-114, <sup>3</sup>Inserm U995, Université Lille-Nord de France, Lille, France, <sup>4</sup>GiulianiSpA, Milano, Italy</italic></p><p><bold>INTRODUCTION:</bold> Lactose intolerance is a frequent condition that causes abdominal discomfort and diarrhea, resulting from lactase (LCT) enzyme deficiency produced by intestinal epithelial cells (IEC). Except for lactose free diet, no treatment can cure lactose intolerance and the regulation of LCT enzyme expression remains unknown. Peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor highly expressed by IEC playing a key role in gut homeostasis and metabolism regulation.</p><p><bold>AIMS&METHODS: Aim</bold>: To evaluate the roles of PPARγ in the regulation of lactase production <italic>in vitro</italic> in IEC and <italic>in vivo</italic> in rodents. <bold>Methods</bold>: Caco2 cells were treated 24 hours with Pioglitazone (Pio; 1µM) and with a new PPARγ modulator named GED (amino-phenyl-methoxy-propionic acid; 1mM) or 5-aminosalycilate (5ASA; 30mM). Transcriptomic profiling was done using Agilent 2-colors 44K Gene Expression Microarrays. LCT mRNA and protein expression was assessed by quantitative RT-PCR and immunostaining. LCT activity was evaluated <italic>in vitro</italic> by standard method measuring the amount of glucose after lactose digestion. Involvement of PPARγ was confirmed using RNA interference, antagonist treatment (GW9662) and intestine-specific PPARγ knock-out C57BL/6 mice (PPAR<sup>ΔIEC</sup>). <italic>In vivo</italic>, LCT expression and activity were determined in the duodenum and jejunum of wild-type rodents orally treated with GED.</p><p><bold>RESULTS:</bold> Both in microarray and qRT-PCR analysis, LCT mRNA expression was upregulated by GED, Pio and 5ASA compared to control cells with a mean fold of 5.7 (p<0.0001), 14.7 (p<0.0001) and 9.5 (p<0.0001) respectively. LCT protein upregulation was also observed by immunostaining of stimulated Caco-2 cells. Importantly, GED and Pio treatments significantly increased LCT enzyme activity of Caco-2 cells (2.5 to 3 fold; p<0.05). LCT mRNA (p=0.0022), protein expression and lactase activity (p=0.0043) were decreased in PPARγ knock-down Caco2 cells. In PPAR<sup>ΔIEC</sup> mice, LCT mRNA expression was significantly decreased both in duodenum (p=0.028) and jejunum (p=0.05) compared to control mice. Both LCT expression and activity were increased in the duodenum (p<0.05) and jejunum (p<0.01) of weaned C57BL/6 mice and Sprague-Dawley rats treated one week with GED compared to animals receiving vehicle.</p><p><bold>CONCLUSION:</bold> PPARγ agonists are able to increase lactase expression and activity <italic>in vitro</italic> and <italic>in vivo</italic>. These findings identify PPARγ as a new master regulator of LCT production by IEC and suggest that modulating PPARγ activity may be a new therapeutic strategy for the management of lactose intolerance.</p><p><bold>Contact E-mail Address:</bold><email>benjamin.bertin-2@univ-lille2.fr</email></p><p><bold>Disclosure of Interest</bold>: M. Fumery Financial support for research from: Giuliani SpA, A. Langlois Financial support for research from: Giuliani SpA, S. Speca Financial support for research from: Giuliani SpA, C. Dubuquoy Financial support for research from: Giuliani SpA, M. Figeac: None Declared, R. Christel Financial support for research from: Giuliani SpA, L. Dubuquoy Financial support for research from: Giuliani SpA, S. Bellinvia Directorship(s) for: Giuliani SpA, P. Desreumaux Financial support for research from: Giuliani SpA, B. Bertin Financial support for research from: Giuliani SpA</p><p><bold>Keywords:</bold> instestinal epithelial cells, lactase gene, lactose intolerance, PPARgamma, small intestine</p></sec><sec><title>OP247 DISTURBED INTESTINAL INTEGRITY IN PATIENTS WITH COPD; EFFECTS OF ACTIVITIES OF DAILY LIVING</title><p><bold>K. Lenaerts</bold><sup>1,*</sup>, E. Rutten<sup>2</sup>, W. Buurman<sup>1</sup>, E. Wouters<sup>2</sup></p><p><italic><sup>1</sup>Department of Surgery, Maastricht University Medical Centre, Maastricht, <sup>2</sup>Centre of expertise for Chronic Organ Failure (Ciro), Horn, Netherlands</italic></p><p><bold>INTRODUCTION:</bold> Chronic obstructive pulmonary disease (COPD) is accepted to be a multicomponent disease with various comorbidities. The contribution of the gastrointestinal tract to the systemic manifestation of COPD has never been investigated. This metabolically active organ may experience recurring local oxygen deficits during daily life, leading to disturbed intestinal integrity in COPD patients.</p><p><bold>AIMS&METHODS:</bold> 18 patients with moderate COPD (mean FEV1: 55±3%pred) and 14 matched healthy controls were tested on two occasions, a baseline measurement at rest and, at another day, during the performance of activities of daily living (ADLs). To assess enterocyte damage, plasma intestinal fatty acid binding protein (IFABP) levels were determined, whereas urinary excretion of orally ingested sugar probes was measured using liquid chromatography and mass spectrometry to assess gastrointestinal permeability.</p><p><bold>RESULTS:</bold> Plasma IFABP concentrations were not different between COPD patients and healthy controls at rest. In contrast, 0-3h urinary lactulose/rhamnose and sucralose/erythritol ratios and 5-24h urinary sucralose/erythritol ratios were significantly higher in COPD patients compared to controls, indicating increased permeability of the small intestine and colon. Furthermore, the performance of ADLs led to significantly increased plasma IFABP concentrations in COPD patients but not in control subjects. In line, the intestinal permeability difference between COPD patients and controls was intensified.</p><p><bold>CONCLUSION:</bold> Besides an altered intestinal permeability in COPD patients at rest, performing ADLs led to enterocyte damage in addition to intestinal hyperpermeability in COPD patients but not in controls, indicating functional alteration in the gastrointestinal tract. Hence, intestinal compromise should be considered as a new component of the multisystem disorder COPD.</p><p><bold>Contact E-mail Address:</bold><email>kaatje.lenaerts@maastrichtuniversity.nl</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Chronic disease, Intestinal epithelial barrier, Intestinal epithelial cells, Intestinal injury, Physical activity</p></sec><sec><title>OP248 FOLATE PRODUCTION IN BIFIDOBACTERIA FROM INFANT AND ADULT HUMANS</title><p><bold>M. R. D'Aimmo</bold><sup>1</sup>, M. Modesto<sup>2</sup>, P. Mattarelli<sup>2,*</sup>, B. Sgorbati<sup>2</sup>, B. Biavati<sup>2</sup>, T. Andlid<sup>1</sup></p><p><italic><sup>1</sup>DEPARTMENT OF CHEMICAL AND BIOLOGICAL ENGINEERING, Chalmers University of Technology , Goteborg, Sweden, <sup>2</sup>DIPSA, BOLOGNA UNIVERSITY, Bologna, Italy</italic></p><p><bold>INTRODUCTION:</bold> Folates – the natural chemically reduced forms of folic acid (vitamin B9) - are cofactors in essential metabolic pathways such as DNA synthesis and methylation pathways. Humans cannot synthesize folate and depend on intake both from the diet (green vegetables, cereals, rice, milk, fermented milk products, etc.) and from indigenous folate synthesizing bacteria of the intestinal microbiota. Low folate levels increase the risk for neural tube defects and may increase the risk for e.g. certain cancer forms, cardiovascular disease and Alzheimer’s.</p><p><bold>AIMS&METHODS:</bold> Screening for folate production of the bifidobacteria isolates from human adult and infant (1-6 month old) was performed. Strains typical of infants, such as <italic>Bifidobacterium longum</italic> subsp. <italic>infantis</italic> and <italic>B. breve,</italic> and of adults (<italic>B. adolescentis</italic>) were selected for characterization. The aim of the present work was to investigate bifidobacteria from human host of different age with different feeding habits in order to establish a possible correlation between diet and the folate production. Folate is present in many different forms in humans. The detectable forms studied in the present work are 5-CH3-H4, H4 and total folate content. Bifidobacteria strains were cultivated in folate free synthetic media. Validated HPLC method was used to analyze deconjugated folates extracted from bacterial biomass.</p><p><bold>RESULTS:</bold> All bifidobacteria tested (both from adult and infant) were able to produce folate. Strains derived from adults were the higher producer of total folate (range from 580 to 935 μg/g dry matter) with the predominance of 5-CH3-H4 folate and a low amount of H4 folate. In infants we obtained the opposite results with strains typical of infant habitat producing low amounts of total folate (range from 35 to 200 μg/g dry matter) and an inverted ratio of 5-CH3-H4/H4 folate in respect to adults.</p><p><bold>CONCLUSION:</bold> In agreement with idea of coevolution of host-gut microbiome (Ley et al., 2008) we find that bifidobacteria present in the adult gut were able to produce high amount of folate whereas strains derived from infants were less able to produce folate. These findings correlate with the diet and the folate requirement of the host: in infants, in fact, milk feeding is able per se to fulfill the folate needs of the individuals whereas in adults a more complex diet is sometime not able to cover all the folate need. The relevance of the different ratio of 5-CH3-H4/H4 folate production in adults and infants has being studied only in few strains and further studies are requested in order to complete this finding and provide an ecological explanation.</p><p><bold>REFERENCES:</bold></p><p>1. Ley RE, et al. (2008) Evolution of mammals and their gut microbes. Science 320:1647–1651</p><p><bold>Contact E-mail Address:</bold><email>paola.mattarelli@unibo.it</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Bifidobacterium adolescentis, Bifidobacterium breve, Bifidobacterium longum subsp. infantis, Folate production, Gut microbiota</p></sec><sec><title>OP249 UNDISSOCIATED GELATIN TANNATE REDUCES INTESTINAL LEAKINESS AND MUCOSA INFLAMMATION BY FORMING A PROTECTIVE BIOFILM: RESULTS FROM IN-VITRO AND IN-VIVO STUDIES</title><p><bold>L. Bueno</bold><sup>1,*</sup>, S. Sekkal<sup>1</sup>, V. Theodoru<sup>1</sup>, M. Dattilo<sup>2</sup></p><p><italic><sup>1</sup>INRA, Tolouse, France, <sup>2</sup>Biogem, Ariano Irpino, Italy</italic></p><p><bold>INTRODUCTION:</bold> Gelatine (GEL) stabilised by cross-linking with tannic acid (TA) forms gelatine tannate (GT). GT is approved as medical device for the oral treatment of diarrhoea as Tasectan<sup>®</sup>. GT is considered as a protective biofilm on the gut mucosa and has been shown to cure diarrhoea but the mechanism of action needs further investigation.</p><p><bold>AIMS&METHODS:</bold> We aimed at investigating the effect of GT and its components (GEL and TA) on the intestinal mucosa using both <italic>in-vitro</italic> and <italic>in-vivo</italic> models.</p><p>The <italic>in-vitro</italic> “filming” activity was evaluated by Corrositex<sup>®</sup>, a standard measure of chemical aggression, and on Caco-Goblet monolayers. The effect of GT (5 or 20 mg/ml) on Caco-Goblet cell permeability was assessed by Trans-Epithelial Electrical Resistance (TEER) and Lucifer Yellow (LY) before and after apical <italic>S. typhimurium</italic>. The tight-junction (TJ) proteins acquaporin-3 (AQP3) and occludin (OCL) were assayed by RT-PCR as markers of TJ integrity.</p><p><italic>In-vivo</italic>, Wistar rats received orally either GT (250 mg/kg), Gel (125 mg/kg), or TA (125mg/kg), and 2 h. later were injected IP with LPS from <italic>E. coli</italic>. Jejunal strips were collected 6 hours later for <italic>in vitro</italic> TJ permeability measurement using FITC-dextran and mucosal myelo-peroxidase (MPO) activity as a marker of inflammation.</p><p><bold>RESULTS:</bold> GT increased the corrosion time (hydrochloric ac. 37%) from 400 to 699 sec (p <0.001) suggesting a chemical biofilm protection. In addition, GT (5 mg/ml) increased TEER of CACO-goblet at 4 hours (from 180.1 to 269.2 ohm*cm2, p<0.05) and decreased the basal permeability to LY in basal conditions at both 2 and 4h. The LY permeability increased from 1.18 to 7.54 after 2 hours of exposure to <italic>S. typhimurium</italic> however a pre-treatment with GT suppressed this increase and decreased bacterial invasion by 72%, such been associated with overexpression of AQP3 and OCL at 4 hours (350 and 200% respectively for GT at 20mg/kg.</p><p>Six hours after LPS injection in rats, both jejunal TJ permeability and MPO activity were dramatically increased. Oral pretreatment with GT reduced by 78.1% the jejunal increase of permeability whereas GEL and TA did not affected it and subsequently reduced significantly the LPS-induced increase in MPO.</p><p><bold>CONCLUSION:</bold> Our results confirm that GT acts by mechanical protection of the gut mucosa. The protective biofilm formed by GT prevents the leakiness of the tight Junctions both in basal conditions and after insult by bacteria (in-vitro) and by LPS (in-vivo). These effects cannot be replicated by either tannic acid or gelatine confirming that GT is the active form to prevent gut leakiness and subsequent inflammation.</p><p><bold>Contact E-mail Address:</bold><email>maurizio.dattilo@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Diarhoea, Gelatin tannate, inflammation, LPS, paracellular permeability </p></sec><sec><title>OP250 DIABETES AND GASTROINTESTINAL DISORDERS: THE EFFECT OF INTESTINAL METHANE PRODUCTION ON GLYCEMIC CONTROL</title><p><bold>V. Cesario</bold><sup>1</sup>, T. A. Di Rienzo<sup>1</sup>, D. Pitocco<sup>2</sup>, M. Campanale<sup>1</sup>, G. D'Angelo<sup>1</sup>, S. Pecere<sup>1</sup>, F. D'Aversa<sup>1</sup>, A. Tortora<sup>1</sup>, F. Barbaro<sup>1</sup>, G. Vitale<sup>1</sup>, G. Gigante<sup>1</sup>, G. Caracciolo<sup>1</sup>, A. Gasbarfrini<sup>1</sup>, V. Ojetti<sup>1,*</sup></p><p><italic><sup>1</sup>Internal Medicine, <sup>2</sup>Diabetology, POLICLINICO GEMELLI, Rome, Italy</italic></p><p><bold>INTRODUCTION:</bold> At the state of art it isn't known the correlation between diabetes and lower gastrointestinal disorders. Some studies show a significantly higher prevalence of small intestinal bacterial overgrowth (SIBO) in patients with type I diabetes. No data exists about gastrointestinal methane (CH4) production in patients with diabetes.</p><p><bold>AIMS&METHODS:</bold> Aim of our study was to evaluate the effect of methaogenic flora eradications on glycemic control and daily insulin requirements in patients with type 1 diabetes in order to identify a possible role of CH4 production on diabetes severity.</p><p>30 consecutive patients (9 males, 21 females; mean age 45 +/-7yrs) affected by type 1 diabetes underwent H2/CH4 lactulose breath test to evaluate the presence of SIBO and CH4 production (CH4 concentration at least 3 ppm over that of room air). The glycemic control was evaluated trought glycated hemoglobin and daily insulin requirement (ratio between total insulin units in a day and body weight). CH4 producers were treated with metronidazole (500 mg bid for 10 days) and underwent a control breath test 8 weeks after the end of therapy. Data were analyzed using paired-data t-test.</p><p><bold>RESULTS:</bold> 12/30 patients (40%) were methane-producers (mean baseline value 6+/-2ppm; mean peak 25+/-8ppm); the mean glycemic control was 7,6% and the daily insulin requirements was 0.68+/-0.12 UI/kg. 9/12 patients (75%) showed a significant (P < 0.001) reduction of their glycemic control (mean HbA1c 7.6% vs 6.8%) and daily insulin requirements (0.68+/-0.12 vs 0.49+/-0.08 UI/kg) after metronidazole therapy.</p><p><bold>CONCLUSION:</bold> Our study showed for the first time a possible role of CH4 production in diabetes metabolic control. In particular, the most interesting data is that poorly controlled diabetes seems to be related to a gut CH4 production as confirmed by its significant improvement after eradication therapy.</p><p><bold>Contact E-mail Address:</bold><email>valecesario@yahoo.it</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> diabetes mellitus type 1, glycemic control, methanogenic flora</p></sec><sec><title>OP251 MEDIUM-CHAIN TRYGLICERIDE INDUCED LEUKOCYTE ACTIVATION IS NOT MEDIATED BY TOLL-LIKE RECEPTOR 4</title><p><bold>E. D. Olthof</bold><sup>1,*</sup>, A. F. Guelich<sup>1</sup>, L. A. Joosten<sup>2</sup>, H. M. Schaap - Roelofs<sup>1</sup>, G. J. Wanten<sup>1</sup></p><p><italic><sup>1</sup>Department of Gastroenterology and Hepatology, <sup>2</sup>Department of General Internal Medicine, RADBOUD UNIVERSITY NIJMEGEN MEDICAL CENTRE, Nijmegen, Netherlands</italic></p><p><bold>INTRODUCTION:</bold> Lipids, as part of parenteral nutrition formulations modulate the function of the immune system. For instance, medium-chain triglycerides (MCTs), but not long-chain triglycerides (LCT), as part of parenteral lipid emulsions activate leukocytes <italic>in vitro</italic> by mechanisms that are still unknown. It has been shown that saturated fatty acids can activate Toll-like receptor 4 (TLR-4) mediated pro-inflammatory signaling pathways in leukocytes.</p><p><bold>AIMS&METHODS:</bold> Aim of our study was to investigate whether TLR-4 is also involved in MCT-induced leukocyte activation. We assessed the <italic>in vitro</italic> effect of the parenteral mixed lipid emulsion LCT/MCT, at a clinically relevant triglyceride concentration of 5 mmol/l, on the expression of leukocyte surface membrane activation markers in the presence or absence of the specific TLR-4 inhibitors TAK-242 (0.5 and 5 µmol/l) and <italic>Bartonella quintana</italic> LPS (0.1, 1 and 2.5 µg/ml).</p><p><bold>RESULTS:</bold> As expected, LCT/MCT activated leukocytes, with an increase in expression of adhesion (55% and 41% in granulocytes and monocytes, respectively), azurophilic and specific degranulation (19% and 22%, respectively in granulocytes) markers, and a decrease in L-selectin (14% and 20% in granulocytes and monocytes, respectively). Inhibition of TLR-4 by TAK-242 and <italic>Bartonella quintana</italic> LPS did not alter the LCT/MCT-induced decrease in L-selectin and increase in adhesion marker expression in granulocytes and monocytes. Furthermore, in granulocytes <italic>Bartonella quintana</italic> LPS did not change the MCT-induced increased expression of specific and azurophilic degranulation markers. The LCT/MCT induced increase in expression of both degranulation markers in granulocytes was abolished during TLR-4 inhibition with 5 µmol/l TAK-242. However, a similar decrease in degranulation marker expression was found after incubation with 5 µmol/l TAK-242 alone.</p><p><bold>CONCLUSION:</bold> MCT-induced immune activation is not mediated by TLR-4 signaling.</p><p><bold>Contact E-mail Address:</bold><email>e.olthof@mdl.umcn.nl</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> immune activation, medium chain triglyceride, parenteral nutrition, toll like receptor-4</p></sec><sec><title></title><p><bold>TUESDAY, OCTOBER 15, 2013 11:00-12:30</bold></p><p><bold>Pancreatitis: Lessons from animal models – Salon 11/12</bold></p></sec><sec><title>OP252 IMPROVEMENT OF ENDOPLASTIC RETICULUM STRESS BY ENHANCED PERK PATHWAY REDUCES MURINE EXPERIMENTAL ACUTE PANCREATITIS</title><p><bold>T. Okazaki</bold><sup>1,*</sup>, A. Nishio<sup>1</sup>, T. Masahiro<sup>2</sup>, T. Inoue<sup>2</sup>, Y. Sakaguchi<sup>1</sup>, T. Fukui<sup>2</sup>, K. Uchida<sup>2</sup>, K. Okazaki<sup>2</sup></p><p><italic><sup>1</sup>Gastroenterology and Hepatology, Kansai Medical University, Moriguchi, <sup>2</sup>Gastroenterology and Hepatology, Kansai Medical University, hirakata, Japan</italic></p><p><bold>INTRODUCTION:</bold> Endoplasmic reticulum (ER) stress causes the accumulation of misfolded proteins inside the ER and initiates unfolded protein response (UPR). UPR is activated during pancreatitis to restore ER homeostasis. Although protein kinase RNA-like ER kinase (PERK) is associated with the UPR through phosphorylation of eukaryotic initiation factor 2-alfa (eIF2-a), the role of PERK signaling pathway in pancreatitis is not fully clarified. We investigated the significance of PERK signaling pathway in severe acute pancreatitis in mice using an elF2-a dephosphorylation inhibitor, salubrinal.</p><p><bold>AIMS&METHODS:</bold> Severe acute pancreatitis was induced by intraperitoneal injection of cerulein (CER) at a dose of 50 mg/kg six times at 1 hour intervals. Moreover, LPS was administered at a dose of 10mg/kg as the septic challenge immediately after the completion of CER injections. Salubrinal was administered intraperitoneally immediately after LPS injection and six hours later. Mice were sacrificed at 24 hours after the first injection of CER and the severity of pancreatitis was histologically graded with a scoring system. Serum amylase and proinflammatory cytokine levels were measured. Expression of ER stress-related proteins was examined by western blotting.</p><p><bold>RESULTS:</bold> The severity of pancreatitis in mice treated with salubrinal was significantly attenuated compared with control mice. Serum amylase and proinflammatory cytokine levels were lower in salubrinal-treated mice than those of control mice. Expression level of 78kDa glucose regulated protein (GRP78), activating transcription factor 4 and phosphorylated eIF2-a protein were elevated in mice treated with salubrinal compared with control groups.</p><p><bold>CONCLUSION:</bold> Inhibition of eIF2-a dephosphorylation decreased ER stress and reduced severe acute pancreatitis in mice. Augmentation of PERK signaling pathway could be a potential therapeutic option for the treatment of acute pancreatitis.</p><p><bold>REFERENCES:</bold></p><p>1. Malo A et al. 4-Phenylbutyric acid reduces endoplasmic reticulum stress, trypsin activation, and acinar cell apoptosis while increasing secretion in rat pancreatic acini. Pancreas. 2013;42:92-101.</p><p>2. Ye R et al. Grp78 heterozygosity regulates chaperone balance in exocrine pancreas with differential response to cerulein-induced acute pancreatitis. Am J Pathol. 2010;177:2827-2836.</p><p>3. Fazio EN et al. Stanniocalcin 2 alters PERK signalling and reduces cellular injury during cerulein induced pancreatitis in mice. BMC Cell Biology. 2011;12:17.</p><p><bold>Contact E-mail Address:</bold><email>okazakta@takii.km.ac.jp</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> ER stress, pancreatitis, PERK signaling, Salubrinal</p></sec><sec><title>OP253 SEROTONIN REGULATES PROGENITOR CELL-BASED BUT NOT CLONAL REGENERATION IN THE ADULT PANCREATIC ACINAR CELL</title><p><bold>E. Saponara</bold><sup>1,*</sup>, S. Sonda<sup>1</sup>, K. Grabliauskaite<sup>1</sup>, Y. Tian<sup>1</sup>, T. Reding<sup>1</sup>, R. Graf<sup>1</sup></p><p><italic><sup>1</sup>Swiss HPB Center, University Hospital Zurich, Zurich, Switzerland</italic></p><p><bold>INTRODUCTION:</bold> Progenitor cell-based regeneration of acinar cells is activated during cerulein-induced pancreatitis. This process requires a preliminary acinar de-differentiation via secretion of zymogens, followed by expression of progenitor cell markers and formation of acinar-to-ductal metaplasia (ADM). Clonal regeneration without loss of zymogens and cell de-differentiation is observed following 60% pancreatectomy. Previously, we demonstrated that serotonin (5-HT) is essential for acinar cell secretion [1]. We now investigate the role of 5-HT in pancreatic regeneration.</p><p><bold>AIMS&METHODS:</bold> Cerulein-induced pancreatitis and 60% pancreatectomy were performed in wild type (WT) and tryptophan hydroxylase-1 knocked-out (TPH1<sup>-/-</sup>) mice, with strongly reduced peripheral 5-HT levels. The regenerative potential of pancreatic acinar cells was evaluated <italic>in vivo</italic>, over two weeks, and <italic>in vitro</italic> in AR42J cells.</p><p><bold>RESULTS:</bold> After experimental pancreatitis, WT mice showed an early up-regulation of 5-HT<sub>2A</sub>/5-HT<sub>2B</sub> receptors, amylase secretion and progenitor cell marker expression, indicative of acinar de-differentiation. These events were followed by the appearance of ADM lesions and acinar cell proliferation. Conversely, in TPH1<sup>-/-</sup> mice these early parameters were blunted and consequent formation of ADM and proliferation of acinar cells were inhibited. After 60% pancreatectomy, clonal regeneration of differentiated acinar cells was comparable in the two strains. Similarly to observations <italic>in vivo</italic>, 5-HT<sub>2A</sub> receptor agonists promoted proliferation of undifferentiated AR42J cells but not of dexamethasone-differentiated cells. 5-HT<sub>2B</sub> receptor agonist was not mitogenic but induced amylase release.</p><p><bold>CONCLUSION:</bold> Our results indicate that 5-HT, likely via 5-HT<sub>2A</sub>/5-HT<sub>2B</sub> receptors, modulates progenitor cell-based but not clonal regeneration. Current investigations aim to elucidate the role of 5-HT in pancreatic proliferation induced by primary mitogen administration.</p><p><bold>REFERENCES:</bold></p><p>1. Sonda, S., et al., <italic>Serotonin regulates amylase secretion and acinar cell damage during murine pancreatitis.</italic> Gut, 2013. <bold>62</bold>(6): p. 890-8.</p><p><bold>Contact E-mail Address:</bold><email>rolf.graf@usz.ch</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Mitogen, Pancreatitis, Regeneration, Serotonin</p></sec><sec><title>OP254 SERUM INTERFERON-GAMMA AND TNF-ALPHA LEVELS AFTER CHRONIC PANCREATITIS TREATMENT BY UDCA</title><p><bold>I. Grigorieva</bold><sup>1,*</sup>, A. Yamlichanova<sup>1</sup>, M. Grishaev<sup>2</sup></p><p><italic><sup>1</sup>Institute of Internal Medicine, <sup>2</sup>LLC "Vector-Best", Novosibirsk, Russian Federation</italic></p><p><bold>INTRODUCTION:</bold> Ursodeoxycholic acid (UDCA) may inhibit the production of the pro-inflammatory cytokine, e.g. IL-1beta<sup>1</sup>. In order to prevent concanavalin A-induced liver injury in mice the treatment with UDCA significantly decreased the intrahepatic levels of TNF-alpha, whereas this compound showed no clear effect on interferon-gamma (IFN-gamma), IL-4, IL-6, or IL-10<sup>2</sup>. We did not find information about the antiinflammatory effect of UDCA in patients with chronic pancreatitis (CP).</p><p><bold>AIMS&METHODS:</bold> to compare IFN-gamma and tumor necrosis factor-alpha (TNF-alpha) serum concentrations in CP patients within standard therapy, and the addition of UDCA.</p><p>The study included 88 CP patients (mean age - 50,8 ± 2,3 years). CP was confirmed by ultrasound, ERCP, CT. IFN-gamma and TNF-alpha serum levels were determined by ELISA. The standard CP treatment regimen included analgesics, antispasmodics, pancreatin, proton pump inhibitors, and in 23 patients - adding of UDCA ("Ursosan», PRO.MED.CS. Praha, as at a dose of 10-15 mg/kg/day) for 3 - 4 months. Statistical analysis was performed by SPSS (11.0).</p><p><bold>RESULTS:</bold> After 3 or 4 months of treatment IFN-gamma serum concentration in all CP patients were 4,8 ± 1,5 pg/ml, TNF-alpha - 4,3 ± 0,6 pg/ml. In the CP patients without UDCA, the corresponding levels were higher (5,1 ± 1,5 and 4,7 ± 0,6 pg/mL, respectively) than in CP patients adding of UDCA (IFN-gamma 2.1 ± 0,8 pg/ml, p <0,05 and TNF-alpha 3,3 ± 0,9 pg/ml, p> 0,05, respectively).</p><p><bold>CONCLUSION:</bold> in CP patients adding of UDCA to standard therapy resulted in a significant decrease of serum IFN-gamma concentration and the slight decrease of TNF-alpha levels, which may indicate the antiinflammatory effect of UDCA.</p><p><bold>REFERENCES:</bold></p><p>1. Joo SS, Kang HC, Won TJ, Lee DI. Arch Pharm Res. 2003;26(12):1067-73.</p><p>2. Ishizaki K, Iwaki T, Kinoshita S, et al. Eur J Pharmacol. 2008;578(1):57-64.</p><p><bold>Contact E-mail Address:</bold><email>igrigorieva@ngs.ru</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Chronic Pancreatitis, interferon-gamma, tnf-alpha, UDCA, treatment</p></sec><sec><title>OP255 CIGARETTE SMOKE EXTRACT INHIBITS FLUID SECRETION BY INHIBITING CFTR ACTIVITY IN GUINEA PIG PANCREATIC DUCT CELLS</title><p><bold>A. Schnúr</bold><sup>1,*</sup>, V. Venglovecz<sup>1</sup>, E. Gál<sup>1</sup>, Z. Rakonczay<sup>1</sup>, P. Hegyi<sup>1</sup></p><p><italic><sup>1</sup>First Department of Medicine, University of Szeged, Szeged, Hungary</italic></p><p><bold>INTRODUCTION:</bold> Smoking represents an independent risk factor for the development of chronic pancreatitis (CP), however, the pathomechanism remains unknown. Pancreatic ductal epithelial cells (PDEC) secrete a bicarbonate rich fluid mediated mainly by cystic fibrosis transmembrane conductance regulator (CFTR), which is responsible for maintaining the integrity of the gland. Cigarette smoke extract (CSE) was found to alter anion transport mechanism in human airway epithelial cells, however, no information is available whether smoking has such effects on PDEC.</p><p><bold>AIMS&METHODS:</bold> Our aim was to investigate the effects of CSE on basal and forskolin-stimulated pancreatic ductal fluid secretion and on CFTR channel activity. Intra/interlobular pancreatic ducts for fluid secretion measurements and single PDEC for patch clamp recordings were isolated from guinea pig pancreas with enzymatic digestion and microdissection. Basal and forskolin (5µM)-stimulated fluid secretion into the closed luminal space of the ducts was followed with video microscopy. Relative volume was calculated with Scion Image software. We used the patch clamp technique to study the effects of CSE on forskolin-stimulated whole cell CFTR currents.</p><p><bold>RESULTS:</bold> Isolated guinea pig pancreatic ducts were capable of secreting fluid in the presence of bicarbonate, the fluid secretion increased up to 1.62±0.06 (n=18). The administration of forskolin induced a sustained increase in the relative luminal volume which reached an average value of 2.03±0.08 (n=23). Parallel administration of 40µg/ml CSE decreased the basal and forskolin stimulated fluid secretion (the relative luminal volume decreased to 1.45±0.03, n=25; and 1.75±0.15, n=10, respectively). Administration of forskolin activated CFTR currents by 10-15-fold in magnitude. 40 µg/ml CSE blocked the forskolin-stimulated currents by 75±9% (n=5).</p><p><bold>CONCLUSION:</bold> Cigarette smoke extract inhibits basal and stimulated pancreatic ductal fluid secretion and also the activity of the CFTR Cl- channel. These inhibitory effects may contribute to the pathogenesis of smoke-induced pancreatic damage and the development of CP.</p><p>This study was supported by OTKA, MTA and NFÜ/TÁMOP</p><p><bold>Contact E-mail Address:</bold><email>schnur.andrea@med.u-szeged.hu</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> chronic pancreatitis, fluid secretion, smoking</p></sec><sec><title>OP256 METHYLENE BLUE AMELIORATES MITOCHONDRIAL FUNCTION OF RAT KIDNEY DURING EXPERIMENTAL ACUTE PANCREATITIS</title><p><bold>I. Kuliaviene</bold><sup>1,*</sup>, S. Virketyte<sup>2</sup>, M. Kincius<sup>3</sup>, G. Semeklis<sup>1</sup>, R. Baniene<sup>2</sup>, A. Gulbinas<sup>3</sup>, L. Kupcinskas<sup>3</sup>, V. Borutaite<sup>2</sup>, S. Trumbeckaite<sup>2</sup></p><p><italic><sup>1</sup>Gastroenterology, <sup>2</sup>Institute of Neurosciences, <sup>3</sup>Institute for Digestive research , LITHUANIAN UNIVERSITY OF HEALTH SCIENCES, Kaunas, Lithuania</italic></p><p><bold>INTRODUCTION:</bold> Systemic inflammatory response syndrome in severe acute pancreatitis (AP) leads to multiple organ dysfunction that is the main cause of death. Renal failure is of utmost importance and has a large impact on mortality rate. Our previous data revealed that mitochondrial energy metabolism in kidney is disturbed during experimental AP and may play an important role in the development and progression of renal failure. The effects of methylene blue on mitochondrial respiratory functions of rat kidney during severe experimental AP were investigated in this study.</p><p><bold>AIMS&METHODS:</bold> AP was induced in 10 male Wistar rats by intraductal application of sodium taurocholate (5%, 1,75 mL/kg). Animals were divided into two groups: experimental group – methylene blue (5mg/kg) was injected intravenously 10 min prior to AP induction; control group – saline solution intravenously 10 min prior to AP induction. Animals were sacrificed after 24 hours from the induction of AP. Kidney were removed for mitochondrial assay by oxygraphic and spectrophotometric methods.</p><p><bold>RESULTS:</bold> We found that AP-induced kidney mitochondrial dysfunction was restored with methylene blue intravenous injection. Thus, our data indicate clear increase in mitochondrial State 3 respiration rate (by 62%, p<0.05) and in respiratory control index (RCI, by 30%) with mitochondrial complex I linked substrate glutamate/malate in the group after methylene blue treatment as compared to untreated group. The Complex I activity was increased by two-fold (p<0.05) after methylene blue treatment. Methylene blue slightly increased RCI with Complex II dependent substrate succinate (by 16%, p<0.05), though had no effect on State 3 respiration rate with this substrate.</p><p><bold>CONCLUSION:</bold> Our data show that disturbances of mitochondrial energy metabolism during AP in kidney mitochondria could be ameliorated with methylene blue intravenous injection. This may be a promising agent for future therapeutic interventions for severe AP treatment.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Acute Pancreatitis, Methylene Blue , Mitochondria</p></sec><sec><title>OP257 INVESTIGATION OF THE ROLE OF NHERF-1 IN PANCREATIC DUCTAL SECRETION AND ACUTE PANCREATITIS IN MICE</title><p><bold>P. Pallagi</bold><sup>1</sup>, Z. Balla<sup>1</sup>, A. K. Singh<sup>2</sup>, S. Dósa<sup>3</sup>, B. Iványi<sup>3</sup>, B. Riederer<sup>2</sup>, K. Jármay<sup>1</sup>, V. Venglovecz<sup>4</sup>, J. Maléth<sup>1</sup>, T. Wittmann<sup>1</sup>, P. Hegyi<sup>1</sup>, U. Seidler<sup>2</sup> Z. Rakonczay Jr <sup>1,*</sup></p><p><italic><sup>1</sup>First Department of Medicine, University of Szeged, Szeged, Hungary, <sup>2</sup>Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany, <sup>3</sup>Department of Pathology, <sup>4</sup>Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary</italic></p><p><bold>INTRODUCTION:</bold> Fluid and bicarbonate secretion is a vital function of pancreatic ductal eptihelia and their role in acute pancreatitis (AP) is poorly characterized. NHERF-1 is a cytosolic scaffolding protein mediating the apical targeting and retention of ion channels and transporters, such as cystic fibrosis transmembrane conductance regulator (CFTR).</p><p><bold>AIMS&METHODS:</bold> The main aims of this study were to investigate the physiological and pathophysiological relevance of NHERF-1 expression in the pancreas. Wild-type and NHERF-1 knock-out mice were used. We analyzed the effects of NHERF-1 deletion on ductal function both in vitro and in vivo. The localization of CFTR was performed by immunohistochemistry. AP was induced by administration of intraperitoneal cerulein or by intraductal sodium-taurocholate. The severity of AP was evaluated by measuring histological and laboratory parameters.</p><p><bold>RESULTS:</bold> We show that pancreatic ductal NHERF-1 expression plays a critical role in modulating the apical localization of pancreatic ductal CFTR. The gross mislocalization of CFTR in NHERF-1 mice resulted in significantly lower pancreatic ductal bicarbonate and fluid secretion. NHERF-1 expression also influenced the development of AP in both mouse models of AP; the disease severity, especially the degree of acinar cell death, was higher in NHERF-1-knock-out vs. wild-type mice.</p><p><bold>CONCLUSION:</bold> NHERF-1 has a crucial role in regulating pancreatic ductal fluid and bicarbonate secretion. We provide the first <italic>in vivo </italic>data that specifically implicates pancreatic ducts in the pathogenesis of AP.</p><p>This study was supported by OTKA, MTA/DFG and NFÜ/TÁMOP.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> acute pancreatitis, NHERF-1, pancreatic ducts, secretion</p></sec><sec><title></title><p><bold>TUESDAY, OCTOBER 15, 2013 14:00-15:30</bold></p><p><bold>Difficulties in the diagnosis of colitis – Hall Copenhagen</bold></p></sec><sec><title>OP258 CHRONOLOGY OF EXTRAINTESTINAL MANIFESTATIONS RELATIVE TO IBD DIAGNOSIS IN THE SWISS INFLAMMATORY BOWEL DISEASE COHORT</title><p><bold>S. Vavricka</bold><sup>1,*</sup>, G. Rogler<sup>1</sup>, E. Safroneeva<sup>2</sup>, N. Fournier<sup>3</sup>, A. Straumann<sup>4</sup>, C. Gantenbein<sup>5</sup>, M. Spoerri<sup>5</sup>, M. Prinz Vavricka<sup>5</sup>, A. Navarini<sup>5</sup>, L. French<sup>5</sup>, F. Froehlich<sup>4</sup>, M. Fried<sup>1</sup>, P. Michetti<sup>1</sup>, A. Schoepfer<sup>6</sup> Swiss Inflammatory Bowel Disease Cohort Study</p><p><italic><sup>1</sup>Gastroenterology and Hepatology, University Hospital Zurich, Zurich, <sup>2</sup>Institute of Social and Preventive Medicine, University of Bern, Bern, <sup>3</sup>Institute of Social and Preventive Medicine, University of Lausanne / CHUV, Lausanne, <sup>4</sup>Gastroenterology and Hepatology, University Hospital Basel, Basel, <sup>5</sup>University Hospital Zurich, Zurich, <sup>6</sup>Gastroenterology and Hepatology, University Hospital Lausanne / CHUV , Lausanne, Switzerland</italic></p><p><bold>INTRODUCTION:</bold> There is a lack of data evaluating the chronology between inflammatory bowel disease (IBD) diagnosis and the occurrence of extraintestinal manifestations (EIM).</p><p><bold>AIMS&METHODS:</bold> We aimed to assess the type and frequency of EIM in IBD patients and to evaluate their chronologic behavior. We analyzed data from the Swiss Inflammatory Bowel Disease Cohort (SIBDCS) which collects data since 2006 on a large sample of IBD patients from hospitals and private practices across Switzerland.</p><p><bold>RESULTS: : </bold>A total of 1,249 patients were analyzed (49.8% female, median age 40 (IQR 30-51 years), 735 (58.8%) with Crohn’s disease (CD), 483 (38.7%) with ulcerative colitis (UC), and 31 (2.5%) with indeterminate colitis (IC). Of these, 366 (29.3%) presented one to five EIM (67.8% with CD, 28.7% with UC, 3.5% with IC). Of those patients suffering from EIM, 26.5% presented two, 4.9% three, 2.5% four, and 2.7% five EIM during lifetime. The initial EIM presented with the following frequencies: peripheral arthritis (PA) 70.0%, aphthous stomatitis 21.6%, ankylosing spondylitis (AS) 16.4%, uveitis 13.7%, erythema nodosum (EN) 12.6%, primary sclerosing cholangitis (PSC) 6.6%, pyoderma gangrenosum 4.9%, and psoriasis 2.7%. In 25.8 % of cases, the first EIM manifested before IBD diagnosis was made (median time 5 months before IBD diagnosis, range 0-25 months), in 74.2% the first EIM manifested after established IBD diagnosis (median 92 months, range 29-183 months).</p><p><bold>CONCLUSION:</bold> In one quarter of patients the EIM appear before IBD is diagnosed. In this population the occurrence of an EIM should motivate the search for underlying IBD.</p><p><bold>Contact E-mail Address:</bold><email>stephan.vavricka@usz.ch</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> extraintestinal manifestations, Inflammatory bowel disease (IBD) </p></sec><sec><title>OP259 MICROSCOPIC COLITIS (MC) OR IRRITABLE BOWEL SYNDROM (IBS) WITH DIARRHEA: PROSPECTIVE MULTICENTER STUDY.</title><p><bold>G. Macaigne</bold><sup>1</sup>, B. Lesgourgues<sup>2,*</sup>, C. Locher<sup>3</sup>, S. Nahon<sup>2</sup> ANGH</p><p><italic><sup>1</sup>CH de Marne La Vallée, Jossigny, <sup>2</sup>GHI Le Raincy Montfermeil, Montfermeil, <sup>3</sup>CH de Meaux, Meaux, France</italic></p><p><bold>INTRODUCTION:</bold> The aims of this prospective and multicenter study were to describe the characteristics of a cohort of patients with MC [lymphocytic (LC) or collagen (CC) colitis] and to compare them to patients with IBS with diarrhea.</p><p><bold>AIMS&METHODS:</bold> Between September 2010 and June 2012, patients fulfilling the following inclusion criteria were prospectively included in 26 centers in France: transit with at least 3 bowel movements daily with change in their consistency, duration of the disorder for more than 3 weeks and normal or near normal colonoscopy. Each patient had a colonoscopy with ileal and colonic biopsies and possible gastroscopy with gastric and duodenal biopsies. The diagnosis of LC was defined by a rate of intraepithelial lymphocytes above 20% and CC by a collagen thickening of the basal epithelial membrane more than 10 microns. We compared characteristic of patients with CM and those with IBS with diarrhea using univariate and multivariate analysis.</p><p><bold>RESULTS:</bold> 433 patients were included, 129 had a MC (87 LC and 42 CC), 278 an IBS with diarrhea (control group) and 26 another organic disease. The two groups of CC and CL were statistically comparable for all studied characteristics. The diagnostic yield of biopsies was higher in the transverse colon, respectively 96% and 98.5% for CC and CL, and lower in the rectum, 83% and 78% for CC and CL. A drug intake was observed in 53% of cases and autoimmune disease was associated in 34% of cases. In univariate analysis, there was a significant difference between MC and IBS groups for the following characteristics: average age (61 vs 47 years ; p<0.005), nocturnal stools (41.2% vs 24.5% ; p=0.01), weight loss (47.7% vs 28.8% ; p<0.0001), hypokalemia (19.1% vs 5.7% ; p<0.0001), absence of abdominal pain (47% vs 28.8% ; p<0.0001), association with autoimmune disease (34.5% vs 11.3% ; p<0.0001) and introduction of a drug during the preceding three months (52.6% vs 24.2% ; p<0.0001). By multivariate analysis, predictors of MC were age > 50 years (OR 3.4, 95% CI [1.9-6.2]), hemoglobin<13g/dl (OR 2.4, 95% [1.4-4.4]), weight loss (OR 2.2, 95% CI [1.2-3.8]), duration of diarrhea<italic><</italic>12 months (OR 2, 95% [1.1-3.5]), introduction of new drugs<3 months (OR 3.7, 95% CI [2.1-6.6]) and autoimmune disease (OR 3.99, 95% CI [2.1-7.7]).</p><p><bold>CONCLUSION:</bold> In this large prospective multicenter study, the following predictive factors of MC were identified: age>50 years, nocturnal stools, weight loss, introduction of new drugs<3 months and autoimmune disease associated. Drugs and autoimmune disorder are frequently associated with CM. The diagnostic yield of colonic biopsies was maximum at the transverse colon and minimum at the rectum.</p><p><bold>Contact E-mail Address:</bold><email>gmacaigne@ch-lagny77.fr</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> microscopic colitis, prospective multicenter french study</p></sec><sec><title></title><p><bold>TUESDAY, OCTOBER 15, 2013 14:00-15:30</bold></p><p><bold>IBD: Therapy beyond anti-TNFs – Hall Helsinki</bold></p></sec><sec><title>OP260 EARLY RESPONSES IN PATIENT-REPORTED OUTCOMES ARE PREDICTORS FOR MUCOSAL HEALING IN PATIENTS WITH MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS TREATED WITH GOLIMUMAB- RESULTS FROM PURSUIT SC INDUCTION</title><p><bold>J. F. Colombel</bold><sup>1,*</sup>, W. Reinisch<sup>2</sup>, B. G. Feagan<sup>3</sup>, C. Marano<sup>4</sup>, R. Strauss<sup>5</sup>, C. Han<sup>6</sup>, J. Johanns<sup>5</sup>, H. Zhang<sup>5</sup>, P. Gibson<sup>7</sup>, J. Collins<sup>8</sup>, G. Jarnerot<sup>9</sup>, P. Rutgeerts<sup>10</sup>, W. Sandborn<sup>11</sup> on behalf of the PURSUIT Steering Committee</p><p><italic><sup>1</sup>Centre Hospitalier Universitaire de Lille, Lille, France, <sup>2</sup>Universitätsklinik für Innere Medizin IV, Vienna, Austria, <sup>3</sup>Robarts Research Institute, London, Canada, <sup>4</sup>Janssen R&D, LLC., Spring Hosue, <sup>5</sup>Janssen R&D, LLC., Spring House, <sup>6</sup>Janssen Global Services, LLC., Malvern, United States, <sup>7</sup>Alfred Hospital, Melbourne, Australia, <sup>8</sup>Oregon Health Sciences University, Portland, United States, <sup>9</sup>Orebro University Hospital, Orebro, Sweden, <sup>10</sup>9.University Hospital Gasthuisberg, Leuven, Belgium, <sup>11</sup>University of California San Diego, La Jolla, United States</italic></p><p><bold>INTRODUCTION:</bold> -</p><p><bold>AIMS&METHODS:</bold> To assess association of pt-reported stool frequency and rectal bleeding with mucosal healing(MH) based on endoscopy in pts with active UC. Pts with active UC defined by Mayo score of 6-12 including an endoscopy subscore of ≥2 were randomized to PBO/PBO; GLM 200mg/100mg; GLM 400mg/200mg at wks0 and 2. Pt reported stool frequency and rectal bleeding from wks0 through wk6 were collected from the most recent consecutive 3-day period within the 2wks prior to a visit. Responder was defined as normalized stool frequency or no rectal bleeding. MH was defined as endoscopy subscore of the Mayo score of 0/1. Odds ration (OR), positive predictive value (PPV) and likelihood ratio positive (LR+) were estimated for predicting MH using normalized stool frequency or no rectal bleeding.</p><p><bold>RESULTS:</bold> A high proportion of pts reported abnormal stool frequency (99%) and rectal bleeding (86.9%) at wk0. In these post-hoc analyses, sig differences were observed between grps as early as wk2(all nominal p-values<0.001) (Table). At wk6, a greater proportion of pts in the pooled GLM grp vs PBO reported normalized stool frequency (17.7%, vs 7.0%) or no rectal bleeding (52.8% vs 34.0%)(all nominal p-values <0.001). Among pts who reported no rectal bleeding consistently from wk2 through wk6, 66.4% achieved MH at wk6, vs 13.2% of pts with rectal bleeding through wk6 (OR=13.0, nominal p<0.001, PPV=0.66, LR=3.7). Among pts with normalized stool frequency consistently from wk2 through wk6, 78.3% achieved MH at wk6 vs. 30.2% of pts with abnormal stool frequency through wk6 (OR=8.3, nominal p<0.001, PPV=0.78, LR=7.1).</p><p>Table: Post-hoc analysis of stool frequency and rectal bleeding score (mean<italic>+</italic>SD)
<table-wrap id="table36-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="2" colspan="1">Visit</th><th colspan="3" rowspan="1"><hr></hr>Stool frequency </th><th colspan="3" rowspan="1"><hr></hr>Rectal bleeding Score</th></tr><tr><th rowspan="1" colspan="1">PBO</th><th rowspan="1" colspan="1">GLM</th><th rowspan="1" colspan="1">P-value (nominal)</th><th rowspan="1" colspan="1">PBO</th><th rowspan="1" colspan="1">GLM</th><th rowspan="1" colspan="1">P-value (nominal)</th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">Wk 0</td><td rowspan="1" colspan="1">2.3 ±0.8</td><td rowspan="1" colspan="1">2.4±0.7</td><td rowspan="1" colspan="1">0.12</td><td rowspan="1" colspan="1">1.50±0.86</td><td rowspan="1" colspan="1">1.55±0.83</td><td rowspan="1" colspan="1">0.40</td></tr><tr><td rowspan="1" colspan="1">Wk 2</td><td rowspan="1" colspan="1">2.1 ±0.9</td><td rowspan="1" colspan="1">1.6±1</td><td rowspan="1" colspan="1"><0.001</td><td rowspan="1" colspan="1">1.20±0.91</td><td rowspan="1" colspan="1">0.83±0.85</td><td rowspan="1" colspan="1"><0.001</td></tr><tr><td rowspan="1" colspan="1">Wk 4</td><td rowspan="1" colspan="1">1.9 ±0.9</td><td rowspan="1" colspan="1">1.5±1.1</td><td rowspan="1" colspan="1"><0.001</td><td rowspan="1" colspan="1">1.04±0.94</td><td rowspan="1" colspan="1">0.70±0.86</td><td rowspan="1" colspan="1"><0.001</td></tr><tr><td rowspan="1" colspan="1">Wk 6</td><td rowspan="1" colspan="1">2.0 ±1</td><td rowspan="1" colspan="1">1.6±1.1</td><td rowspan="1" colspan="1"><0.001</td><td rowspan="1" colspan="1">1.04±0.94</td><td rowspan="1" colspan="1">0.71±0.87</td><td rowspan="1" colspan="1"><0.001</td></tr></tbody></table></table-wrap></p><p><bold>CONCLUSION:</bold> Treatment with SC GLM led to early improvement in pt reported outcomes of stool frequency and rectal bleeding. The normalization of stool frequency and improvement in rectal bleeding associated with MH at wk6.</p><p><bold>Contact E-mail Address:</bold><email>cmarano@its.jnj.com</email></p><p><bold>Disclosure of Interest</bold>: J. Colombel Financial support for research from: Janssen, W. Reinisch Financial support for research from: Janssen, B. Feagan Financial support for research from: Janssen, C. Marano Other: Janssen employee, R. Strauss Other: Janssen employee, C. Han Other: Janssen employee, J. Johanns Other: Janssen employee, H. Zhang Other: Janssen employee, P. Gibson Financial support for research from: Janssen, J. Collins Financial support for research from: Janssen, G. Jarnerot Financial support for research from: Janssen, P. Rutgeerts: None Declared, W. Sandborn Financial support for research from: Janssen</p><p><bold>Keywords:</bold> golimumab, PURSUIT, ulcerative colitis</p></sec><sec><title>OP261 IMA-638 IN ACTIVE ULCERATIVE COLITIS: EFFICACY AND SAFETY FROM A PHASE IIA MULTICENTER STUDY</title><p><bold>W. Reinisch</bold><sup>1,*</sup>, J. Panes<sup>2</sup>, M. P. De Micco<sup>3</sup>, B. Hanlon<sup>4</sup>, G. T. Toth<sup>5</sup>, P. Petrov<sup>6</sup>, G. Yuan<sup>7</sup>, F. Hua<sup>7</sup>, M. Hinz<sup>7</sup>, K. Page<sup>7</sup>, T. McDonnell<sup>7</sup>, P. Gruer<sup>7</sup>, F. Cataldi<sup>7</sup> IMA study</p><p><italic><sup>1</sup>Gastroenterology, University of Vienna , Vienna, Austria, <sup>2</sup>Gastroenterology, HOSPITAL CLINIC I PROVINCIAL DE BARCELONA, Barcelona, Spain, <sup>3</sup>Gastroenterology, Advanced Clinical Research Institute, Anaheim, <sup>4</sup>Gastroenterology, Wasatch Clinical Research, Salt Lake City, United States, <sup>5</sup>Gastroenterology, Fovarosi Onkormanyzat Szent Janos , Budapest , Hungary, <sup>6</sup>Gastroenterology, DKTs Sveta Anna, Sofia , Bulgaria, <sup>7</sup>Gastroenterology, PFIZER INC, Cambridge, United States</italic></p><p><bold>INTRODUCTION:</bold> Anrukinzumab-IMA-638 (IMA) is a humanized antibody (IgG1) that binds and inhibits human IL13. We studied the effect of IMA in UC in a global proof of mechanism study</p><p><bold>AIMS&METHODS:</bold> In this placebo-controlled study, patients age 18-65 years with active UC (Mayo Score 4-10) were randomized to receive IMA 200mg, 400mg, or 600mg or placebo (P). Patients received 5 IV administrations during a 14-week treatment phase with an 18-week safety follow-up period. The primary endpoint was fold change from baseline in fecal calprotectin (FCP) at week 14. Secondary endpoints included safety and total IL13. Exploratory endpoints included total Mayo Score at week 14 and Mayo subscores. Concomitant medications included stable doses of mesalamine</p><p><bold>RESULTS:</bold> The modified intent to treat population (mITT) included 84 patients, 21 patients/arm. At week 14, the superiority of 200mg, 400mg and 600mg compared to P in terms of fold change of FCP from baseline was not met (P-values for comparison between 200mg, 400mg and 600mg vs PBO: 0.53, 0.33, 0.07). Total IL13 increase was observed for all IMA groups but not P. Overall there was no evidence of safety and tolerability concerns and no serious infections seen. Of 14 randomized subjects with SAEs, 4 were in P and 10 across the 3 IMA groups. No statistical differences were observed in the exploratory clinical endpoints
<table-wrap id="table37-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1"></th><th colspan="2" rowspan="1"><hr></hr></th><th colspan="2" rowspan="1"><hr></hr></th><th colspan="2" rowspan="1"><hr></hr></th><th colspan="2" rowspan="1"><hr></hr>(600mg)</th></tr><tr><th rowspan="1" colspan="1"></th><th rowspan="1" colspan="1">n</th><th rowspan="1" colspan="1">Estimate</th><th rowspan="1" colspan="1">n</th><th rowspan="1" colspan="1">Estimate</th><th rowspan="1" colspan="1">n</th><th rowspan="1" colspan="1">Estimate</th><th rowspan="1" colspan="1">N</th><th rowspan="1" colspan="1">Estimate</th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">Estimated<sup>(a)</sup> Fold Change from Baseline in FCP at Week 14 (80% CI)</td><td rowspan="1" colspan="1">7</td><td rowspan="1" colspan="1">0.41 (0.224, 0.767)</td><td rowspan="1" colspan="1">14</td><td rowspan="1" colspan="1">0.29 (0.186, 0.446)</td><td rowspan="1" colspan="1">14</td><td rowspan="1" colspan="1">0.74 (0.476, 1.147)</td><td rowspan="1" colspan="1">13</td><td rowspan="1" colspan="1">1.24 (0.791, 1.951)</td></tr><tr><td rowspan="1" colspan="1">Estimated<sup>(a)</sup> Mean Change from Baseline in Total Mayo Score at Week 14 (80% CI)</td><td rowspan="1" colspan="1">12</td><td rowspan="1" colspan="1">-1.32 (-2.348, -0.288)</td><td rowspan="1" colspan="1">15</td><td rowspan="1" colspan="1">-2.35 (-3.270, -1.426)</td><td rowspan="1" colspan="1">16</td><td rowspan="1" colspan="1">-2.24 (-3.129, -1.346)</td><td rowspan="1" colspan="1">13</td><td rowspan="1" colspan="1">-0.78 (-1.770, 0.207)</td></tr><tr><td rowspan="1" colspan="1">Proportion<sup>(b)</sup> (%) of Subjects with Mucosal Healing at Week 14 (80% CI)</td><td rowspan="1" colspan="1">12</td><td rowspan="1" colspan="1">33.33 (18.86, 51.82)</td><td rowspan="1" colspan="1">15</td><td rowspan="1" colspan="1">33.33 (20.08, 49.88)</td><td rowspan="1" colspan="1">16</td><td rowspan="1" colspan="1">43.75 (29.18, 59.48)</td><td rowspan="1" colspan="1">13</td><td rowspan="1" colspan="1">15.38 (6.58, 31.96)</td></tr><tr><td colspan="9" rowspan="1"><sup>(a)</sup>: Estimation is based on a ANCOVA model with terms for treatment group, baseline (in log scale)<sup>(b)</sup> 0 or 1 endoscopy Mayo subscore</td></tr></tbody></table></table-wrap></p><p><bold>CONCLUSION:</bold> IMA did not meet the primary, secondary or exploratory endpoints. However, a small numerical trend was observed in the 200 and 400 mg groups in the clinical parameters. The study drug was safe and well tolerated. While a negative study, this small pilot is the first study to use fecal calprotectin as a primary endpoint and grants us a better understanding of the role of Th2 biology in UC</p><p><bold>Contact E-mail Address:</bold><email>fabio.cataldi@pfizer.com</email></p><p><bold>Disclosure of Interest</bold>: W. Reinisch Consultancy for: Pfizer, J. Panes Consultancy for: Pfizer, M. De Micco: None Declared, B. Hanlon: None Declared, G. T. Toth: None Declared, P. Petrov: None Declared, G. Yuan Other: Pfizer employee , F. Hua Other: Pfizer employee , M. Hinz Other: Pfizer employee , K. Page Other: Pfizer employee , T. McDonnell Other: Pfizer employee , P. Gruer Other: Pfizer employee , F. Cataldi Other: Pfizer employee</p><p><bold>Keywords:</bold> IMA, IMA-638</p></sec><sec><title>OP262 BUDESONIDE MMX® EFFICACY IS INDEPENDENT OF PREVIOUS MESALAZINE EXPOSURE IN ULCERATIVE COLITIS: POOLED ANALYSIS OF CORE I AND CORE II</title><p><bold>S. Danese</bold><sup>1,*</sup>, L. Kupcinskas<sup>2</sup>, E. D. Ballard<sup>3</sup>, R. Harris-Collazo<sup>4</sup>, Y. Hardiman<sup>5</sup>, M. Huang<sup>5</sup>, S. P. Travis<sup>6</sup></p><p><italic><sup>1</sup>Instituto Clinico Humanitas, Milan, Italy, <sup>2</sup>Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania, <sup>3</sup>Santarus Inc, San Diego, CA, United States, <sup>4</sup>Medical Affairs, <sup>5</sup>Clinical Research, Santarus Inc, San Diego, CA, United States, <sup>6</sup>Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, United Kingdom</italic></p><p><bold>INTRODUCTION:</bold> Budesonide (B) with multi-matrix (MMX®) technology is designed to deliver drug to the colon to treat mild-to-moderate ulcerative colitis (UC). In the CORE I and CORE II studies, once-daily (OD) B-MMX 9mg over 8 weeks was well tolerated and effective at inducing combined clinical and endoscopic remission in these patients (pts). Here we present pooled data from CORE I and CORE II. Since guidelines recommend initial therapy with mesalazine (5-ASA) before escalating to steroid treatment, we compared the efficacy of B-MMX vs placebo (PBO) in both 5-ASA naïve pts and pts previously exposed to 5-ASA. We also looked at the efficacy of B-MMX vs PBO in normalising individual UCDAI components.</p><p><bold>AIMS&METHODS:</bold> Induction of combined clinical and endoscopic remission (total UCDAI≤1, UCDAI=0 for both rectal bleeding and stool frequency, no mucosal friability after colonoscopy, ≥1-point reduction from baseline in the endoscopic index score), and symptom resolution (UCDAI=0 for both rectal bleeding and stool frequency) were assessed in 5-ASA naïve pts and pts previously exposed to 5-ASA. In a separate analysis, the efficacy of B-MMX vs PBO was evaluated as the induction of combined clinical and endoscopic remission, symptom resolution, and normalisation (UCDAI=0) of individual UCDAI components (stool frequency, rectal bleeding, mucosal appearance, physician’s rating of disease activity).</p><p><bold>RESULTS:</bold> Significantly more patients achieved normalisation of stool frequency, rectal bleeding, and mucosal appearance with B-MMX than PBO. The efficacy of B-MMX was independent of 5-ASA exposure.
<table-wrap id="table38-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th colspan="2" rowspan="1">Individual UCDAI component analysis (N=442)</th><th rowspan="1" colspan="1">B-MMX (%) (N=232)</th><th rowspan="1" colspan="1">PBO (%) (N=210)</th><th rowspan="1" colspan="1">p-value*</th></tr></thead><tbody align="left"><tr><td colspan="2" rowspan="1">Combined clinical and endoscopic remission</td><td rowspan="1" colspan="1">18</td><td rowspan="1" colspan="1">6</td><td rowspan="1" colspan="1">.0002</td></tr><tr><td colspan="2" rowspan="1">Symptom resolution</td><td rowspan="1" colspan="1">26</td><td rowspan="1" colspan="1">14</td><td rowspan="1" colspan="1">.0015</td></tr><tr><td colspan="2" rowspan="1">Individual UCDAI components Stool frequency=0 Rectal bleeding=0 Mucosal appearance=0 Physician’s rating of disease activity=0</td><td rowspan="1" colspan="1">29 44 28 20</td><td rowspan="1" colspan="1">18 34 17 16</td><td rowspan="1" colspan="1"> .0069 .0319 .0092 .2737</td></tr><tr><td colspan="2" rowspan="1"><bold>Previous 5-ASA exposure analysis (N=442)</bold></td><td rowspan="1" colspan="1"><bold>B-MMX (%)(N=232)</bold></td><td rowspan="1" colspan="1"><bold>PBO (%) (N=210)</bold></td><td rowspan="1" colspan="1"><bold>p-value</bold></td></tr><tr><td rowspan="1" colspan="1">Combined clinical and endoscopic remission</td><td rowspan="1" colspan="1"><bold>5-ASA naïve (N=146)</bold></td><td rowspan="1" colspan="1">19</td><td rowspan="1" colspan="1">3</td><td rowspan="1" colspan="1">.0051</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"><bold>Prior 5-ASA exposure (N=296) </bold></td><td rowspan="1" colspan="1">17</td><td rowspan="1" colspan="1">7</td><td rowspan="1" colspan="1">.0098</td></tr><tr><td rowspan="1" colspan="1">Symptom resolution</td><td rowspan="1" colspan="1"><bold>5-ASA naïve (N=146)</bold></td><td rowspan="1" colspan="1">27</td><td rowspan="1" colspan="1">13</td><td rowspan="1" colspan="1">.0432</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"><bold>Prior 5-ASA exposure (N=296)</bold></td><td rowspan="1" colspan="1">26</td><td rowspan="1" colspan="1">15</td><td rowspan="1" colspan="1">.0141</td></tr></tbody></table></table-wrap></p><p>*Cochran-Mantel-Haenszel test</p><p><bold>CONCLUSION:</bold> Significantly more patients achieved normalisation of stool frequency, rectal bleeding, and mucosal appearance with B-MMX than PBO. The efficacy of B-MMX was independent of 5-ASA exposure.</p><p><bold>Contact E-mail Address:</bold><email>sdanese@hotmail.com</email></p><p><bold>Disclosure of Interest</bold>: S. Danese Lecture fee(s) from: Schering-Plough, Abbott Laboratories, Merck & Co, UCB Pharma, Ferring, Cellerix, Millenium Takeda, Nycomed, Pharmacosmos, Actelion, Alphawasserman, Genentech, Grunenthal, Pfizer, Astra Zeneca, Novo Nordisk, Cosmo Pharmaceuticals, Novo Nordisk, Cosmo Pharmaceuticals, Vifor, and Johnson and Johnson, Consultancy for: Schering-Plough, Abbott Laboratories, Merck & Co, UCB Pharma, Ferring, Cellerix, Millenium Takeda, Nycomed, Pharmacosmos, Actelion, Alphawasserman, Genentech, Grunenthal, Pfizer, Astra Zeneca, Novo Nordisk, Cosmo Pharmaceuticals, Vifor, and Johnson and Johnson , Other: Schering-Plough, Abbott Laboratories, Merck & Co, UCB Pharma, Ferring, Cellerix, Millenium Takeda, Nycomed, Pharmacosmos, Actelion, Alphawasserman, Genentech, Grunenthal, Pfizer, Astra Zeneca, Novo Nordisk, Cosmo Pharmaceuticals, Vifor, and Johnson and Johnson, L. Kupcinskas: None Declared, E. D. Ballard Other: Employee of Santarus Inc, R. Harris-Collazo Shareholder of: Santarus Inc, Other: Employee of Santarus Inc, Y. Hardiman Shareholder of: Santarus Inc, Other: Employee of Santarus Inc, M. Huang Shareholder of: Santarus Inc, Other: Employee of Santarus Inc, S. Travis Financial support for research from: Abbott, Merck, Warner Chilcott, Lecture fee(s) from: Abbott, Cosmo Pharmaceuticals, Ferring Pharmaceuticals, Merck, Santarus, Tillotts, Warner Chilcott, UCB Pharma, Vifor, Consultancy for: Abbott, Cosmo Pharmaceuticals, Ferring Pharmaceuticals, Genzyme, Merck, Pfizer, Santarus, Warner Chilcott, UCB Pharma, Vifor</p><p><bold>Keywords:</bold> Budesonide, Clinical and endoscopic remission, Mesalazine, Symptom resolution, Ulcerative colitis</p></sec><sec><title>OP263 EFFECTS OF IMMUNOMODULATORS ON THE PHARMACOKINETICS AND EFFICACY OF GOLIMUMAB IN PATIENTS WITH MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS: RESULTS FROM PHASE 2/3 PURSUIT –SC INDUCTION AND MAINTENANCE STUDIES</title><p><bold>O. J. Adedokun</bold><sup>1,*</sup>, Z. Xu<sup>1</sup>, C. Marano<sup>1</sup>, R. Strauss<sup>1</sup>, H. Zhang<sup>1</sup>, H. M. Davis<sup>1</sup>, J. F. Colombel<sup>2</sup>, W. Reinisch<sup>3</sup>, B. Feagan<sup>4</sup>, P. Rutgeerts<sup>5</sup>, W. J. Sandborn<sup>6</sup> on behalf of the PURSUIT SC Steering Committee</p><p><italic><sup>1</sup>Janssen R&D, LLC. , Spring House, United States, <sup>2</sup>2.Centre Hospitalier Universitaire de Lille, Lille, France, <sup>3</sup>3.Universitätsklinik für Innere Medizin IV, Vienna, Austria, <sup>4</sup>Robarts Research Institute, London, Canada, <sup>5</sup>5.University Hospital Gasthuisberg, Leuven, Belgium, <sup>6</sup>University of California San Diego, La Jolla, United States</italic></p><p><bold>INTRODUCTION:</bold> -</p><p><bold>AIMS&METHODS:</bold> To assess effects of concomitant IM on PK and efficacy of GLM. PURSUIT-SC induction randomized UC pts with Mayo scores of 6-12 inclusive, including endoscopic subscore <italic>></italic>2, to PBO/PBO (n=331); GLM100mg/50mg (before Ph3 dose selection only, n=72); GLM200 mg/100mg (n=331) or GLM400 mg/200mg (n=331) at wks0&2. PURSUIT maintenance enrolled 1228 pts from PURSUIT-IV & PURSUIT-SC induction studies. Primary analysis for maintenance were pts (n=464) who responded to GLM induction and were randomized to PBO, GLM50 mg, or GLM100mg at bsl(wk0) and q4wks thru wk52. Serum GLM concentration (SGC) was measured through wk6 of induction and wk54 of maintenance using validated electrochemiluminescent immunoassay. Antibodies to GLM(ATG) were assessed at wk6 of induction, and at wk30 and wk54 of maintenance using an enzyme immunoassay. Efficacy outcomes by IM use were assessed at wk6 (clinical response&remission) for induction; and through wk54 (sustained clinical response) and at wk30 and wk54 (sustained clinical remission) for maintenance.</p><p><bold>RESULTS:</bold> 1227pts had <italic>></italic>1 measurable SGC; 32.2% were receiving IMs at wk0 of induction(AZA/6-MP[n=379] and MTX[n=16]). Among GLM induction responders randomized to GLM or PBO,349 remained on randomized dose of GLM100mg,GLM50mg or PBO thru wk54. Of these,29.5% were receiving IMs. During induction, median SGC levels were similar between pts receiving vs not receiving IMs. During maintenance, IM use had no substantial impact on median SGC in those receiving GLM100mg;median SGC was slightly but consistently higher in GLM50mg in combination with IM vs without IM. During induction and maintenance, there was a positive E-R relationship between SGC and efficacy regardless of IM use. IM use didn't affect efficacy outcomes.Among pts who received <italic>></italic>1 GLM dose, ATG incidence was higher (p=0.02) in pts on PBO during maintenance vs those on GLM 50mg or GLM100mg (8.8% vs 2.6%). ATG incidence was lower in pts receiving IMs vs those who were not (1.5% vs 3.5%, overall 2.8%).Median SGC was lower and there was trend towards lower clinical response rates through wk54 in pts positive for ATG. Among GLM induction responders who remained on PBO during maintenance, those positive for ATG were not receiving IMs.</p><p><bold>CONCLUSION:</bold> Concomitant IM is associated with decreased incidence of ATG, but doesn't substantially affect SGC, efficacy, or E-R.</p><p><bold>Contact E-mail Address:</bold><email>OAdedoku@its.jnj.com</email></p><p><bold>Disclosure of Interest</bold>: O. Adedokun Other: Janssen employee, Z. Xu Other: Janssen employee, C. Marano Other: Janssen employee, R. Strauss Other: Janssen employee, H. Zhang Other: Janssen employee, H. Davis Other: Janssen employee, J. Colombel Financial support for research from: Janssen, W. Reinisch Financial support for research from: Janssen, B. Feagan Financial support for research from: Janssen, P. Rutgeerts Financial support for research from: Janssen, W. Sandborn Financial support for research from: Janssen</p><p><bold>Keywords:</bold> golimumab, pharmacokinetics, PURSUIT</p></sec><sec><title>OP264 SAFETY, PHARMACOLOGY, AND EFFECT OF AMG 181, A HUMAN ANTI-Α4Β7 ANTIBODY, IN SUBJECTS WITH MILD TO MODERATE ULCERATIVE COLITIS</title><p><bold>W.-J. Pan</bold><sup>1,*</sup>, G. Radford-Smith<sup>2,3</sup>, J. Andrews<sup>4</sup>, H. Schwartz<sup>5</sup>, W. Rees<sup>6</sup>, B. Sullivan<sup>7</sup>, C. Evangelista<sup>7</sup>, D. Doherty<sup>1</sup>, P. Prince<sup>1</sup>, K. Reynhardt<sup>6</sup>, K. Zhou<sup>8</sup>, A. Treacy<sup>9</sup>, J. Lee<sup>7</sup>, Z. Yu<sup>7</sup>, D. Borie<sup>10</sup></p><p><italic><sup>1</sup>PKDM, Amgen Inc., Seattle, United States, <sup>2</sup>Gastroenterology Unit, Royal Brisbane and Women's Hospital, Herston, <sup>3</sup>IBD Group, Queensland Institute of Medical Research, and School of Medicine, University of Queensland, Brisbane St Lucia, <sup>4</sup>IBD Service & School of Medicine, University of Adelaide at Royal Adelaide Hospital, Adelaide, Australia, <sup>5</sup>Miami Research Associates, South Miami, <sup>6</sup>Medical Sciences, Amgen Inc., Seattle, <sup>7</sup>Medical Sciences, Amgen Inc., Thousand Oaks, <sup>8</sup>Biostatistics, Amgen Inc., South San Francisco, United States, <sup>9</sup>Clinical Operations, Amgen Inc., Kew, Australia, <sup>10</sup>Clinical Development, Amgen Inc., Thousand Oaks, United States</italic></p><p><bold>INTRODUCTION:</bold> AMG 181 is currently in Phase 2 clinical trials for treating Crohn’s disease (CD) and ulcerative colitis (UC).</p><p><bold>AIMS&METHODS:</bold> To evaluate pharmacokinetics/pharmacodynamics (PK/PD), safety, and effect of subcutaneous (SC) AMG 181, we enrolled subjects with mild to moderate UC (Mayo score 4-10). In one study (completed), 2 male and 2 female white subjects (32-43 yr, 57-77 kg) received a single SC dose of 210 mg AMG 181 or placebo (3:1) and were followed for 7 months. In another study (on-going), 3 male and 1 female subjects (26-51 yr, 73-92 kg) received 21 mg AMG 181 or placebo SC (3:1 ratio) monthly for 3 months and were followed for 5 months. PK, anti-AMG 181 antibodies (ADAs), safety, α<sub>4</sub>β<sub>7</sub> receptor occupancy (RO), CD4+ central memory T cell counts (Tcm), serum high sensitivity C-reactive protein (hsCRP), fecal calprotectin (FC), and Mayo score were measured. Remission was defined as: Mayo score ≤2, with no individual subscore >1; response: Mayo score decrease from baseline by ≥3 and ≥30% + rectal bleeding score decrease of ≥1 or absolute reading of 0 or 1; mucosal healing: endoscopy subscore of ≤1.</p><p><bold>RESULTS:</bold> Median Mayo score was 7 at screening for the 8 UC subjects (6 on active; 2 on placebo). PK profiles were within the range of those observed in healthy subjects. No ADAs were detected. PK and RO profiles were directly correlated, without apparent Tcm count elevation. Under AMG 181 active regimens, both hsCRP and FC showed decreasing trends in some subjects at some visits but small sample size and data variability precluded definitive assessment. Blinded evaluation showed 3, 4, and 1 subjects achieved remission, 6, 6, and 2 subjects were in response, and 5, 5, and 1 subjects achieved mucosal healing at wks 6, 12, and 28, respectively. No AMG 181-related serious adverse events or deaths, except for two early withdrawals due to colitis flare, which were assessed by the investigators as not related to the investigational product. No clinically significant changes in electrocardiograms or neurological examinations were observed.</p><p><bold>CONCLUSION:</bold> Preliminary PK/PD, immunogenicity, safety, and effect profiles of AMG 181 in UC support its further testing in subjects with UC or CD.</p><p><bold>Contact E-mail Address:</bold><email>wpan@amgen.com</email></p><p><bold>Disclosure of Interest</bold>: W.-J. Pan Financial support for research from: Amgen Inc., Shareholder of: Amgen Inc., Other: Amgen Inc. Employee, G. Radford-Smith Financial support for research from: Amgen Inc., Consultancy for: Amgen Inc., J. Andrews Financial support for research from: Amgen Inc., Consultancy for: Amgen Inc., H. Schwartz Financial support for research from: Amgen Inc., Consultancy for: Amgen Inc., W. Rees Financial support for research from: Amgen Inc., Shareholder of: Amgen Inc., Other: Amgen Inc. Employee, B. Sullivan Financial support for research from: Amgen Inc., Shareholder of: Amgen Inc., Other: Amgen Inc. Employee, C. Evangelista Financial support for research from: Amgen Inc., Shareholder of: Amgen Inc., Other: Amgen Inc. Employee, D. Doherty Financial support for research from: Amgen Inc., Shareholder of: Amgen Inc., Other: Amgen Inc. Employee, P. Prince Financial support for research from: Amgen Inc., Shareholder of: Amgen Inc., Other: Amgen Inc. Employee, K. Reynhardt Financial support for research from: Amgen Inc., Shareholder of: Amgen Inc., Other: Amgen Inc. Employee, K. Zhou Financial support for research from: Amgen Inc., Shareholder of: Amgen Inc., Other: Amgen Inc. Employee, A. Treacy Financial support for research from: Amgen Inc., Shareholder of: Amgen Inc., Other: Amgen Inc. Employee, J. Lee Financial support for research from: Amgen Inc., Shareholder of: Amgen Inc., Other: Amgen Inc. Employee, Z. Yu Financial support for research from: Amgen Inc., Shareholder of: Amgen Inc., Other: Amgen Inc. Employee, D. Borie Financial support for research from: Amgen Inc., Shareholder of: Amgen Inc., Other: Amgen Inc. Employee</p><p><bold>Keywords:</bold> AMG 181, Anti-α4β7 Antibody, Crohn's Disease, Inflammatory bowel disease (IBD), MEDI7183, Ulcerative Colitis</p></sec><sec><title>OP265 HIGHLY SIGNIFICANT IMPROVEMENT IN DAI SUBSCORES BY LOCAL APPLICATION OF THE TOLL-LIKE RECEPTOR 9 AGONIST DIMS0150 IN MODERATELY SEVERE ULCERATIVE COLITIS PATIENTS</title><p><bold>T. Knittel</bold><sup>1,*</sup>, R. Löfberg<sup>2</sup>, J. Kowalski<sup>3</sup>, P. von Stein<sup>1</sup>, O. von Stein<sup>1</sup></p><p><italic><sup>1</sup>Index Pharmaceuticals, <sup>2</sup>Stockholm Gastro Center, Sophiahemmet , Stockholm, <sup>3</sup>JK Biostatistics AB, Jönköping, Sweden</italic></p><p><bold>INTRODUCTION:</bold> DIMS0150 is an oligonucleotide that acts as a Toll-like receptor 9 (TLR-9) agonist and elicits its immunomodulating and anti-inflammatory effects through specific target cells. Since the phase II clinical study has shown sustained clinical response and remission but with borderline statistical significance we performed an additional in dept analysis of this study with respect to changes of individual DAI subscores.</p><p><bold>AIMS&METHODS:</bold> A randomized, double-blind, multicenter phase II trial was conducted in steroid refractory patients with ulcerative colitis of moderate degree. 34 patients were randomized to a single rectal administration of either 30 mg of DIMS0150 or placebo with 2:1 allocation. A paired t –test was used to analyse the DAI subscore changes in the per protocol (PP) population on a patient by patient basis between baseline and 4 weeks after therapy.</p><p><bold>RESULTS:</bold> DAI subscore analysis indicated robust levels of a statistically significant mean change at week 4 from baseline in the DIMS0150 treated group in all 4 subscores. By contrast DAI sub score analysis in the placebo group demonstrated no significant change at week 4 from baseline in 3 out of 4 of the subscores.</p><p>The global assessment score showed a statistically significant improvement in DIMS0150 treated patients (p 0,04) and an insignificant change in the placebo group (p 0,108). By considering stool frequency there was a statistically significant change (p 0,005) in the mean frequency when compared to baseline in the DIMS0150 treated group with 52% of those patients having a completely normal stool frequency at week 4. By contrast, only 27% of patients given placebo had a normal stool frequency by week 4 (p 0,02). For the subscore blood in stool there was a significant reduction (p 0,004) in the mean change from baseline in the DIMS0150 treated group with approximately 47% of patients observing no blood in stool at week 4. By contrast for those patient receiving placebo, there was no statistical evidence (p 0,09). In terms of endoscopic assessment, patients treated with DIMS0150 demonstrated a statistically significant reduction (p 0,003) in the mean endoscopic score at week 4 when compared to baseline. Placebo patients demonstrated no statistical evidence of an improved endoscopic score (p 0,117).</p><p><bold>CONCLUSION:</bold> The efficacy results for this TLR-9 agonist in patients with moderately severe ulcerative colitis are encouraging, with highly significant improvements in DAI subscores in comparison to placebo treated patients already 4 weeks after a single dose of a DIMS0150.</p><p><bold>Contact E-mail Address:</bold><email>thomas.knittel@indexpharma.com</email></p><p><bold>Disclosure of Interest</bold>: T. Knittel Directorship(s) for: Index Pharmaceuticals, R. Löfberg Shareholder of: Index Pharamceuticals, J. Kowalski: None Declared, P. von Stein Shareholder of: Index Pharmaceuticals, Directorship(s) for: Index Pharmaceuticals, O. von Stein Shareholder of: Index Pharmaceuticals, Directorship(s) for: Index Pharmaceuticals</p><p><bold>Keywords:</bold> therapeutic development, therapy, ulcerative colitis</p></sec><sec><title></title><p><bold>TUESDAY, OCTOBER 15, 2013 14:00-15:30</bold></p><p><bold>Recent developments in upper GI and small bowel bleeding – Hall 7</bold></p></sec><sec><title>OP266 RISK FACTORS FOR MORTALITY FROM NON VARICEAL BLEEDING SOURCE IN PATIENTS WITH LIVER CIRRHOSIS: AN INDIVIDUAL PATIENT DATA META-ANALYSIS</title><p><bold>G. Rotondano</bold><sup>1,*</sup>, R. Marmo<sup>2</sup>, M. Del Piano<sup>3</sup>, L. Cipolletta<sup>1</sup>, M. Koch<sup>4</sup>, E. Grossi<sup>5</sup>, M. Rea<sup>2</sup>, C. Bucci<sup>2</sup>, S. Sansone<sup>1</sup>, M. A. Bianco<sup>1</sup> PNED and PROMETEO Investigators</p><p><italic><sup>1</sup>Hospital Maresca, Torre del Greco, <sup>2</sup>Hospital Curto, Polla, <sup>3</sup>AO Maggiore della Carità, Novara, <sup>4</sup>ACO San Filippo Neri, Roma, <sup>5</sup>Medical Division Bracco, Milano, Italy</italic></p><p><bold>INTRODUCTION:</bold> Upper GI bleeding in patients with liver cirrhosis is usually related to esophago-gastric varices or hypertensive gastropathy. Nonetheless, the frequency of variceal bleeding is decreasing over time, while the number of cirrhotic patients with non varical UGIB is increasing.</p><p><bold>AIMS&METHODS:</bold> Aim of the study was to assess the risk of death in patients with liver cirrhosis with bleeding from non-variceal source.</p><p>Four national prospective multicentric databases (PNED1, PNED 2, PROMETEO 1 and PROMETEO 2 studies) containing data on consecutive patients admitted to participating hospitals for acute non-variceal UGIB were analysed</p><p><bold>RESULTS:</bold> A total of 3884 pts were included: of these 268 (6.9%) had liver cirrhosis. Cirrhotic pts were younger than non cirrhotic (65.2±0.82 vs.68.6±0.27,p<0.001) and male gender was less frequent (59.8% vs. 66.4%, p<0.03). In patients with cirrhosis, the main causes of nonvariceal UGIB were gastric ulcer (25.0%), duodenal ulcer (23.1%) and gastroduodenal erosions (18.6%). Rebleeding and surgery were not different compared to non cirrhotics, while risk of mortality higher (7.8% vs. 4.1%, OR 1.99 [95% CI 1.23-3.20], p=0.004). Multivariate analysis identified clinical presentation with hematemesis, presence of gastric vascular lesions, chronic renal failure, neoplasia, failure of endoscopic treatment, concurrent presence of duodenal ulcer and gastroduodenal erosions and recurrent bleeding as independent predictors of bleeding-related death (table). Global prognostic accuracy of the model was 94.9%
<table-wrap id="table39-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1">Risk factor</th><th rowspan="1" colspan="1">Odds ratio</th><th rowspan="1" colspan="1">95% confidence interval</th><th rowspan="1" colspan="1">P value</th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">Neoplasia</td><td rowspan="1" colspan="1">1.73</td><td rowspan="1" colspan="1">-.225 to 3.56</td><td rowspan="1" colspan="1">0.084</td></tr><tr><td rowspan="1" colspan="1">Failure of endoscopic treatment</td><td rowspan="1" colspan="1">2.23</td><td rowspan="1" colspan="1">.591 to 9.26</td><td rowspan="1" colspan="1">0.026</td></tr><tr><td rowspan="1" colspan="1">Duodenal ulcer plus GD erosions</td><td rowspan="1" colspan="1">2.36</td><td rowspan="1" colspan="1">.423 to 4.58</td><td rowspan="1" colspan="1">0.018</td></tr><tr><td rowspan="1" colspan="1">Renal failure</td><td rowspan="1" colspan="1">2.66</td><td rowspan="1" colspan="1">.851 to 5.60</td><td rowspan="1" colspan="1">0.008</td></tr><tr><td rowspan="1" colspan="1">Vascular lesion</td><td rowspan="1" colspan="1">2.92</td><td rowspan="1" colspan="1">.0147 to .075</td><td rowspan="1" colspan="1">0.004</td></tr><tr><td rowspan="1" colspan="1">Hematemesis</td><td rowspan="1" colspan="1">3.13</td><td rowspan="1" colspan="1">1.34 to 5.82</td><td rowspan="1" colspan="1">0.002</td></tr><tr><td rowspan="1" colspan="1">Recurrent bleeding</td><td rowspan="1" colspan="1">3.17</td><td rowspan="1" colspan="1">1.36 to 5.75</td><td rowspan="1" colspan="1">0.002</td></tr></tbody></table></table-wrap></p><p><bold>CONCLUSION:</bold> Concurrent duodenal ulcer and gastro-duodenal erosions, together with bleeding form vascular lesions represent the main determinants of death in cirrhotic patients with acute nonvariceal UGIB. Co-factors of mortality are presentation with hematemesis, failure of endoscopic treatment, predence of neoplasia and recurrent bleeding.</p><p><bold>Contact E-mail Address:</bold><email>gianluca.rotondano@virgilio.it</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> mortality in chirrotics, nonvariceal bleeding, risk factors</p></sec><sec><title>OP267 TRANSCATHETER ARTERIAL EMBOLIZATION IS THE TREATMENT OF CHOICE IN PEPTIC ULCER BLEEDING NOT RESPONDING TO ENDOSCOPIC THERAPY</title><p><bold>M. Jakobsen</bold><sup>1</sup>, M. M. Nielsen<sup>1,*</sup>, O. B. Schaffalitzky de Muckadell<sup>2</sup>, S. B. Laursen<sup>2</sup></p><p><italic><sup>1</sup>University of Southern Denmark, <sup>2</sup>Department of medical gastroenterology S, Odense University Hospital, Odense, Denmark</italic></p><p><bold>INTRODUCTION:</bold> In 5-10% of cases with peptic ulcer bleeding (PUB) it is not possible to achieve endoscopic hemostasis. In these patients transcatheter arterial embolization (TAE) is frequently used as an alternative to surgical hemostasis. Studies comparing the outcomes of these methods are needed in order to identify the treatment of choice.</p><p><bold>AIMS&METHODS:</bold> The aim of this study was to examine the efficacy and safety of TAE compared with surgical hemostasis in patients with PUB not responding to endoscopic treatment. The study was conducted as a retrospective study. Consecutive patients treated with TAE or surgery for endoscopy-refractory bleeding in the period June 1997 to June 2012 were included. Patient characteristics, endoscopic findings, received treatment, and outcome were registered. An adjusted 30-day mortality was calculated using multivariate logistic regression analysis.</p><p><bold>RESULTS:</bold> A total of 41 and 75 patients were treated with TAE and surgery, respectively. Patients treated with TAE had a higher level of comorbidity (median Charlson comorbidity index: 2 versus 1; P=0.0084), lower rate of complications (22% versus 60%; p < 0.0001), shorter length of stay (median: 9 versus 13.5 days; p = 0.0016), but higher rate of rebleeding (39% versus 16%; p = 0.012). There was no difference in unadjusted overall 30-day mortality. When adjusting for differences in patient characteristics patients treated with TAE had a lower overall 30-day mortality (OR: 0.30; P = 0.04).</p><p><bold>CONCLUSION:</bold> Transcatheter arterial embolization is associated with lower mortality, lower rate of complications, and lower length of stay compared to surgical hemostasis. TAE seems to be the best first-line treatment in patients with endoscopy-refractory PUB.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Embolization, peptic ulcer bleeding</p></sec><sec><title>OP268 INCREASED CARDIOVASCULAR EVENTS AFTER DISCONTINUATION OF ANTITHROMBOTICS IN PATIENTS WITH PEPTIC ULCER BLEEDING</title><p><bold>S. Y. Kim</bold><sup>1</sup>, J. J. Hyun<sup>1,*</sup>, S. W. Jung<sup>1</sup>, J. S. Koo<sup>1</sup>, R. S. Choung<sup>1</sup>, S. W. Lee<sup>1</sup>, J. H. Choi<sup>1</sup></p><p><italic><sup>1</sup>Korea University Ansan Hospital, Ansan, Korea, Republic Of</italic></p><p><bold>INTRODUCTION:</bold> Peptic ulcer bleeding associated with antithrombotics has increased due to the increase in the proportion of elderly population. Little is known about the long-term effects of discontinuating antrithrmobotics after peptic ulcer bleeding.</p><p><bold>AIMS&METHODS:</bold> The aim of this study was to evaluate whether the risk of cardiovascular events increases when antiplatelets or anticoagulants are discontinued after ulcer bleeding. The medical records of patients diagnosed with ulcer bleeding between January 2006 and December 2011 at Korea University Ansan Hospital were retrospectively reviewed. We enrolled patients who were taking antiplatelet or anticoagulant drugs at the time of ulcer bleeding. We used Cox regression model to adjust potential confounders, and analyze association between discontinuation of antithrombotic drugs after ulcer bleeding and thrombotic events such as ischemic heart disease or stroke.</p><p><bold>RESULTS:</bold> Of the 544 patients with ulcer bleeding, 72 patients who were taking antithrombotic drugs and followed-up to more than 2 months were analyzed. Forty patients discontinued antithrombotics after ulcer bleeding (discontinuation group) and 32 patients continued antithrombotics with or without transient interruption (continuation group). Ischemic heart disease developed in 2 patients, stroke or transient ischemic attack developed in 4 patients, deep vein thrombosis in 1 patient and common iliac artery thrombosis in 1 patient during mean follow-up for 26.6 months. Thrombotic event developed more often in discontinuation group than in continuation group (p=0.019). Hazard ratio for thrombotic event when antithrombotics were discontinued continuously was 15.6 (95% CI, 1.8-135.2). There were no significant differences in recurrent bleeding event between two groups.</p><p><bold>CONCLUSION:</bold> Discontinuation of antithrombotic drugs after peptic ulcer bleeding increases risk of cardiovascular events. Therefore, we should be careful in discontinuating antrithrombotic drugs after ulcer bleeding.</p><p><bold>Contact E-mail Address:</bold><email>seung0md@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> antithrombotics, cardiovascular complication, ulcer bleeding</p></sec><sec><title>OP269 SMALL BOWEL ANGIODYSPLASIAS ARE MORE COMMON AMONG PATIENTS WITH LARGE BOWEL DIVERTICULA.</title><p>P. Tsibouris<sup>1</sup>, P. Apostolopoulos<sup>1</sup>, C. Kalantzis<sup>1</sup>, <bold>E. Vlachou</bold><sup>1,*</sup>, A. Koumi<sup>1</sup>, I. Koumoutsos<sup>1</sup>, P. Dogantzis<sup>1</sup>, C. Beltsidou<sup>1</sup>, G. Alexandrakis<sup>1</sup></p><p><italic><sup>1</sup>GASTROENTEROLOGY, NIMTS GENERAL HOSPITAL, Athens, Greece</italic></p><p><bold>INTRODUCTION:</bold> Lower gastrointestinal bleeding is a common complication of large bowel diverticulosis.</p><p><bold>AIMS&METHODS:</bold> Aim: To define frequency of small bowel ulcerative lesions and angiodysplasias in patients with large bowel diverticulosis, with and without anemia.</p><p>Methods: 984 patients (mean age 60±18 years, 543 men, 256 smokers) undergone small bowel capsule endoscopy, gastroscopy and colonoscopy were evaluated. 490 were evaluated for iron deficiency anemia, 311 for diarrhea, 60 for unexplained abdominal pain and for 123 other causes. Stat: X2, logistic regression analysis.</p><p><bold>RESULTS:</bold> 140 (29%) anemics and 64 (13%) non-anemics presented large bowel diverticula, without any macroscopic inflammation and without any history of lower gastrointestinal bleeding (p<0.0001). Mean small bowel passing time was 380±154 min for patients with large bowel diverticula and 332±136 in those without (p<0.0001). Excluding patients with IBD, 59 (30%) patients with large bowel diverticula and 178 (29%) without presented small bowel ulcerative lesions (p=0.43). Among anemics, 45 (32%) patients with large bowel diverticula and 112 (32%) without presented small bowel ulcerative lesions (p=0.98). 117 (57%) patients with large bowel diverticula and 278 (36%) without presented small bowel angiodysplasias (p<0.0001). Among anemics, 90 (64%) patients with large bowel diverticula and 140 (40%) without presented small bowel angiodysplasias (p<0.0001). In logistic regression analysis, age (p<0.0001), male gender (p=0.006), chronic renal failure (p=0.05) and presence of large bowel diverticula (p=0.01) were independent risk factors for the presence of small bowel angiodysplasias.</p><p>24 (36%) NSAIDs users with large bowel diverticula and 110 (43%) without diverticula presented small bowel ulcerative lesions (p=0.17). Moreover, all 29 patients with large bowel diverticula who received clopidogrel versus 55 (74%) receiving low-dose aspirin presented with anemia (p<0.0001).</p><p><bold>CONCLUSION:</bold> Iron deficiency anemia is more common among patients with large bowel diverticulosis. Anemia could partially attributed in higher frequency of angiodysplasias in this patient group, possibly due to connective tissue structural deficiency. Moreover, patients with large bowel diverticulosis are more susceptible to clopidogrel.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> anemia, angiodysplasia, capsule endoscopy, large bowel diverticula, small bowel ulcerative lesions</p></sec><sec><title>OP270 ELEVATED ANGIOPOIETIN 2 LEVELS IN SMALL BOWEL ANGIODYSPLASIA; FUTURE BIOMARKER OR THERAPEUTIC TARGET</title><p><bold>G. Holleran</bold><sup>1,2,*</sup>, B. Hall<sup>1,2</sup>, S. Smith<sup>1</sup>, D. McNamara<sup>1,2</sup></p><p><italic><sup>1</sup>Department of Clinical Medicine, Trinity College Dublin, Tallaght, <sup>2</sup>Department of Gastroenterology, Adelaide and Meath Hospital, Dublin 24, Ireland</italic></p><p><bold>INTRODUCTION:</bold> Small bowel angiodysplasia (SBA) accounts for up to 50% of cases of obscure gastrointestinal bleeding, which were difficult to diagnose prior to the advent of capsule endoscopy (CE). Little is known about their pathophysiology and therapeutic options are limited. Abnormal serum levels of angiogenic factors have been suggested previously in small cohorts of patients with sporadic colonic, and genetic - Hereditary Haemorrhagic Telangiectasia (HHT), forms of GI angiodysplasia. Angiogenic factors may represent targets for new therapies and act as useful diagnostic and prognostic biomarkers for sporadic small bowel disease.</p><p><bold>AIMS&METHODS:</bold> To assess putative angiogenic factor levels in sporadic SBA compared with controls.</p><p>Following informed consent, serum samples were collected and stored at -80<sup>o</sup>C for batch analysis from patients with a definite diagnosis of sporadic SBA on CE (P2), and from healthy controls in which GI bleeding had been out-ruled by a negative faecal immunochemical test. Patients with features consistent with, or known HHT were excluded. Serum levels of angiopoietin-2 (Ang-2), soluble endoglin (sEnd), vascular endothelial growth factor (VEGF), and platelet derived growth factor (PDGF) were measured using commercially available enzyme-linked immunosorbent assay (ELISA) kits (R&D Systems). Samples were prepared in duplicate as per manufacturer’s guidelines and absorbance read at a wavelength of 450nm. All results were expressed as a mean and compared between patients and controls, a p value of <0.05 was considered significant.</p><p><bold>RESULTS:</bold> In all, serum samples were analysed from 30 patients, 53% (n=16) female and 26 controls, 54% (n=14) female, with mean ages of 68.1 years (34-90) and 55.5 years (26-74) respectively. Levels of Ang-2 were significantly higher in the angiodysplasia group with a mean of 4883pg/ml (842-11767) vs. a mean of 2536pg/ml (792-6243) in controls p<0.001. In addition, there was a trend towards lower levels of sEnd and elevated levels of VEGF and PDGF in the patient group versus controls although not statistically significant.
<table-wrap id="table40-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1">Angiogenic factor</th><th rowspan="1" colspan="1">Angiodysplasia mean</th><th rowspan="1" colspan="1">Angiodysplasia range</th><th rowspan="1" colspan="1">Control mean</th><th rowspan="1" colspan="1">Control range</th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">Ang-2 pg/ml</td><td rowspan="1" colspan="1">4883</td><td rowspan="1" colspan="1">842-11767</td><td rowspan="1" colspan="1">2536</td><td rowspan="1" colspan="1">792-6243</td></tr><tr><td rowspan="1" colspan="1">sEnd ng/ml</td><td rowspan="1" colspan="1">3.69</td><td rowspan="1" colspan="1">2.12-6.84</td><td rowspan="1" colspan="1">4.65</td><td rowspan="1" colspan="1">1.96-9.0</td></tr><tr><td rowspan="1" colspan="1">VEGF pg/ml</td><td rowspan="1" colspan="1">355.9</td><td rowspan="1" colspan="1">45-929</td><td rowspan="1" colspan="1">289.6</td><td rowspan="1" colspan="1">54-1130</td></tr><tr><td rowspan="1" colspan="1">PDGF pg/ml</td><td rowspan="1" colspan="1">4229</td><td rowspan="1" colspan="1">929-39978</td><td rowspan="1" colspan="1">3171</td><td rowspan="1" colspan="1">955-6208</td></tr></tbody></table></table-wrap></p><p><bold>CONCLUSION:</bold> Serum Ang-2 levels are significantly elevated in patients with sporadic SBA and may represent a useful diagnostic and prognostic biomarker. A trend towards decreased levels of sEnd and elevated levels of VEGF and PDGF may be useful in further elucidating the pathogenesis of sporadic angiodysplasia. Additional studies with larger patient numbers are needed to confirm our findings.</p><p><bold>Contact E-mail Address:</bold><email>grainneholleran@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> angiodysplasia, angiogenic factors</p></sec><sec><title>OP271 RESCUE THERAPY WITH OVER THROUGH-THE-SCOPE CLIPS (OTSC) FOR ACUTE GI COMPLEX BLEEDING UNRESPONSIVE TO CONVENTIONAL ENDOSCOPIC TREATMENT: RESULTS OF A MULTICENTER ITALIAN STUDY.</title><p><bold>R. Manta</bold><sup>1,*</sup>, G. Galloro<sup>2</sup>, M. Manno<sup>1</sup>, V. G. Mirante<sup>1</sup>, A. Caruso<sup>1</sup>, H. Bertani<sup>1</sup>, B. Mangiavillano<sup>3</sup>, L. Pasquale<sup>4</sup>, A. Arezzo<sup>5</sup>, L. De Luca<sup>6</sup>, G. Bassotti<sup>7</sup>, R. Conigliaro<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology and Digestive Endoscopy Unit , New Civil S.Agostino Estense Hospital, Modena, <sup>2</sup>Clinical Medicine and Surgery , Surgical Digestive Endoscopy, University of Federico II, Naples, Napoli, <sup>3</sup>Gastroenterology and Digestive Endoscopy Unit , San Paolo Hospital, Milano, <sup>4</sup>Gastroenterology and Digestive Endoscopy Unit , Civil Ariano Irpino Hospital, Ariano Irpino (AV), <sup>5</sup>Surgical Sciences, University of Torino, Torino, <sup>6</sup>Gastroenterology and Digestive Endoscopy Unit , Civil hospital of Pesaro , Pesaro, <sup>7</sup>Clinical and experimental Medicine, Gastroenterology and Hepatology Section,University of Perugia, Perugia, Italy</italic></p><p><bold>INTRODUCTION: BACKGROUND </bold>The efficacy of through the scope clips (TTSC) can be sub-optimal in patients with complex bleeding lesions. The Over-The-Scope Clip (OTSC<sup>R</sup>) could overcome the TTSC by allowing compression of larger amounts of tissue, allowing a more efficient hemostasis.</p><p><bold>AIMS&METHODS: AIM</bold> To analyze the use of OTSC in a consecutive case series of patients with acute GI bleeding unresponsive to conventional endoscopic treatment modalities. <bold>METHODS</bold> In a retrospective analysis of prospectively collected data in tertiary referral centers, patients undergoing emergency endoscopy for severe acute non variceal GI bleeding were treated by OTSC placement after failure of conventional hemostatic therapy. All patients underwent repeat endoscopy 2-4 days after the procedure.Data analysis included primary hemostasis, complications, and one-month follow-up clinical outcome.</p><p><bold>RESULTS: RESULTS</bold> During a 17-month period, 48 patients entered the study consecutively. Bleeding lesions unresponsive to conventional endoscopic treatment (saline/adrenaline injection and through-the scope clipping) were located in the upper and lower GI tract in 40 and 8 cases, respectively. Primary hemostasis was achieved in 46 out of 48 cases (96%). 1 patient with bleeding from duodenal bulb ulcer required emergent selective radiological embolization. 1 patient with massive bleeding from large gastric GIST located in the fundus, needed fibrin glue injection in the same session to obtain definitive hemostasis. Rebleeding occurred in 2 patients 12h and 24h after the procedure: they were successfully treated with conventional saline/adrenaline endoscopic injection.</p><p><bold>CONCLUSION: CONCLUSIONS</bold> The OTSC is an effective and safe therapeutic option for severe acute GI bleeding, when conventional endoscopic treatment modalities fail.</p><p><bold>Contact E-mail Address:</bold><email>r.manta@libero.it</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Hemostatic clips, ulcer bleeding </p></sec><sec><title></title><p><bold>TUESDAY, OCTOBER 15, 2013 14:00-15:30</bold></p><p><bold>Complications of cirrhosis – Hall 6</bold></p></sec><sec><title>OP272 COMPARISON OF SEVEN PROGNOSTIC MODELS FOR SHORT-TERM MORTALITY IN BIOPSY-PROVEN ALCOHOLIC HEPATITIS.</title><p><bold>V. Papastergiou</bold><sup>1</sup>, S. Karatapanis<sup>1,*</sup>, E. Tsochatzis<sup>1</sup>, E. Thalassinos<sup>1</sup>, G. Pieri<sup>1</sup>, A. Burroughs<sup>1</sup></p><p><italic><sup>1</sup>Royal Free Hospital, London, United Kingdom</italic></p><p><bold>INTRODUCTION:</bold> Assessment of mortality is paramount in alcoholic hepatitis (AH). Although several prognostic scores have been proposed, external validation and model comparisons are required as no one score is used universally.</p><p><bold>AIMS&METHODS:</bold> We aimed to validate seven prognostic models for short-term mortality in biopsy-proven AH: Maddrey discriminant function (DF); Lille model; Glascow alcoholic hepatitis score (GAHS); Mayo end-stage liver disease (MELD); age, bilirubin, INR, creatinine score (ABIC); MELD-Na, UK end-stage liver disease (UKELD).Consecutive patients with biopsy-proven AH admitted between November 2006-September 2011 at the Royal Free Hospital, were evaluated. Biochemical data from day 0 and day 7 from admission was used to assess prognostic models with respect to 30- and 90-day mortality.</p><p><bold>RESULTS:</bold> Seventy-one patients (47 males, mean age; 48.4 years) were included. The MELD, DF, GASH, ABIC, and the Lille score demonstrated comparable predictive abilities with C-statistics ranging to 0.71-0.81 for 30-day mortality and 0.74-0.84 for 90-day mortality. C-statistics for 30-day/90-day mortality were for MELD-Na 0.68/0.76 and for UKELD 0.56/0.68. Re-scoring on day-7 yielded a trend towards higher C-statistics for both 30-day (0.69-0.84) and 90-day (0.77-0.86) mortality. All models showed excellent NPV, in most cases >90% (range: 88%>100%), whereas PPV were low, in most instances <50% (range: 21%>70%).</p><p><bold>CONCLUSION:</bold> MELD, DF, GASH, ABIC and Lille score, proved to be clinically useful for the prediction of short-term mortality when assessed in an external cohort of patients with biopsy-proven AH. Modifications of MELD incorporating sodium did not confer any prognostic advantage over MELD. Excellent NPV suggest models are best to exclude, rather than to identify high-risk patients.</p><p><bold>Contact E-mail Address:</bold><email>vasi.pap@hotmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> ALCOHOLIC LIVER DISEASE, prognostic scores</p></sec><sec><title>OP273 THE PHOSPHODIESTERASE-5-INHIBITOR UDENAFIL - A NEW OPTION FOR THERAPY OF PORTAL HYPERTENSION</title><p><bold>W. Kreisel</bold><sup>1,*</sup>, P. Deibert<sup>1</sup>, L. Kupcinskas<sup>2</sup>, J. Sumskiene<sup>2</sup>, B. Appenrodt<sup>3</sup>, M. Neagu<sup>1</sup>, M. Rössle<sup>4</sup>, A. Zipprich<sup>5</sup>, K. Caca<sup>6</sup>, A. Ferlitsch<sup>7</sup>, R. Mohrbacher<sup>8</sup>, R. Greinwald<sup>8</sup>, T. Sauerbruch<sup>9</sup></p><p><italic><sup>1</sup>University Hospital Freiburg, Freiburg, Germany, <sup>2</sup>Kaunas University of Medicine, Kaunas, Lithuania, <sup>3</sup>University Hospital, Homburg, <sup>4</sup>Gastroenterology Centre, Freiburg, <sup>5</sup>University Hospital, Halle, <sup>6</sup>Klinikum Ludwigsburg, Ludwigsburg, Germany, <sup>7</sup>Medical University, Wien, Austria, <sup>8</sup>Dr. Falk Pharma, Freiburg, <sup>9</sup>University Hospital, Göttingen, Germany</italic></p><p><bold>INTRODUCTION:</bold> Non-selective beta-blockers (NSBB) are used as standard for prevention of variceal bleeding in cirrhosis. Long-term treatment should decrease the HVPG by ≥20% or to ≤12 mmHg. HVPG decrease by ≥10% or to ≤12 mmHg in the acute setting predicts clinical response, as well. The response rate to NSBB is about 50%. The efficacy is limited by cardiovascular side effects. Phosphodiesterase-5-inhibitors (PDE-5-I) increased portal venous blood flow and lowered portal pressure in rats with normal liver and in individuals with normal or cirrhotic liver. The clinical relevance is unknown.</p><p><bold>AIMS&METHODS:</bold> The effect of udenafil, a new PDE-5-I with a half-life of 12h, on HVPG in patients with portal hypertension was investigated. Patients with liver cirrhosis, HVPG ≥12 mmHg, and low risk of bleeding were eligible for this open-label, multicenter phase II trial. Patients obtained oral udenafil (12.5 mg/day, 25 mg/day, 50 mg/day, 75 mg/day [5 patients for each dose], and 100 mg/day [10 patients]) once daily (OD) for one week. Routine laboratory tests and systemic hemodynamic parameters were checked regularly. On day 0 and 6 HVPG was measured prior to and one hour after drug administration. Response 1: Decrease of HVPG by ≥10% in the acute setting (day 0 or/and 6). Response 2: Decrease of HVPG by ≥20% in the one week OD setting (day 6 post-dose compared to day 0 pre-dose) or to ≤12 mmHg.</p><p><bold>RESULTS:</bold> 30 patients were evaluated. Table 1 shows the mean decrease of HVPG on day 0 or 6 for the different doses. In the 10 patients treated with 100 mg/day the mean decrease was significant on day 0 (p=0.012) and on day 6 (p=0.045). In 4 of 5 patients treated with 75 mg/day and in 7 of 10 patients treated with 100 mg/day HVPG was lowered by ≥10% on day 0 or/and day 6 (Response 1). 4 out of the 10 patients in the 100 mg/day group reached response 2. There were no cardiovascular side effects due to the drug in any of the groups. Standard liver biochemical tests did not change during the study.
<table-wrap id="table41-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1">12.5 mg/day</th><th rowspan="1" colspan="1">25 mg/day</th><th rowspan="1" colspan="1">50 mg/day</th><th rowspan="1" colspan="1">75 mg/day</th><th rowspan="1" colspan="1">100 mg/day</th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">day 0 day 6</td><td rowspan="1" colspan="1">day 0 day 6</td><td rowspan="1" colspan="1">day 0 day 6</td><td rowspan="1" colspan="1">day 0 day 6</td><td rowspan="1" colspan="1">day 0 day 6</td></tr><tr><td rowspan="1" colspan="1">-3% 0%</td><td rowspan="1" colspan="1">-4% -2%</td><td rowspan="1" colspan="1">-7% -6%</td><td rowspan="1" colspan="1">-25% -11%</td><td rowspan="1" colspan="1">-17%* -13%*</td></tr><tr><td colspan="5" rowspan="1">Table 1 Decrease of HVPG in the acute setting on day 0 and day 6. * p<0.05</td></tr></tbody></table></table-wrap></p><p><bold>CONCLUSION:</bold> The new PDE-5 inhibitor udenafil lowers HVPG in the acute setting and may be a new option for therapy of portal hypertension.</p><p><bold>Disclosure of Interest</bold>: W. Kreisel: None Declared, P. Deibert: None Declared, L. Kupcinskas: None Declared, J. Sumskiene: None Declared, B. Appenrodt: None Declared, M. Neagu: None Declared, M. Rössle: None Declared, A. Zipprich: None Declared, K. Caca: None Declared, A. Ferlitsch: None Declared, R. Mohrbacher Other: Employee of Dr. Falk Pharma, R. Greinwald Other: Employee of Dr. Falk Pharma, T. Sauerbruch: None Declared</p><p><bold>Keywords:</bold> HVPG, liver cirrhosis, Phosphodiesterase-5-Inhibitor, Portal Hypertension, Udenafil</p></sec><sec><title>OP274 CAUSE-SPECIFIC MORTALITY OF PATIENTS WITH CIRRHOSIS IN ENGALND: VARIATION BY AETIOLOGY</title><p><bold>S. Ratib</bold><sup>1,*</sup>, K. M. Fleming<sup>1</sup>, C. J. Crooks<sup>1</sup>, A. J. Walker<sup>1</sup>, J. West<sup>1</sup></p><p><italic><sup>1</sup>Epidemiology & Public Health, UNIVERSITY OF NOTTINGHAM, Nottingham, United Kingdom</italic></p><p><bold>INTRODUCTION:</bold> While the incidence of and overall death from cirrhosis of the liver is inexorably increasing in the UK, we do not know what it is that causes people with cirrhosis to die. Determining the most important causes of death and how this varies by aetiology will demonstrate areas where therapeutic interventions may be best targeted.</p><p><bold>AIMS&METHODS:</bold> We identified adult patients with cirrhosis from the Clinical Practice Research Datalink and the Hospital Episode Statistics database between 1998 and 2009 in England. Causes of death were obtained from the Office for National Statistics and categorized according to the International Cause of Disease classification (ICD10). We examined the cause of death by aetiology of cirrhosis. We calculated (i) cumulative incidence at 2 years (median follow-up) for each cause and (ii) hazard ratios (HR) to compare risk of death, by 2 years, for each cause by aetiology, adjusting for age and sex.</p><p><bold>RESULTS:</bold> 5118 patients with cirrhosis were identified, over a third died by 2 years (n=1934, 37.8%). Of those who died by 2 years, 1019 (52.7%) had a liver-related death. Comparing cryptogenic with alcoholic cirrhosis, the cumulative incidence 2 years from diagnosis was two-fold for circulatory deaths (12% vs 6%) and four-fold for neoplastic deaths (16% vs 4%). Adjusting for age and sex, risks of circulatory and neoplastic death were still significantly increased among cryptogenic cirrhotics compared to those with alcoholic cirrhosis (Table).</p><p><bold>Table: Number of deaths, cumulative incidence and adjusted hazard ratios (& 95% confidence intervals) by aetiology for each cause of death, 2 years from diagnosis</bold></p><p><sup>*</sup>Adjusted for age and sex. <bold><sup>†</sup></bold>Includes hepatocellular carcinoma (HCC) deaths. ¥Excludes HCC deaths. §Includes non-liver related digestive, respiratory, and unknown causes.</p><p><bold>CONCLUSION:</bold> Overall<bold>, </bold>almost half of the underlying causes of death of people with cirrhosis at 2 years following diagnosis are non-liver related. Risk of circulatory and neoplastic death was substantially higher in people with cryptogenic cirrhosis than those with alcoholic cirrhosis. Strategies for prevention or amelioration of circulatory disease may be warranted in people with cryptogenic cirrhosis.
<table-wrap id="table42-2050640613502899" position="float"><label>Table</label><caption><p>OP274</p></caption><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1"></th><th rowspan="1" colspan="1">All deaths</th><th rowspan="1" colspan="1">Liver<bold>†</bold></th><th rowspan="1" colspan="1"></th><th rowspan="1" colspan="1">Circulatory </th><th rowspan="1" colspan="1"></th><th rowspan="1" colspan="1">Neoplasm¥ </th><th rowspan="1" colspan="1"></th><th rowspan="1" colspan="1">Other causes§</th><th rowspan="1" colspan="1"></th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">n</td><td rowspan="1" colspan="1">Cum.incid. (%)</td><td rowspan="1" colspan="1">HR* (95% CI)</td><td rowspan="1" colspan="1">Cum. incid.(%)</td><td rowspan="1" colspan="1">HR* (95% CI)</td><td rowspan="1" colspan="1">Cum. incid. (%)</td><td rowspan="1" colspan="1">HR* (95% CI)</td><td rowspan="1" colspan="1">Cum. incid.(%)</td><td rowspan="1" colspan="1">HR* (95% CI)</td></tr><tr><td rowspan="1" colspan="1">All cases</td><td rowspan="1" colspan="1">1934</td><td rowspan="1" colspan="1">23.9</td><td rowspan="1" colspan="1">-</td><td rowspan="1" colspan="1">6.6</td><td rowspan="1" colspan="1">-</td><td rowspan="1" colspan="1"> 6.8</td><td rowspan="1" colspan="1">-</td><td rowspan="1" colspan="1">11</td><td rowspan="1" colspan="1">-</td></tr><tr><td rowspan="1" colspan="1">Alcohol</td><td rowspan="1" colspan="1">1065</td><td rowspan="1" colspan="1">29.6</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">5.5</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">3.9</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">9.3</td><td rowspan="1" colspan="1">1</td></tr><tr><td rowspan="1" colspan="1">Viral</td><td rowspan="1" colspan="1">167</td><td rowspan="1" colspan="1">18.7</td><td rowspan="1" colspan="1">0.58 (0.47, 0.72)</td><td rowspan="1" colspan="1">3</td><td rowspan="1" colspan="1">0.56 (0.32, 1.0)</td><td rowspan="1" colspan="1">4.3</td><td rowspan="1" colspan="1">1.15 (0.70, 1.87)</td><td rowspan="1" colspan="1">11.7</td><td rowspan="1" colspan="1">1.33 (0.98,1.79)</td></tr><tr><td rowspan="1" colspan="1">Metabolic/Autoimmune</td><td rowspan="1" colspan="1">139</td><td rowspan="1" colspan="1">17.5</td><td rowspan="1" colspan="1">0.49 (0.39, 0.62)</td><td rowspan="1" colspan="1">3</td><td rowspan="1" colspan="1">0.39 (0.21, 0.71)</td><td rowspan="1" colspan="1">2.3</td><td rowspan="1" colspan="1">0.54 (0.28, 1.05)</td><td rowspan="1" colspan="1">9.8</td><td rowspan="1" colspan="1">0.91 (0.65,1.28)</td></tr><tr><td rowspan="1" colspan="1">Cryptogenic</td><td rowspan="1" colspan="1"> 653</td><td rowspan="1" colspan="1">15.1</td><td rowspan="1" colspan="1">0.40 (0.34, 0.48)</td><td rowspan="1" colspan="1">12.2</td><td rowspan="1" colspan="1">1.36 (1.02, 1.82)</td><td rowspan="1" colspan="1">16.2</td><td rowspan="1" colspan="1">3.57 (2.68, 4.77)</td><td rowspan="1" colspan="1">14.9</td><td rowspan="1" colspan="1">1.28 (1.01,1.</td></tr></tbody></table></table-wrap></p><p><bold>Contact E-mail Address:</bold><email>sonia.ratib@nottingham.ac.uk</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> AETIOLOGY, CAUSE OF DEATH, CIRRHOSIS, MORTALITY</p></sec><sec><title>OP275 EFFECT'S EVALUATION OF THE TREATMENT WITH PROPRANOLOL AND LOW DOSE LOSARTAN VERSUS ONLY PROPRANOLOL ADMINISTRATION ON HEPATIC HAEMODYNAMIC PARAMETERS IN PATIENTS WITH LIVER CIRRHOSIS</title><p><bold>E. Tcaciuc</bold><sup>1,*</sup>, O. Corlateanu<sup>1</sup>, S. Matcovschi<sup>1</sup>, A. Tcaciuc<sup>1</sup>, N. Nacu<sup>1</sup></p><p><italic><sup>1</sup>Internal Medicine, State Medical and Pharmaceutical University "Nicolae Testemitanu", Chisinau, Moldova, Republic of</italic></p><p><bold>INTRODUCTION:</bold> Propranolol is indicated for primary prevention of variceal bleeding in patients with liver cirrhosis and portal hypertension for a long period. The effect of low-dose Losartan's administration on hepatic haemodynamic parameters in patients with liver cirrhosis is well known.</p><p><bold>AIMS&METHODS:</bold> This study examined the efficacy of the treatment with propranolol and low dose Losartan versus only Propranolol administration on hepatic haemodynamic parameters in patients with liver cirrhosis. The study included 62 patients with liver cirrhosis of viral HBV or HCV etiology with different cirrhotic stage. We evaluated the portal system and hepatic artery before and after 6 months of treatment using duplex Doppler ultrasonography. 30 patients (gr. 1) received Propranolol (30 - 120 mg/daily) plus Losartan (6,25 - 12,5 mg/daily) and 32 patients received only Propranolol (30 - 120 mg/daily).</p><p><bold>RESULTS:</bold> The treatment with Propranolol and Losartan by one hand and only Propranolol administration by other hand, improves hepatic haemodynamics parameters in cirrhotic patients. The diameter of portal vein the same decreased in both groups (15,8±0,7% vs 14,9±0,6%, p>0,05). Portal blood flow velocity significantly increased in gr. 1 vs gr. 2 (15,3±0,8% vs 9,7±0,7%, p<0,05) and hepatic artery resistance index significantly decreased in gr. 1 vs gr. 2 (16,1±0,9% vs 11,7±0,8%, p<0,05).</p><p><bold>CONCLUSION:</bold> This study indicates that the administration of Losartan in patients with liver cirrhosis improve the hepatic haemodynamics, because Losartan contributes to decrease the intrahepatic resistance in cirrhotic patients.</p><p><bold>Contact E-mail Address:</bold><email>eugentcaciuc@yahoo.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> liver cirrhosis, portal hypertension, treatment</p></sec><sec><title>OP276 THE PROGNOSTIC SIGNIFICANCE OF BACTERIAL DNA IN ASCITIC FLUID FROM CRITICALLY ILL CIRRHOTIC PATIENTS</title><p><bold>T. Bruns</bold><sup>1,2,*</sup>, P. A. Reuken<sup>1,2</sup>, L. Gerber<sup>3</sup>, B. Appenrodt<sup>4</sup>, J. Peter<sup>1</sup>, A. Herrmann<sup>1</sup>, F. Lammert<sup>4</sup>, S. Zeuzem<sup>3</sup>, A. Stallmach<sup>1,2</sup></p><p><italic><sup>1</sup>Department of Internal Medicine IV, <sup>2</sup>Integrated Research and Treatment Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, <sup>3</sup>Department of Medicine I, Frankfurt University Hospital, Frankfurt, <sup>4</sup>Department of Internal Medicine II, Saarland University Hospital, Homburg, Germany</italic></p><p><bold>INTRODUCTION:</bold> The presence of bacterial DNA fragments (bactDNA) in ascitic fluid (AF) has been interpreted as a surrogate marker of bacterial translocation in cirrhosis and is associated with an increased risk of mortality in the absence of overt infections. It is not known, however, whether the identification of AF bactDNA is of prognostic relevance in the high-risk cohort of cirrhotic patients presenting with signs of infection or sepsis.</p><p><bold>AIMS&METHODS:</bold> The aims of the study was to investigate whether the presence of AF bactDNA predicts increased mortality in patients with cirrhosis and signs of inflammation in a prospective multicenter study. Hospitalized patients with decompensated cirrhosis were eligible for this study if they presented with ascites accessible to diagnostic paracentesis and presented with clinical, microbiological or radiological evidence of infection or with two or more positive SIRS criteria. AF and whole blood was investigated for the presence of bactDNA using multiplex PCR. The endotoxemia marker lipopolysaccharide-binding protein (LBP) and the cytokines Interleukin(IL)-6 and IL-10 were quantified in serum and AF using ELISA. 90-days survival was evaluated using Kaplan-Meier estimates.</p><p><bold>RESULTS:</bold> AF BactDNA was detected in 71 (32%) out of 221 patients. BactDNA derived from Gram-negative microorganisms in the majority of cases with E. coli as the most frequently identified microorganism in 36 (51%) samples. AF bactDNA was more frequently detected in patients presenting with SBP (32% vs 13%; p=0.001), severe hepatic encephalopathy (32% vs. 20%; p=0.034) or bacteremia (23% vs. 11%, p=0.042). Even in the absence of SBP, AF bactDNA was associated with decreased peritoneal IL-6 levels (p<0.001) and increased systemic IL-10 levels (p=0.021) and accompanied by the presence of circulating bactDNA (p=0.035). Within 90 days of follow-up 77 patients died and 11 underwent liver transplantation. In contrast to positive bacterial culture results (p=0.007) and the endotoxemia marker LBP (p=0.002), which both predicted poor survival, the presence of AF bactDNA was not associated with lower 90-days survival (64% vs. 59%; p=0.71).</p><p><bold>CONCLUSION:</bold> The presence of AF bactDNA is associated with altered local and systemic cytokine responses in cirrhotic patients. Despite its role as a surrogate marker of subclinical bacterial translocation, the presence of bactDNA did not predict short-term mortality in a large cohort of critically ill cirrhotic patients with overt infection.</p><p><bold>Contact E-mail Address:</bold><email>tony.bruns@med.uni-jena.de</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> ascites, bacterial infection, bacterial translocation, Biomarkers, survival</p></sec><sec><title>OP277 EARLY TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNT (TIPS) AS COMPARED TO ENDOSCOPIC TREATMENT REDUCES REBLEEDING BUT NOT MORTALITY IN CIRRHOTIC PATIENTS WITH A 1ST OR 2ND EPISODE OF VARICEAL BLEEDING: A MULTICENTRE RANDOMIZED CONTROLLED TRIAL</title><p><bold>I. L. Holster</bold><sup>1,1,*</sup>, A. Moelker<sup>2</sup>, E. T. Tjwa<sup>1</sup>, A. Wils<sup>2</sup>, E. J. Kuipers<sup>1</sup>, P. Pattynama<sup>2</sup>, H. R. van Buuren<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology and hepatology, <sup>2</sup>Radiology, Erasmus MC University Medical Centre, Rotterdam, Netherlands</italic></p><p><bold>INTRODUCTION:</bold> It has been shown that in unselected patients with gastro-esophageal variceal bleeding (GEVB), TIPS (with conventional, uncovered stents) compared with endoscopic therapy, is more effective in reducing recurrent variceal bleeding, but does not improve survival and increases the incidence of hepatic encephalopathy (HE). Recent data suggest that PTFE-covered TIPS reduce rebleeding and improve survival in selected high-risk patients (Child-Pugh B with active bleeding and Child-Pugh C).</p><p><bold>AIMS&METHODS:</bold> We aimed to compare the efficacy and safety of early TIPS using PTFE-covered stents vs. endoscopic rubber band ligation (RBL) + propranolol for the secondary prevention of GEVB in all cirrhotic patients presenting with a 1<sup>st</sup> or 2<sup>nd</sup> variceal bleed. After the index bleeding treatment included RBL, antibiotics and vasoactive drugs. Following stabilization, patients were randomly assigned to groups treated with early TIPS or long-term RBL + propranolol. Randomization was stratified according to Child-Pugh (CP) score and center. Kaplan-Meijer (event free) survival analyses with log-rank tests were used for the endpoints rebleeding, death, and HE.</p><p><bold>RESULTS:</bold> From 2007-2013, 71 cirrhotic patients (median age 54 yrs, range 30-75, 56% male) were randomized (35 to TIPS, 36 to RBL). Mean CP score was 7.4 (35% CP-A, 49% CP-B, and 13% CP-C), and the etiology of underlying liver disease was alcohol in 42%, viral hepatitis in 12%, alcohol and viral hepatitis in 9%, and auto-immune biliary or liver disease in 25%. The median bleed-to-TIPS time was 6 days. During a median follow-up of 18 (range 1-30) months, rebleeding occurred in 2 patients in the TIPS group vs. 11 in the RBL group (p=0.008). Fifteen patients died: TIPS group n=8, RBL group n=7; p= 0.675. Deaths were mostly related to multi-organ failure (n=5), progressive liver failure (n=4), and hepatobiliary cancer (n=4). Eighteen patients (25%) experienced a period of HE (TIPS group n=13; RBL group n= 5; p=0.029). This was mild to moderate with good response to medication in all but two patients in the TIPS group, who required shunt reduction.</p><p><bold>CONCLUSION:</bold> Compared to endoscopic + B-blocker treatment, early TIPS using covered stents for secondary prevention of GEVB reduces rebleeding, but not mortality, and increases the risk of HE, in an - with respect to the severity of the underlying disease - unselected population. These results are comparable to those obtained with TIPS using conventional, uncovered stents.</p><p><bold>Contact E-mail Address:</bold><email>i.holster@erasmusmc.nl</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> hepatic encephalopathy, mortality, Rebleeding, Rubber band ligation, TIPS, Variceal bleeding</p></sec><sec><title></title><p><bold>TUESDAY, OCTOBER 15, 2013 14:00-15:30</bold></p><p><bold>Prevention, detection and management of gastric tumours – Hall 9</bold></p></sec><sec><title>OP278 LONG-TERM METFORMIN USE REDUCES GASTRIC CANCER RISK IN TYPE 2 DIABETICS WITHOUT INSULIN TREATMENT: A NATIONWIDE COHORT STUDY</title><p><bold>Y.-I. Kim</bold><sup>1,*</sup>, S.-J. Cho<sup>1</sup>, S. Y. Kim<sup>2</sup>, J.-H. Park<sup>2</sup>, I. J. Choi<sup>1</sup>, Y. J. Lee<sup>3</sup>, E. K. Lee<sup>3</sup>, M.-C. Kook<sup>1</sup>, C. G. Kim<sup>1</sup>, K. W. Ryu<sup>1</sup>, Y.-W. Kim<sup>1</sup></p><p><italic><sup>1</sup>Center for Gastric Cancer, <sup>2</sup>National Cancer Control Institute, <sup>3</sup>Center for Thyroid Cancer, National Cancer Center, Goyang, Korea, Republic Of</italic></p><p><bold>INTRODUCTION:</bold> Metformin use has been associated with a decreased incidence and mortality of various cancers.</p><p><bold>AIMS&METHODS:</bold> This study evaluated the association between metformin use and gastric cancer risk. We randomly selected 100,000 type 2 diabetic patients from the 2004 Korean National Health Insurance claim database, and assessed gastric cancer incidence among 39,989 patients (aged 30–97 years) who were regularly treated with anti-diabetic drugs and followed-up from January 2004 to December 2010. In total, 26,690 patients had used metformin out of 32,978 diabetics who had not regularly used insulin (insulin non-users), and 5,855 patients had used metformin out of 7,011 regular insulin users (regular insulin users).</p><p><bold>RESULTS:</bold> Patients who used metformin showed a lower incidence of gastric cancer than those who did not use metformin, in insulin non-users (<italic>P</italic>=0.047, log-rank test). However, in patients on regular insulin, there was no difference of gastric cancer incidence according to metformin use. In insulin non-users, the adjusted hazard ratio (AHR) for metformin use was 0.73 (95% confidential interval [CI], 0.53–1.01) with borderline statistical significance (<italic>P</italic>=0.059) in a multivariate analysis. Duration of metformin use was associated with the reduction of gastric cancer risk (overall AHR, 0.88; 95% CI 0.81–0.96, <italic>P</italic>=0.003), especially in patients that used metformin for more than 3 years (AHR, 0.57; 95% CI, 0.37–0.87; <italic>P</italic>=0.009).</p><p><bold>CONCLUSION:</bold> Metformin use >3 years in type 2 diabetics who do not use insulin is associated with significantly reduced gastric cancer risk.</p><p><bold>Contact E-mail Address:</bold><email>crystal522@ncc.re.kr</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Gastric cancer, Metformin, Type 2 diabetes</p></sec><sec><title>OP279 INSULIN RESISTANCE ARE ASSOCIATED WITH EARLY GASTRIC CANCER : PROSPECTIVE MULTI-CENTER CASE CONTROL STUDY</title><p><bold>H. J. Kwon</bold><sup>1</sup>, M. I. Park<sup>1</sup>, W. Moon<sup>1</sup>, S. J. Park<sup>1</sup>, S. E. Kim<sup>1,*</sup>, J. W. Kim<sup>2</sup>, C. W. Lee<sup>1</sup></p><p><italic><sup>1</sup>Department of Internal Medicine, <sup>2</sup>Department of Occupational & Environmental Medicine, Kosin University College of Medicine, Busan, Korea, Republic Of</italic></p><p><bold>INTRODUCTION:</bold> Recently, increased body weight has been associated with an increased risk of cancers at multiple specific sites, including gastric cancer. The precise pathogenetic role of hyperglycemia in gastric carcinogenesis remains obscure so far hyperglycemia and its related conditions may act directly as a carcinogenic factor. Insulin-resistance is associated with increased risk of cancers but it is not used as a marker for diseases in clinical practice.</p><p><bold>AIMS&METHODS:</bold> To clarify the factors associated with early gastric cancer and homeostasis model assessment of the insulin resistance(HOMA-IR) index, fasting glucose, lipid proflie as a predictor of early gastric cancer. A total of 63 patients with early gastric cancer between Nov 2012 and March 2013. In this study preoperative serum levels of total cholesterol(TC) and triglyceride(TG), low-density lipoprotein(LDL), high-density lipoprotein(HDL), serum fasting glucose, HOMA-IR, HOMA B cell function, Helipobacter pylori infection, body mass index(BMI) were examined prospectively in patients with early gastric cancer. The same number of controls were evaluated and matched to the early gastric cancer group for age and gender. In these patients, we analyzed the association between plasma glucose, insulin, HOMA-IR, lipid profile and early gastric cancer risk as well as various clinicopathologic characteristics. We performed multivariated logistic regression analysis to determine the independent risk factors for early gastric cancer. HOMA-IR index using the following formula: fasting insulin(μIU/L) × fasting plasma glucose (mmol/L) / 22.5.</p><p><bold>RESULTS:</bold> The univariate analysis showed that risk for early gastric cancer was increase in subjects with diastolic BP, total cholesterol, fasting glucose and HOMA-IR. However, age, body mss index (BMI), abdominal circumference(AC), high-density lipoprotein, low-density lipoprotein, triglyceride, fasting insulin, HOMA b cell function were not associated with early gastric cancer.</p><p>In the multivariate-adjusted model, total cholesterol, fasting glucose, body mass index and diastolic BP were strongly associated with an increased risk of early gastric cancer.</p><p><bold>CONCLUSION:</bold> Hyperglycemia and a lower high density lipoprotein cholesterol level and low level of HOMA-IR appear to be associated with the risk for early gastric cancer. Further large controlled studies are needed to clarify the association of serum glucose, lipid level and gastric cancer.</p><p><bold>REFERENCES:</bold></p><p>1. Kazumi T, Kawaguchi A, Hirano T, Yoshino G. Serum Adiponectin Is Associated With High-Density Lipoprotein Cholesterol, Triglycerides, and Low-Density Lipoprotein Particle Size in Young Healthy Men. Metabolism 2004 May;53(5):589-93.</p><p>2. Tiaka EK, Manolakis AC, Kapsoritakis AN, Potamianos SP. The implication of adiponectin and resistin in gastrointestinal diseases. Cytokine Growth Factor Rev 2011 Apr;22(2):109-19.</p><p>3. Mulholland HG, Murray LJ, Cardwell CR, Cantwell MM. Glycemic index, glycemic load, and risk of digestive tract neoplasms: a systematic review and meta-analysis. Am J Clin Nutr. 2009 Feb;89(2):568-76.</p><p>4. Augustin LS, Gallus S, Negri E, La Vecchia C. Glycemic index, glycemic load and risk of gastric cancer. Ann Oncol. 2004 Apr;15(4):581-4. 5.Larsson SC, Bergkvist L, Wolk A. Glycemic load, glycemic index and carbohydrate intake in relation to risk of stomach cancer: a prospective study. Int J Cancer. 2006 Jun 15;118(12):3167-9.</p><p><bold>Contact E-mail Address:</bold><email>bigbiggirl01@hanmail.net</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Early gastric cancer, HOMA-IR, Hypercholesterolemia, Hyperglycemia</p></sec><sec><title>OP280 CAUSES OF MISSED SYNCHRONOUS GASTRIC EPITHELIAL NEOPLASMS WITH ENDOSCOPIC SUBMUCOSAL DISSECTION: A MULTICENTER STUDY</title><p><bold>H. H. Kim</bold><sup>1,2,*</sup>, J. H. Kim<sup>3</sup>, G. H. Kim<sup>4</sup>, M.-K. Choi<sup>1</sup></p><p><italic><sup>1</sup>Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, <sup>2</sup>Internal Medicine, Kosin University College of Medicine, <sup>3</sup>Internal Medicine, Inje University College of Meidicne, <sup>4</sup>Internal Medicine, Pusan National University School of Medicine, Busan, Korea, Republic Of</italic></p><p><bold>INTRODUCTION:</bold> Unlike surgery, endoscopic submucosal dissection (ESD) removes gastric epithelial neoplasms within a tight margin, leaving most normal tissue around the neoplasm intact, thus resulting in a high risk for missed synchronous gastric epithelial neoplasms (mSGENs).</p><p><bold>AIMS&METHODS:</bold> The purpose of this study was to evaluate the characteristics and risk factors for missed SGENs (mSGENs) compared to simultaneously identified SGENs (siSGENs) in patients who underwent ESD. We retrospectively examined 312 SGENs from 275 patients treated by ESD at 3 hospitals in Korea between January 2004 and May 2011. The incidence and clinicopathological features of SGENs, mSGENs, and siSGENs were investigated. Any second epithelial neoplasm found within 1 year of the first ESD procedure was defined as an mSGEN and any neoplasm detected simultaneously with the first neoplasm was defined as a siSGEN.</p><p><bold>RESULTS:</bold> The overall incidence of ESD patients with SGENs was 9.1% (275/3018 patients). Of the SGENs, 45.2% were siSGENs and 54.8% were mSGENs. Independent risk factors for mSGENs were adenoma as the first gastric lesion (Exp (B) = 2.154, 95% CI = 1.282–3.262), and duration of endoscopic examination before the first ESD (Exp (B) = 1.074, 95% CI = 1.001–1.141). The results suggest that 33% of mSGENs could have been identified during the endoscopic examination prior to ESD.</p><p><bold>CONCLUSION:</bold> Additional effort needs to be expended in identifying siSGENs, particularly prior to ESD for less serious adenomas. This should include sufficient time for endoscopic examination, prior to ESD, to ensure a thorough examination for siSGENs.</p><p><bold>REFERENCES:</bold></p><p>1. Gotoda T, Yanagisawa A, Sasako M, et al. Incidence of lymph node metastasis from early gastric cancer: estimation with a large number of cases at two large centers. Gastric Cancer 2000; 3: 219-225.</p><p>2. Yamao T, Shirao K, Ono H, et al. Risk factors for lymph node metastasis from intramucosal gastric carcinoma Cancer. 1996; 77: 602-606.</p><p>3. Ohkuwa M, Hosokawa K, Boku N, Ohtu A, Tajiri H, Yoshida S. New endoscopic treatment for intramucosal gastric tumors using an insulated-tip diathermic knife. Endoscopy 2001; 33: 221-226.</p><p>4. Moertel CG, Bargen JA, Soule EH. Multiple gastric cancers; review of the literature and study of 42 cases. Gastroenterology 1957; 32: 1095-1103.</p><p>5. Kosaka T, Miwa K, Yonemura Y, et al. A clinicopathologic study on multiple gastric cancers with special reference to distal gastrectomy. Cancer 1990; 65: 2602-2605.</p><p><bold>Contact E-mail Address:</bold><email>drhhkim@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> gastric cancer, neoplasm, synchronous </p></sec><sec><title>OP281 DEEP BIOPSY VIA ESD TECHNIQUE OF SUBEPITHELIAL TUMOR: PROSPECTIVE STUDY</title><p><bold>H. J. Tae</bold><sup>1,*</sup>, H. L. Lee<sup>1</sup>, J. O. Kim<sup>1</sup>, K. N. Lee<sup>1</sup>, D. W. Jun<sup>1</sup>, O. Y. Lee<sup>1</sup>, B. C. Yoon<sup>1</sup>, H. S. Choi<sup>1</sup>, J. S. Hahm<sup>1</sup></p><p><italic><sup>1</sup>Department of Internal Medicine, Hanyang University Hospital, Seoul, Korea, Seoul, Korea, Republic Of</italic></p><p><bold>INTRODUCTION:</bold> Preoperative pathologic diagnosis of a subepithelial tumor(SET) may improve clinical decision making.</p><p><bold>AIMS&METHODS:</bold> The aim of this study was to evaluate diagnostic yield of Deep biopys via ESD technique and the impact on the clinical management of patients with SETs.</p><p>Forty patients with upper GI SETs underwent endoscopic deep biopsy and EUS. EUS images were examined for mass size, echogenicity, invasion layer. Endoscopic deep biopsy was performed by using the ESD technique. An approximately 15-mm-diameter round incision was made in the overlying mucosa. Next submucosal dissection was performed with the IT knife. When a submucosal mass was present, we performed multiple endoscopic biopsies.</p><p><bold>RESULTS:</bold> The diagnostic yield of deep biopsy for the patients with SETs was 90% (36 with diagnostic biopsy; 4 with non diagnostic biopsy). The mean long diameter of the 36 SMT with diagnostic cytology measured EUS was 21 mm (range 10-40 mm). Treatment plans were changed for 13 of 40 patients (32.5%) after deep biopsy. The changes were avoiding unnecessary operation (6 benign SETs ≥3 cm in diameter), scheduling for surgical resection (6 GI stromal tumors and 1 lyphoepithelial carcinoma). Mean procedure time was 13.66±2.91 minutes. There were no complications such as bleeding or perforation during or after the procedures.</p><p><bold>CONCLUSION:</bold> Diagnostic yield of deep biopsy by ESD technique was relatively high in patients with SETs. Because of this, this method also would be able to reduce the need for unnecessary surgery and to receive proper surgery, or surveillance.</p><p><bold>Contact E-mail Address:</bold><email>icarus421@hanmail.net</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> biopsy, endoscopic submucosal dissection (ESD), subepithelial tumors</p></sec><sec><title>OP282 THE INFLUENCE OF ANTIPLATELET THERAPY WITH ITS TEMPORARY DISCONTINUATION ON BLEEDING RISK AFTER GASTRIC ENDOSCOPIC SUBMUCOSAL DISSECTION</title><p><bold>N. Ueki</bold><sup>1,*</sup>, K. Miyake<sup>1</sup>, A. Yamada<sup>1</sup>, Y. Kodaka<sup>1</sup>, H. Nagoya<sup>1</sup>, T. Shindo<sup>1</sup>, M. Kusunoki<sup>2</sup>, T. Kawagoe<sup>1</sup>, S. Futagami<sup>1</sup>, C. Sakamoto<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology, Nippon Medical School, Tokyo, <sup>2</sup>Gastroenterology, Nippon Medical school Chiba Hokusoh Hospital, Chiba, Japan</italic></p><p><bold>INTRODUCTION:</bold> The recently updated guidelines of the Japanese Society for Gastrointestinal Endoscopy recommends a single dose of aspirin or cilostazol as an anticoagulant and antiplatelet (AP) therapy for endoscopic procedures, especially in cases of endoscopic submucosal dissection (ESD) at a high risk of thromboembolism. However, even before the guidelines were updated, patients in whom AP therapies were temporarily discontinued were probably known to have an increased risk of bleeding after ESD.Therefore, we aimed to evaluate the influence of AP therapy and its temporary discontinuation on post-ESD bleeding risk.</p><p><bold>AIMS&METHODS:</bold> This study was performed before the guidelines were updated; we included 364 patients with gastric neoplasms who had undergone ESD at our hospital between October 2005 and December 2012. Patients in whom AP therapy was replaced with heparin were excluded. Post-ESD bleeding was considered if the following was observed: overt hematemesis/hematochezia, a decrease in hemoglobin level by 2 g/dL, or active or possible bleeding spot with visible vessels and clots. Early bleeding was considered if a bleeding episode was observed within 48 hours after ESD, and delayed bleeding was considered if bleeding was observed after 48 hours. To investigate the potential risk factors that influence post-ESD bleeding, the following variables were analyzed in patients who did and did not experience bleeding: age (>70), sex, discontinuation of AP therapy, the location of ESD (antrum), duration of surgery > 120 min, and platelet count (<10 × 10<sup>4</sup>/μL).</p><p><bold>RESULTS:</bold> 340 patients did not experience bleeding (244 men; age, 71.2 years), and 24 experienced bleeding (20 men; age, 71.5 years). The administration of AP after ESD was restarted from the third or subsequent days. The median duration of postoperative hemorrhage was 5 days from ESD, and of the 27 patients, 37.5% experienced early bleeding, and 62.5% experienced bleeding 3–33 days later. Univariate analysis indicated that discontinuation of AP therapy, platelet count, the size of resection, and duration of surgery (P<.100),were related to post-ESD bleeding. Multivariate analysis indicated that discontinuation of AP therapy (OR 4.559; 95%CI, 1.036-20.060; P=.045) and a platelet count (OR 16.186; 95%CI, 2.155-121.589; P=.007) were significant and independent risk factors for early bleeding.</p><p><bold>CONCLUSION:</bold> In addition to thrombocytopenia, the discontinuation of AP therapy may increase the risk of bleeding in the early post-ESD period. Patients who require continuous AP therapy should be assessed more carefully for post-ESD bleeding.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> antiplatelets, endoscopic submucosal dissection, gastric neoplasm</p></sec><sec><title>OP283 THE DECREASING INCIDENCE OF GASTRIC MALT LYMPHOMA OVER THE LAST 20 YEARS</title><p><bold>A. Savio</bold><sup>1,*</sup>, P. Cesari<sup>2</sup>, C. Zambelli<sup>1</sup>, G. Viviani<sup>3</sup>, F. Donato<sup>4</sup>, F. Rolfi<sup>2</sup>, F. Zorzi<sup>1</sup></p><p><italic><sup>1</sup>Histopathology, <sup>2</sup>Endoscopy, Poliambulanza Hospital - Brescia (Italy), Brescia, <sup>3</sup>Endoscopy, Manerbio Hospital, Manerbio (Brescia), <sup>4</sup>Sperimental and Applied Medicine Department, Brescia University, Brescia, Italy</italic></p><p><bold>INTRODUCTION:</bold> In our hospital treatment of gastric MALT lymphoma (GML) with eradication of <italic>H.pylori</italic> (Hp) started in 1992. After the first few years a dramatic reduction of newly diagnosed cases was noticed.</p><p><bold>AIMS&METHODS:</bold> The aim of this study is to verify this drop over the last 20 years and its hypothetical link to Hp eradication in the general population.</p><p>The rates of Hp infection and GML in patients undergoing EGD in our hospital during three different 3-year periods have been considered and compared with the data of the local Cancer Registry (CR).</p><p><bold>RESULTS:</bold> The percentage of newly diagnosed cases of GML decreases from 0,23% (1992-1994) to 0,08% (2002-2004) and to 0,05% (2010-2012) (Tab 1).</p><p> Tab 1: Newly diagnosed cases of gastric cancer and MALT lymphoma at Poliambulanza-HSO hospital in Brescia (Italy) compared with Helicobacter +ve patients
<table-wrap id="table43-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1">YEARS</th><th rowspan="1" colspan="1">EGD</th><th rowspan="1" colspan="1">Gastric cancer</th><th rowspan="1" colspan="1">MALT lymphoma</th><th rowspan="1" colspan="1">Hp +ve patients</th><th rowspan="1" colspan="1">MALT ly/HP +ve</th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">1992- 1994</td><td rowspan="1" colspan="1">15.983</td><td rowspan="1" colspan="1">207(1.3%)</td><td rowspan="1" colspan="1">38(0.23%)</td><td rowspan="1" colspan="1">7.874 (49% EGD)</td><td rowspan="1" colspan="1">0.48%</td></tr><tr><td rowspan="1" colspan="1">2002- 2004</td><td rowspan="1" colspan="1">10.628</td><td rowspan="1" colspan="1">95(0.9%)</td><td rowspan="1" colspan="1">9(0.08%)</td><td rowspan="1" colspan="1">3.431 (32% EGD)</td><td rowspan="1" colspan="1">0.26%</td></tr><tr><td rowspan="1" colspan="1">2012- 2014</td><td rowspan="1" colspan="1">18.624</td><td rowspan="1" colspan="1">204(1.1%)</td><td rowspan="1" colspan="1">10(0.05%)</td><td rowspan="1" colspan="1">3.766 (20% EGD)</td><td rowspan="1" colspan="1">0.26%</td></tr></tbody></table></table-wrap></p><p>The rate of Hp+ve patients varies from 49% to 32% and to 20%. The first interval drop of incidence of GML is much greater than that expected on the basis of the Hp rate decline while it remains aligned during the second interval. The drop of GML is in contrast with the data of the non-Hodgkin lymphomas from the CR.</p><p>The subset of GML resistant to antibiotics or with delayed remission is stable, in spite of the reduction of the total number of cases.</p><p><bold>CONCLUSION:</bold> Introduction of proton pump inhibitors during the first interval may explain the initial excessive GML decline. Eradication of Hp in all cases with dense lymphoid infiltration could explain both the disproportionate drop of GML and their greater tendency to persist after antibiotics.</p><p><bold>Contact E-mail Address:</bold><email>antonella.savio@poliambulanza.it</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Gastric cancer, Helicobacter pylori eradication, incidence, Lymphoma, MALToma</p></sec><sec><title></title><p><bold>TUESDAY, OCTOBER 15, 2013 14:00-15:30</bold></p><p><bold>Optmising colonic polyp detection – Hall 10</bold></p></sec><sec><title>OP284 STANDARD COLONOSCOPY VERSUS CAP-ASSISTED CHROMO-ENDOSCOPY IN THE PROXIMAL POLYP DETECTION</title><p><bold>H.-S. Kim</bold><sup>1</sup>, H. W. Hwang<sup>1,*</sup>, H. J. Park<sup>1</sup>, D. I. Park<sup>2</sup>, J. M. Cha<sup>3</sup>, S.-J. Park<sup>4</sup>, H. Choi<sup>5</sup>, J. E. Shin<sup>6</sup>, C. S. Eun<sup>7</sup>, J. O. Kim<sup>8</sup>, H. G. Kim<sup>8</sup>, S.-E. Kim<sup>9</sup>, C. H. Park<sup>10</sup>, T. I. Kim<sup>11</sup>, S. N. Hong<sup>2</sup>, D. H. Yang<sup>12</sup></p><p><italic><sup>1</sup>Internal medicine, Division of gastroenterology, YONSEI UNIV. WONJU COLLEGE OF MEDICINE, Wonju, <sup>2</sup>Internal medicine, Division of gastroenterology, Sungkyunkwan University College of Medicine, Seoul, <sup>3</sup>Internal medicine, Division of gastroenterology, Kyung Hee University College of Medicine, Hanam, <sup>4</sup>Internal medicine, Division of gastroenterology, Kosin University College of Medicine, Busan, <sup>5</sup>Internal medicine, Division of gastroenterology, The Catholic University of Korea College of Medicine, Incheon, <sup>6</sup>Internal medicine, Division of gastroenterology, Dankook University College of Medicine, Cheonan, <sup>7</sup>Internal medicine, Division of gastroenterology, Hanyang University College of Medicine, Guri, <sup>8</sup>Internal medicine, Division of gastroenterology, Soonchunhyang University College of Medicine, <sup>9</sup>Internal medicine, Division of gastroenterology, Ewha Womans University School of Medicine, Seoul, <sup>10</sup>Internal medicine, Division of gastroenterology, Hallym University College of Medicine, Anyang, <sup>11</sup>Internal medicine, Division of gastroenterology, Yonsei University College of Medicine, <sup>12</sup>Internal medicine, Division of gastroenterology, University of Ulsan College of Medicine, Seoul, Korea, Republic Of</italic></p><p><bold>INTRODUCTION:</bold> Recent studies have raised concerns that screening colonoscopy may not prevent colorectal cancer (CRC) incidence and mortality in the proximal colon.</p><p><bold>AIMS&METHODS:</bold> We investigated whether high quality colonoscopy using cap-assisted chromoendoscopy (CAP-ACE) could enhance the detection of the proximal adenoma and serrated polyp. From March 2010 to March 2012, asymptomatic average risk subjects in the aged 45 to 75 who underwent the first screening colonoscopy were prospectively enrolled at 13 tertiary hospitals. Thirteen expert (> 5,000 procedures) and 4 non-expert colonoscopists have performed procedures. Subjects were randomly allocated to CAP-ACE group or standard colonoscopy (SC) group. Through per-person analysis, we compared proximal adenoma detection rate (PADR), advanced ADR (AADR) and proximal serrated polyp detection rate (PSPDR) between two groups. In addition, we conducted per-adenoma analysis to identify the characteristics of polyps found in CAP-ACE group.</p><p><bold>RESULTS:</bold> Among 2,004 subjects enrolled, 1,884 subjects were finally analyzed; CAP-ACE: 935 (49.6%) and SC: 949 (50.4%). Compared to SC, CAP-ACE significantly enhanced the ADR (54% vs. 44%, p < 0.001), PADR (39% vs. 31%, p = 0.001) and PSPDR (12% vs. 6%, p < 0.001). Compared to SC, interestingly, PADR and PSPDR obtained by CAP-ACE were significantly higher not in male but in female. This effect was even remarkable in female older (> 60 years) sub-population in which CAP-ACE markedly enhanced the ADR (61% vs. 40%, p < 0.001), PADR (46% vs. 25%, p < 0.001), and PSPDR (17% vs. 4%, p < 0.001) compared to SC. By per-polyp analyses, a total of 2,297 adenomas were removed by CAP-ACE (1,273, 55.4%) and by SC (1,024, 44.6%, p < 0.001). The characteristics of adenomas found and removed by CAP-ACE were more flat or sessile (p = 0.016) and smaller in size (< 5 mm, p = 0.003) than those by SC.</p><p><bold>CONCLUSION:</bold> Compared to SC, CAP-ACE detects even more proximal adenomas and serrated polyps in female older population, suggesting the necessity of high quality colonoscopy and individualized screening approach for the better prevention of the proximal CRC. (Funded by Ministry of Health, Welfare & Family Affairs ClinicalTrials.gov number, NCT01112280.)</p><p><bold>Contact E-mail Address:</bold><email>hyskim@yonsei.ac.kr</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> cap-assisted chromoendoscopy, proximal colorectal advanced neoplasia, Quality of colonoscopy, serrated adenoma/polyp</p></sec><sec><title>OP285 FULL SPECTRUM ENDOSCOPY VS. TRADITIONAL FORWARD-VIEWING COLONOSCOPY: FINAL RESULTS OF A RANDOMIZED, MULTICENTER TANDEM STUDY – THE FUSE STUDY</title><p><bold>P. D. Siersema</bold><sup>1,*</sup>, I. M. Gralnek<sup>2</sup>, Z. Halpern<sup>3</sup>, A. Sloyer<sup>4</sup>, O. Segol<sup>5</sup>, A. Suissa<sup>2</sup>, V. K. Dik<sup>1</sup>, L. M. Moons<sup>1</sup>, E. Santo<sup>3</sup>, R. B. D'Agostino<sup>6</sup>, D. K. Rex<sup>7</sup></p><p><italic><sup>1</sup>UMC Utrecht, Utrecht, Netherlands, <sup>2</sup>Elisha Medical Center, Haifa, <sup>3</sup>Sourasky Medical Center, Tel Aviv, Israel, <sup>4</sup>North Shore Gastroenterology Associates, New York, United States, <sup>5</sup>The Lady Davis Carmel Medical Center, Haifa, Israel, <sup>6</sup>Wake Forest School of Medicine, Winston-Salem, <sup>7</sup>Indiana University School of Medicine, Indianapolis, United States</italic></p><p><bold>INTRODUCTION:</bold> Traditional forward-viewing (TFV) colonoscopy is associated with a significant miss rate for adenomas (up to 31.4%) and colorectal cancer (CRC) due to inadequate visualization behind colonic folds and flexures. Recently, Full Spectrum Endoscopy (Fuse™) colonoscopy (EndoChoice, Alpharetta, GA, USA) was introduced which allows 330 degree viewing while maintaining standard colonoscope features.</p><p><bold>AIMS&METHODS:</bold> To determine additional adenoma detection rates comparing Fuse colonoscopy with TFV colonoscopy. In a multicenter, international study, patients were randomly assigned to undergo tandem colonoscopy starting with either TFV or Fuse colonoscopy. Primary endpoint was the number of additional polyps and adenomas detected by Fuse (per lesion analysis). Secondary endpoints included adenoma miss rates, cecal intubation, withdrawal and total procedure times, and adverse events (AE).</p><p><bold>RESULTS:</bold> From 1/2012 – 3/2013, 197 subjects were enrolled. Of these, 185 subjects (54.6% female, mean age 55.8 ± 9.7 years) completed tandem colonoscopies. Indications for colonoscopy were CRC screening n=103 (55.7%), polyp surveillance n=36 (19.5%), and diagnostic work-up n=46 (24.8%). In 88 subjects undergoing TFV first, 50 polyps including 28 adenomas were detected while Fuse yielded 39 additional polyps including 20 adenomas, an increase in polyps and adenomas of 78.0% and 71.4%, resp. In 97 subjects undergoing Fuse first, 102 polyps including 61 adenomas were detected while TFV yielded 11 additional polyps including 5 adenomas, an increase in polyps and adenomas of 10.8% and 8.2%, resp. (Fuse vs TFV p<0.01). The adenoma miss rate with Fuse was 5/66 (7.6%) and with TFV 20/48 (41.7%) (p<0.01). Median times to cecum for TFV and Fuse were 5.1 and 4.8 min (p=NS), withdrawal times 5.6 and 6.2 min (P<0.01) and procedure times 12.2 and 14.5 min (p<0.01). One patient was hospitalized for colitis, while 6 AEs were seen (vomiting, diarrhea, cystitis, gastroenteritis, minor bleeding and colitis).</p><p><bold>CONCLUSION:</bold> The incremental adenomas found by Fuse after TFV was significantly higher (71.4%) compared to TFV after Fuse (8.2%), while the adenoma miss rate for TFV colonoscopy (41.7%) was significantly higher compared to Fuse (7.6%). These results suggest that Fuse colonoscopy is an important advancement in imaging technology and likely will improve the efficacy of CRC screening.</p><p><bold>Contact E-mail Address:</bold><email>p.d.siersema@umcutrecht.nl</email></p><p><bold>Disclosure of Interest</bold>: P. Siersema Consultancy for: Clinical trial support, I. Gralnek: None Declared, Z. Halpern: None Declared, A. Sloyer: None Declared, O. Segol: None Declared, A. Suissa: None Declared, V. Dik: None Declared, L. Moons: None Declared, E. Santo: None Declared, R. D'Agostino: None Declared, D. Rex: None Declared</p><p><bold>Keywords:</bold> adenoma detection, Colonoscopy, polyp detection</p></sec><sec><title>OP286 A NOVEL BALLOON-COLONOSCOPE FOR INCREASED POLYP DETECTION RATE – INTERMEDIATE RESULTS OF A RANDOMIZED TANDEM STUDY</title><p><bold>B. Shpak</bold><sup>1</sup>, Z. Halpern<sup>2,*</sup>, R. Kiesslich<sup>3</sup>, M. Moshkowitz<sup>1</sup>, E. Santo<sup>2</sup>, A. Hoffman<sup>3</sup></p><p><italic><sup>1</sup>Laniado Hospital, Netanya, <sup>2</sup>Tel Aviv Sourasky Medical Center, Tel Aviv, Israel, <sup>3</sup>St. Marienkrankenhaus Frankfurt, Frankfurt, Germany</italic></p><p><bold>INTRODUCTION:</bold> Approximately 30% of polyps are missed during standard colonoscopy (SC), e.g., due to polyps hidden behind haustral folds. This work explores a novel device and technique for increasing polyp and adenoma detection rate (PDR/ADR) during colonoscopy. It employs a unique balloon-colonoscope (NaviAid™ G-EYE, Smart Medical Systems Ltd., Ra’anana, Israel), comprising a standard colonoscope having a reprocessable, permanently integrated balloon at its distal tip. The balloon-colonoscope does not require pre-procedure preparation, mounting or use of any single-use accessory. Balloon pressure is controlled through a unique inflation system providing pre-determined, user-selectable, anchoring and intermediate (low) pressure levels.</p><p><bold>AIMS&METHODS:</bold> This is a multicenter, randomized, tandem study. Patients referred to colonoscopy for screening, surveillance or diagnostic workup, were randomized into two groups. Group A underwent SC followed by Balloon Colonoscopy (BC); group B underwent BC followed by SC. During the BC, the endoscope is inserted with the balloon deflated till the cecum. Then, the balloon is inflated to intermediate pressure and the balloon-colonoscope is withdrawn, thus straightening intestinal folds, smoothening colon topography and improving colon visibility. All polyps detected were removed.</p><p><bold>RESULTS:</bold> Study enrolment plan included 126 patients with interim analysis following the first 74. Interim results of 74 patients are presented. In group A, BC performed following SC detected 23 additional polyps, a 115% additional detection rate of the BC. In group B, SC performed following BC detected 1 additional polyp, a 4.5% additional detection rate of the SC (implying 4.5% miss-rate of the balloon-colonoscope). Balloon-colonoscope’s additional detection rate ratio (ADRR), calculated as the ratio between BC 2<sup>nd</sup> pass additional detection and BC 1<sup>st</sup> pass miss-rate, is 115/4.5=25.5. For comparison, ADRR in published tandem study of retroscope optics (TER, Avantis Medical) is 2.56. Average procedure time of SC and BC was similar. No adverse event occurred.
<table-wrap id="table44-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1"></th><th colspan="3" rowspan="1"><hr></hr>Group A (n=37)</th><th colspan="3" rowspan="1"><hr></hr>Group B (n=37)</th></tr><tr><th rowspan="1" colspan="1"></th><th rowspan="1" colspan="1">1st Pass (SC)</th><th rowspan="1" colspan="1">2<sup>nd</sup> Pass (BC)</th><th rowspan="1" colspan="1">Additional Detection</th><th rowspan="1" colspan="1">1<sup>st</sup> Pass (BC)</th><th rowspan="1" colspan="1">2<sup>nd</sup> Pass (SC)</th><th rowspan="1" colspan="1">Additional Detection</th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">All Polyps</td><td rowspan="1" colspan="1">20</td><td rowspan="1" colspan="1">23</td><td rowspan="1" colspan="1">115%</td><td rowspan="1" colspan="1">22</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">4.5%</td></tr><tr><td rowspan="1" colspan="1">2-5mm</td><td rowspan="1" colspan="1">14</td><td rowspan="1" colspan="1">16</td><td rowspan="1" colspan="1">114%</td><td rowspan="1" colspan="1">14</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">7.1%</td></tr><tr><td rowspan="1" colspan="1">5-10mm</td><td rowspan="1" colspan="1">4</td><td rowspan="1" colspan="1">5</td><td rowspan="1" colspan="1">125%</td><td rowspan="1" colspan="1">3</td><td rowspan="1" colspan="1">0</td><td rowspan="1" colspan="1">0%</td></tr><tr><td rowspan="1" colspan="1">>10mm</td><td rowspan="1" colspan="1">2</td><td rowspan="1" colspan="1">2</td><td rowspan="1" colspan="1">100%</td><td rowspan="1" colspan="1">5</td><td rowspan="1" colspan="1">0</td><td rowspan="1" colspan="1">0%</td></tr></tbody></table></table-wrap></p><p><bold>CONCLUSION:</bold> BC using the balloon-colonoscope and withdrawal technique is safe, easy to use, exhibits substantial increase in PDR, and presents significant reduction in miss rate during colonoscopy.</p><p><bold>Contact E-mail Address:</bold><email>bshpak@laniado.org.il</email></p><p><bold>Disclosure of Interest</bold>: B. Shpak: None Declared, Z. Halpern Consultancy for: Consultant for Smart Medical Systems Ltd., R. Kiesslich: None Declared, M. Moshkowitz: None Declared, E. Santo: None Declared, A. Hoffman: None Declared</p><p><bold>Keywords:</bold> Adenoma Detection Rate, Balloon Colonoscopy, Colorectal cancer, G-EYE Colonoscope, Polyp Detection Rate, Standard Colonoscopy</p></sec><sec><title>OP287 RESECT AND DISCARD STRATEGY CAN BE ACHIEVED WITH HIGH ACCURACY BY USING HIGH-DEFINITION ENDOSCOPY WITH VIRTUAL CHROMOENDOSCOPY</title><p><bold>H. Neumann</bold><sup>1,*</sup>, M. Vieth<sup>2</sup>, C. Günther<sup>1</sup>, R. Atreya<sup>1</sup>, G. E. Tontini<sup>1</sup>, J. Siebler<sup>1</sup>, M. F. Neurath<sup>1</sup></p><p><italic><sup>1</sup>Department of Medicine I, UNIVERSITY OF ERLANGEN-NUREMBERG, Erlangen, <sup>2</sup>Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany</italic></p><p><bold>INTRODUCTION:</bold> The ASGE PIVI statement proposed that a new technology should provide a negative predictive value (NPV) >90% for adenomatous polyp histology to leave distal diminutive colorectal polyps in place without resection. To the best of our knowledge no prior prospective study has evaluated the feasibility of virtual chromoendoscopy based, real-time endoscopic prediction of polyp histology for leaving distal hyperplastic polyps in place.</p><p><bold>AIMS&METHODS:</bold> Study objective was to prospectively assess the real-time prediction of diminutive (≤ 5mm) distal colorectal polyps by using virtual chromoendoscopy (i-scan). Overall, 224 consecutive patients undergoing screening or surveillance colonoscopy were included. 121 distal colorectal polyps from 77 patients were evaluated in real-time by using high-definition endoscopy and i-scan. Before resection, the endoscopist described each polyp according to size, shape and surface characteristics (e.g. pit and vascular pattern, color, depression) and histology was predicted with a level of confidence (high or low).</p><p><bold>RESULTS:</bold> Histology was predicted with high-confidence in 92% of polyps. Overall accuracy for adenomatous polyp histology was 90% with sensitivity, specificity, positive and negative predictive value of 92%, 89%, 89%, and 92%, respectively. When the prediction was made with high-confidence, the accuracy was 96% and the sensitivity, specificity, positive and negative predictive value were 98%, 95, 95%, and 98%, respectively.</p><p><bold>CONCLUSION:</bold> High-definition endoscopy with virtual chromoendoscopy enables prediction of colorectal polyp histology in real-time and is accurate enough to leave distal colorectal polyps in place without resection according to the ASGE PIVI statement. This approach has therefore the potential to reduce costs and risks associated with the redundant removal of diminutive colorectal polyps.</p><p><bold>Contact E-mail Address:</bold><email>helmut.neumann@uk-erlangen.de</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> chromoendoscopy, Detection rate, PIVI, polyps</p></sec><sec><title>OP288 A “RESECT AND DISCARD” STRATEGY USING MAGNIFYING NARROW-BAND IMAGING: A PHASE II PROSPECTIVE STUDY</title><p><bold>Y. Takeuchi</bold><sup>1,*</sup>, M. Hanafusa<sup>1</sup>, H. Kanzaki<sup>1</sup>, T. Ohta<sup>1</sup>, N. Hanaoka<sup>1</sup>, S. Yamamoto<sup>1</sup>, K. Higashino<sup>1</sup>, N. Uedo<sup>1</sup>, H. Iishi<sup>1</sup>, R. Ishihara<sup>1</sup></p><p><italic><sup>1</sup>Gastrointestinal Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan</italic></p><p><bold>INTRODUCTION:</bold> Investigators have proposed “resect and discard” strategies using non-magnifying narrow-band imaging (N-NBI) without taking into consideration the advanced histology (villous histology, high grade dysplasia or adenocarcinoma)<sup>1</sup>. We proposed a new “resect and discard” strategy using magnifying NBI (M-NBI) taking into consideration the advanced histology in a pilot study<sup>2</sup>.</p><p><bold>AIMS&METHODS:</bold> The aim of this study was to investigate the efficacy and safety of the new “resect and discard” strategy taking into consideration advanced histology using M-NBI (compared to N-NBI). This study was carried out by 5 colonoscopists in a Japanese tertiary cancer center and was designed as a prospective phase II trial with the participation of 529 patients with 1236 lesions. All of the lesions were observed using N-NBI followed by M-NBI. Polyp histology was optically diagnosed using each modality and decisions made as to polyp management and post-polypectomy surveillance interval. After all polyps were biopsied or resected, optical and histological diagnosis results were compared.</p><p><bold>RESULTS:</bold> 1152 lesions smaller than 10mm in 464 patients were assessed polyp histology and 389 patients were assessed post-polypectomy surveillance interval. The management of 81% of the small polyps could be decided without formal histopathology using M-NBI. The sensitivity, specificity and accuracy (95% confidence interval) of M-NBI in distinguishing lesions with advanced histology from low-grade adenoma and non-neoplastic lesions were 0.77 (0.60-0.88), 0.93 (0.92-0.93) and 0.92 (0.91-0.93), respectively. Agreements in determining post-polypectomy surveillance interval (BSG, US) using M-NBI (90%, 89%) were higher than that using N-NBI (85%, 84%). Negative predictive value for adenomatous histology for recto-sigmoid polyps using M-NBI (87%) was higher than that using N-NBI (83%).</p><p><bold>CONCLUSION:</bold> M-NBI could differentiate most of the lesions with advanced histology and had a better diagnostic performance compared to N-NBI. M-NBI can be a promising tool for the “resect and discard” strategy taking into consideration the lesions with advanced histology, although further diagnostic improvement is needed (Clinical trial registration number: UMIN 000003740).</p><p><bold>REFERENCES:</bold></p><p>1. Ignjatovic A, East JE, Suzuki N et al. Optical diagnosis of small colorectal polyps at routine colonoscopy (Detect InSpect ChAracterise Resect and Discard; DISCARD trial): a prospective cohort study. Lancet Oncol 2009; 10: 1171-1178</p><p>2. Takeuchi Y, Hanafusa M, Kanzaki H et al. A proposal for a "resect and discard" strategy with optical diagnosis using magnifying narrow-band imaging: a pilot study of diagnostic accuracy. Endoscopy 2012; 44 supple 1: A3.</p><p><bold>Contact E-mail Address:</bold><email>takeuti-yo@mc.pref.osaka.jp</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> advanced neoplasm, colonoscopy, Colonoscopy surveillance, magnifying endoscopy with narrow-band imaging, resect and discard</p></sec><sec><title>OP289 EVALUATION OF THE ADOPTION OF COLONOSCOPIC STRATEGY WITH A "RESECT AND DISCARD" POLICY FOR DIMINUTIVE COLON POLYPS. AN HISTORICAL COHORT STUDY.</title><p><bold>A. Tavernaraki</bold><sup>1</sup>, E. Voudoukis<sup>1</sup>, E. Vardas<sup>1</sup>, A. Theodoropoulou<sup>1</sup>, G. Tribonias<sup>1</sup>, G. Georgiou<sup>1</sup>, E. Giannikaki<sup>1</sup>, N. Chroniaris<sup>1</sup>, G. Paspatis<sup>1,*</sup></p><p><italic><sup>1</sup>Department of Gastroenterology, Benizelion General Hospital, Heraklion-Crete, Greece</italic></p><p><bold>INTRODUCTION:</bold> The prevalence of advanced histological features in diminutive polyps is low. Polypectomy costs are also related to the cost of pathologic examination. Investigators have proposed a colonoscopic strategy with a "resect and discard" policy for diminutive (<0.5cm) colon polyps.</p><p><bold>AIMS&METHODS:</bold> The aim of the present study was to evaluate the adoption of this "resect and discard" colonoscopic strategy for diminutive colon polyps. To the best of our knowledge, this is the first reported study that evaluates this strategy in a long term basis from a clinical point of view. For a 10 years period a colonoscopic strategy with "a resect and discard" policy for diminutive colon polyps was implemented in our unit. A retrospective analysis of the data regarding colon diminutive polyps was performed. The study population included patients aged 18 years and older undergoing colonoscopy for colorectal cancer screening, post polypectomy surveillance or other indications for which the primary goal of the examination was detection of neoplasia. All diminutive polyps were removed using cold snare technique or biopsy forceps combined with the application of gold probe or argon plasma coagulation.</p><p><bold>RESULTS:</bold> According to this policy 10.653 diminutive colon polyps from 3433 consecutive patients were endoscopically removed and they were not sent for pathologic documentation. Follow up colonoscopy was conducted to approximately half of the patients (1484/3433) for at least one more time. The median follow up period was 3.5 years. No case with colon cancer or advanced adenoma in the follow up colonoscopies was identified.</p><p><bold>CONCLUSION:</bold> Our data indicate that the adoption of colonoscopic strategy with a "resect and discard" policy for diminutive colon polyps resulted in an obvious economic benefit without adversely affecting the colonoscopic efficacy. These data may have important implication in the management of diminutive colon polyps.</p><p><bold>Contact E-mail Address:</bold><email>atavernaraki77@yahoo.it</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> diminutive colon polyps, resect and discard</p></sec><sec><title></title><p><bold>TUESDAY, OCTOBER 15, 2013 14:00-15:30</bold></p><p><bold>Basic Science Workshop 2: Autophagy a common pathway in GI-inflammation – Hall 8</bold></p></sec><sec><title>OP290 AUTOPHAGY CAUSING CAGA DEGRADATION IS TRIGGERED BY CYTOPLASMIC ACCUMULATION OF LOW-DENSITY LIPOPROTEIN RECEPTOR-RELATED PROTEIN-1 (LRP1) IN GASTRIC EPITHELIAL CELLS INFECTED WITH <italic>H. PYLORI</italic></title><p><bold>H. Tsugawa</bold><sup>1,*</sup>, J. Matsuzaki<sup>1</sup>, S. Okada<sup>1</sup>, S. Fukuhara<sup>1</sup>, H. Mori<sup>1</sup>, T. Masaoka<sup>1</sup>, A. Sato<sup>2</sup>, H. Saya<sup>3</sup>, M. Hatakeyama<sup>4</sup>, T. Hirayama<sup>5</sup>, H. Suzuki<sup>1</sup></p><p><italic><sup>1</sup>Internal Medicine, Keio University School of Medicine, Tokyo, <sup>2</sup>Faculty of Pharmaceutical Sciences, Okayama University, Okayama, <sup>3</sup>Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, <sup>4</sup>Microbiology, Graduate School of Medicine, University of Tokyo, Tokyo, <sup>5</sup>Bacteriology, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan</italic></p><p><bold>INTRODUCTION:</bold><italic>Helicobacter pylori</italic> CagA acts as an oncoprotein by promoting the early events of gastric cancer development. We previously reported that although intracellular CagA could be degraded by autophagy in host gastric epithelial cells, its autophagic pathway was suppressed in CD44 variant 9-expressing gastric cancer stem-like cells due to their resistance to ROS, resulting in the specific accumulation of CagA in these cells (<bold><italic>Cell Host & Microbe</italic></bold>, 12:764, 2012). The autophagy causing CagA degradation was activated by VacA via binding to low-density lipoprotein receptor-related protein-1 (LRP1). We further demonstrated that not m2-type VacA (m2VacA) but m1-type VacA (m1VacA) induced the autophagy via binding to LRP1, which is a multifunctional member of the LDL receptor family and undergoes regulated intramembrane (ICD) proteolysis in a γ-secretase-dependent process. Although it is known that LRP1 have the ability to bind ligand to several signal transduction pathways, the role of the autophagy induction through LRP1 has remained unclear.</p><p><bold>AIMS&METHODS:</bold> The present study was conducted to examine LRP1-signal transduction to the autophagy. <bold>METHODS:</bold> The participation of LRP1-ICD in autophagy was assessed using a LRP1-siRNA, and the localization was assessed by western blot following subcellular fractionation and immunocytochemistry. LRP1-ICD binding protein was detected by silver-stained proteins following anti-LRP1-ICD antibody immunoprecipitation.</p><p><bold>RESULTS:</bold> Although LRP1-ICD was translocated to nucleus in AGS cells, LRP1-ICD was accumulated in cytoplasm by the repression of nuclear translocation in AGS cells at 15 hr after m1VacA-<italic>H. pylori </italic>infection (during the autophagy induction). The specific LRP1-knockdown in AGS cells using a LRP1-siRNA did not influence the levels of intracellular glutathione (GSH) and did not induce the autophagy, indicating that disappearance of nuclear LRP1-ICD was not required for autophagy. LRP1-ICD in AGS cells at 15 hr after m2VacA-<italic>H. pylori</italic> infection was not accumulated in cytoplasm. Accumulated LRP1-ICD in the cytoplasm of AGS cells at 15 hr after m1VacA-<italic>H. pylori</italic> infection bound to 35-kDa cytoplasmic protein, suggesting that the specific protein recruitment to cytoplasmic LRP1-ICD was important for this autophagy.</p><p><bold>CONCLUSION:</bold> Our findings indicate that 35-kDa cytoplasmic protein recruitment to cytoplasmic LRP1-ICD is important for the induction of autophagy, causing CagA degradation.</p><p><bold>Contact E-mail Address:</bold><email>h.tsugawa@a6.keio.jp</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> autophagy, Nano LC-MS/MS, VacA</p></sec><sec><title>OP291 CASPASE 8 MAINTAINS EPITHELIAL CELL ADHESION AND INTESTINAL HOMEOSTASIS IN VIVO THROUGH REGULATION OF CLATHRIN-DEPENDENT ENDOCYTOSIS AND AUTOPHAGY</title><p><bold>G. Pineton de Chambrun</bold><sup>1,2,*</sup>, C. Manthey<sup>2</sup>, C. McAllister<sup>2</sup>, A. Till<sup>3</sup>, M. Kagnoff<sup>2</sup>, P. Desreumaux<sup>1</sup>, D. Stupack<sup>4</sup>, J. Wang<sup>4</sup>, L. Eckmann<sup>2</sup></p><p><italic><sup>1</sup>Inserm U995, Lille North of France University, Lille, France, <sup>2</sup>Medicine, <sup>3</sup>Molecular biology, <sup>4</sup>Moores Cancer Center, UCSD, La Jolla, United States</italic></p><p><bold>INTRODUCTION:</bold> Caspase 8 is a key mediator of ligand-activated apoptosis, but has other functions, including regulation of endocytosis in epithelial cells. The physiological importance of these different activities is poorly understood. The aim of this study was to study the physiological functions of caspase 8 in intestinal epithelial cells (IECs).</p><p><bold>AIMS&METHODS:</bold> We generated mice specifically lacking <italic>Casp8</italic> in IECs (<italic>Casp8</italic><sup>ΔIEC</sup>) by crossing <italic>Casp8<sup>f</sup></italic><sup>l/fl</sup> mice to Tg(Vil-cre) mice, and examined them for cell death and endocytosis under constitutive and challenge conditions. The role of TNF-dependent signaling and autophagy was tested by additional ablation of <italic>Tnfr1</italic> (<italic>Casp8</italic><sup>ΔIEC</sup>/<italic>Tnfr1</italic><sup>-/-</sup>) or <italic>Atg</italic>7 in IECs (<italic>Casp8</italic><sup>ΔIEC</sup>/<italic>Atg7</italic><sup> ΔIEC</sup>).</p><p><bold>RESULTS:</bold> At 6 weeks <italic>Casp8</italic><sup>ΔIEC</sup> mice did not present any macroscopic or microscopic intestinal abnormalities compared with <italic>Casp8</italic><sup>fl/fl </sup>mice. However, IEC from <italic>Casp8</italic><sup>ΔIEC</sup> mice lacked the normal constitutive degradation of proteins important for clathrin-dependent endocytosis. To examine the consequences of this disturbance in endocytosis, we infected mice with the murine attaching/effacing pathogen, <italic>C. rodentium</italic>. <italic>Casp8</italic><sup>ΔIEC</sup>mice displayed significantly more weight loss and mortality than <italic>Casp8</italic><sup>fl/fl </sup>mice after infection. Microscopically, <italic>Casp8</italic><sup>ΔIEC</sup>mice presented a complete destruction of small intestinal villi and ileitis. Furthermore, stimulation of <italic>Casp8</italic><sup>ΔIEC</sup> mice with LPS for 4 hours caused marked detachment of small intestine IECs and led to villus destruction and mucosal inflammation. LPS-induced IEC detachment was prevented in <italic>Casp8</italic><sup>ΔIEC</sup> mice treated with the endocytosis inhibitor chlorpromazine. LPS-induced IEC detachment was prevented in <italic>Casp8</italic><sup>ΔIEC</sup>/<italic>Tnfr1</italic><sup>-/-</sup> mice, demonstrating a role of TNFα in these events. Furthermore, <italic>Casp8</italic><sup>ΔIEC</sup>mice treated with LPS showed abnormal autophagic activation in IECs compared to<italic> Casp8</italic><sup>fl/fl </sup>mice, and IEC detachment was absent in <italic>Casp8</italic><sup>ΔIEC</sup>/<italic>Atg7</italic><sup> ΔIEC </sup>mice. <italic>Casp8</italic><sup>ΔIEC</sup>/<italic>Atg7</italic><sup> ΔIEC </sup>mice were also protected from intestinal inflammation induced by <italic>C. rodentium</italic>.</p><p><bold>CONCLUSION:</bold> Caspase 8 controls IECs adhesion and maintains intestinal barrier integrity in response to infectious stimuli by regulating clathrin-dependent endocytosis and autophagy. This work demonstrates a major physiologic role of caspase 8 in maintaining intestinal homeostasis and controlling intestinal inflammation.</p><p><bold>Contact E-mail Address:</bold><email>guillaume.pinetondechambrun@chru-lille.fr</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> autophagy, Caspase 8, inflammation</p></sec><sec><title>OP292 THE GCN2/EIF2ALPHA/ATF4 SIGNALING PATHWAY IS NECESSARY FOR AUTOPHAGY RESPONSE TO INFECTION WITH CROHN’S DISEASE-ASSOCIATED ADHERENT-INVASIVE ESCHERICHIA COLI</title><p><bold>H. T. T. Nguyen</bold><sup>1,*</sup>, J. Carrière<sup>1</sup>, G. Dalmasso<sup>1</sup>, A.-C. Maurin<sup>2</sup>, A. Bruhat<sup>2</sup>, A. Darfeuille-Michaud<sup>1</sup></p><p><italic><sup>1</sup>UMR 1071 Inserm, University of Auvergne, Clermont-Ferrand, <sup>2</sup>Human Nutrition Unit, INRA, Theix, France</italic></p><p><bold>INTRODUCTION:</bold> Crohn′s disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract, of which the etiology involves environmental, genetic and microbial factors. Our group and others have shown a high prevalence of the invasive <italic>E. coli </italic>strains, designated adherent-invasive <italic>E. coli </italic>(AIEC), in the intestinal mucosa of CD patients. Upon AIEC infection, autophagy is induced in host cells to restrain the replication of the bacteria. The signaling pathway inducing autophagy response to AIEC infection, however, remains unknown.</p><p><bold>AIMS&METHODS:</bold> Here, we investigated the role of the GCN2/eIF2α/ATF4 pathway in such mechanism. Intestinal epithelial cells (IECs) were infected with the AIEC reference strain LF82, a non-pathogenic K12 or the commensal<italic> E. coli</italic> HS strain. Activation of the GCN2/eIF2α/ATF4 pathway was assessed by Western blot and qRT-PCR analyses. Autophagy was assessed by Western blot analysis and immunofluorescent labelling of LC3 and p62. The number of intracellular bacteria was determined by a bacterial invasion assay and confocal microscopy.</p><p><bold>RESULTS:</bold> We found that infection of IECs with AIEC LF82, but not with K12 or <italic>E. coli</italic> HS, increased the levels of phospho-GCN2, phospho-eIF2α and enhanced ATF4 protein expression. The later consequently led to upregulated mRNA expression levels of target genes of ATF4, such as <italic>ASNS</italic>, <italic>TRB3</italic>, <italic>GLYT</italic>, <italic>CHOP</italic>, <italic>ATF3</italic>, and autophagy genes (<italic>MAP1LC3B</italic>, <italic>p62</italic>). Intracellular multiplication of AIEC was increased in GCN2<sup>-/-</sup> and ATF4<sup>-/-</sup> mouse embryonic fibroblasts (MEFs) compared with that in wild type MEFs as determined by bacterial invasion assay and confocal microscopy using a LF82-GFP strain. These results were validated <italic>in vivo</italic> using GCN2 knockout mice and a model of AIEC infection that we previously established. AIEC infection induced a stronger pro-inflammatory response in GCN2<sup>-/-</sup> and ATF4<sup>-/-</sup> MEFs than in wild type MEFs, and in GCN2 knockout mice versus wild type mice. Autophagy induction in response to infection, assessed by Western blot and immunofluorescent analyses of LC3 levels, was decreased in GCN2<sup>-/-</sup> and ATF4<sup>-/-</sup> MEFs compared with wild type MEFs.</p><p><bold>CONCLUSION:</bold> Our study shows that upon AIEC infection, the GCN2/eIF2α/ATF4 signaling pathway is activated in host cells, which is served as a host defense mechanism to induce a functional autophagy-mediated control of AIEC intracellular replication.</p><p><bold>Contact E-mail Address:</bold><email>hang.nguyen@udamail.fr</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p>, adherent-invasive E. coli, autophagy, Crohn's disease</p></sec><sec><title>OP293 ER STRESS AND AUTOPHAGY, ERMERGING PATHWAYS IN CROHN’S DISEASE</title><p><bold>K. Nys</bold><sup>1,*</sup>, E. Hoefkens<sup>1</sup>, I. Cleynen<sup>1</sup>, P. Rutgeerts<sup>1</sup>, P. Agostinis<sup>2</sup>, S. Vermeire<sup>1</sup></p><p><italic><sup>1</sup>Dept. of Clinical and Experimental Medicine, <sup>2</sup>Dept. of Cellular and Molecular Medicine, K.U.Leuven, Leuven, Belgium</italic></p><p><bold>INTRODUCTION:</bold> With the recent advances in treatment of Crohn’s disease (CD), there is an urgent need for efficient diagnostic/prognostic and (personalized) therapeutic strategies. Large-scale genetic (GWAS) and transcriptional (microarray) studies have identified several stress and inflammatory signalling pathways to be important during Crohn’s pathogenesis. However, it remains unclear whether the genetic variants correlate with a functional response and/or a specific disease subphenotype.</p><p><bold>AIMS&METHODS:</bold> We wanted to evaluate whether specific CD-associated genetic variants in innate immunity, ER stress and autophagy genes in patient-derived cell types can be functionally translated into a characteristic stress response (inflammation, ER stress, autophagy). We also investigated if patients carrying a low (<4 of total 11) or a high number (>7 of total 11) of risk alleles behave differently for these functional readouts, ideally leading to a better and functional characterization of patients.</p><p>We isolated peripheral blood-myeloid cells from 69 healthy controls/Crohn’s diseased patients (all controls/patients were genotyped for SNPs in genes involved in innate immunity (<italic>NOD2</italic>), ER stress signaling (<italic>XBP1, ORMDL3</italic>) or autophagy (<italic>ATG16L1, IRGM, ULK1, MTMR-3, LRRK2</italic>) as part of the immunochip project) and exposed them to an inflammatory stimulus (LPS), ER stress (thapsigargin) and autophagy modulation (stimulation with rapamycin; inhibition with chloroquine).</p><p><bold>RESULTS:</bold> CD patients showed a significant increase of LPS-induced TNF, IL-6/10/1beta/8 secretion (29.4 – 139 % increase) and a decreased upregulation of Bip (32.4 % decrease), an important ER chaperone, during ER stress as compared to controls. Moreover, when comparing patients with a ‘high’ or ‘low’ number of risk alleles, we found an increased activation of autophagy (36.8 % more accumulation of p62, an autophagy-related tagging protein, after autophagy inhibition) and a 4.6 – 45.1 % increased release of TNF, IL-6/10/1beta/8 after LPS exposure in ‘high risk’ patients compared to ‘low risk’ patients. Finally, preliminary data show an augmented LPS-induced cytokine release with increasing risk alleles in: <italic>ATG16L1, IRGM, XBP1 or NOD2</italic>.</p><p><bold>CONCLUSION:</bold> Our data suggest, for the first time, that blood-myeloid cells from CD patients typically show a more severe LPS-induced cytokine response which correlates with a decreased capacity to deal with ER stress. Our study also highlights that the burden of risk alleles in these pathways or in individual Crohn’s susceptibility genes (<italic>ATG16L1, IRGM, XBP1 or NOD2</italic>) might positively correlate with the LPS-induced cytokine response and the autophagic rate.</p><p><bold>Disclosure of Interest</bold>: K. Nys: None Declared, E. Hoefkens: None Declared, I. Cleynen: None Declared, P. Rutgeerts Financial support for research from: UCB Pharma, Abbvie, Janssen Biologics, Merck, Prometheus, Lecture fee(s) from: Abbvie, Merck, Consultancy for: Amgen, Merck, UCB Pharma, Genentech, BMS, Abbvie, Janssen Biologics, Millenium, Neovacs, Actogenics, Prometheus, P. Agostinis: None Declared, S. Vermeire Financial support for research from: UCB Pharma, MSD, Abbvie, Lecture fee(s) from: Abbvie, Merck, Ferring, UCB Pharma, Centocor, Consultancy for: UCB Pharma, AstraZeneca, Ferring, Abbvie, Merck, Ferring, Shire, Pfizer</p><p><bold>Keywords:</bold> autophagy, Crohn's disease, ER stress, inflammation</p></sec><sec><title></title><p><bold>TUESDAY, OCTOBER 15, 2013 14:00-15:30</bold></p><p><bold>Pancreatic cancer: Pre-clinical models – Salon 11/12</bold></p></sec><sec><title>OP294 VARIATION IN PRECURSOR LESIONS OF PANCREATIC CANCER AMONG HIGH-RISK GROUPS</title><p><bold>T. P. Potjer</bold><sup>1,*</sup>, I. Schot<sup>2</sup>, P. Langer<sup>3</sup>, J. T. Heverhagen<sup>4</sup>, M. N. Wasser<sup>5</sup>, E. P. Slater<sup>3</sup>, G. Klöppel<sup>6</sup>, H. M. Morreau<sup>7</sup>, B. A. Bonsing<sup>8</sup>, W. H. de Vos tot Nederveen Cappel<sup>9</sup>, M. Bargello<sup>3</sup>, T. M. Gress<sup>10</sup>, H. F. Vasen<sup>2</sup>, D. Bartsch<sup>3</sup></p><p><italic><sup>1</sup>Department of Clinical Genetics, <sup>2</sup>Department of Gastroenterology & Hepatology, Leiden University Medical Center, Leiden, Netherlands, <sup>3</sup>Department of Surgery, <sup>4</sup>Department of Radiology, Philipps University Marburg, Marburg, <sup>5</sup>Department of Radiology, Leiden University Medical Center, Leiden, <sup>6</sup>Institute of Pathology, Consultation Center for Pancreatic and Endocrine Tumors, Technical University Munich, Munich, Germany, <sup>7</sup>Department of Pathology, <sup>8</sup>Department of Surgery, Leiden University Medical Center, Leiden, <sup>9</sup>Department of Gastroenterology & Hepatology, Isala Clinics, Zwolle, Netherlands, <sup>10</sup>Department of Gastroenterology & Hepatology, Philipps University Marburg, Marburg, Germany</italic></p><p><bold>INTRODUCTION:</bold> Pancreatic ductal adenocarcinoma (PDAC) surveillance programs are currently offered to high-risk individuals aiming to detect precursor lesions or PDAC at an early stage. We assessed differences in frequency and behavior of precursor lesions and PDAC between two high-risk groups.</p><p><bold>AIMS&METHODS:</bold> Individuals with a p16-<italic>Leiden</italic> germline mutation (N=116; median age 54 years) and individuals from familial pancreatic cancer (FPC) families (N=125; median age 47 years) were offered annual surveillance by MRI and magnetic resonance cholangiopancreatography (MRCP) with or without endoscopic ultrasound (EUS) for a median surveillance period of 34 months (0–127 months) or 36 months (0–110 months), respectively. Detailed information was collected on pancreatic cystic lesions detected on MRCP and precursor lesions in surgical specimens of patients who underwent pancreatic surgery.</p><p><bold>RESULTS:</bold> Cystic lesions were more common in the FPC cohort (42% vs. 16% in p16-Leiden cohort), whereas PDAC was more common in the p16-<italic>Leiden</italic> cohort (7% vs. 0.8% in FPC cohort). Intraductal papillary mucinous neoplasm (IPMN) was a common finding in surgical specimens of FPC-individuals, and was only found in two patients of the p16-<italic>Leiden</italic> cohort. In the p16-<italic>Leiden</italic> cohort, a substantial proportion of cystic lesions showed growth or malignant transformation during follow-up, whereas in FPC individuals most cystic lesions remain stable.</p><p><bold>CONCLUSION:</bold> In p16-<italic>Leiden</italic> mutation carriers, cystic lesions have a higher malignant potential than in FPC-individuals. On the basis of these findings, a more intensive surveillance program may be considered in this high-risk group.</p><p><bold>Contact E-mail Address:</bold><email>t.p.potjer@lumc.nl</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> CDKN2A-gene, familial pancreatic carcinoma, magnetic resonance cholangiopancreatography, Pancreatic ductal adenocarcinoma, precursor lesions, surveillance</p></sec><sec><title>OP295 SNAIL BYPASSES SENESCENCE AND ACCELERATES TUMOR PROGRESSION IN A KRAS-DRIVEN MOUSE MODEL OF PANCREATIC CANCER</title><p><bold>M. C. Paul</bold><sup>1,*</sup>, B. M. Walter<sup>1</sup>, B. Seidler<sup>1</sup>, A. Schnieke<sup>2</sup>, G. Schneider<sup>1</sup>, R. M. Schmid<sup>1</sup>, D. Saur<sup>1</sup></p><p><italic><sup>1</sup>II. Medizinische Klinik, Klinikum rechts der Isar der TU München, München, <sup>2</sup>Lehrstuhl für Biotechnologie der Nutztiere, TU München WZW Weihenstephan, Freising, Germany</italic></p><p><bold>INTRODUCTION:</bold> Pancreatic ductal adenocarcinoma (PDAC) is a life-threatening disease with 5 year survival rates below 3 percent. The transcription factor Snail plays a crucial role in epithelial-mesenchymal transition (EMT) and is overexpressed in PDAC. We investigated the role of Snail for pancreatic carcinogenesis, metastasis and EMT in a genetically engineered mouse model of PDAC.</p><p><bold>AIMS&METHODS:</bold> We generated a latent <italic>Snail</italic> allele silenced by a lox-stop-lox (LSL) cassette as a knock-in at the murine <italic>Rosa26</italic> locus (<italic>LSL-R26<sup>Snail/+</sup></italic>). Expression of Snail in the pancreas can be activated in this model using a pancreas specific Cre driver line (<italic>Ptf1a<sup>Cre/+</sup></italic>). To investigate the role of Snail during pancreatic carcinogenesis, the <italic>LSL-R26<sup>Snail/+</sup></italic> line was crossed into the established Kras<sup>G12D</sup> dependent PDAC model. Phenotypes were examined by macroscopic and microscopic pathological examination and molecular biology methods. Kaplan-Meier survival curves were used to compare the different compound mutant mice.</p><p><bold>RESULTS:</bold> Mice with pancreas specific Snail expression from one <italic>Rosa26</italic> allele (<italic>Snail<sup>KI/+</sup></italic>) exhibited normal development. Increasing gene dose by expressing Snail from both <italic>Rosa26 </italic>alleles (<italic>Snail<sup>KI/KI</sup></italic>) resulted in dramatic growth retardation, dedifferentiation of acinar cells and development of acinar cell carcinoma. In the context of concomitant Kras<sup>G12D</sup> expression, <italic>Kras;Snail<sup>KI/+</sup></italic> mice developed invasive PDAC. The median survival of these animals was shortened to 6 months compared to 16 months in <italic>Kras</italic> mice. Biallelic Snail expression in <italic>Kras;Snail<sup>KI/KI</sup></italic> mice led to a dramatic acceleration of PDAC formation and reduced median survival to 2 months. Interestingly, all PDAC from Snail-expressing mice showed a well differentiated morphology without signs of EMT or increased metastasis. Investigation of precursor lesions revealed acceleration of PanIN formation and progression due to bypass of senescence and increased PanIN proliferation.</p><p><bold>CONCLUSION:</bold> Snail expression accelerates pancreatic tumor progression in a gene dose dependent fashion by blocking senescence and inducing proliferation; however, it is not sufficient to induce overt EMT and metastasis of PDAC. Our findings provide new insights into Snail gene function as tumor promoter <italic>in vivo</italic>. Investigation of the underlying mechanisms will open potential novel therapeutic strategies for this life-threatening disease.</p><p><bold>Contact E-mail Address:</bold><email>mariel.paul@lrz.tum.de</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> EMT, PDAC, Senescence, Snail</p></sec><sec><title>OP296 SUPERPARAMAGNETIC NANOPARTICLES (MNPS) COUPLED TO PLK-1-SIRNA ARE REPRESENT A NOVEL TREATEMENT OPTION FOR PANCREATIC DUCTAL ADENOCARCINOMA IN MICE</title><p><bold>U. M. Mahajan</bold><sup>1,*</sup>, S. Teller<sup>1</sup>, M. Sendler<sup>1</sup>, T. Schwaiger<sup>1</sup>, L. I. Partecke<sup>2</sup>, G. Glöckl<sup>3</sup>, K. Aurich<sup>3</sup>, S. Hadlich<sup>4</sup>, F. U. Weiss<sup>1</sup>, J. P. Kühn<sup>4</sup>, M. M. Lerch<sup>1</sup>, J. Mayerle<sup>1</sup></p><p><italic><sup>1</sup>Department of Medicine A, <sup>2</sup>Department of visceral, thoracic and vascular surgery, University Medicine Greifswald, Ernst-Moritz-Arndt-University, <sup>3</sup>Institute of Pharmacy,, Ernst-Moritz-Arndt-University, <sup>4</sup>Institute of Radiology, University Medicine Greifswald, Ernst-Moritz-Arndt-University, Greifswald, Germany</italic></p><p><bold>INTRODUCTION:</bold> Pancreatic ductal adenocarcinoma is one of the most aggressive malignancies. Despite considerable knowledge about the cell biology and the genetic changes of malignant cells, therapeutic options for PDCA remain ineffective. One plausible explanation for the poor tumor response to therapy is an insufficient delivery of anticancer drugs to the tumour site. Superparamagnetic nanoparticles (MNPs) could serve a dual purpose: the delivery of antiproliferative substances to tumour cells and noninvasive assessment of this delivery in vivo by MRI. Here, we investigate the efficiency of the PLK-1 inhibitor BI6727 in comparison and in combination to capecitabine as well as the efficiacy and toxicity of nanoparticle-coupled PLK-1 siRNA.</p><p><bold>AIMS&METHODS:</bold> Animals were treated treated with BI6727, and/or Capecitabine in an orthotopic snygenic tumor model. MNPs were designed with a membrane translocation peptide (MPAP-) and with tumour selective peptides (EPPT-) to increase intracellular delivery and tumour specificity, respectively. Tumor growth was detected by small animal MRI. Animal survival as well as tumour proliferation, apoptosis, stroma composition and PLK-1 expression was evaluated.</p><p><bold>RESULTS:</bold> Weekly injections of the PLK-1 inhibitor BI6727 was as effective as daily feeding with capecitabine on survival of the animals, tumor size, tumor cell proliferation and apoptosis. BI6727/capecitabine treated tumors showed enlarged necrotic fields. Due to the therapy associated side effects of systemic treatment with the inhibitor, a target directed delivery method was established, using a MUC1 binding peptide overexpressed on pancreatic tumor cells. <italic>In vitro</italic> and <italic>in vivo </italic>experiments revealed significant accumulation of MNPs in pancreatic cancer as well as efficient protein silencing. PLK1 silencing resulted in a highly significant reduction in tumour size to less than 20% compared to controls in the absence of significant systemic side effects.</p><p><bold>CONCLUSION:</bold> Targeting the activity and expression of the cell cycle relevant protein PLK-1 is as efficient as treatment with capecitabine. Drug delivery via tumor directed nanoparticles can overcome systemic dose limitations. Therefore, tumor directed nanoparticles coupled to anti-tumorigenic substances are a promising tool for future treatment</p><p><bold>Contact E-mail Address:</bold><email>mayerle@uni-greifswald.de</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> pancreatic cancer, PLK-1 inhibitor BI6727, siRNA, Superparamagnetic nanoparticles (MNPs)</p></sec><sec><title>OP297 NEXT GENERATION MOUSE MODELS FOR SEQUENTIAL AND HOST SPECIFIC GENETIC MANIPULATION OF PANCREATIC CANCER</title><p><bold>N. Reiff</bold><sup>1,*</sup>, B. Seidler<sup>1</sup>, K. Gottschalk<sup>1</sup>, R. Rad<sup>1</sup>, R. M. Schmid<sup>1</sup>, G. Schneider<sup>1</sup>, D. Saur<sup>1</sup></p><p><italic><sup>1</sup>Klinikum rechts der Isar, TUM, München, Germany</italic></p><p><bold>INTRODUCTION:</bold></p><p>Genetically engineered Cre-loxP based mouse models have dramatically improved our understanding of pancreatic carcinogenesis. However, manipulating pancreatic cancer stem cells, modelling sequential multi-step carcinogenesis and selective targeting of host factors is impossible in these models.</p><p><bold>AIMS&METHODS:</bold> We aimed to generate a conditional mouse model for sequential gene (in)activation and targeting of different pancreatic compartments by combining two different recombination-systems, Flp-frt and Cre-loxP. To achieve Flp-dependent expression of oncogenic Kras<sup>G12D</sup> a G12D mutation and a 5’ frt-flanked stop cassette (FSF) were inserted into the endogenous <italic>Kras</italic> locus. Transgenic mice with <italic>Pdx1 </italic>promoter-driven Flp-expression were generated to activate oncogenic Kras<sup>G12D</sup> in the pancreas. For site and time-specific Cre-activation, two FSF silenced knock-in mouse strains were generated, which express a Tamoxifen-inducible CreER<sup>T2</sup> fusion protein in the Flp-lineage under the control of the ubiquitous <italic>CAG</italic> promoter or the proliferation marker PCNA.</p><p><bold>RESULTS:</bold> Pancreas-specific expression of Flp-recombinase was shown by a conditional alkaline phosphatase reporter strain (<italic>FSF-R26<sup>hpAP/+</sup></italic>). <italic>Pdx1-Flp;FSF-Kras<sup>G12D/+</sup></italic> double-transgenic animals develop PanIN lesions and pancreatic cancer similar to the <italic>Pdx1-Cre;LSL-Kras<sup>G12D/+</sup></italic> model. Flp-mediated recombination of the <italic>FSF</italic> cassette results in CreER<sup>T2</sup> expression selectively in Kras<sup>G12D</sup> positive pancreatic cells. Tamoxifen treatment allows sequential and site specific genetic manipulation of recombined cells in vitro and in vivo as shown by conditional activation of reporter genes (EGFP) or mutant p53.</p><p><bold>CONCLUSION:</bold> By means of this novel model we are for the first time able to 1) sequentially (in)activate genes in the pancreas, 2) manipulate pancreatic cancer subpopulations and, 3) target different pancreatic compartments and the host.</p><p><bold>Contact E-mail Address:</bold><email>nina.reiff@lrz.tum.de</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> dual recombination mouse model, PDAC</p></sec><sec><title>OP298 K-RAS-DEPENDENT SIGNALLING MODULATES THE ACTIVATION OF INFILTRATING MACROPHAGES ASSOCIATED WITH A DISTINCT MIRNA PROFILE IN PANCREATIC CANCER</title><p><bold>L. Muehlberg</bold><sup>1,*</sup>, B. Kuehnemuth<sup>1</sup>, H. Griesmann<sup>1</sup>, M. Buchholz<sup>1</sup>, T. M. Gress<sup>1</sup>, P. Michl<sup>1</sup></p><p><italic><sup>1</sup>Dept. of Gastroenterology, University of Marburg, Marburg, Germany</italic></p><p><bold>INTRODUCTION:</bold> Tumour-associated macrophages (TAM) play an important role in mediating tumour progression. In pancreatic cancer, infiltrating macrophages have been identified not only in invasive tumours, but also in early preinvasive pancreatic intraepithelial neoplasias (PanIN lesions) harbouring activating K-Ras mutations. Based on these observations, we hypothesized that, by modulating secreted effectors, K-Ras dependent signalling is able to influence the polarisation and transcriptional program of infiltrating macrophages, thereby facilitating tumorigenesis and tumour progression.</p><p><bold>AIMS&METHODS:</bold> To study the interaction between preinvasive pancreatic cells and macrophages in vitro, we used human macrophages differentiated from buffy coats which were cultured with conditioned media from the human pancreatic ductal epithelial cell line HPDE stably expressing constitutively active K-Ras or wild-type K-Ras. Established markers for classically (M1) or alternatively (M2) activated macrophages were investigated by FACS and qRT-PCR. Furthermore, a comprehensive analysis of coculture-dependent changes in miRNA expression levels was performed by using miRNA PCR profilers comprising 754 miRNA´s.</p><p><bold>RESULTS:</bold> Conditioned media of HPDE cells with constitutively active K-Ras led to a marked upregulation of established M2-markers in human macrophages such as CD206. In contrast, M1-markers such as CD197 or MHCII were not significantly altered, as assessed by FACS and qRT-PCR. miRNA profiling revealed a distinct set of miRNA´s up- or downregulated upon incubation with conditioned media of mutant or wild-type K-Ras-expressing HPDE cells. Interestingly, several of the miRNA´s upregulated by K-Ras have been implicated in tumour promotion and angiogenesis, whereas several miRNA´s downregulated by K-Ras have been described as tumour suppressive.</p><p><bold>CONCLUSION:</bold> The data suggest that activating K-Ras mutations in preinvasive pancreatic precursor lesions are able to trigger an alternatively activated phenotype in infiltrating macrophages, which is associated with a distinct miRNA profile facilitating tumour progression.</p><p><bold>Contact E-mail Address:</bold><email>michlp@med.uni-marburg.de</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> miRNA, pancreatic cancer, Tumor-associated macrophages</p></sec><sec><title>OP299 ANTIDROMIC NFATC1 AND P53 SIGNALING AT THE EDGE OF DIFFERENTIATION AND STEMNESS IN PANCREATIC CANCER</title><p><bold>S. Singh</bold><sup>1,*</sup>, N. Völker<sup>1</sup>, S. Vogt<sup>1</sup>, I. Esposito<sup>2</sup>, T. M. Gress<sup>1</sup>, V. Ellenrieder<sup>1</sup></p><p><italic><sup>1</sup>Division of internal medicine, Dept. of Gastroenterology, Philipps University of Marburg, Marburg, <sup>2</sup>Institut für Pathologie, Technische Universität München , Munich, Germany</italic></p><p><bold>INTRODUCTION:</bold> The current concept suggests a direct link between EMT and stemness induction in pancreatic cancer, thereby coupling cell motility and de-differentiation with self-renewal capacities and drug resistance. Both key features of cellular plasticity are controlled by distinct intracellular signaling and transcription pathways. We have shown that activation of the NFATc1 transcription factor promotes pancreatic cancer development and metastasis through its ability to integrate extrinsic stimuli into coordinated gene regulation.</p><p><bold>AIMS&METHODS:</bold> To assess whether NFATc1 controls transcription of EMT genes and stemness in PDAC, particularly upon p53 inactivation.We generated mouse strains with combined pancreas-specific expression of NFATc1, p53<sup>R172H</sup> and Kras<sup>G12D </sup>using Cre-Lox technology. These mice showed a highly aggressive tumor growth (median survival of <50 days). Mouse primary tumour cells were used to identify NFATc1 targets by gene expression profiling and pathway analyses (ChIP seq, miRNA analyses and GSEA). NFATc1 mediated EMT and stemness were assessed in human and murine pancreatic cancer models using migration and spheroid assay as well as xenograft mouse models.</p><p><bold>RESULTS:</bold> Here, we identified antidromic NFATc1 and p53 signaling pathways in transcriptional control over EMT and stemness. We show that p53 activation prevents cells from EMT in a miR200 dependent manner. However, disruption of the tumor suppressor pathway enables NFATc1/Sox2 chromatin complex formation and transcription of EMT programmes, resulting in highly invasive and metastatic PDACs. Finally, re-expression of miR200c or NFATc1 inactivation suppresses EMT/stemness genes and re-sensitizes PDAC to chemotherapy.</p><p><bold>CONCLUSION:</bold> Antidromic NFATc1 and p53 signaling pathways control key features of cellular plasticity and tumor progression at the level of gene transcription. These findings implicate key roles for NFATc1 in transcriptional regulation of differentiation and self-renewal in PDAC</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> drug resistance, EMT, metastasis, therapeutic development</p></sec><sec><title></title><p><bold>TUESDAY, OCTOBER 15, 2013 15:45-17:15</bold></p><p><bold>Video Cases – Hall 1</bold></p></sec><sec><title>OP300 FIRST SUCCESSFUL TRANSPLANTATION OF GASTRIC MUCOSA INTO THE OESOPHAGUS FOR STRICTURE PREVENTION AFTER ENDOSCOPIC SUBMUCOSAL DISSECTION (ESD) FOR EARLY ESOPHAGEAL SQUAMOUS CELL CARCINOMA</title><p><bold>J. Hochberger</bold><sup>1,*</sup>, E. Wedi<sup>2</sup>, P. Koehler<sup>3</sup>, M. Delvaux<sup>1</sup>, S. Gluer<sup>4</sup>, H. Niemann<sup>3</sup>, A. Hilfiker<sup>5</sup>, R. Rothstein<sup>6</sup>, E. Kruse<sup>7</sup></p><p><italic><sup>1</sup>Hepatogastroenterology, NHC, <sup>2</sup>Hepatogastroenterology, UNIVERSITY HOSPITAL OF Strasbourg, Strasbourg, France, <sup>3</sup>Animall Health, Friedrich Loeffler Institute, Mariensee, <sup>4</sup>Paediatric Surgery, St Bernward hospital, Hildesheim, <sup>5</sup>Rebirth DFG, Leibnitz Research Laboratory, Hannover, Germany, <sup>6</sup>Hepatogastroenterology, Darmouth College, Hannover, United States, <sup>7</sup>Hepatogastroenterology, St Bernward hospital, Hildesheim, Germany</italic></p><p><bold>INTRODUCTION:</bold> ESD allows <italic>en bloc</italic> resection of oesophageal superficial cancers with complete pathological examination of the specimen. However, oesophageal stricture is the major complication after resections involving > 75% of the circumference, requiring multiple dilations or stent placement. Previous approaches for prevention of such stenoses included transplantation of buccal or dermal cells as well as systemic or local steroid applications with limited clinical experience and uncertain outcomes. Following experiments of re-transplantation of gastric mucosal patches in pigs (approval NLVL33-42502-06/1151), we performed a first case of transplantation of gastric mucosa into the oesophagus in a patient treated for an oesophageal cancer by long circular ESD.</p><p><bold>AIMS&METHODS:</bold> Video case presentation</p><p><bold>RESULTS:</bold> In a 72 years old male patient admitted for dysphagia, OGD showed an early squamous cell carcinoma (Paris IIa; EUS UT1a, m, N0) involving >75% of the mucosal circumference in the cervical oesophagus 17-25 cm from teeth and confirmed by biopsies. In April 2011, during an EGD under general anaesthesia with tracheal intubation, an ESD was performed, removing a 10cm long tubular segment of oesophageal mucosa. After specimen retrieval, a 9×4cm patch of mucosa was removed by ESD from the gastric antrum and cut longitudinally in 3 stripes, which were attached to the denuded oesophageal wall by means of hemoclips and maintained by placement of a non-covered self-expanding metal stent to allow adhesion to the oesophageal wall and vascular nutrition. The oesophageal specimen showed a non-invasive low horny early squamous cell cancer (pT1a G2 L-,V-) and R0 resection . The stent was removed at day 20 despite areas of mucosal overgrowth through it. After stent removal, the oesophageal wall showed multiple islets of healthy gastric mucosa at the resection site. The patient was discharged on day 24 and further endoscopic controls showed progressive growth of the HP-negative antral mucosa and no stenosis.</p><p><bold>CONCLUSION:</bold> The so far unique case of a gastro-oesophageal endoscopic mucosal transplantation with 2 years follow-up after long ESD of an early oesophageal squamous cell cancer opens a new perspective for systematic research in this field.</p><p><bold>I declare that I will send the corresponding DVD/CD-ROM:</bold> Yes</p><p><bold>Contact E-mail address:</bold><email>juehochber@me.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> en bloc resection, mucosa transplantation, Oesophageal carcinoma, oesophageal stenosis</p></sec><sec><title>OP301 CLOSING A TRACHEOESOPHAGEAL FISTULA WITH ATRIAL SEPTAL DEFECT OCCLUDER</title><p><bold>J. C. Biasuz</bold><sup>1,*</sup>, T. A. Couto<sup>1</sup>, R. B. Villaça<sup>2</sup></p><p><italic><sup>1</sup>Unit of Gastroenterology, Hospital de Base do DF, <sup>2</sup>Unit of Gastroenterology, Hospital das Forças Armadas, Brasilia, Brazil</italic></p><p><bold>INTRODUCTION:</bold> Tracheoesophageal fistula is one of the known late complications of tracheostomy. Injury to the tracheal wall can occur because of high cuff pressure or direct mechanical trauma from the tracheostomy tube. Nowadays we have surgical treatment and endoscopic treatment with endoclips, hystoacril, stents. We report a case that we tried to close the fistula with endoclips for 3 times without success and then we used the Atrial Septal Deffect Occluder.</p><p><bold>AIMS&METHODS:</bold> The objective of this case is to show a new use for the Atrial Septal Deffect Occluder. The patient developed a tracheoesophageal fistula after long-period under mechanical ventilation.</p><p>He was ambulatory treated under conscious sedation. After locating the fistula using endoscopy, we placed a guidewire thru it. The self-expanding nitinol made occluder was delivered under direct endoscopic view over a loader wire into the fistula. We reviewed the Atrial Septal Deffect Occluder position in esophagus and in trachea.</p><p><bold>RESULTS:</bold> Patient was discharged right after the procedure. He started liquid diet in the same day and resumed soft diet on the next day. One week after that, the tracheostomy metal tube was removed. Thirty days followed-up he complained mild dysphagia for large solids. One year followed-up he stills with same mild dysphagia but he learned how to avoid it.</p><p><bold>CONCLUSION:</bold> Compared with surgery, this is easier and faster method to close a tracheoesophageal fistula. Other endoscopic treatments are available and can achieve the same results. We think it is a new kind of use for this device that is originally design to cardiovascular use.</p><p><bold>I declare that I will send the corresponding DVD/CD-ROM:</bold> Yes</p><p><bold>Contact E-mail address:</bold><email>jbiasuz@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> atrial septal defect occluder, endoscopy, tracheoesophageal fistula</p></sec><sec><title>OP302 EVIDENCE OF OESOPHAGEAL REGENERATION IN A HUMAN SUBJECT</title><p><bold>K. S. Dua</bold><sup>1,*</sup>, A. Aadam<sup>1</sup>, M. Gasparri<sup>2</sup>, A. Babaei<sup>1</sup>, W. Hogan<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology and Hepatology, <sup>2</sup>Surgery, MEDICAL COLLEGE OF WISCONSIN, Milwaukee, United States</italic></p><p><bold>INTRODUCTION:</bold> In animal models, researchers have successfully regenerated the oesophagus using a stent platform. It is not known if the human oesophagus has similar potentials to regrow.</p><p><bold>AIMS&METHODS:</bold> We present a unique case of oesophageal regeneration in a human.</p><p>A 24-year old quadriplegic patient presented with odynophagia, fever and chills. CT scan showed an eroding cervical spine meal plate with a pharyngeal-mediastinal abscess that completely destroyed a 5 cm long segment of the upper oesophagus. This resulted in direct communication between the hypopharynx and the mediastinum. At surgery, the metal plate was removed, abscess drained, and a percutaneous gastrostomy tube placed. As he was not a candidate for major immediate reconstructive surgery, he was referred to GI.</p><p>On endoscopy, after traversing the upper oesophageal sphincter (UOS), the mediastinum was seen where copious pus was visualized. No oesophageal tissue was identified. The remnant oesophagus was intubated retrogradely using a thin endoscope passed via the gastrostomy stoma. The endoscope was then retrogradely advanced into the mediastinum and then across the UOS into the mouth. The distance between the upper end of the remnant oesophagus and the UOS was 5 cm. Three covered expandable metal stents were deployed in a telescoped fashion with the upper end of the proximal stent positioned in the hypopharynx. Patient started tolerating liquid/soft diet and refused stent removal for fear of stricture/fistula formation. He presented 3.5 years later with new onset dysphagia secondary to granulation tissue. Stents were removed by initially ablating the granulation tissue with a snear and causing pressure necrosis using the stent-in-stent technique.</p><p><bold>RESULTS:</bold> After stent removal, the patient continued to tolerate an oral diet. Follow up endoscopy one year later revealed a normal appearing neo-oesophagus with stratified squamous epithelium. Endoscopic ultrasound showed normal 5-layer neo-oesophageal wall: mucosa, muscularis mucosa, submucosa, muscularis propria, and adventitia. On high-resolution impedance-manometry, peristaltic motility with bolus transit was noted. Patient did not cough during any of the 25 swallows evaluated. At 3 year follow up after stent removal (over 6 years after the initial presentation), the patient continues to eat per-orally.</p><p><bold>CONCLUSION:</bold> This case illustrates the potentials of the human oesophagus to regenerate. As observed in animals, we postulate that, while the stents maintained the morphology, progenitor myoblast from the broken oesophagus, granulation tissue, and recruitment of pluripotent cells may have contributed to this regeneration.</p><p><bold>I declare that I will send the corresponding DVD/CD-ROM:</bold> Yes</p><p><bold>Contact E-mail address:</bold><email>kdua@mcw.edu</email></p><p><bold>Disclosure of Interest</bold>: K. Dua Lecture fee(s) from: Boston Scientific, Other: Anti-reflux valve Cook Medicals, A. Aadam: None Declared, M. Gasparri: None Declared, A. Babaei: None Declared, W. Hogan: None Declared</p><p><bold>Keywords:</bold> oesophageal, Regeneration, Stenting</p></sec><sec><title>OP303 ENDOSCOPIC RESECTION OF HILAR PAPILLOMATOSIS AFTER WHIPPLE PROCEDURE FOR AMPULLARY ADENOMA</title><p><bold>R. Law</bold><sup>1,*</sup>, M. D. Topazian<sup>1</sup>, T. H. Baron<sup>1</sup></p><p><italic><sup>1</sup>Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, United States</italic></p><p><bold>INTRODUCTION:</bold> 73-year-old female presented for definitive treatment of biliary papillomatosis. Evaluation for acute pancreatitis in 2006 noted an ampullary adenoma with intraductal extension. She underwent Whipple procedure. Histology demonstrated adenomatous tissue with acute and chronic inflammation. In 2011, she was incidentally found to have abnormal liver chemistries. CT scan revealed intrahepatic bile duct dilatation; however, ERCP was unsuccessful due to altered anatomy. Percutaneous transhepatic cholangiography (PTC) showed a possible mass at the hilum but brushings were negative. Cholangioscopic biopsies (via PTC) demonstrated pyloric gland adenoma with acute and chronic inflammation and low grade dysplasia. The patient was offered surgery but declined. She was then referred to our institution for endoscopic intervention.</p><p><bold>AIMS&METHODS:</bold> The aim of our case was to provide endoscopic therapy to this patients biliary papilloma. The PTC catheters were injected with water-soluble contrast. Injection of the left catheter revealed a large left hepatic duct with a multilobulated filling defect at the bifurcation. An intraductal ultrasound probe placed over a guidewire demonstrated an echogenic lobulated polyp within the left hepatic duct. A single-balloon enteroscope was successfully passed into the afferent limb roughly 10cm distal to the hepaticojejunal anastomosis.The left guidewire was grasped with a snare and the snare was pulled from the tip of the endoscope through the anastomosis and out the percutaneous site. It could then be grasped on both sides. The scope was advanced through the hepaticojejunostomy into the common hepatic duct. The lesion was visualized and resected using a combination of snare polypectomy, retrieval basket, needle knife, and argon plasma coagulation.</p><p><bold>RESULTS:</bold> Following complete resection all guidewires were removed and internal drainage was unnecessary. No obstruction was evident endoscopically or cholangiographically. Histologic analysis was consistent with pyloric gland adenoma and no evidence of dysplasia was identified.</p><p><bold>CONCLUSION:</bold> -In patients with ampullary adenomas and intraductal extension, preoperative evaluation of the proximal biliary tree may be indicated to evaluate for additional lesions</p><p>-Direct endoscopic therapy to the proximal bile duct is feasible in patients with surgically-altered anatomy; however, advancement of the endoscope to the anastomosis remains challenging</p><p><bold>I declare that I will send the corresponding DVD/CD-ROM:</bold> Yes</p><p><bold>Contact E-mail address:</bold><email>law.ryan@mayo.edu</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> biliary papilloma, cholangioscopy, cholestasis</p></sec><sec><title>OP304 PURE TRANSGASTRIC NATURAL ORIFICE TANSLUMINAL ENDOSCOPIC SURGERY IN ADNEXAL PROCEDURES:THE FIRST HUMAN CASE REPORT</title><p><bold>B. Liu</bold><sup>1,*</sup>, X. Kong<sup>2</sup>, G. Cui<sup>1</sup>, J. Song<sup>1</sup></p><p><italic><sup>1</sup>Department of Gastroenterology and Hepatology, <sup>2</sup>Department of Gynaecology and Obstetrics, The Second Affiliated Hospital of Harbin Medical University, Harbin, China</italic></p><p><bold>INTRODUCTION:</bold> Natural orfice transluminal endoscopy surgery (NOTES) is an innovative procedure that represents a further evolvement of minimally invasive surgery. To date, pure transgastric NOTES for adnexal procedures has not been reported yet in human being, though some were carried out in animal experiments.</p><p><bold>AIMS&METHODS:</bold> This study aims to describ the first clinical application of pure transgastric NOTES for adnexal diseases and evaluate its feasibility, safety and efficiency.</p><p>On December 15, 2012, a 36-year-old female patient presented with the symptoms of vaginal bleeding 20 days and left lower abdominal pain 3 days. She has no history of abdominal surgery. The serum beta-human chorionic gonadotropin (β-hCG) was 547.23 mIU/ml(normal less than 5mIU/ml). Transvaginal ultrasonography confirmed the diagnosis with left fallopian tubal ectopic pregnancy and right simple ovarian cyst. A pure transgastric NOTES procedure was performed after approved by the hospital ethical committee. The operation process including: (1)Creation of gastric access by using PEG-like technique; (2)Establishing pneumoperitoneum with a 8 Fr drainage catheter which was placed on the right lower abdomen and connected to a laparoscopic insufflator; (3)Detection of bilateral adnexa: a superficial endometriosis lesion was occasionally found on the right ovarian surface and the left fallopian tubal ectopic pregnancy mass and right ovarian cyst were observed; (4)Cystotomy of the ovarian cyst with injection needle; (5)Electric cautery of the endometriosis lesion with coagrasper; (6)Salpingostomy and dissection of the ectopic pregnancy lesion from the tubal wall without laparoscopic assistance; (7)Removal of the lesion and observation of any remnant; (8)Closure of the gastric incision with endoclips and nylon loops under the help of extraction balloon.</p><p><bold>RESULTS:</bold> The ectopic pregnancy lesion was removed successfully with the size of 4.0cm×2.5cm. The patient did well postoperatively without any complications. The pain was relieved without any pain-killer. Temporary drainage of peritoneal cavity was withdrawn without any evidence of intraabdominal infection or bleeding. Serumβ-hCG returned to normal 3 day after operation. The histological examination confirmed the presence of chorionic villi in the specimen. Follow-up endoscopy on the 5<sup>th</sup> postoperative day showed well healing of the gastric incision.</p><p><bold>CONCLUSION:</bold> Pure transgastric NOTES is feasible, safe and effective in performing adnexal procedures in selected patients. Our initial case was successful with no complications, minimal pain and optimal cosmetic effect.</p><p><bold>I declare that I will send the corresponding DVD/CD-ROM:</bold> Yes</p><p><bold>Contact E-mail address:</bold><email>liubingrong@medmail.com.cn</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> adnexal diseases, Natural orfice transluminal endoscopy surgery, Pure NOTES, transgastric NOTES</p></sec><sec><title>OP305 RADIOFREQUENCY ABLATION: A NEW OPTION FOR TREATMENT OF REFRACTORY GASTRIC ANTRAL VASCULAR ECTASIA</title><p><bold>M. Camus</bold><sup>1,*</sup>, A. Repici<sup>2</sup>, P. Gonzalez<sup>3</sup>, S. Kantsevoy<sup>4</sup>, C. Fristrup<sup>5</sup>, D. Wengrower<sup>6</sup>, A. Carlino<sup>2</sup>, F. Pérez-Roldán<sup>3</sup>, T. Adar<sup>6</sup>, P. Rask<sup>7</sup>, P. Elbe<sup>8</sup>, S. Lecleire<sup>9</sup>, P. Marteau<sup>1</sup>, X. Dray<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology, Paris 7 University & APHP Lariboisière Hospital, Paris, France, <sup>2</sup>Istituto Clinico Humanitas, Milano, Italy, <sup>3</sup>Hospital General Mancha Centro, Alcazar de San Juan, Spain, <sup>4</sup>Mercy Medical Center, Baltimore MD, United States, <sup>5</sup>Odense University Hospital, Odense, Denmark, <sup>6</sup>Shaare Zedek Medical Center and Hebrew University Medical School, Jerusalem, Israel, <sup>7</sup>Aalborg Hospital, Aalborg, Denmark, <sup>8</sup>Karolinska Universitetssjukhus , Stockholm, Sweden, <sup>9</sup>Rouen University Hospital, Rouen, France</italic></p><p><bold>INTRODUCTION:</bold> Gastric antral vascular ectasia (GAVE) is a rare cause of chronic gastrointestinal bleeding, where endoscopic treatments often fail.</p><p><bold>AIMS&METHODS:</bold> Our aim was to evaluate the feasibility, efficacy and safety of radiofrequency ablation (RFA) for treatment of GAVE. Data from 8 European and 1 US centres were retrospectively collected. The Wilcoxon matched-pairs signed-ranks test was used to estimate the difference in response in the 6 months before and after RFA treatment.</p><p><bold>RESULTS:</bold> 18 patients were enrolled (12 female, aged 61 to 85). Underlying conditions included cirrhosis (7), chronic renal failure (2), diabetes (6), and Sjogren (1). 4 patients were treated with aspirin. 14 patients had received argon plasma coagulation (APC) treatment (1 to 24 sessions), 2 had bipolar electrocoagulation, 1 had cryotherapy. 10 patients had endoscopic signs of recent hemorrhage at initial endoscopy. RFA was performed with the Halo<sup>90</sup> ablation catheter and the HaloFlex system (Covidien), with a power varying between 12 and 15 J/cm<sup>2</sup>. Treatment was found technically easy by all users. Repeated withdrawal and re-introduction of the endoscope were needed to adjust the position of the probe and to repeat device applications in a circumferentially manner, until all areas of GAVE were treated. Patients received 2.2 ± 0.9 RFA sessions (range 1 to 4). 1 patient was referred for additional APC during follow-up. Mean estimated extent of gastric lesions treated was 93 ± 8 %. Duration of sedation for a RFA session was 37 ± 17 minutes. No complication was observed. Number of RBC packs significantly decreased from 7.2 ± 10.1 (range 0 to 47) in the 6 months before RFA treatment to 2.3 ± 6.1 (range 0 to 27) in the 6 months after RFA treatment (p<0.001). Among 16 patients who where tranfusion-dependent, 7 patients (44%) were off RBC transfusions. Lowest hemoglobin rate significantly increased from 7.0 ± 1.2 g/dL (range 5.0 to 9.6 g/dL) in the 6 months before RFA treatment to 10.2 ± 1.6 g/dL (range 6.4 to 14.2 g/dL) in the 6 months after RFA treatment (p<0.001).</p><p><bold>CONCLUSION:</bold> RFA allowed a complete treatment of GAVE in a safely and timely manner. RFA significantly decreased the need for RBC transfusions, and lead to a significant increase of the hemoglobin rate. A prospective evaluation of RFA as a first-line treatment of GAVE should be considered.</p><p><bold>I declare that I will send the corresponding DVD/CD-ROM:</bold> Yes</p><p><bold>Contact E-mail address:</bold><email>marine.camus@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Gastric antral vascular ectasia, radiofrequency ablation</p></sec><sec><title>OP306 SUBMUCOSAL ENDOSCOPIC TUMOR RESECTION FOR TREATMENT OF GI STROMAL TUMORS AT GASTRIC CARDIA</title><p><bold>P. Chiu</bold><sup>1,*</sup>, A. Teoh<sup>1</sup>, S. K. Wong<sup>1</sup>, E. K. Ng<sup>1</sup>, J. Y. Lau<sup>1</sup></p><p><italic><sup>1</sup>Department of Surgery, The Chinese University of Hong Kong, Hong Kong, Hong Kong</italic></p><p><bold>INTRODUCTION:</bold> Gastric submucosal tumors located at the cardia are notoriously difficult to treat, sometimes necessitate total gastrectomy. Endoscopic resection utilizing the principles of submucosal endoscopic tunneling can potentially treat submucosal tumors without inducing full thickness gastric perforation and avoid major surgical resection. This video will illustrate the techniques of submucosal endoscopic tumor resection at the gastric cardia.</p><p><bold>AIMS&METHODS:</bold> This is a prospective cohort study to examine the feasibility, safety and clinical outcomes of submucosal endoscopic tumor resection for treatment of gastric submucosal tumors at the cardia. Patients with gastric submucosal tumors of 10 to 40mm in size were recruited. Under general anesthesia, the location of submucosal tumor at cardia was identified upon endoscopy. The endoscope would then be withdrawn to the distal esophagus 5cm above the tumor with straight alignment to the tumor. A 2cm longitudinal mucosal incision was opened after adequate submucosal injection using triangle tip knife. A submucosal tunnel was developed in line to the cardia submucosal tumor. Dissection was performed around the submucosal tumor after positive identification. After complete dissection, the tumor would be retrieved through the mouth and the muscosal entrance would be closed by endoclips.</p><p><bold>RESULTS:</bold> From 2012 to 2013, 5 patients received submucosal endoscopic tumor resection for gastric submucosal tumors at cardia. There were 3 female and 2 male with a mean age of 50 years. The average operative time was 106.4 minutes, and the mean size of the tumors was 3.8cm<sup>2</sup>. All the submucosal tumors were successfully resected without conversion, and there was no major postoperative complication. The mucosal entrances were closed with an average of 5 endoclips. The average hospital stay was 2.4 days, and all the patients tolerated full diet 2 days after the surgery. The histopathology confirmed 3 cases of GIST, one leiomyoma and one case of ectopic pancreas with clear resection margins</p><p><bold>CONCLUSION:</bold> This study showed that submucosal endoscopic tumor resection is a feasible and safe approach for treatment of submucosal tumors less than 4cm in size at the gastric cardia. This approach will avoid major surgical resection and difficulties when treating submucosal tumors at the cardia.</p><p><bold>I declare that I will send the corresponding DVD/CD-ROM:</bold> Yes</p><p><bold>Contact E-mail address:</bold><email>philipchiu@surgery.cuhk.edu.hk</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> endoscopic resection, submucosal endoscopy, Submucosal tumor</p></sec><sec><title>OP307 HEMOSTATIC POWDER FOR THE TREATMENT OF ACUTE BLEEDING FROM DUODENAL VARICES.</title><p><bold>M. Ibrahim</bold><sup>1,2,*</sup>, A. El-Mikkawy<sup>1</sup>, I. Mostafa<sup>1</sup>, J. Deviere<sup>2</sup></p><p><italic><sup>1</sup>Department of Gastroenterology and hepatology, Theodor Bilharz Research Institute, Cairo, Egypt, <sup>2</sup>Gastroenterology & Hepato-Pancreatology, ERASME HOSPITAL UNIVERSITÉ LIBRE DE BRUXELLES, Brussels, Belgium</italic></p><p><bold>INTRODUCTION:</bold> Bleeding from ectopic varices is rare. However, once the bleeding starts, it becomes difficult to control and is sometimes fatal. Moreover, treatment may be technically challenging and treatment failures are reported in 10-15% of the cases.</p><p>An hemostatic powder (Hemospray - Cook Medical, Winston-Salem, North Carolina, USA) has recently been introduced for management of non variceal upper GI bleeding and was shown effective in preliminary studies for managing peptic ulcer bleeding, cancer related bleeding or temporizing uncontrollable bleeding in severe situations.</p><p><bold>AIMS&METHODS:</bold> We are presenting two patients with ruptured duodenal varices was successfully controlled by hemostatic powder. After identification of a bleeding site, the hemostatic powder was administered, the catheter being initially located two cm proximal to site of bleeding and the powder being delivered all over the bleeding site, the bleeding site was observed for 5 minutes under endoscopy. After successful hemostasis had been achieved, standard medical therapy for variceal bleeding was continued in the form of continuous infusion of somatostatine and institutional standard of care. Oral food and fluid were withheld from the patient for 24 hours. Patients were closely monitored for signs of recurrent bleeding for maximum of 24 hours post procedure. A second endoscopy was performed within 24 hours after initial therapy with hemostatic powder for control and possible further endoscopic therapy.</p><p><bold>RESULTS:</bold> Patients were discharged 2 days after the procedure with standards of follow up. Patients were contacted by phone at 15 days post procedure to record the occurrence of any serious adverse event or complications that might be related to the use of Hemospray. No major adverse events (e.g. embolization, bowel obstruction, allergic reaction) were observed. No mortality was reported for all those patients over 15 days follow-up.</p><p><bold>CONCLUSION:</bold> Hemospray is a safe, easy to use and effective therapeutic option to control haemorrhage from ectopic varices.</p><p><bold>I declare that I will send the corresponding DVD/CD-ROM:</bold> Yes</p><p><bold>Contact E-mail address:</bold><email>mostafa.ibrahim@me.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> DUODENAL VARICES., HEMOSTATIC POWDER</p></sec><sec><title>OP308 CLINICAL CASE REVIEW OF A NOVEL COLONOSCOPE: FULL SPECTRUM ENDOSCOPY</title><p><bold>I. M. Gralnek</bold><sup>1,2,*</sup>, P. D. Siersema<sup>3</sup>, O. Segol<sup>4</sup>, A. Suissa<sup>5</sup>, Z. Halpern<sup>5</sup></p><p><italic><sup>1</sup>Gastroenterology, RAMBAM HEALTH CARE CAMPUS, <sup>2</sup>Rapaport Faculty of Medicine, TECHNION-ISRAEL INSTITUTE OF TECHNOLOGY, Haifa, Israel, <sup>3</sup>Utrecht University Medical Center, Utrecht, Netherlands, <sup>4</sup>Carmel Medical Center, <sup>5</sup>Rambam Health Care Campus, Haifa, Israel</italic></p><p><bold>INTRODUCTION:</bold> This video case series highlights the clincal utilization of novel Full Spectrum Endoscope (FUSE). Standard colonoscopy techniques were utilized for multicenter tandem study including scope advancement, cecal & terminal ileum intubation, right colon and rectal vault retroflexion and polypectomy are shown utilizing the Fuse Colonoscope.</p><p><bold>AIMS&METHODS:</bold> Multi-Center Tandem Study</p><p><bold>Study Aims:</bold></p><p>Multicenter tandem study (N=185)</p><p>Sites performed back-to-back tandem colonoscopies to compare Traditional Forward View (TFV) colonoscopy to Fuse Colonoscopy: Measured endpoints include: 1. The additional number of polyps and adenomas found using Fuse colonoscopy; 2. The polyp and adenoma miss rates for both TFV colonoscopy and Fuse colonoscopy.</p><p>Randomized (computer generated, block design, concealed allocation); Tandem colonoscopy design; Same day, back-to- back colonoscopies - same endoscopist; Olympus 160 or 180 series (170° forward view) vs. Fuse 330°; January 2012 - March 2013; Multicenter, 6 sites - Israel (3) The Netherlands (1) USA (2).</p><p>Inclusion criteria: Subjects: 18 - 70 years old; Colonoscopy performed for: CRC screening, polyp surveillance, diagnostic evaluation. Exclusion criteria: History of colonic resection; History of IBD; History of polyposis syndrome; Suspected colonic stricture, diverticulitis or toxic megacolon; History of radiation therapy to abdomen or pelvis; Acute lower GI bleeding.</p><p><bold>RESULTS: Multicenter Tandem Study Results N=185:</bold><table-wrap id="table45-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1"></th><th rowspan="1" colspan="1"><bold>Adenoma Miss Rate</bold></th><th rowspan="1" colspan="1"><bold>Additional Adenomas Detected</bold></th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">Traditional Forward View (TFV)</td><td rowspan="1" colspan="1">41.7% </td><td rowspan="1" colspan="1">8.2%</td></tr><tr><td rowspan="1" colspan="1">Fuse™</td><td rowspan="1" colspan="1">7.6%</td><td rowspan="1" colspan="1">71.4%</td></tr><tr><td rowspan="1" colspan="1">P-Value</td><td rowspan="1" colspan="1"><.0001</td><td rowspan="1" colspan="1"><.0001</td></tr></tbody></table></table-wrap></p><p><bold>CONCLUSION:</bold> - As compared to traditional forward viewing colonoscopy, Fuse Colonoscopy found significantly more polyps and adenomas.</p><p> - As compared to traditional forward view colonoscopy, Fuse Colonoscopy had a significantly lower adenoma miss rate.</p><p><bold>I declare that I will send the corresponding DVD/CD-ROM:</bold> Yes</p><p><bold>Contact E-mail address:</bold><email>i_gralnek@rambam.health.gov.il</email></p><p><bold>Disclosure of Interest</bold>: I. Gralnek Consultancy for: EndoChoice, P. Siersema Consultancy for: EndoChoice, O. Segol: None Declared, A. Suissa: None Declared, Z. Halpern: None Declared</p><p><bold>Keywords:</bold> adenoma detection rate, colonoscopy, colonoscopy performance, new technique, Polyp Detection Rate</p></sec><sec><title>OP309 PERCUTANEOUS TRANSHEPATIC RETRIEVAL OF A DISPLACED BILIARY STENT</title><p><bold>V. Huberty</bold><sup>1,*</sup>, M. Ibrahim<sup>1</sup>, A. Vandermeeren<sup>1</sup>, J. Deviere<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology department, Hopital Erasme, Brussels, Belgium</italic></p><p><bold>INTRODUCTION:</bold> Percutaneous transhepatic cholangiography is a difficult method to reach the bile tract. It is usually performed when patients have surgically altered anatomy (no endoscopic access to the biliary tract) or Endoscopic Retrograde Cholangio-Pancreatography failure.</p><p>It allows therapeutics interventions including stent placement. Biliary stents are primarily introduced endoscopically whereas the percutaneous transhepatic technique is employed after endoscopic failure.</p><p>Proximal and distal stent displacement or migration is a rare complication, but there is a risk of considerable morbidity and mortality, so that the extraction of the prosthesis is recommended in these cases. Again, endoscopic removal is the approach of choice. However, in patients following hepaticojejunostomy or Bilroth II procedure an endoscopic retrieval cannot be performed for obvious technical reasons. Consequently, percutaneous transhepatic stent removal could be considered.</p><p><bold>AIMS&METHODS:</bold> We report a case of a successful outcome after retrievable biliary stent management in a patient with misplaced uncovered biliary expandable stent. A 68 years old man with a previous Pancreaticoduodenectomy intervention for a pancreatic adenocarcinoma was admitted with clinical and laboratory picture suggesting cholangitis. A Magnetic Resonance Imaging (MRI) shows tumour recurrence at the site of the anastomosis between common bile duct and jejunum.</p><p>A fully uncovered metal stent was inserted at the site of the stenosis. Unfortunately, the release of the stent was performed in free peritoneum due to a false path inside the tumour.</p><p><bold>RESULTS:</bold> After placement of an Internal-External biliary drain and three sessions of dilation, it was possible to extract the stent. We used a tooth-rat forceps of 5Fr inside an One Action Stent Introduction System (OASIS) of 10Fr via the epigastric approach accessing left hepatic duct.</p><p><bold>CONCLUSION:</bold> Endoscopic retrieval of biliary stents is the gold standard however ensuring a correct technique trans-hepatic removal is equally successful and safe, thus eliminating the risks of a surgical procedure.</p><p><bold>I declare that I will send the corresponding DVD/CD-ROM:</bold> Yes</p><p><bold>Contact E-mail address:</bold><email>vincent.huberty@erasme.ulb.ac.be</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> biliary stenting, percutaneous transhepatic cholangiography</p></sec><sec><title>OP310 EUS-GUIDED DRAINAGE OF LIVER ABSCESS USING A LUMEN-APPOSING METAL STENT</title><p>N. Alcaide Suarez<sup>1</sup>, A. L. Vargas Garcia<sup>1</sup>, <bold>I. Peñas Herrero</bold><sup>1,*</sup>, C. de la Serna Higuera<sup>1</sup>, P. Gil Simon<sup>1</sup>, M. Pérez Miranda<sup>1</sup></p><p><italic><sup>1</sup>Hospital Universitario Rio Hortega, Valladolid, Spain</italic></p><p><bold>INTRODUCTION:</bold> Percutaneous drainage is the treatment of first choice for hepatic abscess. If drainage is not possible, surgery may be necessary. EUS-guided drainage has been described as an alternative feasible, safe and useful. The Axios stent was designed to provide robust anchorage across nonadherent luminal structures. We describe a case of hepatic abscess managed by EUS-guided drainage with this stent.</p><p><bold>AIMS&METHODS:</bold> Our aim was to assess the feasibility and usefulness of EUS-guided drainage of hepatic abscess with an Axios stent.</p><p><bold>RESULTS:</bold> A 92-year-old man presented with cholangitis. ERCP was performed with incomplete removal of multiple choledocholithiasis. Two plastic biliary stents were inserted to attempt extraction at repeat ERCP. Two months later, the patient was admitted with relapsing cholangitis. CT demonstrated a 10-cm abscess in the left lobe of the liver (Fig 1). Intravenous antibiotic therapy was started and the patient underwent ERCP for stone clearance. During this procedure, an obvius bulge was observed on the gastric wall (fig 2). The liver abscess was visualized using a linear-array echoendoscope (fig 3) and it was decided to perform EUS-guided drainage through a transgastric approach. The abscess was punctured with a 19-gauge needle and a 0.035-inch guidewire was inserted within the abscess cavity. The transmural tract was dilated with an 6.5F cystotome and an 8-mm balloon dilation. A lumen-apposing stent was inserted over the guidewire, a fully-covered 10x10-mm Axios stent (X-lumena). 800 ml of pus drained and the cavity was irrigated with saline solution after dilation of the fistula. A double-pigtail stent was placed through the Axios stent to prevent flange impaction. There were no procedure-related complications. CT at 6 days revealed completed resolution of the abscess (figu 4). Culture grew Staphylococcus aureus. The transgastric stents were removed after 3 months and the patient remains asymptomatic at 6 months follow-up.</p><p><bold>CONCLUSION:</bold> This EUS-guided approach, similar to pancreatic pseudocyst drainage, might be preferable to percutaneous drainage for left-lobe liver abscesses.</p><p><bold>Contact E-mail Address:</bold><email>noelialcaide@hotmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> EUS-guided drainage, Liver abscess, Metal stent </p></sec><sec><title></title><p><bold>TUESDAY, OCTOBER 15, 2013 15:45-17:15</bold></p><p><bold>Inherited liver diseases – Hall Stockholm</bold></p></sec><sec><title>OP311 IMPACT OF ATP7B DEFICIENCY ON HEPATIC CHOLESTEROL METABOLISM AND ATHEROSCLEROTIC PLAQUE FORMATION IN ATP7B-/-MICE, AN ANIMAL MODEL FOR WILSON DISEASE</title><p><bold>W. Schirrmeister</bold><sup>1,2,*</sup>, D. Teupser<sup>3</sup>, D. Huster<sup>2,4</sup></p><p><italic><sup>1</sup>Department for Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Magdeburg, Magdeburg, <sup>2</sup>Institute of Medical Physics and Biophysics, University of Leipzig, Leipzig, <sup>3</sup>Institute for Laboratory Medicine, Ludwig-Maximilians-University Munich, Munich, <sup>4</sup>Department for Gastroenterology and Oncology, Deaconess Hospital Leipzig, Leipzig, Germany</italic></p><p><bold>INTRODUCTION:</bold> Wilson disease (WD) is a severe hereditary metabolic disease, which leads to copper accumulation in the liver and brain. WD is caused by mutations in the copper transporting P<sub>1</sub>-type ATPase ATP7B. The Atp7b<sup>-/-</sup>mouse is a suitable animal model to study hepatic copper accumulation and toxicity. In this model, copper accumulation leads to hepatic nekro-inflammation followed by regeneration and neoplastic proliferation. Recently an unexpected link between hepatic copper overload and cholesterol metabolism was uncovered. Copper accumulation alters gene expression and cholesterol biosynthesis in hepatocytes resulting in reduced liver and serum cholesterol.</p><p><bold>AIMS&METHODS:</bold> To further analyze these findings, Ldlr/Atp7b-DKO (double knockout) mice were generated and characterized. The Ldlr<sup>-/-</sup>(low density lipoprotein receptor) mouse is a widely used model for hypercholesterolemia and atherosclerotic plaque formation. After weaning at 4 weeks DKO and control mice were fed a cholesterol-enriched diet for 16 weeks. At 20 weeks mice were euthanized and blood, liver, heart, brachiocephalic artery (BCA) and aorta were removed. Serum lipids were quantified; histological analysis and microarray-based gene expression analysis were carried out in liver tissue. Atherosclerotic lesions were quantified in BCA and aortic root.</p><p><bold>RESULTS:</bold> In 20-week-old Ldlr<sup>-/-</sup>Atp7b<sup>-/-</sup>(DKO) mice expression of 9 genes involved in cholesterol biosynthesis was reduced, among them, the rate-limiting enzyme HMG-CoA-reductase (3,6fold down). The DKO mice had significantly reduced serum cholesterol levels (males: 3,79±1,56mmol/l; females: 2,74±1,23mmol/l) compared to Ldlr<sup>-/-</sup>Atp7b<sup>+/+</sup>controls (5,33±2,6mmol/l vs. 4,85±3,15mmol/l; p≤0,01). Moreover DKO mice showed significant lower hepatic steatosis compared to controls (controls 61,3% steatosis grade II+III; DKO 76,2% grade 0+I). Atherosclerotic plaque formation was significantly reduced in female DKO mice (71400±36500μm<sup>2</sup>) compared to female controls (143300±79000μm<sup>2</sup>).</p><p><bold>CONCLUSION:</bold> In conclusion, hepatic copper accumulation has direct impact on expression of genes of hepatic cholesterol metabolism accompanied by lower serum lipids, less liver steatosis and partial reduction of atherosclerosis. These new findings further underline the relevance of the new link between copper and lipid metabolism and are relevant for our understanding of the mechanisms of WD and may facilitate development of specific therapeutic strategies for hepatic WD.</p><p><bold>Contact E-mail Address:</bold><email>w.schirrmeister@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> atherosclerosis, Atp7b knockout mice, copper toxicity, liver, steatosis, Wilson Disease</p></sec><sec><title>OP312 DEVELOPMENT OF HEPATOCELLULAR CARCINOMA IN HEPATIC GLYCOGENOSIS DURING LONG-TERM FOLLOW-UP</title><p><bold>H. J. Jang</bold><sup>1,*</sup>, H. R. Yang<sup>1</sup>, J. S. Ko<sup>1</sup>, J. S. Moon<sup>1</sup>, J. Y. Jang<sup>1</sup>, J. K. Seo<sup>1</sup></p><p><italic><sup>1</sup>Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea, Republic Of</italic></p><p><bold>INTRODUCTION:</bold> Hepatic Glycogen Storage Disease(GSD) is an autosomal recessive disorder that leads to abnormal glucose metabolism and glycogen accumulation. It can have various complications such as hyperuricemia, hyperlipidemia, hypoglycemia, and failure to thrive. Hepatic adenoma and hepatocellular carcinoma(HCC) are the most severe and fatal complications.</p><p><bold>AIMS&METHODS:</bold> Among 70 patients who were diagnosed as GSD at Seoul National University Children's Hospital, 60 were GSD type I, 8 type III, 1 type IIa, and 1 type IV, respectively. 32 patients out of total developed hepatic adenoma at age range of 8-25 years(mean 14.0 years). Among the 32 patients of hepatic adenoma, 4 patients developed hepatocellular carcinoma on average interval of 9.0 years between the diagnosis of adenoma and HCC. 50 patients out of total underwent genetic analysis.</p><p><bold>RESULTS:</bold> Cases of HCC in GSD :</p><p><bold>CONCLUSION:</bold> There is very few study about malignant change of hepatic adenoma in GSD and about an adequate timing of liver transplantation as the ultimate curative therapy. The point of this case report is to suggest that early liver transplantation is beneficial before malignant change of hepatic adenoma and metastasis to other organs. Regular and meticulous follow-up of imaging study is needed for cancer surveillance and MRI is recommended rather than CT for pediatric patients. The tumor marker such as AFP is not a much help as an index of suspicion for HCC as shown in our cases. Further study is needed when to perform liver transplantation in GSD patients with hepatic adenoma and about the risk factors of malignant change.
<table-wrap id="table46-2050640613502899" position="float"><label>Table</label><caption><p>OP312</p></caption><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1"></th><th rowspan="1" colspan="1"><bold>Case 1</bold></th><th rowspan="1" colspan="1"><bold>Case 2</bold></th><th rowspan="1" colspan="1"><bold>Case 3</bold></th><th rowspan="1" colspan="1"><bold>Case 4</bold></th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1"><bold>Liver biopsy & Enzyme study</bold></td><td rowspan="1" colspan="1">GSD Ia</td><td rowspan="1" colspan="1">GSD Ia</td><td rowspan="1" colspan="1">GSD Ia</td><td rowspan="1" colspan="1">GSD Ia</td></tr><tr><td rowspan="1" colspan="1"><bold>Gene sequencing</bold></td><td rowspan="1" colspan="1">homozygote</td><td rowspan="1" colspan="1">compound heterozygote</td><td rowspan="1" colspan="1">not conducted</td><td rowspan="1" colspan="1">homozygote</td></tr><tr><td rowspan="1" colspan="1"><bold>Age of diagnosis</bold></td><td rowspan="1" colspan="1">6-year-old</td><td rowspan="1" colspan="1">4-year-old</td><td rowspan="1" colspan="1">9-year-old</td><td rowspan="1" colspan="1">8-year-old</td></tr><tr><td rowspan="1" colspan="1"><bold>Initial presenting symptom</bold></td><td rowspan="1" colspan="1">Abdominal distension</td><td rowspan="1" colspan="1">Hepatomegaly</td><td rowspan="1" colspan="1">Epistaxis</td><td rowspan="1" colspan="1">Hepatomegaly</td></tr><tr><td rowspan="1" colspan="1"><bold>Onset age of adenoma</bold></td><td rowspan="1" colspan="1">16-year-old</td><td rowspan="1" colspan="1">14-year-old</td><td rowspan="1" colspan="1">26-year-old</td><td rowspan="1" colspan="1">11-year-old</td></tr><tr><td rowspan="1" colspan="1"><bold>Interval to carcinoma</bold></td><td rowspan="1" colspan="1">15 years</td><td rowspan="1" colspan="1">8 years</td><td rowspan="1" colspan="1">10 years</td><td rowspan="1" colspan="1">3 years</td></tr><tr><td rowspan="1" colspan="1"><bold>AFP(ng/ml)</bold></td><td rowspan="1" colspan="1">normal</td><td rowspan="1" colspan="1">normal</td><td rowspan="1" colspan="1">normal</td><td rowspan="1" colspan="1">normal</td></tr><tr><td rowspan="1" colspan="1"><bold>Complication</bold></td><td rowspan="1" colspan="1">hyperuricemia, hyperlipidemia, lung metastasis of HCC</td><td rowspan="1" colspan="1">hyperuricemia, hyperlipidemia, lung & bone metastasis of HCC</td><td rowspan="1" colspan="1">hyperuricemia, hyperlipidemia, failure to thrive, HCC</td><td rowspan="1" colspan="1">hyperuricemia, hyperlipidemia, hypercalciuria, HCC</td></tr><tr><td rowspan="1" colspan="1"><bold>Management</bold></td><td rowspan="1" colspan="1">cornstarch, portocaval shunt, palliative chemotherapy</td><td rowspan="1" colspan="1">cornstarch, liver transplantation, palliative chemotherapy</td><td rowspan="1" colspan="1">cornstarch, portocaval shunt, palliative chemotherapy</td><td rowspan="1" colspan="1">cornstarch, portocaval shunt, liver transplantation</td></tr></tbody></table></table-wrap></p><p><bold>Contact E-mail Address:</bold><email>bearinspring@hotmail.com</email>,
<email>jkseo@snu.ac.kr</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> glycogen storage disease, hepatic adenoma, Hepatocellular cancinoma</p></sec><sec><title></title><p><bold>TUESDAY, OCTOBER 15, 2013 15:45-17:15</bold></p><p><bold>Controversies in oesophageal squamous cell cancer – Hall Prague</bold></p></sec><sec><title>OP313 FAMILIAL AGGREGATION OF ESOPHAGEAL SQUAMOUS CELL CARCINOMA -- A CASE-CONTROL STUDY IN A HIGH-RISK AREA OF CHINA</title><p><bold>M. Lu</bold><sup>1,*</sup>, T. Chen<sup>1</sup>, W. M. Ye<sup>2</sup>, The Fudan-Taizhou, CMC Institute of health scicene</p><p><italic><sup>1</sup>Clinical epidemiology , Qilu hospital of Shandong University, Jinan, China, <sup>2</sup>medical epidemiology and biostatistics, Karolinska Institutete, stockholm, Sweden</italic></p><p><bold>INTRODUCTION:</bold> The possibility of familial influence on esophageal squamous cell carcinoma (ESCC) has not been systematically investigated</p><p><bold>AIMS&METHODS:</bold> During Oct 2010 – Mar 2012, we conducted a population-based case-control study in Taixing of China, a high-risk area for ESCC, to investigate familial aggregation of ESCC through two approaches: 1)whether patients with ESCC have an increased likelihood of having a positive family history of cancer, and 2) whether the relatives of an affected individual have an increased risk of the disease. Detailed information of family history of cancer was collected by in-person interviews using a standard questionnaire. The data were analyzed using the unconditional logistic regression model for case-control design or Cox proportional hazards regression model for reconstructed cohort design. The cumulative risk of cancer was also estimated in 4646 and 5784 first-degree relatives of the cases and controls respectively by Kaplan-Meier method.</p><p><bold>RESULTS:</bold> 619 clinical and histopathologically confirmed newly diagnosed ESCC cases and 774 controls were finally analyzed.A positive family history of any cancer was reported by 54.9% of case subjects and 45.5% of control subjects. Excess ESCC risk was associated with a reported family history of any cancer (odds ratio [OR] =1.44, 95% confidence interval [CI]: 1.15-1.80, adjusted for age, sex, education, marriage, smoking, alcohol and family size) or digestive tract cancer (adjusted OR = 1.54, 95% CI: 1.23-1.93). Esophageal cancer was significantly more common in the first degree relatives of the cases than in those of the controls, (adjusted OR=1.83; 95%CI, 1.41-2.37). When the affected relative was a parent of the proband, the adjusted OR was 1.71 (95% CI, 1.26-2.31), and when it was a sibling, the adjusted OR was 2.39 (95% CI, 1.65-3.47). The relative risks of ESCC increased with increasing number of first-degree relatives with esophageal cancer. In particular, when both of the parents were affected a more than 9-fold excess risk was observed (adjusted OR=9.32; 95% CI, 2.07-42.06). In the reconstructed cohort study design, the cumulative risk of esophageal cancer at age 75 in the first degree relatives of cases was 14.1% <italic>versus</italic> 8.2% for the controls (hazard ratio, 1.92; 95% CI, 1.58-2.33). A total of 246 (5.3%) and 173 (3.0%) relatives of case and control subjects, respectively, were reported to have had a diagnosis of esophageal cancer.</p><p><bold>CONCLUSION:</bold> Our study suggests that familial factors are important in the etiology of ESCC. Whether the observed familial aggregation is due to shared genetic susceptibility or environmental exposures (or both) needs further studies.</p><p><bold>Contact E-mail Address:</bold><email>lvming@sdu.edu.cn</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> esophageal cancer, Family history, population-based, risk factor </p></sec><sec><title>OP314 SCHEDULED ENDOSCOPIC SURVEILLANCE AND MANAGEMENT OF METACHRONOUS SUPERFICIAL ESOPHAGEAL SQUAMOUS CELL CARCINOMA AFTER ESD</title><p><bold>Y. Nagami</bold><sup>1,*</sup>, M. Shiba<sup>1</sup>, Y. Fujiwara<sup>1</sup>, S. Sugimori<sup>1</sup>, T. Tanigawa<sup>1</sup>, T. Watanabe<sup>1</sup>, K. Tominaga<sup>1</sup>, T. Arakawa<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan</italic></p><p><bold>INTRODUCTION:</bold> Recently, endoscopic submucosal dissection (ESD) has become accepted due to its high quality control of the treatment for superficial esophageal squamous cell carcinoma (ESCC) without regional lymph node metastasis. However, the residual esophageal mucosa after ESD has maintained a high potential for the development of metachronous ESCC (MEC).</p><p><bold>AIMS&METHODS:</bold> The aim of this study was to evaluate whether scheduled endoscopic surveillance could control the development of MEC and efficacy of a repeat ESD for MEC.</p><p>Between May 2004 and December 2011, a total of 196 patients with 269 superficial ESCC underwent ESD in our hospital. Fifty-five patients who received chemotherapy, radiotherapy, chemoradiotherapy or esophagectomy were excluded. Consequently, 141 patients were enrolled in this study. Endoscopic surveillance using chromoendoscopy with iodine staining was scheduled at 2, 6, 12, and every 6 months after the initial ESD, and repeat ESD was performed when MEC was detected. We defined a second multiple cancers found at first endoscopic surveillance using chromoendoscopy with iodine staining after the initial ESD as synchronous ESCC and at after that as MEC. The cumulative incidence rates and long term outcome of MEC were calculated using Kaplen-Meier method.</p><p><bold>RESULTS:</bold> Of 141 patients, 115 and 26 patients had solitary ESCC and synchronous multiple ESCC at the initial ESD. MEC were detected in 16 (11.3%) patients among median follow up period of 824 (range 7- 2984) days. The median interval to detection of MEC after the initial ESD was 477 (range, 178-1746) days. The cumulative incidence rate of MEC at 1, 2 and 3 years was 4.9%, 9.9% and 16.2%, respectively. The incidence rate of MEC did not differ between solitary and synchronous ESCC at the initial ESD (Log Rank test p=0.81).</p><p> All patients underwent ESD with cancer free margin and no serious complications such as delayed bleeding and perforation were encountered. One patient with muscularis mucosae invasion and no lympho-vascular invasion was received additional chemoradiotherapy. There was no recurrence during the follow-up period of 1127 days in median and the survival rate was not significant difference with patients without MEC (Log Rank test <italic>p</italic>=0.28).</p><p><bold>CONCLUSION:</bold> MEC was detected in 11.3% of patients with ESD treatment for ESCC. Repeat ESD was effective for the management of MEC in patients with scheduled endoscopic surveillance.</p><p><bold>Contact E-mail Address:</bold><email>yasuaki1975@hotmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> ESD (endoscopic submucosal dossection), Squamous cell carcinoma</p></sec><sec><title></title><p><bold>TUESDAY, OCTOBER 15, 2013 15:45-17:15</bold></p><p><bold>Interactions between <italic>H.pylori</italic> and epithelial cells – Roof Garden</bold></p></sec><sec><title>OP315 AUTOPHAGY CAUSING CAGA DEGRADATION IS TRIGGERED BY CYTOPLASMIC ACCUMULATION OF LOW-DENSITY LIPOPROTEIN RECEPTOR-RELATED PROTEIN-1 (LRP1) IN GASTRIC EPITHELIAL CELLS INFECTED WITH <italic>H. PYLORI</italic></title><p><bold>H. Tsugawa</bold><sup>1,*</sup>, J. Matsuzaki<sup>1</sup>, S. Okada<sup>1</sup>, S. Fukuhara<sup>1</sup>, H. Mori<sup>1</sup>, T. Masaoka<sup>1</sup>, A. Sato<sup>2</sup>, H. Saya<sup>3</sup>, M. Hatakeyama<sup>4</sup>, T. Hirayama<sup>5</sup>, H. Suzuki<sup>1</sup></p><p><italic><sup>1</sup>Internal Medicine, Keio University School of Medicine, Tokyo, <sup>2</sup>Faculty of Pharmaceutical Sciences, Okayama University, Okayama, <sup>3</sup>Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, <sup>4</sup>Microbiology, Graduate School of Medicine, University of Tokyo, Tokyo, <sup>5</sup>Bacteriology, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan</italic></p><p><bold>INTRODUCTION:</bold><italic>Helicobacter pylori</italic> CagA acts as an oncoprotein by promoting the early events of gastric cancer development. We previously reported that although intracellular CagA could be degraded by autophagy in host gastric epithelial cells, its autophagic pathway was suppressed in CD44 variant 9-expressing gastric cancer stem-like cells due to their resistance to ROS, resulting in the specific accumulation of CagA in these cells (<bold><italic>Cell Host & Microbe</italic></bold>, 12:764, 2012). The autophagy causing CagA degradation was activated by VacA via binding to low-density lipoprotein receptor-related protein-1 (LRP1). We further demonstrated that not m2-type VacA (m2VacA) but m1-type VacA (m1VacA) induced the autophagy via binding to LRP1, which is a multifunctional member of the LDL receptor family and undergoes regulated intramembrane (ICD) proteolysis in a γ-secretase-dependent process. Although it is known that LRP1 have the ability to bind ligand to several signal transduction pathways, the role of the autophagy induction through LRP1 has remained unclear.</p><p><bold>AIMS&METHODS:</bold> The present study was conducted to examine LRP1-signal transduction to the autophagy. <bold>METHODS:</bold> The participation of LRP1-ICD in autophagy was assessed using a LRP1-siRNA, and the localization was assessed by western blot following subcellular fractionation and immunocytochemistry. LRP1-ICD binding protein was detected by silver-stained proteins following anti-LRP1-ICD antibody immunoprecipitation.</p><p><bold>RESULTS:</bold> Although LRP1-ICD was translocated to nucleus in AGS cells, LRP1-ICD was accumulated in cytoplasm by the repression of nuclear translocation in AGS cells at 15 hr after m1VacA-<italic>H. pylori </italic>infection (during the autophagy induction). The specific LRP1-knockdown in AGS cells using a LRP1-siRNA did not influence the levels of intracellular glutathione (GSH) and did not induce the autophagy, indicating that disappearance of nuclear LRP1-ICD was not required for autophagy. LRP1-ICD in AGS cells at 15 hr after m2VacA-<italic>H. pylori</italic> infection was not accumulated in cytoplasm. Accumulated LRP1-ICD in the cytoplasm of AGS cells at 15 hr after m1VacA-<italic>H. pylori</italic> infection bound to 35-kDa cytoplasmic protein, suggesting that the specific protein recruitment to cytoplasmic LRP1-ICD was important for this autophagy.</p><p><bold>CONCLUSION:</bold> Our findings indicate that 35-kDa cytoplasmic protein recruitment to cytoplasmic LRP1-ICD is important for the induction of autophagy, causing CagA degradation.</p><p><bold>Contact E-mail Address:</bold><email>h.tsugawa@a6.keio.jp</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> autophagy, Nano LC-MS/MS, VacA</p></sec><sec><title></title><p><bold>TUESDAY, OCTOBER 15, 2013 15:45-17:15</bold></p><p><bold>Interactions between H.pylori and epithelial cells – Roof Garden</bold></p></sec><sec><title>OP316 ALTERATION IN THE PATTERN OF DISTRIBUTION OF GASTRIC PARIETAL CELLS AND CELL PROLIFERATION IN GASTRIC CORPUS AFTER CHRONIC HELICOBACTER PYLORI INFECTION IN MONGOLIAN GERBILS</title><p><bold>M. Murakami</bold><sup>1,*</sup>, M. Fukuzawa<sup>1</sup>, T. Murakami<sup>2</sup>, K. Amagase<sup>2</sup>, K. Takeuchi<sup>2</sup></p><p><italic><sup>1</sup>Pharmacotherapy, Doshisha Women's College of Liberal Arts, Kyotanabe, <sup>2</sup>Kyoto Pharmaceutical University, Kyoto, Japan</italic></p><p><bold>INTRODUCTION:</bold> Parietal cell has the central role in the organization of gastric unit. In the atrophic gastritis, loss of parietal cells disorganizes gastric units leading to metaplastic gastric mucosa, which has increased risk of gastric malignancy. The characteristic form of H pylori induced mucosal injury is the loss of parietal cells and SPEM followed by the intestinal metaplasia. In H pylori infection, the niche of the organism is in the surface mucus on pit cells or parietal cells, and is close to the isthmus. It is reported that proliferation occurs only in units lacking parietal cells. However, the pattern and sequences of parietal cell loss after H pylori infection is unclear in terms of the proliferation of progenitor cells or stem cell in the isthmus.</p><p><bold>AIMS&METHODS:</bold> We investigated the sequence of parietal cell loss and studied proliferation pattern of gastric glandular units at 2, 8, 12 weeks, and at 2 years after infection of H pylori in Mongolian gerbils. The gerbils were fasted for 24 h before <italic>H. pylori</italic> inoculation, and drinking water was also withheld after the inoculation. A cagA- and vacA-positive strain of <italic>H. pylori</italic>, incubated in brain-heart infusion broth containing 10% fetal bovine serum at 37℃ overnight under a microaerophilic atmosphere, and H pylori was orally inoculated to each animal. Then, both food and water were freely available to the animals from 4 h after the inoculation.</p><p><bold>RESULTS:</bold> At early stage of infection, rapid diffuse parietal cell loss was observed in the lesser curvature side, but afterwards, atrophy of oxyntic gland progressed slowly. At the atrophic border zone, parietal cells and mucus cells were intermingled and staining of Ki67 were markedly increased after parietal cell loss, and the zone moved to the greater curvature side of the gastric corpus. Small amount of parietal cells were still observed at 2 years.</p><p><bold>CONCLUSION:</bold> The increase in the width of proliferative zone, which is represented by Ki67 positive cells, occurred in the area where parietal cells are replaced by non-parietal cell lineages. It is likely that parietal cell lineages are arrested at pre-parietal cell level after H pylori infection.These results shows that the animal model of oxyntic atrophy and cell proliferation is important for the study of parietal cell loss, which is crucial for the premalignant state of gastric mucosa.</p><p><bold>REFERENCES:</bold></p><p>1. Syder AJ et al. Proc Natl Acad Sci 2003:18; 100(6): 3467–3472</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> gastric, gerbil, Helicobacter, pylori</p></sec><sec><title></title><p><bold>TUESDAY, OCTOBER 15, 2013 15:45-17:15</bold></p><p><bold>IBD epidemiology: New insights – Hall Helsinki</bold></p></sec><sec><title>OP317 HIGH INCIDENCE OF CROHN'S DISEASE IN UPPSALA, SWEDEN - RESULTS FROM THE ICURE STUDY</title><p><bold>D. Sjöberg</bold><sup>1,*</sup>, T. Holmström<sup>2</sup>, M. Larsson<sup>3</sup>, A.-L. Nielsen<sup>3</sup>, L. Holmquist<sup>4</sup>, A. Ekbom<sup>5</sup>, A. Rönnblom<sup>6</sup></p><p><italic><sup>1</sup>Department of Medicine, Falu Hospital, Falun, Sweden, <sup>2</sup>Department of Medicine, Ålands Centralsjukhus, Mariehamn, Finland, <sup>3</sup>Department of Medicine, Mälarsjukhuset, Eskilstuna, <sup>4</sup>Department of Pediatrics, Akademiska sjukhuset, Uppsala, <sup>5</sup>Clinical epidemiology, Karolinska institute, Stockholm, <sup>6</sup>Department of Gastroenterology, Institution of Medical Science, Uppsala, Sweden</italic></p><p><bold>INTRODUCTION:</bold> Since the Montreal classification was presented, only a few population based studies regarding the natural history of Crohn's disease (CD) have been published. Meanwhile, the treatment of CD has changed dramatically with widespread and early use of azathioprine and anti-TNF alpha antibodies. As a result, there is hope that surgery rates för CD patients continue to drop.</p><p><bold>AIMS&METHODS:</bold> The aim of this study was to evaluate the current incidence, treatment and surgery rate of CD patients in the Uppsala region, Sweden, during the first year after diagnosis.</p><p>In Uppsala county data collecting began January 2005 and in the remaining counties Januari 2007. The study inclusion was closed December 2009. The population was 305 381 in 2005-2006 and 642 117 in 2007-2009. All CD patients were included in the study prospectively. Data regarding location, behaviour, medication and surgery was collected.</p><p><bold>RESULTS:</bold> A total of 264 patients were identified. The mean annual incidence was 9.9/100 000 inhabitants. The incidence for children under the age of 10 was 3.8 and for children under the age of 17 it was 10.0.
<table-wrap id="table47-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th colspan="2" rowspan="1">Location, n (%)</th><th rowspan="1" colspan="1"></th><th rowspan="1" colspan="1"></th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">L1: Ileal</td><td rowspan="1" colspan="1">73</td><td rowspan="1" colspan="1">(27.7)</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">L2: Colonic</td><td rowspan="1" colspan="1">129</td><td rowspan="1" colspan="1">(48.9)</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">L3: Ileocolonic</td><td rowspan="1" colspan="1">62</td><td rowspan="1" colspan="1">(23.5)</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">L4: Upper GI</td><td rowspan="1" colspan="1">47</td><td rowspan="1" colspan="1">(17.8)</td></tr><tr><td colspan="2" rowspan="1">Behaviour, n (%)</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">B1: Inflammatory</td><td rowspan="1" colspan="1">204</td><td rowspan="1" colspan="1">(77.3)</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">B2: Stenosing</td><td rowspan="1" colspan="1">34</td><td rowspan="1" colspan="1">(12.9)</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">B3: Penetrating</td><td rowspan="1" colspan="1">26</td><td rowspan="1" colspan="1">(9.8)</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">Perianal</td><td rowspan="1" colspan="1">27</td><td rowspan="1" colspan="1">(10.2)</td></tr></tbody></table></table-wrap></p><p>Patients with a complicated disease (B2 or B3) had significantly longer symtom duration before diagnosis compared to patients with pure inflammatory disease (p=0.0032). 79% were treated with systemic steroids, 42% with thiopurines and 11% with anti-TNF-alpha during the first 12 months.</p><p>12 patients (4.5%) were diagnosed at the time of surgery. A further 21 patients (8.0%) required surgery during the first 12 months. In a Cox regression analysis, age 40 years or older was associated with an increased risk of surgery (HR: 2.03, 95% CI: 1.01-4.08, p=0.0457). Both stricturating and penetrating disease were strongly associated with an increased risk for surgery (HR: 10.59, 95% CI: 3.84-29.23 and HR 36.55, 95% CI: 12.82-104.16, p<0.0001), whereas location was not.</p><p><bold>CONCLUSION:</bold> The incidence of CD in our region is one of the highest reported this far in Europe. The overall surgery rate during the first 12 months was 12.5%. Patients with complicated disease had longer symptom duration and of the total number of surgical procedures performed 36% were at the time of diagnosis. Old age, stricturing or penetrating disease were independent risk factors for surgery.</p><p><bold>Contact E-mail Address:</bold><email>daniel.sjoberg@ltdalarna.se</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> CROHN´S DISEASE, epidemiology</p></sec><sec><title>OP318 SMOKING IS THE KEY RISK FACTOR THAT DOUBLES THE RISK OF POSTOPERATIVE RECURRENCE OF CROHN’S DISEASE DESPITE PREVENTIVE DRUG TREATMENT. RESULTS FROM THE POCER STUDY</title><p><bold>P. De Cruz</bold><sup>1,*</sup>, M. Kamm<sup>1</sup>, A. Hamilton<sup>1</sup>, K. Ritchie<sup>1</sup>, S. Krejany<sup>1</sup>, A. Gorelik<sup>1</sup>, D. Liew<sup>1</sup>, L. Prideaux<sup>1</sup>, I. Lawrance<sup>1</sup>, J. Andrews<sup>1</sup>, P. Bampton<sup>1</sup>, M. Sparrow<sup>1</sup>, T. Florin<sup>1</sup>, P. Gibson<sup>1</sup>, H. Debinski<sup>1</sup>, R. Gearry<sup>1</sup>, F. Macrae<sup>1</sup>, R. Leong<sup>1</sup>, I. Kronborg<sup>1</sup>, G. Radford-Smith<sup>1</sup>, W. Selby<sup>1</sup>, M. Johnston<sup>1</sup>, R. Woods<sup>1</sup>, R. Elliott<sup>1</sup>, S. Bell<sup>1</sup>, S. Brown<sup>1</sup>, W. Connell<sup>1</sup>, P. Desmond<sup>1</sup></p><p><italic><sup>1</sup>St Vincent's Hospital and University of Melbourne, Melbourne, Australia</italic></p><p><bold>INTRODUCTION:</bold> Smoking, perforating disease and previous resection have been identified individually from retrospective cohort studies as factors associated with increased risk of earlier post-operative Crohn’s disease recurrence. We assessed prospectively whether these factors are associated with increased recurrence in the setting of optimal drug therapy.</p><p><bold>AIMS&METHODS:</bold> In this Post Operative Crohn’s Endoscopic Recurrence “POCER” study, after resection patients were stratified as high (smoker, perforating disease, ≥2nd operation) or low risk. All patients received 3 months metronidazole 400mg bd. High risk patients also received daily azathioprine 2mg/kg or 6 mercaptopurine 1.5mg/kg. High risk patients intolerant of thiopurine received adalimumab 40mg fortnightly. Patients were randomised 2:1 to colonoscopy at 6 months (“active care”) or no colonoscopy (“standard care”). Endoscopic remission was defined as Rutgeerts score i0 or i1 and recurrence as ≥i2. For endoscopic recurrence at 6 months low risk patients stepped up to thiopurine, high risk patients on thiopurine stepped up to adalimumab 40mg fortnightly, and high risk thiopurine-intolerant patients stepped up to weekly adalimumab. All patients were colonoscoped at 18 months, with primary end-point endoscopic recurrence at 18 months.</p><p><bold>RESULTS:</bold> 145 high risk (median age 38 years) & 29 low risk patients (median 36 years) were studied. Of high risk patients: 55 (38%) were current smokers, 101 (70%) had perforating disease and 50 (34%) had ≥1 prior resection. Smokers had an OR of 2.2 (95% CI 1.1-4.2; P=0.02) for recurrence at 18 months. Recurrence occurred in 24/38 (63%) of smokers in the active and 13/17 (76%) of smokers in the standard care arms (P=0.33). The OR for recurrence for previous resection and penetrating disease were 1.9 (1.0-3.8; P=0.06) and 0.9 (0.5-1.7; P=0.79) respectively. The OR for recurrence if >1 one risk factors was present was 2.8 (1.2-7.0; P=0.023) compared to 0 risk factors.</p><p><bold>CONCLUSION:</bold> Despite optimised drug therapy smoking doubles the risk of Crohn’s disease recurrence short term. The risk increases when more than one risk factor is present. These prospectively validated risk factors identify patients in whom more intensive preventive therapy may be warranted. Smoking should be discouraged vigorously.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Crohn's disease, Inflammatory bowel disease (IBD), Postoperative recurrence </p></sec><sec><title>OP319 RISK OF ADVERSE PREGNANCY OUTCOME AMONG WOMEN WITH INFLAMMATORY BOWEL DISEASE: A POPULATION BASED CASE-CONTROL STUDY</title><p><bold>A. Abdul Sultan</bold><sup>1,*</sup>, J. West<sup>1</sup>, T. Card<sup>1</sup></p><p><italic><sup>1</sup>University of Nottingham, Nottingham, United Kingdom</italic></p><p><bold>INTRODUCTION:</bold> Knowledge about adverse birth outcome and pregnancy related complications is useful when counselling pregnant women with inflammatory bowel disease (IBD). Limited population based data exist observing the association between IBD and pregnancy related complication and birth outcome however. This study therefore attempts to provide estimates of these complications and assess their variation by IBD type.</p><p><bold>AIMS&METHODS:</bold> We calculated the proportion of pregnancies in women with and without IBD between 1997 and 2010 throughout England using linked primary care Clinical Practice Research Datalink (CPRD) and secondary care Hospital Episode Statistics (HES) data. Risk of pregnancy complication (postpartum haemorrhage, pre-eclampsia and emergency caesarean section) and adverse birth outcome (pre-term birth, stillbirth and low birth weight) of women with IBD were compared to risks in women without IBD in terms of odds ratio (OR). The analysis was also stratified by ulcerative colitis (UC) and Crohn’s disease (CD).</p><p><bold>RESULTS:</bold> Of 250,793 singleton pregnancies resulting in live or stillbirths, 1 in 200 (0.5%) were in women with IBD. Pregnancy related complications occurred in 25.9% of pregnancies in women with IBD (of 22.4% of those without). The largest contributor to this composite measure was emergency caesarean section (16.6% vs 14.2%). There was also an increased risk of adverse birth outcomes with one or more occurring in 12.5% of pregnancies of mothers with IBD compared to 9.5% of controls. The largest contributor here was pre-term birth (9.4% vs 7%). The corresponding ORs are presented as table 1.</p><p><bold>Table 1: Pregnancy related complication and adverse birth outcome in women with IBD</bold><table-wrap id="table48-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1">Variable</th><th rowspan="1" colspan="1">IBD OR<sup>1</sup> (95%CI)</th><th rowspan="1" colspan="1">CD OR<sup>1</sup> (95%CI)</th><th rowspan="1" colspan="1">UC OR<sup>1</sup> (95%CI)</th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">Any one pregnancy relatedcomplication</td><td rowspan="1" colspan="1">1.18 (1.04-1.34)</td><td rowspan="1" colspan="1">1.20 (1.01-1.43)</td><td rowspan="1" colspan="1">1.14 (0.94-1.39)</td></tr><tr><td rowspan="1" colspan="1">Emergency Caesarean delivery</td><td rowspan="1" colspan="1">1.29 (1.10-1.52)</td><td rowspan="1" colspan="1">1.31 (1.04-1.64)</td><td rowspan="1" colspan="1">1.35 (1.06-1.71)</td></tr><tr><td rowspan="1" colspan="1">Pre-eclampsia/eclampsia</td><td rowspan="1" colspan="1">0.78 (0.51-1.18)</td><td rowspan="1" colspan="1">0.83 (0.47-1.47)</td><td rowspan="1" colspan="1">0.75 (0.39-1.46)</td></tr><tr><td rowspan="1" colspan="1">Postpartum haemorrhage</td><td rowspan="1" colspan="1">1.23 (1.03-1.46)</td><td rowspan="1" colspan="1">1.27 (0.99-1.62)</td><td rowspan="1" colspan="1">1.16 (0.88-1.53)</td></tr><tr><td rowspan="1" colspan="1">Any one adverse outcome</td><td rowspan="1" colspan="1">1.37 (1.15-1.64)</td><td rowspan="1" colspan="1">1.35 (1.06-1.72)</td><td rowspan="1" colspan="1">1.36 (1.03-1.81)</td></tr><tr><td rowspan="1" colspan="1">Low birth weight (<2500 grams)</td><td rowspan="1" colspan="1">1.25 (0.97-1.60)</td><td rowspan="1" colspan="1">1.41 (1.03-1.94)</td><td rowspan="1" colspan="1">1.04 (0.66-1.62)</td></tr><tr><td rowspan="1" colspan="1">Pre-term birth</td><td rowspan="1" colspan="1">1.37 (1.11-1.67)</td><td rowspan="1" colspan="1">1.30 (0.98-1.72)</td><td rowspan="1" colspan="1">1.38 (1.00-1.90)</td></tr><tr><td rowspan="1" colspan="1">Stillbirth</td><td rowspan="1" colspan="1">1.31 (0.70-2.45)</td><td rowspan="1" colspan="1">1.79 (0.84-3.74)</td><td rowspan="1" colspan="1">0.96 (0.31-2.97)</td></tr></tbody></table></table-wrap></p><p><sup>1</sup>Adjusted for smoking status, age and BMI</p><p><bold>CONCLUSION:</bold> Our results have demonstrated that women with IBD are more likely to develop pregnancy related complications and adverse birth outcome. A large proportion of these however can be medically determined (caesarean section and via induction pre-term birth), and so to what extent these associations are directly caused by IBD remains unclear.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> inflammatory bowel disease, pregnancy outcome</p></sec><sec><title>OP320 FERTILITY RATES IN WOMEN WITH INFLAMMATORY BOWEL DISEASE (IBD): A UNITED KINGDOM POPULATION-BASED COHORT STUDY</title><p><bold>L. Ban</bold><sup>1,*</sup>, L. J. Tata<sup>1</sup>, D. Humes<sup>1</sup>, L. Fiaschi<sup>1</sup>, T. Card<sup>1</sup></p><p><italic><sup>1</sup>Univerisity of Nottingham, Nottingham, United Kingdom</italic></p><p><bold>INTRODUCTION:</bold> Our objectives were to compare fertility rates in women with IBD to those in the general female population and to assess whether relative fertility was different before and after a clinical IBD diagnosis or bowel surgery for IBD.</p><p><bold>AIMS&METHODS:</bold> We included all women aged 15 to 44 years between 1990 and 2010 from a large United Kingdom primary care database. Women with IBD were defined as those with a clinical diagnosis of IBD in their medical records. Each woman was assigned an IBD diagnosis date corresponding to the date of the first record of IBD or the date of the first prescription of 5-aminosalicylic acid, whichever was earliest. We estimated overall and age-specific fertility rates by 5-year age bands as the number of live births per 1000 person-years for all women with IBD (and their subtypes Crohn’s disease (CD) and ulcerative colitis (UC)), using Poisson regression to compare these with rates in women without IBD adjusting for maternal age, smoking and socioeconomic status. Fertility rates in women with IBD were then calculated separately during the time before and after their diagnosis and also before and after bowel surgery (and specifically pouch surgery for women with UC).</p><p><bold>RESULTS:</bold> Fertility rates were 46.2 (95% confidence interval [95%CI] 44.6-47.9) and 49.3 (95%CI 49.2-49.5) live births per 1000 person-years in 9,639 women with IBD and 2,131,864 without IBD respectively (Adjusted Rate Ratio [ARR]=0.93, 95%CI 0.89-0.96). Age-specific fertility rates showed that the lower fertility rates in women with IBD were restricted to the 15-19 and 30-44 year age groups. Before diagnosis, relative fertility for women with IBD was similar to the general population (ARR=0.98, 95%CI 0.93-1.04), and was slightly higher for women with UC (ARR=1.07, 95%CI 0.99-1.16) but lower for women with CD (ARR=0.88, 95%CI 0.81-0.97). After diagnosis, the ARRs compared with women without IBD were 0.87 (95%CI 0.82-0.94) for women with CD and 0.92 (95%CI 0.86-1.00) for women with UC. Compared with women without IBD, fertility was also lower in women undergoing surgery for IBD (ARR=0.84, 95%CI 0.77-0.92) especially in women aged 30-39 years. In women with UC, fertility was particularly low after pouch surgery (rate=23.4 per 1,000 live births, 95%CI 12.2-45.0; ARR compared with women without IBD=0.48, 95%CI 0.23-0.99) but not before pouch surgery.</p><p><bold>CONCLUSION:</bold> Compared with women in the general population, women with IBD have decreased fertility. Fertility is further decreased following any surgical intervention for inflammatory bowel disease with absolute rates being lowest in those having pouch surgery.</p><p><bold>Contact E-mail Address:</bold><email>lu.ban@nottingham.ac.uk</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Epidemiology, Fertility, Inflammatory Bowel Diseases, Surgery</p></sec><sec><title>OP321 DRUG EXPOSURE AND RISK OF MICROSCOPIC COLITIS - A NATIONWIDE DANISH CASE-CONTROL STUDY WITH 5751 CASES</title><p><bold>O. K. Bonderup</bold><sup>1</sup>, T. Wigh<sup>2</sup>, M. Fenger-Grøn<sup>3,4</sup>, G. L. Nielsen<sup>5,*</sup></p><p><italic><sup>1</sup>Diagnostic Center, Regionalhospital Silkeborg, Silkeborg, <sup>2</sup>Medical department, Regional Hospital, Randers, <sup>3</sup>Research Unit for General Practice, Aarhus University, <sup>4</sup>Department of Clinical Epidemiology, Aarhus Universityhospital, Aarhus, <sup>5</sup>Medical department, Regionalhospital Himmerland, Farsø, Denmark</italic></p><p><bold>INTRODUCTION:</bold> Microscopic colitis includes a group of chronic bowel diseases characterized by chronic diarrhea in patients with a normal or near-normal mucosa at colonoscopy. The etiology of the disease is unknown but it has been reported that drug consumption can increase the risk of microscopic colitis.</p><p><bold>AIMS&METHODS:</bold> The aim was to explore the potential association between exposure to proton pump inhibitors (PPI), non-steroid anti-inflammatory drugs (NSAID), selective serotonin reuptake inhibitor (SSRI) and statins and the risk of microscopic colitis in a nationwide case-control study based on Danish national registries.</p><p>In a case-control study with randomly selected population based controls we included all patients with a recorded diagnosis of either collagenous colitis (CC) or lymphocytic colitis (LC) registered in the Danish Pathology Register during the period January 2005 to December 2011. As controls we identified 100 persons per case, matched on sex and age, randomly selected from the nationwide Danish Civil Registration System. For both cases and controls we registered drug exposure from the Danish Prescription Registry in a one-year period preceding the case index date. Crude and adjusted odds ratios of collagenous and lymphocytic colitis according to drug prescription were calculated</p><p><bold>RESULTS:</bold> The case group consisted of a total of 5751 patients, hereof 3474 (60%) with CC and 2277 (40%) with LC.</p><p>The observed OR between PPI and both CC (adjusted OR 7.04; 95% CI: 6.55-7.56) and LC (adjusted OR 3.37; 95% CI: 3.08-3.69) were highly significant, whereas the association between SSRI and LC (adjusted OR 2.89; 95% CI: 2.61-3.20) is weaker albeit significant. All other recorded associations were also statistically significant but with ORs well below 2.</p><p>Incorporating correction for increased endoscopic surveillance in our final model attenuated most of the associations between drug exposure and risk of microscopic colitis, but they remained significant in case of PPI and CC (adjusted OR 2.03; 95% CI: 1.77-2.33) and SSRI and LC (adjusted OR 1.77; 95% CI: 1.42-2.21)</p><p><bold>CONCLUSION:</bold> Our observations confirm the association between intake of PPI, NSAID, statin and SSRI and the diagnosis of microscopic colitis. However, further evaluation indicates a substantial impact of bias due to more intense endoscopic surveillance. A possible role of PPI exposure and development of collagenous colitis and also SSRI exposure and development of lymphocytic colitis should be further explored.</p><p><bold>Contact E-mail Address:</bold><email>okb@dadlnet.dk</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> drugs, etiology, Microscopic colitis</p></sec><sec><title>OP322 EPIDEMIOLOGY OF MICROSCOPIC COLITIS – A 10-YEAR NATIONWIDE DANISH COHORT STUDY.</title><p><bold>O. K. Bonderup</bold><sup>1,*</sup>, T. Wigh<sup>2</sup>, G. L. Nielsen<sup>3</sup>, M. Fenger-Grøn<sup>4,5</sup></p><p><italic><sup>1</sup>Diagnostic Center, Regionalhospital Silkeborg, Silkeborg, <sup>2</sup>Medical department, Regional Hospital, Randers, <sup>3</sup>Medical department, Regionalhospital Himmerland, Farsø, <sup>4</sup>Research Unit for General Practice, Aarhus University, <sup>5</sup>Department of Clinical Epidemiology, Aarhus Universityhospital, Aarhus, Denmark</italic></p><p><bold>INTRODUCTION:</bold> Microscopic colitis includes two types of colitis: collagenous colitis (CC) and lymphocytic colitis (LC). European and North American studies have investigated the epidemiology of microscopic colitis and found an increasing incidence during the period 1990 - 2000 (1,2). A recent study from US indicated a combined annual incidence of microscopic colitis of 19.7/100.000. Previous studies are mainly based on regional registries and we found it of interest to study the epidemiology based on a comprehensive nationwide cohort.</p><p><bold>AIMS&METHODS:</bold> In a nationwide cohort study based on Danish national registries to estimate the incidence and demographic data of microscopic colitis in Denmark during the period from 2002-2011. In addition, we wanted to study the trend incidence and demographic data during the ten-year period.</p><p>This registry study was based on the datasets covering the entire Danish population of around 5.4 mio. inhabitants. The cohort consisted s of all patients with a recorded diagnosis of either CC or LC registered in the Danish Pathology Register during the period January 2002 to December 2011. The <italic>Danish Pathology Register </italic>was established in 1990 and in 1997 it became a legal obligation for all departments of pathology in Denmark to report pathology data statements and the diagnoses were coded after a Danish version of the Systematized Nomenclature of Medicine (SNOMED). The data is used by the pathologists in the daily diagnostic process and covers all pathology data in Denmark</p><p><bold>RESULTS:</bold> The cohort consisted of a total of 7.777 patients, hereof 4.749 (61%) with CC and 3.028 (39%) with LC. In the 10-year period the annual incidence of diagnosed cases of CC increased from 2.9/100.000 to 14.9/100.000 and of LC from 1.7/100.000 to 9.8/100.000. There was no observed change in the distribution of CC and LC during the period. The female:male ratio was 3:1 for CC and 1.8:1for LC. The mean age at diagnosis was 67 years for CC and 64 years for LC. There was no change of female:male ratio or age of diagnosis during the 10-year period. The annual number of persons with registered colon-biopsies in the pathology register increased from 21.583 in 2002 to 39.733 in 2011 indicating an increased diagnostic activity.</p><p><bold>CONCLUSION:</bold> In a nationwide cohort study the incidence of CC and LC was increasing in a ten-year period from 2002 to 2011. A combined incidence of microscopic colitis of 24.7/100.000 in 2011was found. There was no change in the distribution of gender or age of diagnosis in the period. An increased diagnostic activity seems to explain the increase of diagnosed cases.</p><p><bold>REFERENCES:</bold></p><p>1. Olesen M, Eriksson S, Bohr J, et al. Microscopic colitis: a common diarrhoeal disease. An epidemiological study in Orebro,Sweden, 1993–1998. Gut 2004;53:346–350.</p><p>2. Pardi DS, Loftus EV Jr, Smyrk TC, et al. The epidemiology of microscopic colitis: a population based study in Olmsted County, Minnesota. Gut 2007;56:504–508.</p><p><bold>Contact E-mail Address:</bold><email>okb@dadlnet.dk</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> epidemiology, microscopic colitis</p></sec><sec><title></title><p><bold>TUESDAY, OCTOBER 15, 2013 15:45-17:15</bold></p><p><bold>Screening for colorectal cancer: The facts and the future – Hall 7</bold></p></sec><sec><title>OP323 FAECAL OCCULT BLOOD TEST ANALYSIS WITHIN THE UNITED KINGDOM BOWEL CANCER SCREENING PROGRAMME</title><p><bold>J. Geraghty</bold><sup>1,*</sup>, J. Snowball<sup>2</sup>, P. Butler<sup>2</sup>, S. Sarkar<sup>1</sup>, R. Blanks<sup>3</sup>, S. Halloran<sup>2</sup>, C. Rees<sup>4</sup></p><p><italic><sup>1</sup>Gastroenterology, Royal Liverpool University Hospital, Liverpool, <sup>2</sup>Bowel Cancer Screening Southern Programme Hub, University of Surrey, Guildford, <sup>3</sup>Cancer Epidemiology Unit , University of Oxford, Oxford, <sup>4</sup>Gastroenterology, South Tyneside NHS Foundation Trust, South Shields, United Kingdom</italic></p><p><bold>INTRODUCTION:</bold> Increased vascularity of colorectal neoplasia creates bleeding detected by Faecal Occult Blood tests (FOBt). As bleeding is sporadic & unevenly distributed within stools, multiple testing may be required. UK bowel cancer screening programme (BCSP) kits contain 6 windows & returning 5 or 6 positive results is termed “Abnormal” & referred to colonoscopy. If 1-4 windows are positive, the result is initially “Unclear” & 2 further kits are submitted, further positivity leads to colonoscopy (“Weak positive”). If no further blood is detected, subjects are deemed ”Normal” & retested in 2 years.</p><p><bold>AIMS&METHODS:</bold> To study FOBt positivity & if particular patterns are associated with neoplasia rates that indicate the screening algorithm should be changed. We selected all subjects from one area completing 2 screening episodes between 2007-9. Each episode included up to 3 kits and 18 windows. 95 possible combinations were identified. The number of positive windows compared to the total in a given episode was expressed as a “positivity ratio”, ranging from 0-100%. Each combination leading to colonoscopy was analysed. Abnormal (83-100% positivity) & Unclear (11-83% positivity) groups were matched to neoplasia detection rates. Subjects with cancer detected in episode 2 following an Unclear result in episode 1, had their episode 1 pattern analysed.</p><p><bold>RESULTS:</bold> FOBt from 284,387 subjects resulted in 4,000 colonoscopies, diagnosing 286 (7.1%) cancers. The rate was 21.3% in the Abnormal group and 5.8% in the Weak positive group. Cancer detection increased from 1.9-24.5% in linear correlation with increasing positivity of windows, ranging from 11-83% of windows positive. Equivalent percentage positivity rates may or may not lead to colonoscopy depending on the particular pattern. 4 positive windows in kit 1 followed by 2 normal kits (4NN) equates to a positivity rate of 22% & is currently categorised in the Normal group & doesn’t lead to colonoscopy. Other combinations with 22% window positivity lead to colonoscopy & a cancer detection rate of 3%. There were 260 subjects with a 4NN combination in episode 1 not leading to colonoscopy & 5 of these subsequently had cancers detected following different combinations in episode 2.</p><p><bold>CONCLUSION:</bold> This study demonstrates higher ratios of positive windows; detect higher rates of cancer. At present, in the UK some subjects with 11% positive windows proceed to colonoscopy, while others with a rate of 22% (all at kit 1) do not. Based on these findings, further work examining the entire BCSP population, including the costs & benefits of changing the algorithm is in progress.</p><p><bold>Contact E-mail Address:</bold><email>Colin.Rees@stft.nhs.uk</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> colorectal cancer, screening, associated factors, advanced neoplasm, adenoma, Faecal Occult Blood test (FOBt)</p></sec><sec><title>OP324 IMPACT ON MORTALITY AND SURVIVAL OF THE FIRST FOBT MASS COLORECTAL CANCER SCREENING ORGANIZED IN THE FINISTERE DISTRICT (FRANCE)</title><p><bold>C. Agnello</bold><sup>1</sup>, M. Cariou<sup>2</sup>, Y. Foll<sup>3</sup>, O. Pennec<sup>1</sup>, F. Cholet<sup>1</sup>, J.-B. Nousbaum<sup>1</sup>, M. Robaszkiewicz<sup>1,*</sup></p><p><italic><sup>1</sup>Gastroenterology, <sup>2</sup>Digestive Tumor Registry of Finistere, <sup>3</sup>ADEC 29, University Hospital, Brest, France</italic></p><p><bold>INTRODUCTION:</bold> Several trials have shown that screening for colorectal cancer (CRC) by fecal occult blood tests (FOBTs) can reduce CRC mortality. The objective of this study was to estimate the impact of the FOBT screening on the stage at diagnosis, CRC mortality and 5-years survival in a mass screening program from conducted between September 1<sup>st</sup> 2004 and September 1<sup>st</sup> 2006 in the Finistere district (France).</p><p><bold>AIMS&METHODS:</bold> All CRC diagnosed in individuals aged 50-74 years and registered in the database of the Finistere registry of digestive cancers were cross-referenced with the database of the Cancer Prevention Coordination Center (ADEC 29) to analyze their screening status.</p><p>During this period, all CRC diagnosed in the screening population were classified into three groups: screen-detected (203 CRC), screen-excluded for medical reasons (53 CRC) and individuals who had declined the screening, called non-responder (478 CRC). In each group 5-years survival was estimated using the Kaplan-Meier method. The log-rank test was used for univariable comparisons of time-to-event end points. End of follow-up date due to death or censoring was 1st September 2011.</p><p><bold>RESULTS:</bold> The distribution of cancer stages (I,II,III and IV) in the three group of CRC was respectively :</p><p>Screen Detected group : 40.9%, 24.1%, 22.6%, 12,4%</p><p>Screen Excluded group : 34.4%, 31.2%, 15.6%, 18.8%</p><p>Non responder group : 19.5%, 23.0%, 29.5%, 28.0%</p><p>CRC mortality was significantly lower in the screen-detected group (mortality rates : 0.23/1000) than the non responder group group (mortality rates : 0.44/1000).</p><p>The overall and specific cumulative survival rates in the three groups were :
<table-wrap id="table49-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1">Cumulative survival</th><th rowspan="1" colspan="1">Screen detected group</th><th rowspan="1" colspan="1">Screen-excluded group</th><th rowspan="1" colspan="1">Non responder group</th></tr><tr><th rowspan="1" colspan="1">rates</th><th rowspan="1" colspan="1">Overall / specific</th><th rowspan="1" colspan="1">Overall / specific</th><th rowspan="1" colspan="1">Overall / specific</th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">1 year</td><td rowspan="1" colspan="1">95.6% 95.8%</td><td rowspan="1" colspan="1">94.3% 97.9%</td><td rowspan="1" colspan="1">85.9% 87.3%</td></tr><tr><td rowspan="1" colspan="1">2 years</td><td rowspan="1" colspan="1">92.1% 93.6%</td><td rowspan="1" colspan="1">88.7% 91.5%</td><td rowspan="1" colspan="1">75.8% 77.8%</td></tr><tr><td rowspan="1" colspan="1">3 years</td><td rowspan="1" colspan="1">89.1% 92.0%</td><td rowspan="1" colspan="1">88.7% 91.5%</td><td rowspan="1" colspan="1">70.1% 72.9%</td></tr><tr><td rowspan="1" colspan="1">4 years</td><td rowspan="1" colspan="1">86.1% 89.3%</td><td rowspan="1" colspan="1">84.8% 87.1%</td><td rowspan="1" colspan="1">65.2% 69.8%</td></tr><tr><td rowspan="1" colspan="1">5 years</td><td rowspan="1" colspan="1">85.1% 88.8%</td><td rowspan="1" colspan="1">76.9% 80.4%</td><td rowspan="1" colspan="1">60.9% 67.1%</td></tr></tbody></table></table-wrap></p><p>The overall and specific survival curves were statistically different between the three groups (p < 0.0001).</p><p><bold>CONCLUSION:</bold> The mass CRC screening organized in the Finistere district allowed diagnosis of CRC at an earlier stage, with for corollary a CRC related mortality reduced by 47% and a 5-years specific survival increased by 21,7% in screen-detected group in comparison with non-responder population.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> colorectal cancer screening, mortality rate, Survival Rate</p></sec><sec><title>OP325 COMPARISON OF FECAL IMMUNOCHEMICAL TEST VS COLONOSCOPY IN FAMILIAL COLORECTAL CANCER SCREENING: A CONTROLLED RANDOMIZED TRIAL.</title><p><bold>E. Quintero</bold><sup>1,*</sup>, M. Carrillo Palau<sup>1</sup>, A. Z. Gimeno Garcia<sup>1</sup>, I. Alonso Abreu<sup>1</sup>, M. Hernandez Guerra<sup>1</sup>, D. Nicolás Pérez<sup>1</sup>, A. Jimenez<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology, University Hospital of Canary Islands, La Laguna, Spain</italic></p><p><bold>INTRODUCTION:</bold> Colonoscopy is empirically considered the gold standard screening test in familial colorectal cancer (FCC). However, sensitive fecal immunochemical tests (FIT) might be equally efficient for detecting advanced colorectal neoplasia (ACN: colorectal cancer or advanced adenoma).</p><p><bold>AIMS&METHODS: Aim:</bold> to compare the efficacy of FIT vs colonoscopy to detect ACN in FCC screening. <bold>Methods:</bold> This randomised controlled trial was carried out between January 2006 and December 2010. Asymptomatic first degree relatives (FDR) of colorectal cancer patients were allocated 1:1 to receive one-time colonoscopy vs annual FIT (OC-Sensor®, cut-off 50 ng Hb/ml). We hypothesized that FIT was equivalent to colonoscopy for detecting ACN. Assuming a prevalence of 7.7% for ACN in FCC, a participation rate to FIT 20% higher than that to colonoscopy, an ACN detection rate of 56.5% and 96.5% for FIT and colonoscopy, respectively with an equivalence margin of 0.03, a sample of 1464 FDR (732 in each study group) would provide a power of 80%.</p><p><bold>RESULTS:</bold> 1918 FDR aged 40-75 years (59% female, median age 51±10 years) of 972 index cases, were randomized to colonoscopy (n=952) vs FIT (n=966). Among them, 170 (16.5%) and 182 (19.1%) were excluded in the colonoscopy and FIT groups, respectively. In the FIT group 96.7% of FDR had a valid test, whereas in the colonoscopy group 97.9% had a complete colonoscopy. Overall, 61/724 (8.4%), 41/526 (7.8%) and 10/272 (3.7%) had a positive FIT in the first, second and third test, respectively. In the intention-to-screen analysis, ACN was detected in 28/784 (3.6%) and 41/782 (5.2%) FDR in the FIT and colonoscopy arms, respectively (OR 0.63, 95% CI [0.38-1.04], p=0.07). In the per-protocol analysis, 24/709 (3.4%) and 40/703 (5.7%) had ACN in the FIT and colonoscopy groups, respectively (OR 0.59, 95% CI [0.35-0.99], p=0.049). Considering the estimated difference in participation rate and the observed ACN detection rate, the absolute difference between both strategies did fall within the equivalence margin either in the intention-to-screen analysis (0.001, 95% CI [-0.0130 – 0.0149]) or in the per-protocol analysis (0.0004: 95% CI [-0.0142-0.0149]).</p><p><bold>CONCLUSION:</bold> Screening with annual FIT is equivalent to one-time colonoscopy to detect ACN in FCC. This strategy should be considered in countries with a higher compliance to FIT than colonoscopy. (ClinicalTrials.gov: NCT01075633).</p><p><bold>Contact E-mail Address:</bold><email>antozeben@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Colonoscopy, Familial colorectal cancer screening, Immunochemical faecal occult blood test</p></sec><sec><title>OP326 SELECTION OF HIGH RISK SUBJECTS FOR EARLY COLONOSCOPY IN COLORECTAL CANCER SCREENING USING ASIA PACIFIC COLORECTAL SCREENING SCORES: A STUDY FROM 10 ASIAN COUNTRIES</title><p><bold>J. J. Y. Sung</bold><sup>1,*</sup> on behalf of Asia Pacific Working Group on Colorectal Cancer, H. M. Chiu<sup>2</sup> on behalf of Asia Pacific Working Group on Colorectal Cancer, K.-L. Goh<sup>3</sup> on behalf of Asia Pacific Working Group on Colorectal Cancer and Asia Pacific Working Group on Colorectal Cancer</p><p><italic><sup>1</sup>Chinese University of Hong Kong, Shatin, Hong Kong, <sup>2</sup>National Taiwan University, Taipei, Taiwan, Province of China, <sup>3</sup>University of Malaya, Kuala Lumpur, Malaysia</italic></p><p><bold>INTRODUCTION:</bold> We have reported the Asia Pacific Colorectal Screening (APCS) score based on age, gender, family history and smoking is a useful tool in selecting asymptomatic Asian subjects for priority of colorectal screening.</p><p><bold>AIMS&METHODS:</bold> We set to conduct a prospective study to test the validity of APCS score in selecting high risk subjects for priority colonoscopy.</p><p>Asymptomatic subjects over the age of 18 years were included. The APCS using 4 parameters: 1. Age (score 0-3), 2. Gender (score 0-1), 3. Family history (score 0-2) and 4 Smoking (score 0-1) were applied. Subjects were classified into high-risk (score 4-7), moderate-risk (score 2-3) and low-risk (score 0-1). High-risk subjects were offered early colonoscopy (within 4 weeks) for colorectal screening. Moderate-risk and low-risk subjects were offered FIT. FIT positive subjects were also offered early colonoscopy. Low-risk and moderate-risk subjects with negative FIT were offered routine colonoscopy. Primary outcome of the study is to evaluate the effects of applying APCS in detecting advanced neoplasia in the colon.</p><p><bold>RESULTS:</bold> Up to the time of analysis, 3,915 subjects were enrolled from Hong Kong, Taiwan, Malaysia, Thailand, Australia, Pakistan, Singapore, Philippines, China and Brunei. There were 2,056 (52.5%) male and the mean age (SD) was 54.4 (11) years. Stratified by APCS, there were 940 subjects (24.0%) categorized as high-risk; 2,173 (55.5%) as moderate-risk and 802 (20.5%) as low-risk. There were 142 advanced neoplasia (AN) (excluding invasive cancer) and 14 invasive cancer (CA) found. Comparing the results of high-risk vs moderate or low-risk subjects, the detection of AN/CA was 8.2% vs 2.7% respectively (P<0.001). When combining the results of high-risk with FIT positive cases and compare against moderate or low-risk subjects with negative FIT, the detection of AN/CA was 8.9% vs 1.9% respectively (P<0.001).</p><p>Finding of advance neoplasia (AN) or invasive cancer (CA) by APCS and FIT
<table-wrap id="table50-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1"></th><th rowspan="1" colspan="1">APCS Low-risk</th><th rowspan="1" colspan="1">APCS Low-risk</th><th rowspan="1" colspan="1">APCS Mod-risk</th><th rowspan="1" colspan="1">APCS Mod-risk</th><th rowspan="1" colspan="1">APCS High-risk</th></tr><tr><th rowspan="1" colspan="1"></th><th rowspan="1" colspan="1">FIT negative</th><th rowspan="1" colspan="1">FIT positive</th><th rowspan="1" colspan="1">FIT negative</th><th rowspan="1" colspan="1">FIT positive</th><th rowspan="1" colspan="1">FIT NA</th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">AN (exclude CA)</td><td rowspan="1" colspan="1">2</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">47</td><td rowspan="1" colspan="1">25</td><td rowspan="1" colspan="1">67</td></tr><tr><td rowspan="1" colspan="1">CA</td><td rowspan="1" colspan="1">0</td><td rowspan="1" colspan="1">0</td><td rowspan="1" colspan="1">2</td><td rowspan="1" colspan="1">2</td><td rowspan="1" colspan="1">10</td></tr><tr><td rowspan="1" colspan="1">Other</td><td rowspan="1" colspan="1">756</td><td rowspan="1" colspan="1">43</td><td rowspan="1" colspan="1">1,934</td><td rowspan="1" colspan="1">163</td><td rowspan="1" colspan="1">863</td></tr><tr><td rowspan="1" colspan="1">Total</td><td rowspan="1" colspan="1">758</td><td rowspan="1" colspan="1">44</td><td rowspan="1" colspan="1">1,983</td><td rowspan="1" colspan="1">190</td><td rowspan="1" colspan="1">940</td></tr></tbody></table></table-wrap></p><p><bold>CONCLUSION:</bold> APCS score select majority of subjects that requires early colonoscopy for colorectal screening. Moderate-risk or low-risk subjects can be offered FIT for further triaging subjects that might be benefited from early colonoscopy.</p><p><bold>Contact E-mail Address:</bold><email>jjysung@cuhk.edu.hk</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> asia pacific, colorectal cancer screening, Early Detection, high risk</p></sec><sec><title>OP327 A BLOOD GENE EXPRESSION-BASED TEST FOR EARLY DETECTION OF COLORECTAL CANCER: FINAL REPORT OF AN INTERNATIONAL MULTI-CENTER CASE-CONTROL STUDY</title><p><bold>C. Nichita</bold><sup>1,*</sup>, S. Monnier-Benoit<sup>2</sup>, L. Ciarloni<sup>2</sup>, N. Imaizumi<sup>2</sup>, S. Hosseinian<sup>2</sup>, G. Dorta<sup>1</sup>, DGNP-COL-0310 on behalf of study</p><p><italic><sup>1</sup>Gastroenterology and Hepatology Department, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, <sup>2</sup>DIAGNOPLEX, Lausanne 25, Switzerland</italic></p><p><bold>INTRODUCTION:</bold> Non-invasive, accurate tests to screen for early stages of colorectal cancer (CRC) are not available today. In a previous exploratory study (Nichita et al., DDW2010, DDW2011) we demonstrated the feasibility of detecting pre-cancerous lesions and CRC from a blood sample.</p><p><bold>AIMS&METHODS:</bold> The aim of this study is to further develop and validate a test that differentiates subjects with colorectal cancer and adenomas from healthy controls.</p><p>An international multi-center case-control study including three South Korean and six Swiss centers was conducted from June 2010 to December 2011. 1579 patients older than 50 years were prospectively enrolled and 1333 resulted evaluable subjects. Among them, 680 samples were allocated to the three main study groups including control subjects (Swiss n=124, Korean n=99), patients with adenomas ≥1cm (Swiss n=100, Korean n=154) and patients with CRC (Swiss n=74, Korean n=129). These subjects were referred for colonoscopy or scheduled for interventional surgery. The remaining 653 subjects were diagnosed with other types of solid cancers or other diseases such as inflammatory bowel diseases or diverticulitis and were included to test the algorithm specificity. Upon blood collection, PBMC were isolated and analyzed for gene expression by RT-PCR with a panel of 29 biomarkers. Subjects belonging to the three main study groups were randomly assigned to training, validation and test set, at a proportion of 40%, 20% and 40%, respectively. The training and validation set were used for algorithm development. The independent test set was used for clinical performance determination.</p><p><bold>RESULTS:</bold> Statistical analyses revealed gene expression differences between Korean and Swiss populations. This prevented the generation of a single classifier, therefore two separated Korean and Swiss predictive algorithms have been developed and applied on the independent test set. The Swiss algorithm showed a specificity of 88% and a sensitivity of 71% for CRC stage I-II (76% CRC I-IV) and of 51% for adenoma detection. The Korean algorithm showed a specificity of 69% and a sensitivity of 63% for CRC stage I-II (70% CRC I-IV) and of 46% for adenoma detection.</p><p><bold>CONCLUSION:</bold> This study confirmed the blood transcriptome to be a source of biomarkers for CRC detection. Moreover, we validated a test for diagnosis of early CRC stages and adenomas that has the potential to be a non-invasive compliant screening test with performances in the same range of tests currently used by national programs. The differences observed between Korean and Swiss population will require further clinical investigations.</p><p><bold>Contact E-mail Address:</bold><email>lciarloni@diagnoplex.com</email></p><p><bold>Disclosure of Interest</bold>: C. Nichita: None Declared, S. Monnier-Benoit Other: Diagnoplex Employee, L. Ciarloni Other: Diagnoplex Employee, N. Imaizumi Other: Diagnoplex Employee, S. Hosseinian Other: Diagnoplex Employee, G. Dorta Consultancy for: Diagnoplex</p><p><bold>Keywords:</bold> Adenoma, biomarkers, Blood, Colorectal cancer, gene expression, Screening test</p></sec><sec><title>OP328 VARIATION IN THE RISK OF VENOUS THROMBOEMBOLISM IN PEOPLE WITH COLORECTAL CANCER BY STAGE OF DISEASE AND TREATMENT RECEIVED: A POPULATION BASED COHORT STUDY FROM ENGLAND, UK</title><p><bold>A. J. Walker</bold><sup>1,*</sup>, J. West<sup>1</sup>, T. R. Card<sup>1</sup>, C. Crooks<sup>1</sup>, D. J. Humes<sup>1</sup>, M. J. Grainge<sup>1</sup></p><p><italic><sup>1</sup>Epidemiology and Public Health, The University of Nottingham, Nottingham, United Kingdom</italic></p><p><bold>INTRODUCTION:</bold> Patients with colorectal cancer are at high risk of venous thromboembolism (VTE) and recent international guidelines have advised extended prophylaxis for some of these patients following surgery or during chemotherapy. However, our understanding of which patients are at increased risk and what the magnitude is, is limited.</p><p><bold>AIMS&METHODS:</bold> We analysed data from 4 linked databases; the Clinical Practice Research Datalink, linked to Hospital Episode Statistics, Cancer Registry data and Office for National Statistics cause of death data all from England. Absolute and relative rates of VTE among colorectal cancer patients according to Dukes stage, surgical intervention and chemotherapy received were calculated using Cox regression.</p><p><bold>RESULTS:</bold> There were 10,309 patients with colorectal cancer and 570 developed VTE (5.5%). The incidence varied by Dukes stage being threefold higher among Dukes D patients compared to Dukes A (HR 3.08, 95% CI 1.95-4.84) and 40% higher for those who received chemotherapy compared to those who did not (HR 1.39 CI 1.14-1.69).The risk following surgery varied by stage of disease and chemotherapy with those patients with Dukes A stage having a low incidence of VTE (0.74% CI 0.28-1.95) at 6 months with all events occurring within 28 days of surgery compared to Dukes B and C patients whose risk persisted until 6 months to around 2-3%.
<table-wrap id="table51-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="2" colspan="1"></th><th rowspan="2" colspan="1"></th><th colspan="4" rowspan="1"><hr></hr>28 days</th><th colspan="4" rowspan="1"><hr></hr>180 days</th></tr><tr><th rowspan="1" colspan="1">Events</th><th rowspan="1" colspan="1">%</th><th rowspan="1" colspan="1">95%</th><th rowspan="1" colspan="1">CI</th><th rowspan="1" colspan="1">Events</th><th rowspan="1" colspan="1">%</th><th rowspan="1" colspan="1">95%</th><th rowspan="1" colspan="1">CI</th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">All patients</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">27</td><td rowspan="1" colspan="1">0.54</td><td rowspan="1" colspan="1">0.37</td><td rowspan="1" colspan="1">0.78</td><td rowspan="1" colspan="1">23</td><td rowspan="1" colspan="1">1.62</td><td rowspan="1" colspan="1">1.30</td><td rowspan="1" colspan="1">2.01</td></tr><tr><td rowspan="3" colspan="1">No chemotherapy</td><td rowspan="1" colspan="1">Dukes A</td><td rowspan="1" colspan="1">4</td><td rowspan="1" colspan="1">0.82</td><td rowspan="1" colspan="1">0.31</td><td rowspan="1" colspan="1">2.16</td><td rowspan="1" colspan="1">0</td><td rowspan="1" colspan="1">0.82</td><td rowspan="1" colspan="1">0.31</td><td rowspan="1" colspan="1">2.16</td></tr><tr><td rowspan="1" colspan="1">Dukes B</td><td rowspan="1" colspan="1">8</td><td rowspan="1" colspan="1">0.40</td><td rowspan="1" colspan="1">0.20</td><td rowspan="1" colspan="1">0.81</td><td rowspan="1" colspan="1">4</td><td rowspan="1" colspan="1">1.25</td><td rowspan="1" colspan="1">0.84</td><td rowspan="1" colspan="1">1.85</td></tr><tr><td rowspan="1" colspan="1">Dukes C</td><td rowspan="1" colspan="1">8</td><td rowspan="1" colspan="1">0.61</td><td rowspan="1" colspan="1">0.30</td><td rowspan="1" colspan="1">1.21</td><td rowspan="1" colspan="1">4</td><td rowspan="1" colspan="1">1.76</td><td rowspan="1" colspan="1">1.16</td><td rowspan="1" colspan="1">2.67</td></tr><tr><td rowspan="3" colspan="1">Chemotherapy</td><td rowspan="1" colspan="1">Dukes A</td><td rowspan="1" colspan="1">0</td><td rowspan="1" colspan="1">0.00</td><td rowspan="1" colspan="1">0.00</td><td rowspan="1" colspan="1">0.00</td><td rowspan="1" colspan="1">0</td><td rowspan="1" colspan="1">0.00</td><td rowspan="1" colspan="1">0.00</td><td rowspan="1" colspan="1">0.00</td></tr><tr><td rowspan="1" colspan="1">Dukes B</td><td rowspan="1" colspan="1">2</td><td rowspan="1" colspan="1">0.54</td><td rowspan="1" colspan="1">0.14</td><td rowspan="1" colspan="1">2.15</td><td rowspan="1" colspan="1">3</td><td rowspan="1" colspan="1">2.18</td><td rowspan="1" colspan="1">1.10</td><td rowspan="1" colspan="1">4.32</td></tr><tr><td rowspan="1" colspan="1">Dukes C</td><td rowspan="1" colspan="1">5</td><td rowspan="1" colspan="1">0.60</td><td rowspan="1" colspan="1">0.25</td><td rowspan="1" colspan="1">1.44</td><td rowspan="1" colspan="1">12</td><td rowspan="1" colspan="1">2.55</td><td rowspan="1" colspan="1">1.67</td><td rowspan="1" colspan="1">3.89</td></tr></tbody></table></table-wrap></p><p>*Patients with no surgery excluded, follow-up starts from surgery date</p><p><bold>CONCLUSION:</bold> 28 day prophylaxis following surgery for colorectal cancer is appropriate for patients with Dukes A however patients with Dukes B and C disease who are having chemotherapy post-operatively may be worth targeting for a longer duration of prophylaxis.</p><p><bold>Contact E-mail Address:</bold><email>alex.walker@nottingham.ac.uk</email></p><p><bold>Disclosure of Interest</bold>: A. Walker: None Declared, J. West: None Declared, T. Card Other: The spouse of TRC is an employee of Astrazeneca, C. Crooks: None Declared, D. Humes: None Declared, M. Grainge: None Declared</p><p><bold>Keywords:</bold> Chemotherapy, Colorectal cancer, surgery, venous thromboembolism</p></sec><sec><title></title><p><bold>TUESDAY, OCTOBER 15, 2013 15:45-17:15</bold></p><p><bold>NAFLD and general hepatology: Important updates – Hall 6</bold></p></sec><sec><title>OP329 THE CHARACTERISTICS AND CLINICAL DIFFERENCES BETWEEN IGG4-RELATED SCLEROSING CHOLANGITIS AND PRIMARY SCLEROSING CHOLANGITIS</title><p><bold>R. Koyama</bold><sup>1,*</sup>, T. Tamura<sup>1</sup>, Y. Koizumi<sup>1</sup>, T. Imamura<sup>1</sup>, K. Takeuchi<sup>1</sup></p><p><italic><sup>1</sup>gastroenterology, TORANOMON HOSPITAL, tokyo, Japan</italic></p><p><bold>INTRODUCTION:</bold> IgG4-related sclerosing cholangitis (IgG4-SC) is a characteristic sclerosing cholangitis and frequently coexists with autoimmune pancreatitis (AIP). IgG4-SC shows various cholangiographic features similar to those of primary sclerosing cholangitis (PSC). As it is not easy to discriminate IgG4-SC from PSC, new clinical diagnostic criteria of IgG4-SC 2012 (JJBA 2012;26:59-63) was proposed in Japan in order to avoid the misdiagnosis of PSC and malignant diseases.</p><p><bold>AIMS&METHODS:</bold> A total of 26 patients were diagnosed as IgG4-SC by the above criteria at our hospital between 2000 and 2012. On the other hand, 15 PSC pts were treated during the same period. We retrospectively analyzed the clinical course, imaging findings, mainly US/IDUS, and the discrimination between IgG4-SC and PSC.</p><p><bold>RESULTS:</bold> The table shows the characteristics and clinical differences between IgG4-SC and PSC pts. The mean age of IgG4-SC pts was significantly older than PSC pts and males were predominant in IgG4-SC pts. Serum IgG4 levels and positive rates were significantly higher in IgG4-SC than PSC pts. Coexistence of AIP was recognized in 96.2% of IgG4-SC pts, and inflammatory bowel disease (IBD) in 40% of PSC pts. All IgG4-SC pts were treated with PSL, with immediate improvement, whereas bile duct stenosis of PSC pts were gradually progressive and 2 pts had to receive liver transplantation therapy. We could reveal the characteristic bile duct wall thickening on US in 76.9% and on IDUS in 100% of IgG4-SC pts. When we examined the US imaging of IgG4-SC and PSC cases, the thickening wall of IgG4-SC showed lower echoic than that of PSC (low echoic wall thickening was detected in 80% of IgG4-SC and 16.7% of PSC cases; most of PSC cases had higher echoic wall thickening), and the mucosal surface of IgG4-SC was smooth in 80% of cases, whereas PSC was mostly irregular (only 16.7% was smooth).
<table-wrap id="table52-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1">Parameters</th><th rowspan="1" colspan="1">IgG4-SC (n=26)</th><th rowspan="1" colspan="1">PSC (n=15)</th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">Mean age</td><td rowspan="1" colspan="1">66(48-82)</td><td rowspan="1" colspan="1">46.5(18-80)</td></tr><tr><td rowspan="1" colspan="1">Male/Female</td><td rowspan="1" colspan="1">22/4</td><td rowspan="1" colspan="1">6/9</td></tr><tr><td rowspan="1" colspan="1">Serum IgG4 positive (≧135mg/dl)</td><td rowspan="1" colspan="1">96.2%</td><td rowspan="1" colspan="1">10%</td></tr><tr><td rowspan="1" colspan="1">Serum IgG4 level (mg/dl)</td><td rowspan="1" colspan="1">549</td><td rowspan="1" colspan="1">63.8</td></tr><tr><td rowspan="1" colspan="1">Coexistence of AIP</td><td rowspan="1" colspan="1">96.2%</td><td rowspan="1" colspan="1">0%</td></tr><tr><td rowspan="1" colspan="1">Coexistence of IBD</td><td rowspan="1" colspan="1">0%</td><td rowspan="1" colspan="1">40%</td></tr><tr><td rowspan="1" colspan="1">Response to PSL</td><td rowspan="1" colspan="1">100%</td><td rowspan="1" colspan="1">0%</td></tr><tr><td rowspan="1" colspan="1">Liver transplantation</td><td rowspan="1" colspan="1">0%</td><td rowspan="1" colspan="1">13.3%</td></tr></tbody></table></table-wrap></p><p><bold>CONCLUSION:</bold> It is very important to discriminate IgG4-SC from PSC, because the prognosis and the effectiveness of PSL therapy are different. We concluded that US and IDUS are useful tools in detecting biliary tract lesions in IgG4-SC pts. In addition, US findings of thickened bile duct wall could become one way of discriminating between IgG4-SC and PSC.</p><p><bold>Contact E-mail Address:</bold><email>rikako@pm.highway.ne.jp</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> AIP, IgG4-SC, PSC</p></sec><sec><title>OP330 THE NEW ORAL IRON CHELATOR PREVENTS LIVER FIBROSIS AND PRENEOPLASTIC LESIONS IN LIVER CANCER AND LIVER CIRRHOSIS MODEL</title><p><bold>N. Yamamoto</bold><sup>1,2,*</sup>, T. Yamasaki<sup>2</sup>, K. Uchida<sup>2</sup>, T. Takami<sup>2</sup>, K. Fujisawa<sup>2</sup>, M. Maeda<sup>2</sup>, I. Saeki<sup>2</sup>, S. Terai<sup>2</sup>, I. Sakaida<sup>2</sup></p><p><italic><sup>1</sup>Health Administration Center, <sup>2</sup> Gastroenterology & Hepatology , Yamaguchi University Graduate School of Medicine, UBE, Japan</italic></p><p><bold>INTRODUCTION:</bold> Hepatitis B,C,non-alcoholic steatohepatitis(NASH)can progress to advanced liver fibrosis and ultimately to hepatocellular carcinoma.Deferasirox(DFX)is a new oral iron chelator which inhibits proliferation of some cancer cells.</p><p><bold>AIMS&METHODS:</bold> The aim of this study is to investigate whether Deferasirox has any effects on the development of liver fibrosis as well as preneoplastic lesions. In vitro)We examined cell grouth by MTS assay and apoptosis by Caspase 3 activity using human hepatoma cell(HepG2,HuH7,Hep3B).In vivo)The effects of DFX were examined using the choline-deficient L-amino acid-defined(CDAA)diet-induced rat liver fibrosis model.The total study periods were 16,20weeks.One group received CDAA diet with DFX(20mg/kg/adult),the other received CDAA diet only.Liver fibrosis was analyzed by Azan,Sirius–red,aSMA expression,hydroxyproline level.Development of preneoplastic lesions was assessed by glutathione S-transferase placental form (GST-P)expression.The change of laboratory data was analyzed.Type I procollagen,TIMP1,TIMP2,TGFb mRNA expression were analyzed using both RT-PCR and DNA array.We examined the the effects of DFX using N-nitrosodiethylnitrosamine(DEN)-induced liver cancer mice model.One group received with DFX(20mg/kg/adult) from 5 months to 8 months after DEN injection(1mg/kg)at 14days of age,the other received DEN injection only.Liver cancer was analyzed by HE,AFP,PCNA,CD44 expression.The oxidative stress was analyzed by 4HNE,8OHdG.We compared many different gene expressions of cancer and non cancer tissues between DFX group and control.</p><p><bold>RESULTS:</bold> In vitro,the cell growth of hepatoma cells was inhibited with DFX in a dose-dependent manner.The caspase3 activity of hepatoma cells was increased with DFX in a dose-dependent manner(P<0.05).In rat CDAA model,DFX prevented liver fibrosis by Azan,Sirius-red,aSMA expression(p<0.05),hepatic hydroxyproline level was decreased.DFX reduced both the area and numbers of GST-P positive preneoplastic lesions(p<0.01).Administration of DFX significantly reduced levels of 4HNE (Deferasirox 3.3,CDAA only 8.0,p<0.01),8OHdG (Deferasirox 1.3,CDAA only 2.0,p<0.05).DFX inhibited Type 1 procollagen,TIMP-1,2 mRNA expression(all of p<0.01).In mice DEN model,DFX reduced both the area and numbers of tumor lesions(p<0.01).DFX prevented AFP,CD44 expression(p<0.05)and reduced levels of 4HNE,8OHdG.</p><p><bold>CONCLUSION:</bold> Our results indicated that Deferasirox inhibited liver fibrosis and preneoplastic lesions.We suggested that Deferasirox will be the new drug for Liver Fibrosis and Hepatocellular Carcinoma.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Cancer prevention, drug bioavailability, Hepatocellular cancinoma, liver diseases, liver fibrosis</p></sec><sec><title>OP331 INCRETINS IN NASH/NAFLD: PATHOPHYSIOLOGICAL IMPLICATIONS</title><p><bold>A. C. Meyer-Gerspach</bold><sup>1,*</sup>, C. Bernsmeier<sup>1</sup>, L. Blaser<sup>1</sup>, L. Jeker<sup>1</sup>, R. E. Steinert<sup>1</sup>, M. H. Heim<sup>1</sup>, C. Beglinger<sup>1</sup></p><p><italic><sup>1</sup>Department of Biomedicine and Division of Gastroenterology, University Hospital Basel, Basel, Switzerland</italic></p><p><bold>INTRODUCTION:</bold> Non-alcoholic fatty liver disease (NAFLD) is one of the most frequent chronic liver diseases in Western countries. Non-alcoholic steatohepatitis (NASH) is a subgroup of NAFLD and carries the risk of disease progression and complications such as cirrhosis, liver failure or hepatocellular carcinoma. Both NASH and NAFLD are associated with obesity, insulin resistance, and type 2 diabetes mellitus (T2DM).</p><p>Incretins, such as glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), are gastrointestinal peptide hormones regulating postprandial insulin release from the pancreatic β-cell. GLP-1 agonism has been approved as treatment strategy in T2DM using GLP-1 agonists. The role of incretins in NAFLD is insufficiently understood. Experimental studies in mice suggest improvement of hepatic steatosis by GLP-1 agonism probably through a mechanism involving hepatic GLP-1 receptors. The aims of this study were to determine the concentrations of incretins (GLP-1 and GIP), glucose and insulin after a standard glucose tolerance test in NAFLD patients. The results were compared to a cohort of healthy controls.</p><p><bold>AIMS&METHODS:</bold> The study included a cohort of 52 non-diabetic patients with NAFLD and 50 matched, healthy, normal-weight, controls. A standardized oral 75 g glucose tolerance test (oGTT) was performed. Plasma levels of GLP-1, GIP, insulin, glucose and glucagon were measured sequentially for 120 minutes before and after the glucose administration using specific assay systems. Insulin resistance was estimated as the homeostasis model of assessment for insulin resistance (HOMA-IR) index.</p><p><bold>RESULTS:</bold> Based on the HOMA-IR, NAFLD patients were insulin resistant (p < 0.0001) with increased fasting and postprandial insulin concentrations; the glucose lowering effect was, however, diminished. Glucose induced GLP-1 secretion was markedly decreased in patients with fatty liver disease compared to normal weight controls (p < 0.001) with no difference in GLP-1 secretion between NAFLD and NASH subgroups. In contrast, GIP secretion was unchanged in NAFLD/NASH compared to controls. Glucagon secretion was significantly higher in NAFLD (p < 0.001) compared to controls.</p><p><bold>CONCLUSION:</bold> Patients with NAFLD are insulin resistant and show an impaired glucose homeostasis. Incretins show a dissociated response to oral glucose: GLP-1 secretion is impaired in both NAFLD and NASH subgroups, but GIP release is unchanged. Our data support the hypothesis that dysregulation of GLP-1 secretion is involved in the pathogenesis of human NAFLD. GLP-1 analogues might therefore be beneficial in the treatment of NAFLD.</p><p><bold>Contact E-mail Address:</bold><email>Anne.Gerspach@usb.ch</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> glucagon-like peptide-1 , glucose-dependent insulinotropic polypeptide (GIP), NAFLD, NASH</p></sec><sec><title>OP332 ASSOCIATION OF GENETIC VARIANTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE IN AN URBAN SRI LANKAN COMMUNITY</title><p><bold>A. Kasturiratne</bold><sup>1</sup>, K. Akiyama<sup>2</sup>, M. A. Niriella<sup>1,*</sup>, F. Takeuchi<sup>2</sup>, M. Isono<sup>2</sup>, A. Dassanayake<sup>1</sup>, A. De Silva<sup>1</sup>, R. Wickramasinghe<sup>1</sup>, N. Kato<sup>2</sup>, H. De Silva<sup>1</sup></p><p><italic><sup>1</sup>Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka, <sup>2</sup>National Centre for Global Health and Medicine, Tokyo, Japan</italic></p><p><bold>INTRODUCTION:</bold> Genome-wide association studies (GWAS) have identified loci associated with susceptibility to non-alcoholic fatty liver disease (NAFLD) in populations of European descent. No large-scale genetic studies have been performed in South Asian populations.</p><p><bold>AIMS&METHODS:</bold> We investigated genetic susceptibility to NAFLD and associated phenotypes in an ongoing, prospective, community-based study among urban Sri Lankan adults (n=2992). We selected 10 single nucleotide polymorphisms (SNPs), previously reported to be associated with NAFLD in populations of European and South Asian ancestry, for a case-control replication study. They included loci derived from GWAS [<italic>PNPLA3</italic> (rs738409), <italic>LYPLAL1</italic> (rs12137855), <italic>GCKR</italic> (rs780094), <italic>PPP1R3B</italic> (rs4240624), <italic>NCAN</italic> (rs2228603)] [one-tailed <italic>P</italic><0.05 (two-tailed <italic>P</italic><0.1) considered significant] plus those from candidate gene studies [<italic>APOC3</italic> (rs2854117, rs2854116), <italic>ADIPOR2</italic> (rs767870), <italic>STAT3</italic> (rs6503695, rs9891119)] [<italic>P</italic> derived by Bonferroni correction for multiple testing]. Genotype data of 2988 participants were analysed.</p><p><bold>RESULTS:</bold> A significant association was observed for <italic>PNPLA3</italic> (rs738409) with NAFLD [OR=1.25, 95% CI 1.08–1.44, <italic>P</italic>=0.003)]; rs738409 also showed a trend towards lower serum triglycerides. <italic>APOC3</italic> variants were significantly (<italic>P</italic>=7.3-7.5×10<sup>-8</sup>) associated with higher triglycerides, but not NAFLD. Significant SNP-lipid associations, <italic>GCGK </italic>(for TG), <italic>PPP1R3B</italic> (for LDL- and HDL-cholesterol) and <italic>NCAN </italic>(for TG), were also observed (<italic>P</italic>=0.0004-0.09).</p><p><bold>CONCLUSION:</bold><italic>PNPLA3</italic> variant is significantly associated with NAFLD in this Sri Lankan cohort, the first community based study in a South Asian population to demonstrate this association. Our failure to demonstrate previously reported associations for NAFLD at other loci reinforces the importance of further large-scale studies on genetic variants in diverse populations to better understand its pathophysiology.</p><p><bold>Contact E-mail Address:</bold><email>maduniln@yahoo.co.uk</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> fatty liver, genetic variants, genetics, NAFLD</p></sec><sec><title>OP333 ASSOCIATION BETWEEN HELICOBACTER PYLORI INFECTION DIAGNOSED BY SEROLOGICAL STATUS AND NONALCOHOLIC FATTY LIVER DISEASE: A CROSS-SECTIONAL STUDY</title><p><bold>Z. Shen</bold><sup>1,*</sup>, Y. Qin<sup>2</sup>, Y. Lu<sup>1</sup>, C. Yu<sup>1</sup>, Y. Li<sup>1</sup></p><p><italic><sup>1</sup>Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejinag Province, China., <sup>2</sup>International Health Care Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejinag Province, China., Hangzhou, China</italic></p><p><bold>INTRODUCTION:</bold><italic>Helicobacter pylori</italic> (<italic>H.pylori)</italic> infection is associated with metabolic syndrome, atherosclerosis, cardiovascular disease and diabetes mellitus in previous studies[1-7]. The potential mechanisms are that <italic>H.pylori</italic> infection may have a pathogenic role in the development of oxidative stress, immunologic cross-reactivity, increased blood pressure, modifications of serum lipids levels, impaired glucose tolerance and insulin resistance. Nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity, type 2 diabetes mellitus, dyslipidemia and hypertension, which form a cluster of metabolic disorders. Insulin resistance plays a key role in the pathogenesis of NAFLD. A recent study of small sample sizes with 28 NAFLD patients and 25 controls found that <italic>H.pylori</italic> infection could represent one more hit contributing to the pathogenesis of NAFLD, however, the possible link could be not so clear because of small samples.</p><p><bold>AIMS&METHODS:</bold> The aim of this study was to investigate the association of <italic>H.pylori</italic> infection with NAFLD. A cross-sectional study was performed among the subjects who underwent general health screening including hepatic ultrasonography and <italic>H.pylori</italic> immunoglobulin G (IgG) antibody detection in serum from The First Affiliated Hospital, College of Medicine, Zhejiang University, China.</p><p><bold>RESULTS:</bold> The study included 9091 subjects (4375 men) with a mean age of 43 years. The prevalence rates of anti-<italic> H.pylori</italic> IgG seropositivity and NAFLD were 20.6% and 26.1%, respectively. The NAFLD prevalence was significantly higher in anti- <italic>H.pylori</italic> IgG seropositivity group than the control group (30.2% <italic>vs.</italic> 25.0%, <italic>P</italic> < 0.001). When subjects were assessed relative to their serological <italic>H.pylori</italic> status in the adjusted model which were adjusted for age, gender, systolic and diastolic blood pressure, the anti- <italic>H.pylori</italic> IgG seropositivity group had higher body mass index (BMI), total cholesterol (TC), very low density lipoprotein cholesterol (VLDL-C), fasting plasma glucose (FPG) and had a higher prevalence of NAFLD (all <italic>P</italic> < 0.05). The prevalence rate of anti- <italic>H.pylori</italic> IgG seropositivity increased with progressively higher BMI, TC, VLDL-C and FPG levels, respectively (all <italic>P<sub>trend</sub></italic> < 0.001).</p><p><bold>CONCLUSION:</bold><italic>H.pylori</italic> infection is significantly associated with NAFLD and its risk factors including BMI, TC, VLDL-C and FPG.</p><p><bold>REFERENCES:</bold></p><p>1. Gunji T, Matsuhashi N, Sato H, et al. Helicobacter pylori infection is significantly associated with metabolic syndrome in the Japanese population. Am J Gastroenterol 2008;103(12):3005-10.</p><p>2. Shin DW, Kwon HT, Kang JM, et al. Association between metabolic syndrome and Helicobacter pylori infection diagnosed by histologic status and serological status. J Clin Gastroenterol 2012;46(10):840-5.</p><p>3. Longo-Mbenza B, Nkondi Nsenga J, Vangu Ngoma D. Prevention of the metabolic syndrome insulin resistance and the atherosclerotic diseases in Africans infected by Helicobacter pylori infection and treated by antibiotics. Int J Cardiol. 2007 Oct 18;121(3):229-38.</p><p>4. Oshima T, Ozono R, Yano Y, et al. Association of Helicobacter pylori infection with systemic inflammation and endothelial dysfunction in healthy male subjects. J Am Coll Cardiol 2005;45(8):1219-22.</p><p>5. de Luis DA, Lahera M, Cantón R, et al. Association of Helicobacter pylori infection with cardiovascular and cerebrovascular disease in diabetic patients. Diabetes Care 1998;21(7):1129-32.</p><p>6. Sung KC, Rhee EJ, Ryu SH, et al. Prevalence of Helicobacter pylori infection and its association with cardiovascular risk factors in Korean adults. Int J Cardiol. 2005 Jul 20;102(3):411-7.</p><p>7. Gasbarrini A, Ojetti V, Pitocco D, et al. <italic>Helicobacter pylori</italic> infection in patients affected by insulin-dependent diabetes mellitus. Eur J Gastroenterol Hepatol 1998;10(6):469-72.</p><p><bold>Contact E-mail Address:</bold><email>shenzhe39@126.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> association, Helicobacter pylori, nonalcoholic fatty liver disease</p></sec><sec><title>OP334 SKELETAL MUSCLE MIRNAS IN NON-ALCOHOLIC FATTY LIVER DISEASE AND TARGETING BY TAUROURSODEOXYCHOLIC ACID IN VITRO</title><p><bold>D. M. S. Ferreira</bold><sup>1</sup>, P. M. Borralho<sup>1,2</sup>, M. V. Machado<sup>3,4</sup>, H. Cortez-Pinto<sup>3,4</sup>, C. M. P. Rodrigues<sup>1,2</sup>, R. E. Castro<sup>1,2,*</sup></p><p><italic><sup>1</sup>Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), <sup>2</sup>Department of Biochemistry and Human Biology, Faculty of Pharmacy, University of Lisbon, <sup>3</sup>Institute of Molecular Medicine (IMM), Faculty of Medicine, University of Lisbon, <sup>4</sup>Department of Gastroenterology, Hospital de Santa Maria, Lisbon, Portugal</italic></p><p><bold>INTRODUCTION:</bold> We have recently shown that intramyocellular lipids associate with muscle insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD) in morbid obese patients. In turn, NAFLD severity is associated with activation of the microRNA (miRNA or miR)-34a pro-apoptotic pathway, targeted by tauroursodeoxycholic (TUDCA) acids in primary rat hepatocytes. Recent studies suggest that miRNAs may also regulate IR in skeletal muscle.</p><p><bold>AIMS&METHODS:</bold> The aim of this study was to profile miRNA expression in the skeletal muscle of patients at different NAFLD stages and ascertain the potential therapeutic use of TUDCA. Muscle and matching liver biopsies were obtained from morbid obese patients undergoing bariatric surgery and classified as simple steatosis, less severe and more severe non-alcoholic steatohepatitis (NASH). Muscle RNA was run in TaqMan MicroRNA arrays. C2C12 cells were incubated with or without palmitic acid (PA), in the presence or absence of TUDCA. The insulin signalling pathway was evaluated by Western blot.</p><p><bold>RESULTS:</bold> Our results show a progressive and significant increase in the expression of 45 muscle miRNAs from steatosis to more severe NASH (<italic>p</italic> < 0.05). These included muscle specific miRNAs miR-133a and b, as well as miR-34a, miR-10b, miR-29a, let-7a, and others. Incubation of C2C12 cells with PA also increased miR-34a and let-7a expression (<italic>p</italic> < 0.05), as well as apoptosis (<italic>p</italic> < 0.05). In addition, PA induced IR in C2C12 cells, as evidenced by the inhibition of the insulin signalling pathway (<italic>p</italic> < 0.05), suggesting that miR-34a and let-7a might mediate free fatty acid-induced cytotoxicity and IR in the muscle. Finally, incubation of C2C12 cells with TUDCA reduced miR-34a induction, IR and apoptosis (<italic>p</italic> < 0.05).</p><p><bold>CONCLUSION:</bold> Overall, our results indicate that miRNAs are differently modulated with NAFLD severity in the muscle, correlating with changes in liver. In particular, miR-34a is increased in the muscle of NAFLD patients and targeted by TUDCA in C2C12 cells. TUDCA further inhibits evidence of IR and apoptosis. A better understanding of the overlapping roles of miRNAs in different tissues during the metabolic syndrome, and how to target them, may help in establishing new therapeutic options (PTDC/SAU-OSM/102099/2008, PTDC/SAU-OSM/100878/2008, PTDC/SAU-ORG/111930/2009, Pest-OE/SAU/UI4013/2011 and SFRH/BD/60521/2009)</p><p><bold>Contact E-mail Address:</bold><email>ruieduardocastro@ff.ul.pt</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> apoptosis, insulin resistance, microRNA-34a, non-alcoholic fatty liver disease, skeletal muscle, tauroursodeoxycholic acid</p></sec><sec><title></title><p><bold>TUESDAY, OCTOBER 15, 2013 15:45-17:15</bold></p><p><bold>Improving EUS-guided diagnosis – Hall 9</bold></p></sec><sec><title>OP336 DIFFERENTIAL DIAGNOSIS OF SMT AND EVALUATION OF MALIGNANT POTENTIAL GISTS BY CONTRAST ENHANCED HARMONIC EUS</title><p><bold>H. Sakamoto</bold><sup>1,*</sup>, M. Kitano<sup>1</sup>, M. Kudo<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterolgy and Hepatology, Kinki University Faculty of Medicine, osakasayama, Japan</italic></p><p><bold>INTRODUCTION:</bold> Contrast-enhanced harmonic EUS (CH-EUS) is a new sonographic technique that uses US contrast-agents and depicts intratumoral vessels in real time.<sup> 1)</sup></p><p><bold>AIMS&METHODS:</bold> The purpose of present study was to employ this novel technique for observation of microvessels in submucosal tumor (SMT) of gastrointestinal tract and for evaluation whether assessment of tumor vascularity by CH-EUS can predict the preoperative malignancy risk of GI stromal tumors (GISTs).Between June 2008 and May 2012, 121 consecutive patients having a SMT underwent CH-EUS and contrast enhanced multidetector CT (CE-MDCT).Tumors were observed in a real-time fashion of CH-EUS after the injection, a contrast-agent ,Sonazoid. Final diagnoses based on histological findings were cyst (n= 5), lipoma (n= 7), leiomyoma (n= 13), schwannoma (n= 7), ectopic pancreas (n= 16), glomus tumor (n=2), inflammatory fibroid polyp (n= 3) and GIST (n=68). Resected GIST specimens were divided into high-grade and low-grade malignancy groups based on mitotic activity. The sensitivities with which CE-MDCT and CEH-EUS detected intratumoral vessels in high-grade malignancy GISTs were compared.</p><p><bold>RESULTS:</bold> The image patterns of the SMTs by CH-EUS were classified into four types: type I, no enhancement ; type II, homogeneous enhancement with fine vessels; type III, heterogeneous enhancement with abundant irregular vessels flowing from periphery to center of the tumor; type IV, heterogeneous enhancement with fine vessels. The values of diagnostic accuracy in SMT of EUS alone and EUS plus CH-EUS were 67% and 82%, respectively. EUS plus CH-EUS was higher than EUS. CH-EUS identified irregular vessels and thereby predicted GIST malignancies with a sensitivity, specificity, and accuracy of 100%, 67%, and 82%, respectively. The sensitivity for detecting intratumorual tumor vessels in malignant GISTs by CE-MDCT and CH-EUS were 31% and 100%.</p><p><bold>CONCLUSION:</bold> CH-EUS successfully visualized intratumoral vessels in SMTs and may play an important role in predicting the malignancy risk of GISTs.</p><p><bold>REFERENCES:</bold></p><p>1. Sakamoto H, Kitano M, Kudo M, et al. Estimation of malignant potential of GI stromal tumors by contrast-enhanced harmonic EUS.Gastrointest Endosc 2011;73:227-37.</p><p><bold>Contact E-mail Address:</bold><email>hirokizzzz88@yahoo.co.jp</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Contrast-enhanced endoscopic ultrasonography, contrast-enhanced ultrasound, EUS, SMTs</p></sec><sec><title>OP337 PITFALLS IN THE INTERPRETATION OF PANCREATIC ENDOSCOPIC ULTRASOUND GUIDED NEEDLE CONFOCAL LASER ENDOMICROSCOPY</title><p><bold>J. G. Karstensen</bold><sup>1,*</sup>, T. Cârţână<sup>2</sup>, D. I. Gheonea<sup>2</sup>, H. Hassan<sup>1</sup>, J. P. Hasselby<sup>3</sup>, C. P. Hansen<sup>4</sup>, C. Popescu<sup>5</sup>, D. Linnemann<sup>6</sup>, A. Săftoiu<sup>1,2</sup>, P. Vilmann<sup>1</sup></p><p><italic><sup>1</sup>Department of Gastroenterology, Copenhagen University Hospital Herlev, Herlev, Denmark, <sup>2</sup>Department of Gastroenterology, Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy Craiova, Craiova, Romania, <sup>3</sup>Department of Pathology, Rigshospital, University of Copenhagen, <sup>4</sup>Department of Gastrointestinal Surgery, Rigshopital, University of Copenhagen, Copenhagen, Denmark, <sup>5</sup>Department of Cytology, Emergency County Clinical Hospital Craiova, Craiova, Romania, <sup>6</sup>Department of Pathology, Copenhagen University Hospital Herlev, Herlev, Denmark</italic></p><p><bold>INTRODUCTION:</bold> Endoscopic ultrasound (EUS) is an established tool in diagnosing and staging pancreatic masses and enables guided fine needle aspiration (FNA). However, EUS-FNA has its drawbacks, due to a relatively low negative predictive value. Confocal laser endomicroscopy (CLE) has emerged in recent years as a novel method that enables <italic>in vivo</italic> microscopic analysis during ongoing endoscopy. Recently, CLE has gone beyond the superficial luminal indications with the development of a new microprobe (nCLE). The aim of the present preliminary case series was to study the feasibility of EUS guided nCLE and to correlate the findings with microscopy.</p><p><bold>AIMS&METHODS:</bold> A total number of 25 patients with pancreatic masses were included for EUS guided nCLE examinations. During the procedure, an nCLE fibre preloaded into a 19G FNA needle was advanced into the lesion under EUS guidance. Five mL of fluorescein 10% was administered intravenously and imaging performed until reproducible movies were obtained. Afterwards EUS-FNA was performed for cytology smears in the same location. Safety and feasibility were evaluated and the nCLE data was digitally stored for post procedural analysis, where structures like finger-like projections, thin grey lines, round lobular structures, tortuous vessel etc. were registered and correlated to the standard H&E cytopathology specimens, and in some cases histopathology. Moreover, additional topical acriflavine-enhanced <italic>ex vivo</italic> examinations on fresh pancreatic specimens were conducted using endoscope based CLE as well as nCLE.</p><p><bold>RESULTS:</bold> EUS-guided nCLE procedures were accomplished in all patients. No adverse advents were registered. Furthermore, it was feasible to do nCLE inside pathological lesions and relatively easy to visualize organ specific tissue. Despite selecting predefined structures the diagnostic value was limited mainly due to the missing ability to elucidate the cell nuclei, which is essential to discriminate between inflamed and carcinomatous tissue. In the <italic>ex vivo</italic> examinations, where acriflavine was administered topically on excised pancreatic tissue, the nuclei were clearly visualized, thus increasing the diagnostic value.</p><p><bold>CONCLUSION:</bold> EUS-guided nCLE procedures on focal pancreatic masses are feasible and safe, but the diagnostic value seems limited. Thus, further studies using different contrast agents and possibly targeted fluorescent markers are required to optimize the diagnostic accuracy.</p><p><bold>Contact E-mail Address:</bold><email>john.gasdal.karstensen.01@regionh.dk</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> confocal laser endomicroscopy, needle-based confocal laser endomicroscopy, pancreas, pancreatic adenocarcinoma</p></sec><sec><title>OP338 NEEDLE-BASED CONFOCAL LASER ENDOMICROSCOPY (NCLE) FOR THE DIAGNOSIS OF LYMPH NODES : PRELIMINARY CRITERIA (CONTACT STUDY)</title><p><bold>F. Caillol</bold><sup>1,*</sup>, M. Giovannini<sup>1</sup>, B. Napoléon<sup>2</sup>, B. Pujol<sup>2</sup>, A.-I. Lemaistre<sup>3</sup></p><p><italic><sup>1</sup>Gastroenterology and Hepatology, Institut Paoli Calmettes, Marseille, <sup>2</sup>Gastroenterology and Hepatology, Hôpital privé Jean Mermoz, <sup>3</sup>Pathology, Centre Léon Bérard, Lyon, France</italic></p><p><bold>INTRODUCTION:</bold> Needle-based Confocal Laser Endomicroscopy (nCLE) is an imaging technique , which enables microscopic observation of solid organs, <italic>in vivo</italic> and in real-time, during an EUSFNA procedure.</p><p><bold>AIMS&METHODS:</bold> This study aims at building an image atlas, and define interpretation criteria for nCLE images in the lymph nodes, within the frame of cancer staging.</p><p>3 centres in France (7 investigators) took part in this prospective study. Any suspicious lymph node studied by EUSFNA, with a size superior to 5mm, could be imaged by nCLE, but if a patient had multiple lymph nodes, only one of them could be imaged. The definition of the preliminary interpretation criteria was done by consensus, with 5 investigators, including one pathologist. 17 patients with suspicious lymph node were included over 8 months (August 2012 to March 2013) and the recorded nCLE sequences for each of these patients were reviewed. For each case, the investigators had the following data: patient's clinical history, information on the EUS procedure preceding nCLE imaging, cytology, histology findings, nCLE sequences, and, in certain cases, histological images. When reviewing the video sequences, they were asked to identify characteristic descriptive criteria, and correlate them with a final diagnosis if possible. The localization of the lymph nodes was : mediastinal (6 cases), celiac (6 cases), intra-abdominal (3 cases), hepatic hile (1 case) and hepatic pedicule (n=1). There were 14 men, and 3 women, mean age 59 years old, (extreme : 35-69 years old). The puncture of the lymph node was done in all cases with a 19G puncture needle. All had a size superior to 10mm.</p><p><bold>RESULTS:</bold> No complication occured during the nCLE procedure or the puncture. A definitive histological diagnosis was obtained in 14/17 patients. It was the following : 7 malignant (metastasis of primary cancer : pancreas, stomach, lung, kidney, prostate and lymphoma), 7 benign. During this review, all normal lymph nodes showed one sign : a reticular background, consisting in lymphocytes. On the other hand, tumoral lymph nodes presented dark clumps or aggregates of dark cells, and tumoral glands. Finally, a few criteria could be observed in all cases : white bands (blood vessels), macrophages, fat cells (bubbles), and thin straight bands over a regular dark aggregate which corresponds to fibrosis in the capsula of the lymph node.</p><p><bold>CONCLUSION:</bold> This preliminary classification of nCLE images obtained in lymph nodes could help in the differentiation of malignant and benign lymph nodes. nCLE could therefore facilitate the diagnosis of these lesions, by bringing <italic>in vivo</italic> microscopic information, in real-time.</p><p><bold>Contact E-mail Address:</bold><email>alexandras@maunakeatech.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> cancer staging, endomicroscopy, lymph node metastases</p></sec><sec><title>OP339 CONTRAST-ENHANCED ENDOSCOPIC ULTRASONOGRAPHY (CH-EUS) IN THE DIFFERENTIAL DIAGNOSIS OF PANCREATIC CYSTIC LESIONS (PCLS)</title><p><bold>P. Fusaroli</bold><sup>1,*</sup>, M. Serrani<sup>1</sup>, C. D'Ercole<sup>1</sup>, L. Ceroni<sup>1</sup>, S. Guglielmo<sup>1</sup>, G. Caletti<sup>1</sup></p><p><italic><sup>1</sup>University of Bologna, Imola, Italy</italic></p><p><bold>INTRODUCTION:</bold> EUS with fine needle aspiration (FNA) is widely used in the differential diagnosis of PCLs. However a definitive diagnosis is obtained by cytopathology only in a third of cases. The detection of biomarkers in the cystic fluid can add to the diagnostic yield but is still far from optimal accuracy.</p><p>CH-EUS has been reported as an useful adjunct in the differential diagnosis of pancreatic tumours.</p><p><bold>AIMS&METHODS:</bold> Our aim was to evaluate the potential role of CH-EUS in the differential diagnosisbetween mucinous and non-mucinous PCLs.</p><p>We performed a retrospective analysis of a prospective database. Inclusion criteria was a definitive diagnosis of either serous cystadenoma or mucinous PCL in a patient who had undergone CH-EUS after injection of 4.8 ml Sonovue®. Patients with simple cysts, pseudocysts and undetermined cysts were excluded. CH-EUS was used to assess the enhancement of cystic wall, septae and internal solid components. EUS-FNA and/or surgical pathology and/or long term follow up constituted our gold standard.</p><p><bold>RESULTS:</bold> In the period 2008-2012, 59 patients matched the inclusion criteria (37 F, 22 M; mean age 65.3 years, range: 39-82). The final diagnosis was as follows: 22 intraductal papillary mucinous neoplasms (IPMNs) (2 main duct, 19 branch type, 1 mixed type), 3 mucinous cystadenomas, 34 serous cystoadenomas. The main patterns observed at CH-EUS are shown in the table.
<table-wrap id="table53-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1"></th><th rowspan="1" colspan="1"><bold>Serous cystadenomas (n=34)</bold></th><th rowspan="1" colspan="1"><bold>Mucinous PCLs (n=25)</bold></th></tr></thead><tbody align="left"><tr><td rowspan="2" colspan="1">Hyperenhancing</td><td colspan="2" rowspan="1"><bold>Wall/Septae</bold></td></tr><tr><td rowspan="1" colspan="1">29</td><td rowspan="1" colspan="1">2</td></tr><tr><td rowspan="1" colspan="1">Hypoenhancing</td><td rowspan="1" colspan="1">5</td><td rowspan="1" colspan="1">23</td></tr></tbody></table></table-wrap></p><p><italic>Chi-square statistics: p<0.0001</italic></p><p>Internal solid components were detected at EUS in 12 patients with IPMN (10/12 unenhanced, 2/12 hyperenhanced). Interestingly, the patients with hyperenhanced solid components were finally diagnosed with malignant IPMN, unlike the patients with unenhanced solid components who turned out to have benign IPMN.</p><p><bold>CONCLUSION:</bold> Serous and mucinous PCLs exhibited distinctive patterns at CH-EUS, the former being hyperenhanced and the latter being hypoenhanced. Malignant vegetations were clearly shown by CH-EUS as hyperenhanced solid components. These different patterns may allow to use EUS-FNA in selected cases, avoid further diagnostic testing and possibly influence the clinical outcome of patients affected from PCLs.</p><p><bold>Contact E-mail Address:</bold><email>ptrfusa@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Contrast agents, Contrast harmonic, endoscopic ultrasonography, Pancreatic cysts</p></sec><sec><title>OP340 EVALUATION OF PRINCIPAL FACTORS IN PERFORMANCE OF EUS-GUIDED BIOPSIES FOR HIGH-YIELDS OF DNA AND MICRO-RNA EXTRACTED FROM PANCREAS</title><p><bold>L. Benesova</bold><sup>1,*</sup>, B. Belsanova<sup>1</sup>, R. Cuperkova<sup>1</sup>, B. Bunganic<sup>2</sup>, T. Dvorakova<sup>2</sup>, M. Zavoral<sup>2</sup>, M. Minarik<sup>1</sup></p><p><italic><sup>1</sup>Center for applied genomics of solid tumors, Genomac Research Institute, <sup>2</sup>Internal clinic, 1st Faculty of Medicine, Charles University and Central Military Hospital, Military Faculty Hospital, Prague, Czech Republic</italic></p><p><bold>INTRODUCTION:</bold> The continuing dismal prognosis of pancreatic cancer prompts sustained effort towards finidng better tools for diagnosis and treatment. Combining surgical treatment with chemotherapy if often without an apparent effect. Examination of molecular markers including somatic mutations and cell-surface proteins has long been adopted in diagnosis of pancreatic lesions and in estimation of prognosis. Recently, reports demonstrating utility of micro-RNA (miRNA) and DNA hypermethylation have generated a considerable interest from clinicians. Although these markers are frequently studied in other solid tumors, research on pancreatic tissue is far more difficult, expecially when it comes to getting sufficient yields of quality material collected from EUS-guided biopsies.</p><p><bold>AIMS&METHODS:</bold> The aim of the present work was to optimize all stages leading up to the analysis of levels of miRNA and DNA hypermethylation, both subsequently useful for estimation of prognosis and response to treatment. The EUS-guided biopsies were performed using three types of biopsy needles. Tissue from suspected lesions was acquired from 45 patients. DNA and RNA were extracted using four different commercial kits. From the extracted RNA a cDNA was created using two commercial kits and then miRNA analysis was performed by real-time PCR. Ammounts and integrity of the extracted DNA were tested by evaluating hypermethylation status in a panel 40 cancer-related genes by MLPA technique. Success rates for miRNA and DNA hypermethylation analyses were correlated to the clinical parameters of size, location of the tumor, the aspiration, bloodiness.</p><p><bold>RESULTS:</bold> The highest yields were obtained from bloodless biopsies acquired without aspiration from body and tail of the pancreas. This regardless of the type of the needle used, tumor size and, most notably, largely independent from the total volume panceatic mass collected. From the total levels of extracted RNA and the sucess rates for the DNA methylation analysis, an ideal protocol for extraction and RT-PCT was constructed and subsequently verified by sucesfully processing 20 pancreatic tissue samples.</p><p><bold>CONCLUSION:</bold> We evaluated the key factors in process of EUS-guided needle biopsy leading to reliable results of subsequent miRNA and DNA hypermethylation analyses. The results show that the sampling should preferably be carried out without aspiration and that any needle type, appropriate for the localization of the tumor, is generally applicable to yield genetic testing material.</p><p><bold>REFERENCES:</bold></p><p>1. Zavoral M et al. World J Gastroenterol. 2011, 28, 2897-2908.</p><p>2. Salek C et al. World J Gastroenterol. 2007, 21, 3714-3720.</p><p>3. Ali S et al. Br J Cancer. 2012, 107, 1354-1360.</p><p>4. Kida M et al. J Interv Gastroenterol. 2011, 1, 102–107.</p><p>5. Supported by the Czech Ministry of Health grant no. NT13638</p><p><bold>Contact E-mail Address:</bold><email>mminarik@email.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> DNA methylation, EUS FNA, miRNAs, Pancreatic Cancer, endosonography</p></sec><sec><title></title><p><bold>TUESDAY, OCTOBER 15, 2013 15:45-17:15</bold></p><p><bold>Identifying high risk colonic polyps – Hall 10</bold></p></sec><sec><title>OP341 MULTICENTER, PROSPECTIVE, COMPARATIVE TRIAL OF MAGNIFYING CHROMOENDOSCOPY AND ENDOSCOPIC ULTRASONOGRAPHY FOR STAGE DIAGNOSIS OF EARLY COLORECTAL CANCER</title><p><bold>M. Ebi</bold><sup>1,*</sup>, T. Shimura<sup>1,2</sup>, T. Yamada<sup>3</sup>, Y. Hirata<sup>4</sup>, H. Nishiwaki<sup>1</sup>, T. Mizushima<sup>5</sup>, K. Asukai<sup>6</sup>, S. Togawa<sup>6</sup>, S. Takahashi<sup>7</sup>, T. Joh<sup>1</sup></p><p><italic><sup>1</sup>Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan, <sup>2</sup>Boston Children’s Hospital and Harvard Medical School , Boston, United States, <sup>3</sup>Nagoya Daini Red Cross Hospital, Nagoya, <sup>4</sup>Kasugai Municipal Hospital, Kasugai, <sup>5</sup>Gifu Prefectural Tajimi Hospital, Tajimi, <sup>6</sup>Social Insurance Chukyo Hospital, <sup>7</sup>Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan</italic></p><p><bold>INTRODUCTION:</bold> Colorectal cancer (CRC) with intramucosal (M) and slight submucosal invasion (invasion depth <1000µm, SM<sub>S</sub>) has been currently considered as the indication of endoscopic resection, while surgical resection is recommended for deep submucosal invasion (invasion depth ≥1000µm, SM<sub>D</sub>). Magnifying chromoendoscopy (MC) and endoscopic ultrasonography (EUS) has been used to estimate the invasion depth of CRC, and both tools have shown the high accuracy in many retrospective studies.There have been two prospective studies, which showed the superiority of EUS to MC, but these studies could not provide definitive conclusion because definitions of MC were old and several biases existed by problems of study design. Thus, a prospective, comparative study of MC and EUS was performed.</p><p><bold>AIMS&METHODS:</bold> Patients with early flat CRCs were prospectively enrolled from 6 Japanese institutions and randomly allocated to primary MC followed by EUS (A group) and to primary EUS followed by MC (B group) in a back-to-back fashion. Diagnoses of invasion depth by each tool were divided into M-SMs and SM<sub>D</sub> and then collated with the final pathological diagnosis by an independent pathologist blinded to the clinical data. All endoscopists attended the consensus meeting and were trained before the trial to standardize diagnosis among examiners, and this trial was started after achievement of a mean k value ≥0.6 among all participating examiners. The primary end point was diagnostic accuracy for invasion depth.</p><p><bold>RESULTS:</bold> In total, 70 patients with 70 lesions were enrolled from February 2011 to December 2012, and the results of MC and EUS were finally analyzed for a total of 66 lesions, including 35 lesions in A group and 31 lesions in B group. The accuracy of invasion depth was 71.2% for both MC and EUS, and the sensitivity and specificity for ≥SM<sub>D</sub> were 74.2% and 68.6% for MC and 67.7% and 74.3% for EUS, respectively. No significant differences were found between MC and EUS. On the other hand, observation time was significantly shorter for MC than for EUS (361.7±164.5s <italic>vs.</italic> 451.2±209.4s; <italic>P</italic>=0.002).</p><p><bold>CONCLUSION:</bold> The present study could eliminate several biases which are concerned in the previous prospective studies by novel study design. MC did not improve the accuracy of invasion depth compared with EUS, but MC would be a substitute for EUS due to feasibility.</p><p><bold>Contact E-mail Address:</bold><email>tshimura@med.nagoya-cu.ac.jp</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Colorectal cancer, endoscopic ultrasound, magnifying endoscopy, Prospective Studies, staging</p></sec><sec><title>OP342 HIGH-MAGNIFYING COLONOSCOPY USING NBI INTERNATIONAL COLORECTAL ENDOSCOPIC (NICE) CLASSIFICATION IMPROVES HIGH CONFIDENCE RATE OF OPTICAL DIAGNOSIS FOR COLORECTAL POLYPS IN DIFFERENTING NEOPLASTIC AND NON-NEOPLASTIC LESIONS</title><p><bold>M. Iwatate</bold><sup>1,*</sup>, Y. Sano<sup>1</sup>, T. Ikumoto<sup>1</sup>, S. Hattori<sup>1</sup>, W. Sano<sup>1</sup>, N. Hasuike<sup>1</sup>, M. Kotaka<sup>1</sup>, Y. Murakami<sup>2</sup>, T. Kaltenbach<sup>3</sup>, R. Soetikno<sup>3</sup>, T. Fujimori<sup>4</sup></p><p><italic><sup>1</sup>Gastrointestinal Center, Sano Hospital, Kobe, <sup>2</sup>Department of Medical Statistics, Shiga University of Medical Science, Shiga, Japan, <sup>3</sup>Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto, California, United States, <sup>4</sup>Department of Surgical and Molecular Pathology, Dokkyo University School of Medicine, Tochigi, Japan</italic></p><p><bold>INTRODUCTION:</bold> NBI based real-time optical diagnosis has given us high performance characteristics to save formal histopathological assessment when the prediction was made with high confidence. Increasing high confidence rate of optical diagnosis is clinically important because this leads to the increase in finding the polyp we could apply for real-time optical diagnosis.</p><p><bold>AIMS&METHODS:</bold> The main purpose is to clarify that high-magnifying colonoscopy can improve high confidence rate of NBI without magnification using the NBI international colorectal endoscopic (NICE) classification. A consecutive patients who underwent total colonoscopy with a high-magnification (×80, max) colonoscope (CF-H260AZI, Olympus) between April 2012 and August 2012 at Sano hospital were eligible for our study. Two specialized colonoscopists (SC) and three general endoscopists (GE) predicted real-time polyp histology with confidence level followed by three steps: first by white light imaging (WLI), subsequently NBI with non-magnification (NBI-NM), finally NBI with high-magnification (NBI-HM). The high confidence rate of optical diagnosis by NBI-HM were compared with that by NBI-NM in differentiating between neoplastic and non-neoplastic lesions.</p><p><bold>RESULTS:</bold> 124 patients (56.4±9.2, M/F: 72/52) with 248 polyps resected (n of diminutive=210, n of small =38) were included. Of all 248 polyps, 81 were non neoplastic, 165 were adenoma (LG: 160, HG: 5), and, 2 were invasive cancer. The high confidence rate of NBI-HM was significantly superior to that of NBI-NM in both diminutive polyp (92.9% vs 79.5%, p<0.001, McNemar's Test) and small polyp (94.7% vs 84.2%, p=0.048, McNemar's Test). Subgroup analysis of doctors’ carrier showed that high diagnostic accuracy of high confidence prediction was observed in SC group (WLI, NBI-NM, and NBI-HM were 88.9%, 90.7%, and 90.1% in diminutive polyps, and all 100% in small polyps, respectively), but not in GE group (79.6%, 82.3% and 82.3% in diminutive polyps, and 91.7%, 91.7%, and 92.3% in small polyps, respectively).</p><p><bold>CONCLUSION:</bold> The high-magnifying colonoscopy is promising method to apply more diminutive and small polyps for NBI-based optical diagnosis with increasing high confidence rate. However performance characteristics of high confidence prediction made by GE group for diminutive polyp were not satisfactory. We need to establish efficient training system <italic>in vivo</italic> for general endoscopists.</p><p><bold>Contact E-mail Address:</bold><email>m.iwatate15@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> NBI, NICE classification, optical diagnosis, resect and discard</p></sec><sec><title>OP343 PREDICTIVE FACTORS OF ADENOMAS WITH HIGH-RISK CHARACTERISTICS BASED ON TWO PREVIOUS COLONOSCOPY FINDINGS</title><p><bold>J. S. Koo</bold><sup>1</sup>, J. J. Hyun<sup>1,*</sup>, S. Y. Kim<sup>1</sup>, S. W. Jung<sup>1</sup>, R. S. Choung<sup>1</sup>, S. W. Lee<sup>1</sup>, J. H. Choi<sup>1</sup></p><p><italic><sup>1</sup>Division of Gastroenterology Departmemt of Internal Medicine, Korea Univiversity Ansan Hospital, Ansan, Korea, Republic Of</italic></p><p><bold>INTRODUCTION:</bold> It is well known that the suggested intervals for surveillance colonoscopy are currently based on the findings of most recent examination. However, it was not established whether the previous two colonoscopies have the effects on third colonoscopy findings.</p><p><bold>AIMS&METHODS:</bold> We evaluated the risk factors of advanced or multiple adenomas or cancer on third colonoscopy and investigated the effects of previous two colonoscopies on third colonoscopy findings. Among the subjects who underwent screening colonoscopy from Jan. 2002 to Dec. 2009 at Korea University Ansan Hospital, the patients with third colonoscopy until Jun. 2012 were enrolled in this study. Baseline clinical characteristics and three colonoscopy and histopathologic findings of the subjects were reviewed retrospectively. In the study, ‘no adenoma’ was defined as hyperplastic polyp(s) or no adenoma. ‘Low-risk findings’ were defined as one or two small (<1 cm) tubular adenomas. ‘High-risk findings’ were defined as advanced adenoma or cancer or any sized multiple (≥3) adenomas.</p><p><bold>RESULTS:</bold> Among a total 1,066 subjects who underwent successfully the third colonoscopy, 72 (6.8%) had high-risk findings at the third colonoscopy. Multivariate analysis showed that the high-risk findings on third colonoscopy was associated with age (p <0.01) and the high-risk findings on first colonoscopy (p <0.01). The high-risk and low-risk findings on second colonoscopy were also a significant predictor of the high risk findings on third colonoscopy (respectively, p<0.01 and p <0.01). In the subjects with high-risk findings on second colonoscopy, the results from the first colonoscopy added no significant information about the probability of detecting high-risk findings on the third colonoscopy. In the subjects with low-risk findings or no adenoma on second colonoscopy, the first examination results such as high-risk findings added a significant information about the probability of detecting high-risk findings on the third colonoscopy (p<0.01).</p><p><bold>CONCLUSION:</bold> The surveillance intervals of third colonoscopy should be decided with the consideration of two previous colonoscopy findings.</p><p><bold>Contact E-mail Address:</bold><email>jskoo@korea.ac.kr</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> adenoma, surveillance colonoscopy</p></sec><sec><title>OP344 CLINICOPATHOLOGICAL FEATURES OF LATERALLY SPREADING TUMOR OF THE COLORECTUM</title><p><bold>N. Toyoshima</bold><sup>1,*</sup>, S.-E. Kudo<sup>1</sup>, T. Ishigaki<sup>1</sup>, Y. Yagawa<sup>1</sup>, K. Sudo<sup>1</sup>, Y. Mori<sup>1</sup>, T. Kudo<sup>1</sup>, T. Hayashi<sup>1</sup>, K. Wakamura<sup>1</sup>, H. Miyachi<sup>1</sup></p><p><italic><sup>1</sup>Digestive disease center, SHOWA UNIVERSITY NORTHERN YOKOHAMA HOSPITAL, Yokohama, Japan</italic></p><p><bold>INTRODUCTION:</bold> Laterally spreading tumors (LSTs) are usually good indication for endoscopic treatment because they are rather benign in spite of their large diameter. There are four subtypes in LSTs; granular type (homogeneous type (H) / nodular mixed type (M)), and non-granular type (flat-elevated type (F)/pseudo-depressed type (PD)). Their pathological features are different among subtypes.</p><p><bold>AIMS&METHODS:</bold> The aim of this study is to evaluate the clinicopathologial features of LSTs focusing on their locations and to clarify indications for EMR/EPMR and ESD.</p><p>In a retrospective review of the colonoscopy database (Apr 2001 to Dec 2012) at the Showa University Northern Yokohama Hospital, we selected cases of colorectal neoplasms based on the following criteria; endoscopically diagnosed cases of LSTs that underwent subsequent endoscopic or surgical resection. We evaluated clinicopathological features (gender, age, LSTs subtype, size, rate of submucosal invasion, treatment method) focusing on their locations. For analysis, the locations were divided into three group; right colon, left colon and rectum. We used chi-square test and one way ANOVA post hoc test for statistical analysis.</p><p><bold>RESULTS:</bold><table-wrap id="table54-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="2" colspan="1">N</th><th rowspan="1" colspan="1">Total</th><th rowspan="1" colspan="1">Right colon</th><th rowspan="1" colspan="1">Left colon</th><th rowspan="1" colspan="1">Rectum</th><th rowspan="2" colspan="1">P- value</th></tr><tr><th rowspan="1" colspan="1">1936</th><th rowspan="1" colspan="1">1173</th><th rowspan="1" colspan="1">507</th><th rowspan="1" colspan="1">256</th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">Age</td><td rowspan="1" colspan="1">66.9±10.5</td><td rowspan="1" colspan="1">67.3±10.1</td><td rowspan="1" colspan="1">66.6±10.7</td><td rowspan="1" colspan="1">65.3±11.7</td><td rowspan="1" colspan="1">P<0.001*</td></tr><tr><td rowspan="1" colspan="1">Gender</td><td rowspan="1" colspan="1">1164/772</td><td rowspan="1" colspan="1">721/452</td><td rowspan="1" colspan="1">296/211</td><td rowspan="1" colspan="1">147/109</td><td rowspan="1" colspan="1">N.S</td></tr><tr><td rowspan="1" colspan="1">Size(mm)</td><td rowspan="1" colspan="1">24.4±15.1</td><td rowspan="1" colspan="1">22.8±13.4</td><td rowspan="1" colspan="1">23.8±14.2</td><td rowspan="1" colspan="1">33.1±20.5</td><td rowspan="1" colspan="1">P<0.001*</td></tr><tr><td rowspan="1" colspan="1">G(H) / G(M) / NG(F) / NG(PD)</td><td rowspan="1" colspan="1">514/379/ 845/198</td><td rowspan="1" colspan="1">353/141/ 557/122</td><td rowspan="1" colspan="1">91/122/ 238/56</td><td rowspan="1" colspan="1">70/116/ 50/20</td><td rowspan="1" colspan="1">P<0.001†</td></tr><tr><td rowspan="1" colspan="1">Rate of submucosal invasion (%)</td><td rowspan="1" colspan="1">12.9</td><td rowspan="1" colspan="1">9.9</td><td rowspan="1" colspan="1">15.6</td><td rowspan="1" colspan="1">21.1</td><td rowspan="1" colspan="1">P<0.001†</td></tr><tr><td rowspan="1" colspan="1">ESD / EMR (EPMR)</td><td rowspan="1" colspan="1">1357/485</td><td rowspan="1" colspan="1">870/246</td><td rowspan="1" colspan="1">360/125</td><td rowspan="1" colspan="1">127/114</td><td rowspan="1" colspan="1"></td></tr></tbody></table></table-wrap></p><p>A total of 1961 LSTs were eligible for inclusion. The main results were shown in the table.</p><p>✓As the three types of LST(G(M)/NG(F)/NG(PD)) became larger, the ratio of submucosal invasion became higher. But LST-G(H) showed low rate of that even when they were large in diameter.</p><p>✓LST-NG(PD) had higher ratio of submucosal invasion (45.5%) than the other types.</p><p>✓In ESD, there was no significant difference of treatment results depend on the location(p>0.05).</p><p>✓In EMR/EPMR, over 20mm in diameter, residual tumor/recurrence rate was high at cecum(58.8%) and rectum(20.1%).</p><p><bold>CONCLUSION:</bold> We have to select the treatment method carefully according to LST subtypes and location, because their Clinicopathological features of LSTs are different.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Clinicopathological characteristics, colon cancer , ESD, LST</p></sec><sec><title>OP345 MOLECULAR FEATURES OF COLORECTAL POLYPS PRESENTING KUDO’S TYPE II PIT PATTERN</title><p><bold>K. Shinmura</bold><sup>1,*</sup>, K. Konishi<sup>1</sup>, Y. Kubota<sup>1</sup>, Y. Yano<sup>1</sup>, A. Katagiri<sup>1</sup>, T. Muramoto<sup>1</sup>, T. Kihara<sup>1</sup>, M. Tojo<sup>1</sup>, K. Konda<sup>1</sup>, T. Tagawa<sup>1</sup>, T. Yamochi<sup>2</sup>, H. Yoshida<sup>1</sup></p><p><italic><sup>1</sup>Division of Gastroenterology, Department of Medicine, <sup>2</sup>Department of Pathology , Showa university School of Medicine, Tokyo, Japan</italic></p><p><bold>INTRODUCTION:</bold> Hyperplastic polyp (HP), sessile serrated adenoma (SSA) and traditional serrated adenoma (TSA) are thought to be precursor lesions of serrated pathway. However, hyperplastic mucosal crypt patterns (so-called Kudo’s type II) are frequently observed in these lesions under chromoendoscopy. We hypothesized that there are biological or molecular differences among the serrated polyps (SPs) with hyperplastic crypt pattern and that these features are associated with their different pathways of progression to CRC. To test this hypothesis, we evaluated the molecular features of SPs with hyperplastic crypt pattern.</p><p><bold>AIMS&METHODS:</bold> We examined the clinicopathological and molecular features of 112 SPs with hyperplastic [stellar or papillary pits] crypt pattern that were resected endoscopically at Showa University Hospital from February 2009 to August 2012. We investigated the frequency of mutations of <italic>KRAS</italic> and <italic>BRAF</italic>; microsatellite instability (MSI); and CpG island methylator phenotype (CIMP), including the methylation of two or more CIMP-related genes (MINT1, 2, 31, p16, and MLH1). HPs were classified into microvesicular HP (MVHP), goblet cell–rich HP (GCHP), and mucin-poor HP (MPHP) variants on the basis of WHO classification.</p><p><bold>RESULTS:</bold> 112 SPs with hyperplastic pattern comprised 65 serrated neoplasias (SNs) (5 TSAs, 62 SSAs), 35 MVHPs and 10 GCHPs. TSAs and SSAs were frequently located in the proximal colon, compared to others (P < 0.01). We found no significant difference in the frequency of <italic>BRAF</italic> mutation among SPs except GCHP (60% for TSAs, 45% for SSAs, 49% for MVHPs and 0% for GCHPs). Furthermore, a significant difference was observed in the frequency of CIMP between TSAs or SSAs and GCHPs (60% for TSAs, 56% for SSAs, 32% for MVHPs and 10% for GCHPs) (P < 0.05). When we classified SPs into proximal and distal lesions, proximal lesions had a macroscopically superficial appearance, whereas distal lesions had a protruding appearance (P < 0.01). Moreover, the frequency of CIMP was significantly higher in the proximal than the distal lesions (60% vs. 14%, <italic>P</italic> < 0.05).</p><p><bold>CONCLUSION:</bold> We observed distinct molecular features between proximal and distal SPs with hyperplastic crypt pattern. Proximal SPs with hyperplastic pattern may develop from MVHPs through SSAs/TSAs to colon cancers.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> colonoscopy, molecular alterlation</p></sec><sec><title></title><p><bold>TUESDAY, OCTOBER 15, 2013 15:45-17:15</bold></p><p><bold>Gastroduodenal and small intestinal tumours – Hall 8</bold></p></sec><sec><title>OP346 NEURONAL ADHESION MOLECULE CHL1 IS EXPRESSED IN GASTROINTESTINAL STROMA TUMORS (GIST) AND ITS SERUM LEVELS SERVE AS PROGNOSTIC MARKER</title><p><bold>M. Tachezy</bold><sup>1,*</sup>, H. Zander<sup>1</sup>, K. von Loga<sup>2</sup>, F. Gebauer<sup>1</sup>, M. Schachner<sup>3</sup>, J. R. Izbicki<sup>1</sup>, M. Bockhorn<sup>1</sup></p><p><italic><sup>1</sup>General, Visceral and Thoracic Surgery, <sup>2</sup>Pathology, <sup>3</sup>Center for Molecular Neurobiology, Department of Biosynthesis of Neural Structures, University Medical Center Hamburg-Eppendorf, Hamburg, Germany</italic></p><p><bold>INTRODUCTION:</bold> Until now, diagnosis of gastrointestinal stroma tumors (GIST) is based on endoscopic or surgical biopsy or resection. An established tumor marker is lacking. Recently, the neural cell adhesion molecul L1 (CD171) was identified as a specific marker for GIST tumors. Elevated L1 expression in the tumor and L1 serum levels are associated with a shortened recurrence free survival and might serve as a prognostic marker for GIST. Another family member of the so called L1-family is the Close Homologue to L1 (CHL1).</p><p><bold>AIMS&METHODS:</bold> This current study was conducted to evaluate the expression of CHL1 in GIST and to determine whether or not the ectodomain shedding of CHL1 could serve as a biomarker in the peripheral blood of GIST patients.</p><p>Immunohistochemical CHL1 staining of 46 GIST on a tisue microarray (TMA) were performed. A high sensitive and specific sandwich ELISA test was established. Western blots and quantitative real time PCR experiments (rt-PCR) were performed in tumor material and GIST cell line (GIST884). CHL1 levels were measured in 101 GIST patients und 92 healthy control sera. Results were statistically correlated with clinical-pathological data.</p><p><bold>RESULTS:</bold> CHL1 is expressed in 70% of GIST in immunohistochemical and Western-blot analysis, also an expression was detected in GIST884 cell line. Quantitative rt-PCR showed an overexpression of one of the known CHL1 splice variants in GIST specimen. CHL1 serum level are significantly elevated in GIST patients compared to the control group (p<0.01, t-test). Elevated CHL1 levels are significantly associated with larger tumors, the tumor staging according Fletcher and a localization in the small bowel. Moreover, patients with a higher CHL1 serum level showed a significantly shortened recurrence free survival (p<0.0001, Log-rank Test). Median recurrence free survival in patients with an elevated CHL1 level is 20 months, compared to 83 months in the group of a low CHL1 level. Multivariate survival analysis showed a significantly independent effect on recurrence free survival (HR 3.9, p=0,011)</p><p><bold>CONCLUSION:</bold> The results of the study indicate a potential role of serum CHL1 as a prognostic marker in GIST, additional experiments with larger patient cohorts must validate these preliminary data.</p><p>Further study should investigate the functional role of CHL1 in GIST. Its high rate of expression and its nature as a membrane protein make it an ideal structure for targeted therapy, potentially with Isoform-selective.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> GIST, Tumor Markers</p></sec><sec><title>OP347 ELEVATED SOLUBLE IL-2 RECEPTOR LEVEL CORRELATED WITH TUMOR BULK IN FOLLICULAR LYMPHOMA WITH INTESTINAL INVOLVEMENT</title><p><bold>M. Iwamuro</bold><sup>1,*</sup>, H. Okada<sup>2</sup>, K. Shinagawa<sup>3</sup>, K. Takata<sup>4</sup>, T. Yoshino<sup>4</sup>, K. Yamamoto<sup>1</sup></p><p><italic><sup>1</sup>Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, <sup>2</sup>Department of Endoscopy, Okayama University Hospital, <sup>3</sup> Department of Hematology and Oncology, <sup>4</sup>Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan</italic></p><p><bold>INTRODUCTION:</bold> Serum-soluble interleukin 2 receptor (sIL-2R) is widely used as a tumor marker in lymphoma patients, but its clinical utility in follicular lymphoma patients with gastrointestinal involvement has never been studied.</p><p><bold>AIMS&METHODS:</bold> To reveal the correlation between sIL-2R levels and other clinical characteristics in follicular lymphoma patients with gastrointestinal involvement, a total of 44 patients were retrospectively examined. Patients were subdivided into two groups according to the serum-soluble interleukin 2 receptor (sIL-2R) levels (normal vs. elevated). Clinical characteristics of the two groups were compared.</p><p><bold>RESULTS:</bold> Patients with elevated sIL-2R levels likely had systemic involvement (Ann Arbor system staging IIIES/IV or Lugano system staging II-2/IV), 5 or more nodal areas, and bulky tumors in the gastrointestinal tract. Such patients also had a greater risk of an inferior Follicular Lymphoma International Prognostic Index (FLIPI) score, suggesting a poorer prognosis. In addition, though the difference was not statistically significant, more patients with elevated sIL-2R tended to have lower hemoglobin levels (< 12 g/dL) than patients with normal sIL-2R. No differences were found in other clinical characteristics such as sex, age at diagnosis of lymphoma, histological grade, LDH levels, bone marrow involvement, and tracer accumulation in gastrointestinal lesions by PET scanning.</p><p><bold>CONCLUSION:</bold> sIL-2R levels may be an independent prognostic index in these patients, because it was correlated with FLIPI. Moreover, since high sIL-2R levels reflected large tumor bulk, sIL-2R may be a good tool for monitoring of disease relapse or progression.</p><p><bold>Contact E-mail Address:</bold><email>iwamuromasaya@yahoo.co.jp</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> follicular lymphoma, gastrointestinal lymphoma, soluble interleukin 2 receptor</p></sec><sec><title>OP348 USEFULNESS OF ULTRASONOGRAPHY FOR DIAGNOSIS OF SMALL BOWEL TUMORS; CONSIST OF CAPSULE ENDOSCOPY AND DOUBLE BALLOON ENDOSCOPY.</title><p><bold>M. Fujita</bold><sup>1,*</sup>, N. Manabe<sup>2</sup>, J. Hata<sup>2</sup>, K. Honda<sup>3</sup>, T. Murao<sup>1</sup>, K.-I. Tarumi<sup>1</sup>, T. Akiyama<sup>4</sup>, A. Shiotani<sup>1</sup>, K. Haruma<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology, <sup>2</sup>Endoscopy and Ultrasonography, <sup>3</sup>General Medicine, <sup>4</sup>Pathology, Kawasaki Medical School, Kurashiki, Japan</italic></p><p><bold>INTRODUCTION:</bold> Recently, many papers showed that an ultrasonography (US) is a conventional and non-invasive modality for the examination of abdominal cavity.</p><p><bold>AIMS&METHODS:</bold> The aim of this study was to evaluate the usefulness of US for the diagnosis of small bowel tumors (SBTs). Three hundreds and eighty five consecutive patients (201 male, 184 female, mean age 70.1) who underwent capsule endoscopy (CE) and/or balloon assisted endoscopy (BAE) were enrolled in this study. All patients underwent US prior to CE and BAE. The sensitivity and specificity of US in detecting SBTs, size of detected SMTs, detection rate of SBTs by US were evaluated.</p><p><bold>RESULTS:</bold> A total of 75 tumors detected by CE and/or BAE were retrospectively analyzed. The sensitivity and specificity of US in the detection of SBTs were 54.7% (41/75) and 99.4% (308/310). The detection rate for tumors was only 3.6% (1/28) when the tumor size is less than 10mm in diameter, while the detection rate for tumors which size were 10 mm or larger was 85.1% (40/47). All SBTs with partial ulcerative and circumferential lesions were detected by US.</p><p><bold>CONCLUSION:</bold> US examination is considered to be a useful modality for detecting small bowel lesions. We consider that US examination is the first choice modality for examining SBTs because it is a conventional and non-invasive procedure.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> balloon-assisted enteroscopy, capsule endoscopy, small bowel tumor, ultrasonography</p></sec><sec><title>OP349 SMALL BOWEL ADENOCARCINOMA PHENOTYPING, RESULTS OF THE AGEO STUDY</title><p><bold>T. Aparicio</bold><sup>1,*</sup>, M. Svrcek<sup>2</sup>, A. Zaanan<sup>3</sup>, E. Beohou<sup>4</sup>, A. Laforest<sup>5</sup>, P. Afchain<sup>6</sup>, E. Mitry<sup>7</sup>, J. Taieb<sup>3</sup>, P. Laurent-Puig<sup>8</sup></p><p><italic><sup>1</sup>Gastroenterology, CHU Avicenne, Bobigny, <sup>2</sup>Pathology, CHU Saint Antoine, <sup>3</sup>Gastroenterology, CHU G. Pompidou, Paris, <sup>4</sup>Methodology, CHU Besançon, Besançon, <sup>5</sup>UMR-S775 , Paris-Sorbonne cité, <sup>6</sup>Oncology, CHU Saint Antoine, <sup>7</sup>Gastroenterology, Institut Curie, <sup>8</sup>INSERM UMR-S775, Paris-Sorbonne cité, Paris, France</italic></p><p><bold>INTRODUCTION:</bold> Small bowel adenocarcinoma (SBA) is a rare tumor with poor prognosis. Data about molecular biology on SBA carcinogenesis are lacking.</p><p><bold>AIMS&METHODS:</bold> Formalin-fixed and paraffin-embedded SBA from 63 patients were included. Ampullary tumors were excluded. DNAs were extracted from formalin fixed paraffin embedded samples. HER2, β-catenin, TP53 and mismatch repair (MMR) protein expression were assessed by immunohistochemistry. Overexpression of TP53 was defined as more than 50% of cells with nuclear staining. Abnormal expression of β-catenin was defined as a nuclear staining. <italic>KRAS</italic>, V600E <italic>BRAF</italic> mutations and microsatellite instability were investigated. Patients were enrolled in the study at all stage of disease.</p><p><bold>RESULTS:</bold> We obtained samples from 63 SBA pts (median age, 58 years; tumour stage: I-II, n=19 (30%); III, n=22 (35%); IV, n=20 (32%); locally advanced, n=2 (3%)). HER2 overexpression (3+) was observed in 2/62 pts. Overexpression of TP53 was observed in 26/62 (42%) pts, abnormal expression of β-catenin in 12/62 (19%) pts and MMR deficiency (dMMR) in 14/61 (23%) pts, consistent with Lynch syndrome in 7/14 (50%) pts. All of the dMMR tumours were in duodenum or jejunum. Only one of dMMR tumour was stage IV. A <italic>KRAS</italic> mutation was observed in 21/49 (43%) pts and <italic>BRAF</italic> V600E mutation in only 1/40 pt. Median overall survival (OS) was 36.6 months (95% confidence interval [CI], 26.9-72.2). For all patients, in univariate analysis, stage I-II (p<0.001), WHO PS 0-1 (p=0.01) and dMMR phenotype (p=0.02) were significantly associated with longer OS. In multivariate analysis, disease stage (p=0.01) and WHO PS 0-1 (p=0.001) independently predicted longer OS. For stage I-III pts median recurrence-free survival (RFS) was 26.7 months. A trend for a better RFS was observed if tumour was dMMR HR: 0.41 (CI, 0.13 – 1.28), p=0.12. For stage IV pts, median OS was 17.9 months. In multivariate analysis, WHO PS 0-1 (p=0.001) and mutated <italic>KRAS</italic> status (p=0.04) independently predicted longer OS</p><p><bold>CONCLUSION:</bold> This large study suggests that molecular alterations in SBA are closer to those in colorectal cancer (CRC) than those in gastric cancer, with low levels of HER 2 overexpression and high rates of <italic>KRAS</italic> mutations. The seemingly higher rate of dMMR than in CRC may be explained by the higher frequency of Lynch syndrome in SBA. A trend for good prognosis was associated with dMMR.</p><p><bold>Contact E-mail Address:</bold><email>thomas.aparicio@avc.aphp.fr</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> adenocarcinoma, Molecular biomarker, Prognostic factors, Small Bowel</p></sec><sec><title>OP350 COMPARISON OF ENDOSCOPIC AND CLINICOPATHOLOGICAL FEATURES OF GASTRIC AGGRESSIVE B-CELL LYMPHOMA ACCORDING TO HUMAN IMMUNODEFICIENCY VIRUS INFECTION STATUS</title><p><bold>S. Nakazuru</bold><sup>1,*</sup>, T. Uehira<sup>2</sup>, A. Sugimoto<sup>1</sup>, T. Iwasaki<sup>1</sup>, R. Iwasaki<sup>1</sup>, H. Hasegawa<sup>1</sup>, T. Yamada<sup>1</sup>, Y. Sakakibara<sup>1</sup>, T. Yoshio<sup>1</sup>, T. Toyama<sup>1</sup>, H. Ishida<sup>1</sup>, Y. Kodama<sup>3</sup>, E. Mita<sup>1</sup></p><p><italic><sup>1</sup>Department of Gastroenterology and Hepatology, <sup>2</sup>AIDS Medical Center, <sup>3</sup>Department of Pathology, Osaka National Hospital, Osaka, Japan</italic></p><p><bold>INTRODUCTION:</bold> Human immunodeficiency virus (HIV)-associated non-Hodgkin lymphoma is the most common HIV-associated malignancy despite the advent of combination antiretroviral therapy. The gastrointestinal (GI) tract is one of the most common extranodal sites, and the stomach is the most common site.</p><p><bold>AIMS&METHODS:</bold> We investigated the endoscopic and clinicopathological features of gastric lymphoma patients according to HIV infection status. We retrospectively analyzed the medical records of GI lymphoma and HIV-associated lymphoma patients from April 2000 to March 2013. The macroscopic types of gastric lymphoma were classified into protruded, fold thickening, multiple lymphomatous polyposis, ulcerative, superficial, or mixed type.</p><p><bold>RESULTS:</bold> Of 2,314 HIV-positive patients, 16 were diagnosed with GI lymphoma. The stomach was the most common site of GI involvement (n = 10, 63%), followed by the duodenum (n = 5, 31%). One patient was diagnosed upon autopsy with gastric diffuse large B-cell lymphoma (DLBCL). Of the 9 HIV-positive gastric lymphoma patients, 6 (67%) had Burkitt lymphoma and 3 (33%) had DLBCL. Of the 49 HIV-negative gastric lymphoma patients evaluated, 24 (49%) were diagnosed with DLBCL. Burkitt lymphoma was not recognized in the HIV-negative patients. In total, 9 HIV-positive and 24 HIV-negative patients with aggressive gastric B-cell lymphoma were evaluated. Age at diagnosis was lower and lactate dehydrogenase levels were higher in HIV-positive patients than in HIV-negative patients. A variety of endoscopic appearances of gastric lesions was noted. Mixed type lesions were more frequent in HIV-positive patients than in HIV-negative patients (44% vs 21%), but this difference was not significant. In HIV-positive patients, Burkitt lymphoma presented as the protruded type in 4 patients and as the mixed type in 2. DLBCL presented as the mixed type in 2 patients and as the superficial type in 1. HIV-positive patients had more lesions than HIV-negative patients, and Burkitt lymphoma patients had more lesions than DLBCL patients. The median follow-up time of DLBCL patients was 22 months (range, 1–138 months). The overall survival rate did not differ significantly between HIV-positive and HIV-negative DLBCL patients (<italic>P</italic> = 0.771).</p><p><bold>CONCLUSION:</bold> Burkitt lymphoma was seen in only HIV-infected gastric lymphoma patients. Gastric lymphoma patients with HIV-infection or Burkitt lymphoma had more lesions. The macroscopic type was not associated with HIV infection status.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Endoscopy, HIV, Lymphoma, Stomach</p></sec><sec><title>OP351 ANTITUMOR EFFECTS OF NOVEL PHOTODYNAMIC THERAPY WITH GLUCOSE CONJUGATED CHLORIN FOR GIST</title><p><bold>M. Tanaka</bold><sup>1,*</sup>, H. Kataoka<sup>1</sup>, S. Yano<sup>2</sup>, T. Joh<sup>1</sup></p><p><italic><sup>1</sup>Departments of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, <sup>2</sup>Graduate School of Materials Science, Nara Institute of Science and Technology, Nara, Japan</italic></p><p><bold>INTRODUCTION:</bold> Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Except for surgical resection, no effective treatment strategies have been established. Photodynamic therapy (PDT) consists of intravenous administration of a photosensitizer, activated by a specific wavelength of light, which produces reactive oxygen species that directly kill tumor cells. GIST cells uptake glucose as shown in PET scans and the long wavelengths of the light spectrum -red, 630-670nm- can penetrate to the deep layer of the stomach wall. We analyzed the efficacy of PDT using a newly developed photosensitizer, 5, 10, 15, 20-tetrakis [4-[b-D-glucopyranosylthio-2, 3, 5, 6-tetrafluorophenyl]-2, 3,[methano[<italic>N-</italic>methyl] iminomethano] chlorin (H<sub>2</sub>TFPC-SGlc) for the GIST treatment.</p><p><bold>AIMS&METHODS:</bold> Various photosensitizers were administered <italic>in vitro </italic>to GIST (GIST-T1) and fibroblast (WI-38) cells, followed by irradiation of 650nm red light, after which cell death was compared. We additionally established xenograft mouse models with GIST-T1 tumors and examined the accumulation by measuring the spectral waveforms and antitumor effects of these photosensitizers <italic>in vivo</italic>.</p><p><bold>RESULTS:</bold><italic>In vitro, </italic>the expression of the glucose transporters GLUT1, GLUT3, and GLUT4, the cellular uptake of H<sub>2</sub>TFPC-SGlc, and apoptosis mediated by PDT with H<sub>2</sub>TFPC-SGlc were significantly higher in GIST-T1 than in WI-38 cells. <italic>In vivo</italic>, H<sub>2</sub>TFPC-SGlc accumulation was higher in xenograft tumors of GIST-T1 cells than in the adjacent normal tissue, and tumor growth was significantly suppressed following PDT.</p><p><bold>CONCLUSION:</bold> As chemotherapy and/or radiation therapy are not solely effective for GIST treatment, novel treatments for GIST have been explored. In this study, we conclude that H<sub>2</sub>TFPC-SGlc-mediated PDT had specificity for GIST-T1 cells and effectively suppressed the growth of xenograft tumors through apoptosis without observable damage to the adjacent normal tissue. Based on the properties and characteristics of H<sub>2</sub>TFPC-SGlc presented in this study, we suggest that H<sub>2</sub>TFPC-SGlc is a potential photosensitizer for PDT of GIST.</p><p><bold>REFERENCES:</bold></p><p>1. Tanaka M, Kataoka H, Mabuchi M, et al. Anticancer Effects of Novel Photodynamic Therapy with Glycoconjugated Chlorin for Gastric and Colon Cancer Anticancer Res March 2011 31 (3) 763-769</p><p><bold>Contact E-mail Address:</bold><email>mtanaka@med.nagoya-cu.ac.jp</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> apoptosis, photodynamic therapy (PDT), reactive oxygen species (ROS)</p></sec><sec><title></title><p><bold>TUESDAY, OCTOBER 15, 2013 15:45-17:15</bold></p><p><bold>Autoimmune pancreatitis: Mechanism and treatment – Salon 11/12</bold></p></sec><sec><title>OP352 IGG4-RELATED AUTOIMMUNE PANCREATITIS AND CHOLANGITIS IS ASSOCIATED WITH EXTRA-PANCREATIC ORGAN FAILURE, MALIGNANCY AND MORTALITY IN A PROSPECTIVE UK COHORT.</title><p><bold>M. Huggett</bold><sup>1,2</sup>, E. Culver<sup>3,4,*</sup>, M. Kumar<sup>2</sup>, M. Chapman<sup>2</sup>, G. Johnson<sup>2</sup>, S. Pereira<sup>1</sup>, R. Chapman<sup>3,5</sup>, G. Webster<sup>2</sup>, E. Barnes<sup>3,6</sup></p><p><italic><sup>1</sup>UCL Institute for Liver and Digestive Health, University College London, <sup>2</sup>Department of Gastroenterology, University College Hospital, London, <sup>3</sup>Translational Gastroenterology Unit , John Radcliffe Hospital, <sup>4</sup>NDM, Oxford University, <sup>5</sup>NDM , Oxford University, <sup>6</sup>Oxford NIHR BRC, Oxford University, Oxford, United Kingdom</italic></p><p><bold>INTRODUCTION:</bold> Autoimmune pancreatitis (AIP) is now recognised as one component of a multi-system IgG4-related disease (IgG4-RD). Consensus on diagnostic criteria has been reached, but the course of clinical disease is less well defined. We report data from a prospective cohort of 116 UK patients with IgG4-related autoimmune pancreatitis and/or cholangitis, followed from diagnosis for a median of 3 years.</p><p><bold>AIMS&METHODS:</bold> Data were collected from two UK tertiary referral centres, University College Hospital, London, and The John Radcliffe Hospital, Oxford, from 2004-2013, in whom a diagnosis of AIP or IgG4-related cholangiopathy (IRC) was made. All patients were followed prospectively and data added to an AIP/IgG4-RD database. Diagnoses were initially made using the Japan Pancreas Society criteria and then, since 2007, the HISORt criteria for AIP and IRC [1,2]. The recent Boston Consensus Histopathological Criteria for IgG4-RD (2012) was applied to those with surgical resection specimens [3].</p><p><bold>RESULTS:</bold> Presentation with obstructive jaundice occurred in 74% and acute pancreatitis in only 3%. Raised serum IgG4 was found in 76% at some point in the disease course, and positive IgG4 immunostaining in 74% of tissue samples. Extra-pancreatic involvement occurred in 72% of patients. Whilst there was an initial response to steroids in 97%, subsequent relapse occurred in 50%. Extra-pancreatic disease was a significant predictor of relapse (P=0.002).</p><p>Six patients (5%) developed liver cirrhosis during follow-up and one of these underwent a successful liver transplantation. Exocrine insufficiency occurred in 53% of patients and diabetes in 37%. Other complications included sialadenitis, renal infiltrates, interstitial lung disease, retroperitoneal fibrosis, inflammatory arthropathy, and neurological sequelae including a pituitary mass and a rapidly progressive autoimmune encephalitis.</p><p>Malignancy occurred in 11% shortly before, or following, the diagnosis of IgG4-RD, including 3 HPB cancers. In total, eleven patients (9%) in our cohort died during follow-up.</p><p><bold>CONCLUSION:</bold> The findings suggest that IgG4-related pancreatic disease is associated with significant morbidity and mortality due to extra-pancreatic organ failure and malignancy. Detailed clinical evaluation for associated malignancy at first presentation, and careful long-term follow up of patients with IgG4-RD, is required.</p><p><bold>REFERENCES:</bold></p><p>1. Chari ST, Smyrk TC, Levy MJ, et al. Diagnosis of autoimmune pancreatitis: the Mayo Clinic experience. Clin Gastroenterol Hepatol 2006;4:1010-6.</p><p>2. Bjornsson E, Chari ST, Smyrk TC, Lindor K. Immunoglobulin G4 associated cholangitis: description of an emerging clinical entity based on review of the literature. Hepatology 2007;45(6):1547-54.</p><p>3. Deshpande V, Zen Y, Chan JK, et al. Consensus statement on the pathology of IgG4-related disease. Mod Pathol 2012;25:1181-92.</p><p><bold>Contact E-mail Address:</bold><email>george.webster@uclh.nhs.uk</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> autoimmune pancreatitis, IgG4-related cholangiopathy, IgG4-related systemic disease</p></sec><sec><title>OP353 THE LONG-TERM OUTCOME OF AUTOIMMUNE PANCREATITIS: PANCREATIC FUNTION AND QUALITY OF LIFE</title><p><bold>J. Buijs</bold><sup>1,*</sup>, D. Cahen<sup>1</sup>, M. van Heerde<sup>1</sup>, E. Rauws<sup>2</sup>, L. Maillette de Buij Wenniger<sup>2</sup>, B. Hansen<sup>1</sup>, K. Biermann<sup>1</sup>, J. Verheij<sup>2</sup>, F. Vleggaar<sup>3</sup>, M. Brink<sup>4</sup>, U. Beuers<sup>2</sup>, H. van Buuren<sup>1</sup>, M. Bruno<sup>1</sup></p><p><italic><sup>1</sup>Erasmus University Medical Center, Rotterdam, <sup>2</sup>Academic Medical Center, Amsterdam, <sup>3</sup>University Medical Center , Utrecht, <sup>4</sup>Meander Medical Center, Amersfoort, Netherlands</italic></p><p><bold>INTRODUCTION:</bold> Autoimmune pancreatitis (AIP) is the pancreatic manifestation of a systemic IgG4-related fibroinflammatory disorder (IgG4-RD). The long-term course of this form of pancreatitis is scarcely described.</p><p><bold>AIMS&METHODS:</bold> The aim of this study was to investigate the long-term outcome of AIP, in terms of pancreatic function, quality of life (QoL), pancreatic carcinoma, and mortality. From our AIP database registry, we identified patients with a minimum follow-up of 2 years. Information was subtracted regarding treatment (outcome), pancreatic carcinoma, and mortality. If informed consent was obtained, additional follow-up data was collected prospectively. To evaluate the pancreatic function, a fecal elasase-1 test was performed (normal value > 200 µg/g) and fasting blood glucose (FBG) and glycated haemoglobin were determined. Patients were considered to be endocrine insufficient if they received treatment for glycaemic control, or when FBG was above 7.0 mmol/l and the HbA1c level was more than 48 mmol/mol (6.5%). QoL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) and the Short Form-36 (SF-36). Scores were compared to those obtained from a Dutch reference population, matched for sex and age.</p><p><bold>RESULTS:</bold> A total of 111 patients were identified from the database (96 males; median age 72 yrs; IQR 61-78), with a median follow-up of 84 months (IQR 52-120). From 43 patients, only retrospective data were obtained (39%); 21 (19%) had died, 10 (9%) were lost to follow-up, and 12 (11%) did not agree to participate. Sixty-eight patients were followed prospectively, with a median follow-up of 73 months (IQR 49-103). IgG4-associated cholangitis was present in 36/66 (55%) patients. In total, 55/68 (81%) of patients received steroid therapy, with a response rate of 100%. At follow-up, exocrine insufficiency was present in 56/67 patients (84%) and endocrine insufficiency in 44/64 patients (69%). No significant differences in QoL scores were found between AIP patients and the reference population. None of the patients developed pancreatic carcinoma during follow-up.</p><p><bold>CONCLUSION:</bold> At long-term follow up, most AIP patients are found to have both exo- and endocrine pancreatic insufficiency. Therefore, regular evaluation of the pancreatic function is recommended. Long-term QoL is not impaired and we did not observe any occurrence of pancreatic cancer in our series.</p><p><bold>Contact E-mail Address:</bold><email>j.buijs.1@erasmusmc.nl</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> autoimmune pancreatitis, long-term outcome, pancreatic function, quality of life</p></sec><sec><title>OP354 UTILITY OF SERUM CARBONIC ANHYDRASE II, IGG AND IGG4 IN DISTINGUISHING AUTOIMMUNE PANCREATITIS FROM PANCREATIC CANCER AND IDIOPATIC CHRONIC PANCREATITIS.</title><p><bold>R. Talar-Wojnarowska</bold><sup>1,*</sup>, A. Gasiorowska<sup>1</sup>, M. Olakowski<sup>2</sup>, P. Lampe<sup>3</sup>, M. Kujawiak<sup>4</sup>, J. Grzegorczyk<sup>4</sup>, E. Malecka-Panas<sup>1</sup></p><p><italic><sup>1</sup>Department of Digestive Tract Diseases, Medical University, Lodz, <sup>2</sup>Department of Digestive Tract Surgery, <sup>3</sup>Department of Digestive Tract Diseases, Silesian Medical University, Katowice, <sup>4</sup>Department of Microbiology and Laboratory Medical Immunology, Medical University, Lodz, Poland</italic></p><p><bold>INTRODUCTION:</bold> Autoimmune pancreatitis (AIP) can mimic pancreatic cancer in its clinical presentation, imaging features and laboratory parameters. In the present study, sera from patients with AIP, pancreatic adenocarcinoma (PA) and chronic pancreatitis (CP) were evaluated for IgG, IgG4 and carbonic anhydrase II (CAII).</p><p><bold>AIMS&METHODS:</bold> The study included 124 patients: 45 with PA, 24 with AIP and 55 with CP. The serum levels of IgG, IgG4 and CAII were measured and the associations of the IgG, IgG4, and CAII and clinical data at diagnosis have been evaluated.</p><p><bold>RESULTS:</bold> Serum levels of IgG, IgG4 and CAII were higher in AIP patients compared to PA and CP patients (p<0,001). In AIP patients the median IgG levels were 19,7 g/l, IgG4 301,9 mg/dl and CAII 81,82 ng/ml. In PA patients respectively 10,61g/l, 123,2 mg/dl and 28,6 ng/ml. There was no statistically significant difference between IgG, IgG4 and CAII serum level in PA and CP patients. However 17 (37,1%) patients with PA and 15 (27,3%) patients with CP had IgG4 levels greater than 140 mg/dl, moreover 3 (6,67%) PA patients had IgG4 greater than 280 mg/dl.</p><p><bold>CONCLUSION:</bold> IgG4 at level 240 mg/dl showed the best sensitivity and specificity in AIP diagnosis compared to IgG and CAII. However elevations of serum IgG4 are seen in up to 30% of subjects without AIP, including pancreatic cancer, and cannot be used alone to distinguish AIP from pancreatic cancer.</p><p><bold>Contact E-mail Address:</bold><email>r-wojnarowska@wp.pl</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> autoimmune pancreatitis, Chronic Pancreatitis, pancreatic adenocarcinoma</p></sec><sec><title>OP355 P21WAF1/CIP1 DOWN-REGULATION IS CRITICAL FOR ACINAR-TO-DUCTAL METAPLASIA FORMATION DURING PANCREATITIS</title><p><bold>K. Grabliauskaite</bold><sup>1,*</sup>, S. Sonda<sup>1</sup>, E. Saponara<sup>1</sup>, T. Reding<sup>1</sup>, R. Graf<sup>1</sup></p><p><italic><sup>1</sup>Swiss HPB Center, University Hospital Zurich, Zurich, Switzerland</italic></p><p><bold>INTRODUCTION:</bold> Transdifferentiation of pancreatic acinar cells into ductal-like lesions, a process defined as acinar-to-ductal metaplasia (ADM), is observed during organ regeneration following pancreatitis. ADM is found in association with pre-malignant PanIN lesions and correlates with an increased risk of pancreatic cancer. As the regulatory mechanisms governing ADM are not well understood, we investigated whether this transdifferentiation is modulated by p21<sup>WAF1/Cip1</sup>, a key regulator of cell cycle progression.</p><p><bold>AIMS&METHODS:</bold> Pancreatitis was induced in wild type (WT) and p21 deficient (p21<sup>-/-</sup>) mice by multiple injections of cerulein. Recovery from pancreatitis was analyzed in mice one week after termination of cerulein treatment. The expression of proliferation markers, cell cycle regulators, and the severity of tissue inflammation and fibrosis were analyzed by immunohistochemistry, western blotting and qRT-PCR.</p><p><bold>RESULTS:</bold> During pancreatitis, we found that p21<sup>WAF1/Cip1</sup> was strongly up-regulated in WT acinar cells but absent in cells forming ADM. p21<sup>-/-</sup> mice showed a significant increase in the number and size of ADM without affecting ADM regression. Surprisingly, the loss of p21 did not increase cell replication rates but resulted in a compensatory activation of positive and negative cell cycle regulators. In addition, the lack of p21<sup>WAF1/Cip1</sup> accelerated the expression of progenitor cell markers and the re-localization of β-catenin.</p><p><bold>CONCLUSION:</bold> Our findings reveal that p21<sup>WAF1/Cip1</sup> is a gate-keeper of acinar cell de-differentiation and formation of metaplastic epithelium. These results suggest an interaction between p21<sup>WAF1/Cip1</sup> and β-catenin signalling which is implicated in the development of malignant lesions.</p><p><bold>Contact E-mail Address:</bold><email>sabrina.sonda@usz.ch</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> cell cycle inhibitor, Metaplasia, pancreatitis, regeneration</p></sec><sec><title>OP356 ANALYSIS OF ENDOSCOPIC ULTRASOUND (EUS)-GUIDED FINE NEEDLE ASPIRATION (FNA) SAMPLES FROM PATIENTS WITH SUSPECTED PANCREATIC DUCTAL ADENOCARCINOMAS (PDACS) USING PLECTIN-1 (PLEC1) AND KRAS ONCOGENE MUTATION ANALYSIS</title><p><bold>J. Park</bold><sup>1,*</sup>, B. J. Song<sup>1</sup>, W. H. Paik<sup>1</sup>, J. K. Ryu<sup>1</sup>, J. M. Park<sup>1</sup>, S. H. Lee<sup>1</sup>, Y.-T. Kim<sup>1</sup>, S. Y. Yang<sup>1</sup></p><p><italic><sup>1</sup>INTERNAL MEDICINE, GASTROENTEROLOGY, SEOUL NATIONAL UNIVERSITY HOSPITAL, SEOUL, Korea, Republic Of</italic></p><p><bold>INTRODUCTION:</bold> Pancreatic cancer remains an incurable and rapidly lethal cancer, with a 5-year survival rate of less than 10%. Little to nothing is known about advanced pancreatic cancer because of problems with tissue availability and usually insufficient quantity of tissue available for diagnosis and study. One of the key features of genetic basis of PDAC is the point mutation of KRAS oncogene occurred in 95 % of its pathogenesis. Plec1 was also recently identified as PDAC specific biomarker.</p><p><bold>AIMS&METHODS:</bold> The aim of this study was to find out the techniques using minimal specimens in order to achieve accurate diagnosis of patients with suspected PDACs. DNA was extracted from EUS-guided FNA samples in 80 patients with suspected PDACs. Seven different somatic mutations of KRAS oncogene were evaluated using ARMS and Scorpions technology and immunohistochemical staining of Plec1 antibody was done.</p><p><bold>RESULTS:</bold> The total of 80 study patients with suspected of PDACs underwent EUS-guided FNA and the final diagnosis were as follows; PDAC: 63 patients, pancreas neuroendocrine tumor: 4, autoimmune pancreatitis: 3, chronic pancreatitis: 1, metastasis to pancreas: 6, others: 3. The sensitivity and specificity of pathologic diagnosis in EUS-guided FNA samples were 87% and 88% respectively. When we combine KRAS oncogene mutational analysis and pathologic reports of FNA samples, we could get the following sensitivities and specificities; 95% vs. 97%. Also, adding the results of plectin-1 antibodies of immunohistochemical staining could increase the sensitivity of PDAC diagnosis.</p><p><bold>CONCLUSION:</bold> Triple combinations of the techniques (pathologic reports, KRAS oncogene mutational analysis, Plec1 staining) could increase accuracy, however, cost-effectiveness and laborious work should be taken into consideration in clinical practice. Further investigation of using minimal specimens to study PDACs may enable us to understand biological behavior and to identify better tools for the diagnosis and treatment of this deadly cancer.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> endoscopic ultrasound , fine needle aspiration, KRAS oncogene, Pancreatic ductal adenocarcinoma, Plectin-1</p></sec><sec><title>OP357 CLINICAL SIGNIFICANCE OF SERUM AND BILE INSULIN-LIKE GROWTH FACTOR I, TUMOUR M2-PYRUVATE KINASE, INTERLEUKIN-6 AND NEUTROPHIL GELATINASE-ASSOCIATED LIPOCALIN IN DIFFERENTIATION MALIGNANT FROM BENIGN BILIARY STRICTURES</title><p><bold>A. Budzynska</bold><sup>1,*</sup>, E. Nowakowska-Dulawa<sup>1</sup>, T. Marek<sup>1</sup>, A. Nowak<sup>1</sup>, M. Hartleb<sup>1</sup></p><p><italic><sup>1</sup>Dept. of Gastroenterology&Hepatology, SILESIAN MEDICAL UNIVERSITY, Katowice, Poland</italic></p><p><bold>INTRODUCTION:</bold> An early diagnosis is difficult to obtain in patients with bile ducts strictures causing substantial delay in possible treatment. Markers to discriminate between benign and early stage of malignant diseases of extrahepatic biliary ducts are urgently needed.</p><p><bold>AIMS&METHODS:</bold> To investigate the value of serum and bile insulin-like growth factor I (IGF-I), tumour M2-pyruvate kinase (Tu M2-PK), interleukin-6 (IL-6) and neutrophil gelatinase-associated lipocalin (NGAL) in distinguishing pancreatobiliary cancers from benign biliary strictures.</p><p>The study was performed prospectively on patients admitted for biliary decompression because of obstructive jaundice. Forty patients including 16 cases of cholangiocarcinoma, 6 cases of pancreatic cancer, and 18 cases of benign biliary stricture were enrolled. Their sera and bile were collected to measure IGF-I, Tu M2-PK, IL-6 and NGAL by using enzyme-linked immunosorbent assay. Routine biochemistry including measurement of serum levels of carbohydrate antigens (CA) 19-9 and carcinoembryonic antigen (CEA) was also performed.</p><p><bold>RESULTS:</bold> Serum levels of CA19-9 (5689.9±13000 vs. 38.3±75), CEA (27.7±65 vs. 1.7±1), IGF-I (74.4±43 vs. 117.2±72 ng/ml) and IL-6 (37.9±47 vs. 16.0±23 pg/ml) as well as bile level of NGAL (1243.9±1185 vs. 674.4±965 ng/ml) were significantly different in patients with malignant strictures as compared with patients with benign biliary diseases. Serum and bile Tu M2-PK as well as bile IGF-I and IL-6 and serum NGAL had no significant value for discriminating between malignant and benign biliary strictures. Serum IGF-I, serum IL-6 and bile NGAL levels had a receiver characteristic area under the curve of 0.34, 0.69 and 0.74, respectively, sensitivity of 100, 90.9 and 77.3%, respectively and specificity of 94, 50.0 and 72.2%, respectively for discriminating between pancreatobiliary cancer and benign biliary diseases.</p><p><bold>CONCLUSION:</bold> Measurement of serum IGF-I, serum IL-6 and biliary NGAL may differentiate malignant from benign biliary stricture, serving as a complementary biomarker for serum CEA and CA19-9.</p><p><bold>REFERENCES:</bold></p><p>1. Alvaro D, Macarri G, Mancino MG et al. Serum and biliary insulin-like growth factor I and vascular endothelial growth factor in determining the cause of obstructive cholestasis. Ann Intern Med 2007; 147: 451-459</p><p>2. Li YG, Zhang N. Clinical significance of serum tumour M2-PK and CA19-9 detection in the diagnosis of cholangiocarcinoma. Dig Liver Dis. 2009 Aug;41(8):605-8. doi: 10.1016/j.dld.2008.11.010. Epub 2009 Jan 24.</p><p>3. Braconi C, Huang N, Patel T. MicroRNA-dependent regulation of DNA methyltransferase-1 and tumor suppressor gene expression by interleukin-6 in human malignant cholangiocytes. Hepatology. 2010 Mar;51(3):881-90.</p><p>4. Zabron AA, Horneffer-van der Sluis VM, Wadsworth CA et al. Elevated levels of neutrophil gelatinase-associated lipocalin in bile from patients with malignant pancreatobiliary disease. Am J Gastroenterol. 2011;106:1711-1717.</p><p>5. Leelawat K, Narong S, Wannaprasert J, Leelawat S. Serum NGAL to clinically distinguish cholangiocarcinoma from benign biliary tract diseases. Int J Hepatol. 2011:873548.</p><p><bold>Contact E-mail Address:</bold><email>budzynskaagnieszka@poczta.onet.pl</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> cholangiocarcinoma, insulin-like growth factor I, interleukin-6, neutrophil gelatinase-associated lipocalin, pancreatic cancer, tumour M2-pyruvate kinase</p></sec><sec><title></title><p><bold>WEDNESDAY, OCTOBER 16, 2013 8:30-10:30</bold></p><p><bold>Safety profile of immunosuppressive therapy in IBD – Hall 2</bold></p></sec><sec><title>OP358 IMPACT OF ANTI-TNFΑ THERAPY FOR MATERNAL INFLAMMATORY BOWEL DISEASE DURING PREGNANCY ON IMMUNE SYSTEM OF EXPOSED CHILDREN</title><p><bold>D. Duricova</bold><sup>1,*</sup>, N. Machkova<sup>1</sup>, M. Bortlik<sup>1</sup>, J. Kozeluhova<sup>2</sup>, P. Kohout<sup>3</sup>, L. Hrdlicka<sup>1</sup>, M. Durilova<sup>4</sup>, K. Mitrova<sup>4</sup>, O. Hradsky<sup>4</sup>, J. Bronsky<sup>4</sup>, M. Lukas<sup>1</sup></p><p><italic><sup>1</sup>IBD CLINICAL AND RESEARCH CENTRE, ISCARE A.S, Charles University in Prague, Prague, <sup>2</sup>Department of Internal Medicine, University Hospital Plzen, Plzen, <sup>3</sup>Department of Internal Medicine, Thomayer University Hospital in Prague, <sup>4</sup>Department of Paediatrics , 2nd Faculty of Medicine, University Hospital Motol, Charles University, Prague, Czech Republic</italic></p><p><bold>INTRODUCTION:</bold> There is increasing evidence on safety of infliximab (IFX) and adalimumab (ADA) on pregnant women and foetal development. However, data on long-term outcome of exposed children are missing.</p><p><bold>AIMS&METHODS:</bold> Our aim was to assess the impact of prenatal exposure of anti-TNFα on children development with respect to their immune system. Methods: Consecutive children exposed to anti-TNFs in utero for maternal inflammatory bowel disease treated with biologicals in 3 centres in the Czech Republic were enrolled. Infants ≥6 months of age were prospectively examined at paediatric clinic, and following data were obtained: child personal history, physical examination and blood samples for immunological investigation (full blood count + differential count on the leucocytes; lymphocyte subset analysis; serum immunoglobulins; response to vaccination).</p><p><bold>RESULTS:</bold> Fifteen IFX and 2 ADA exposed children were included (median age 21 months, range: 10-64; median birth weight 2900g, range: 2350-4450; preterm birth n=3). Cellular immunity was normal in all infants. Immunoglobulin levels were decreased in seven children: IgA in 5 (of them, 4 had also low IgG), IgG and IgM in 1 each. However, no increased infection rate or antibiotic use was observed compared to children with normal immunoglobulin levels. All children had adequate response to tetanus, <italic>Streptococcus pneumoniae</italic> and diphtheria vaccination. Similarly, all infants already vaccinated to rubella, morbilli and parotitis had normal serology except for 1 child having low antibody titre to parotitis. Regarding <italic>Haemophilus influenzae</italic> B (HiB) vaccination, 6 children failed to develop protective titre of antibodies (>1.00 mg/L); their levels ranged from 0.09 to 0.88 mg/mL. No infection caused by HiB was observed in infants insufficiently responding to vaccination by the end of the follow-up.</p><p><bold>CONCLUSION:</bold> Exposure to anti-TNFα preparations seems to be safe for postnatal development of children. No significant impact on cellular or humoral immunity including serologic response to vaccinations was observed.</p><p>Acknowledgement: This study was supported by IBD-COMFORT foundation.</p><p><bold>Contact E-mail Address:</bold><email>dana.duricova@seznam.cz</email></p><p><bold>Disclosure of Interest</bold>: D. Duricova Financial support for research from: IBD-COMFORT foundation , Lecture fee(s) from: MSD, AbbVie, N. Machkova Financial support for research from: IBD-COMFORT foundation , Lecture fee(s) from: MSD, AbbVie, M. Bortlik Financial support for research from: IBD-COMFORT foundation , Lecture fee(s) from: MSD, AbbVie, J. Kozeluhova: None Declared, P. Kohout: None Declared, L. Hrdlicka Lecture fee(s) from: MSD, AbbVie, M. Durilova: None Declared, K. Mitrova: None Declared, O. Hradsky: None Declared, J. Bronsky: None Declared, M. Lukas Lecture fee(s) from: MSD, AbbVie</p><p><bold>Keywords:</bold> adalimumab, children , foetal exposure, immune system, inflixmab , Pregnancy</p></sec><sec><title>OP359 LONG-TERM SAFETY OF VEDOLIZUMAB FOR THE TREATMENT OF ULCERATIVE COLITIS OR CROHN’S DISEASE</title><p><bold>J.-F. Colombel</bold><sup>1,*</sup>, B. Sands<sup>1</sup>, S. Hanauer<sup>2</sup>, P. Rutgeerts<sup>3</sup>, W. Sandborn<sup>4</sup>, S. Danese<sup>5</sup>, G. D’Haens<sup>6</sup>, R. Panaccione<sup>7</sup>, S. Sankoh<sup>8</sup>, I. Fox<sup>8</sup>, A. Parikh<sup>9</sup>, C. Milch<sup>8</sup>, B. Feagan<sup>10</sup></p><p><italic><sup>1</sup>Icahn School of Medicine at Mount Sinai, New York, <sup>2</sup>University of Chicago Medical Center, Chicago, United States, <sup>3</sup>Katholieke Universiteit and University Hospital Gasthuisberg, Leuven, Belgium, <sup>4</sup>University of California San Diego, La Jolla, United States, <sup>5</sup>Istituto Clinico Humanitas, Milan, Italy, <sup>6</sup>Academic Medical Center, Amsterdam, Netherlands, <sup>7</sup>University of Calgary, Calgary, Canada, <sup>8</sup>Millennium Pharmaceuticals, Inc, Cambridge, <sup>9</sup>Takeda Pharmaceuticals International, Inc, Deerfield, United States, <sup>10</sup>Robarts Research Institute, University of Western Ontario, London, Canada</italic></p><p><bold>INTRODUCTION:</bold> Vedolizumab (VDZ) is an investigational, humanized monoclonal antibody targeting α<sub>4</sub>β<sub>7</sub> integrin for treating ulcerative colitis (UC) or Crohn’s disease (CD).</p><p><bold>AIMS&METHODS:</bold> An ongoing open-label extension study (NCT00790933) assesses VDZ safety in patients (pts) with moderate/severe UC/CD who were VDZ naive or had participated in either a phase 2 or 3 VDZ trial. Pts receive 300 mg VDZ intravenously every 4 weeks in the extension study. Adverse events (AEs) were summarized by descriptive statistics for interim data collected through July 2012.</p><p><bold>RESULTS:</bold> Mean (standard deviation) baseline ages were 41.3 (13.30) and 37.7 (12.52) y in UC and CD, respectively. Across VDZ studies, VDZ exposure was ≥6, ≥12, and ≥24 months for 1534, 1149, and 502 pts, respectively. AEs are summarized in the Table. Drug-related AEs were similar for UC and CD, most commonly including headache, 6%; nasopharyngitis, 4%; nausea, 4%; arthralgia, 4%; upper respiratory infection, 3%; and fatigue, 3%. Except for anal abscess in CD (2%), all serious infection incidences were <1% both overall and by indication. No cases of systemic candidiasis, disseminated herpes zoster, cytomegalovirus hepatitis or encephalitis, pneumocystis pneumonia, or progressive multifocal leukoencephalopathy were noted. AEs that most commonly led to discontinuation were gastrointestinal, with UC and CD exacerbations being most common (5% each). Malignancies were observed in <1% of pts (2 colon cancers, 2 malignant melanomas).
<table-wrap id="table55-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1">AE Category, n (%)</th><th rowspan="1" colspan="1">UC (n=704)</th><th rowspan="1" colspan="1">CD (n=1118)</th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">Drug-related AE</td><td rowspan="1" colspan="1">258 (37)</td><td rowspan="1" colspan="1">447 (40)</td></tr><tr><td rowspan="1" colspan="1">AE leading to discontinuation</td><td rowspan="1" colspan="1">61 (9)</td><td rowspan="1" colspan="1">108 (10)</td></tr><tr><td rowspan="1" colspan="1">Serious AE</td><td rowspan="1" colspan="1">127 (18)</td><td rowspan="1" colspan="1">285 (25)</td></tr><tr><td rowspan="1" colspan="1"> Serious infection</td><td rowspan="1" colspan="1">30 (4)</td><td rowspan="1" colspan="1">74 (7)</td></tr><tr><td rowspan="1" colspan="1"> Drug related</td><td rowspan="1" colspan="1">15 (2)</td><td rowspan="1" colspan="1">51 (5)</td></tr><tr><td rowspan="1" colspan="1"> Leading to discontinuation</td><td rowspan="1" colspan="1">23 (3)</td><td rowspan="1" colspan="1">65 (6)</td></tr><tr><td rowspan="1" colspan="1">Death</td><td rowspan="1" colspan="1">3 (<1)<sup>a</sup></td><td rowspan="1" colspan="1">3 (<1)<sup>b</sup></td></tr></tbody></table></table-wrap></p><p><sup>a</sup>Respiratory failure, acute stroke, pulmonary embolism.</p><p><sup>b</sup>Septicemia, traumatic intracranial hemorrhage, suicide.</p><p><bold>CONCLUSION:</bold> Results support the long-term safety of VDZ treatment in UC and CD. The safety profile was similar to that observed in previous 1-year phase 3 trials.</p><p><bold>Disclosure of Interest</bold>: J.-F. Colombel Financial support for research from: Ferring, MSD, Abbott Laboratories, Lecture fee(s) from: Abbott Laboratories, Centocor, Ferring, Given Imaging, Shire, MSD, UCB Pharmaceuticals, Tillotts, Consultancy for: Takeda Pharmaceuticals, Abbott Laboratories, Amgen, Biogen Idec Inc, Boehringer-Ingelheim, Bristol-Myers-Squibb, Cellerix SL, Chemocentryx Inc, Centocor, Cosmo Technologies, Elan Pharmaceuticals, Genentech, Giuliani, Given Imaging, Glaxo Smith Kline, Hospira, Immune Pharmaceuticals, MSD, Neovacs, Ocerra Therapeutics, Pfizer, Prometheus, Shire Pharmaceuticals, Synta Pharmaceuticals, Teva Pharmaceuticals, Therakos, UCB Pharmaceuticals, TXCell, Wyeth, Shareholder of: Intestinal Biotech Development, Other: Takeda Pharmaceuticals, Schering-Plough, Abbott Laboratories, Centocor, MSD, B. Sands Financial support for research from: Takeda Pharmaceuticals, Abbott Immunology, Janssen Biotech, Celgene, Pfizer, UCB, Glaxo SmithKline, Prometheus Laboratories, Lecture fee(s) from: Mechanisms in Medicine, Creative Educational Concepts, Curatio CME, IMEDEX, Consultancy for: Takeda Pharmaceuticals, Abbott Immunology, Amgen, Astellas Pharmaceutical Global Development, Avaxia Biologics, Axcan Pharmaceuticals, Biogen Idec, Bristol-Myers Squibb, Janssen Biotech, Chandler Chicco Agency, Cornerstones, Emmi Solutions, Elan Pharmaceuticals, Merrimack Pharmaceuticals, Pfizer, Prometheus Laboratories, Kyowa Hakko Kirin Pharma Inc, Vertex Pharmaceuticals, Strategic Consultants International, Dyax, GlaxoSmithKline, Puretech Ventures, Novartis, Baxter Healthcare Corporation, Dainippon Sumitomo Pharm Co, Immune Pharmaceuticals Corporation, Teva Pharmaceutical, Shareholder of: Avaxia Biologics, S. Hanauer Financial support for research from: Millennium Pharmaceuticals, Takeda Pharmaceuticals, Consultancy for: Takeda Pharmaceuticals, Millennium Pharmaceuticals, Other: Takeda Pharmaceuticals, Millennium Pharmaceuticals, P. Rutgeerts Financial support for research from: Takeda Pharmaceuticals, Millennium Pharmaceuticals, Centocor (J&J), Merck, UCB, Abbott, Lecture fee(s) from: Centocor (J&J), Merck, UCB, Abbott, Genentech, Consultancy for: Takeda Pharmaceuticals, Centocor (J&J), Merck, UCB, Abbott, Millennium, Genentech, Neovacs, Merck-Serono, BMS, Robarts, Tillotts, Pfizer, Falk Pharma, W. Sandborn Financial support for research from: Millennium Pharmaceuticals, Abbott Laboratories, Bristol Meyers Squibb, Genentech, Glaxo Smith Kline, Janssen (previously Centocor), Novartis, Pfizer, Procter and Gamble Pharmaceuticals, Shire Pharmaceuticals, UCB Pharma, Lecture fee(s) from: Abbott Laboratories, Bristol Myers Squibb, Janssen (previously Centocor) , Consultancy for: Takeda Pharmaceuticals, Millennium Pharmaceuticals, Abbott Laboratories, ActoGeniX NV, AGI Therapeutics Inc, Alba Therapeutics Corporation, Albireo, Alfa Wasserman, Amgen, AM-Pharma BV, Anaphore, Astellas Pharmaceuticals, Athersys Inc, Atlantic Healthcare Limited, Axcan Pharma (now Aptalis), BioBalance Corporation, Boehringer-Ingelheim Inc, Bristol Myers Squibb, Celegene, Celek Pharmaceuticals, Cellerix SL, Cerimon Pharmaceuticals, ChemoCentryx, CoMentis, Cosmo Technologies, Coronado Biosciences, Cytokine Pharmasciences, Eagle Pharmaceuticals, Eisai Medical Research Inc, Elan Pharmaceuticals, EnGene Inc, Eli Lilly, Enteromedics, Exagen Diagnostics Inc, Ferring Pharmaceuticals, Flexion Therapeutics Inc, Funxional Therapeutics Limited, Genzyme Corporation, Genentech (now Roche), Gilead Sciences, Given Imaging, GlaxoSmithKline, Human Genome Sciences, Ironwood Pharmaceuticals (previously Microbia Inc), Janssen (previously Centocor), KaloBios Pharmaceuticals Inc, Lexicon Pharmaceuticals, Lycera Corporation, Meda Pharmaceuticals (previously Alaven Pharmaceuticals), Merck Research Laboratories, MerckSerono, Millennium Pharmaceuticals (subsequently merged with Takeda), Nisshin Kyorin Pharmaceuticals Co Ltd, Novo Nordisk A/S, NPS Pharmaceuticals, Optimer Pharmaceuticals, Orexigen Therapeutics Inc, PDL Biopharma, Pfizer, Procter and Gamble, Prometheus Laboratories, ProtAb Limited, Purgenesis Technologies Inc, Relypsa Inc, Salient Pharmaceuticals, Salix Pharmaceuticals Inc, Santarus, Schering Plough Corporation (acquired by Merck), Shire Pharmaceuticals, Sigmoid Pharma Limited, Sirtris Pharmaceuticals Inc (a GSK company), S.L.A. Pharma (UK) Limited, Targacept, Teva Pharmaceuticals, Therakos, Tillotts Pharma AG (acquired by Zeria Pharmaceutical Co Ltd), TxCell SA, UCB Pharma, Viamet Pharmaceuticals, Vascular Biogenics Limited (VBL), Warner Chilcott UK Limited, Wyeth (now Pfizer), Shareholder of: Enteromedics, Other: Millennium Pharmaceuticals, Dickinson, Prud'Homme, Adams & Ingram, S. Danese Lecture fee(s) from: Vifor Pharma, MSD, Consultancy for: Ferring, Takeda Pharmaceuticals, Abbott, MSD, Vifor Pharma, Novo Nordisk, AstraZeneca, UCB, Pfizer, Other: MSD, G. D’Haens Financial support for research from: Abbott Laboratories, Janssen Biologics, Given Imaging, MSD, DrFalk Pharma, Photopill, Lecture fee(s) from: Abbott Laboratories, Tillotts, Tramedico, Ferring, MSD, UCB, Norgine, Shire and Vifor Pharma, Consultancy for: Abbott Laboratories, Actogenix, Centocor, Cosmo, Engene, Ferring Pharmaceuticals, GlaxoSmithKline, Janssen Biologics, Millennium Pharmaceuticals, MSD, Novo Nordisk, PDL Biopharma, Pfizer, SetPoint, Shire, Takeda Pharmaceuticals, Teva Pharmaceuticals, UCB, Directorship(s) for: Robarts Clinical Trials, ON, Canada, R. Panaccione Financial support for research from: AbbVie, Janssen, GSK, Amgen, Prometheus, BMS, Pfizer, Chemocentryx, Takeda Pharmaceuticals, Lecture fee(s) from: Abbvie, Janssen, Ferring, Warner Chilcott, Takeda Pharmaceuticals, UCB, Merck, Shire, Consultancy for: Abbvie, Janssen, Ferring, Warner Chilcott, Takeda Pharmaceuticals, UCB, Merck, Shire, Aptalis, Salix, Falk Pharma, Prometheus, S. Sankoh Other: Employee of Millennium Pharmaceuticals, I. Fox Shareholder of: Millennium Pharmaceuticals, Other: Employee of Millennium Pharmaceuticals, A. Parikh Shareholder of: Takeda Pharmaceuticals, Other: Employee of Takeda Pharmaceuticals, C. Milch Shareholder of: Millennium Pharmaceuticals, Other: Employee of Millennium Pharmaceuticals, B. Feagan Financial support for research from: Takeda Pharmaceuticals, Lecture fee(s) from: Johnson and Johnson, Abbott Laboratories, UCB, Shire, Consultancy for: Takeda Pharmaceuticals, Johnson and Johnson, Centocor, Elan/Biogen, Bristol Myers Squibb, Celgene, Combinatorx, UCB Pharma, Napo Pharma, Abbott Laboratories, Procter and Gamble, Berlex, Ore Pharmaceuticals, Cerimon Pharma, Genentech, Tillotts, Unity Pharmaceuticals, Albireo Pharma, Salix Pharma, Novo Nordisk, GSK, Astra Zeneca, Serono, Given Imaging Inc, Actogenix, Prometheus Therapeutics and Diagnostics, Athersys, Axcan, Gilead, Nektar, Pfizer, Shire, Wyeth, Zealand Pharma, Zyngenia, GICare Pharma, Sigmoid Pharma</p><p><bold>Keywords:</bold> Crohn’s disease, safety, ulcerative colitis, vedolizumab</p></sec><sec><title></title><p><bold>WEDNESDAY, OCTOBER 16, 2013 8:30-10:30</bold></p><p><bold>East meets West: Colorectal cancer screening – Hall Stockholm</bold></p></sec><sec><title>OP360 BEWARE THE CAECUM: COLONOSCOPIC ADVERSE EVENTS IN THE ENGLISH NHS BOWEL CANCER SCREENING PROGRAMME</title><p><bold>M. D. Rutter</bold><sup>1</sup>, NHS BCSP on behalf of, E. Evaluation Committee, C. Derbyshire<sup>1,*</sup>, J. Nickerson<sup>2</sup>, C. Patnick<sup>2</sup>, R. Rees<sup>3</sup>, NHS BCSP Blanks<sup>4</sup> Evaluation Committee</p><p><italic><sup>1</sup>Gastroenterology, University Hospital of North Tees, Stockton on Tees, <sup>2</sup>Cancer Screening, Public Health England, Sheffield, <sup>3</sup>Gastroenterology, South Tyneside Foundation Trust, South Shields, <sup>4</sup>Cancer Epidemiology Unit, Oxford University, Oxford, United Kingdom</italic></p><p><bold>INTRODUCTION:</bold> The English NHS bowel cancer screening programme (NHSBCSP) is one of the world’s largest organised screening programmes. Minimising adverse events (AEs) is essential for any screening programme.</p><p><bold>AIMS&METHODS:</bold> The study examined perforation, bleeding and post-procedure pain in all NHSBCSP colonoscopies between August 2006 and January 2012. AE rates were calculated and logistic regression used to examine risk factors including age, gender, polyp size, morphology and location. Further analysis was conducted on single polypectomy procedures, allowing accurate AE attribution.</p><p><bold>RESULTS:</bold> 130,831 colonoscopies (167,208 polypectomies) were analysed, including 30,896 single polypectomy procedures. Caecal location (but not elsewhere in the proximal colon) and increasing polyp size were the two most important risk factors for bleeding, post-procedure pain and perforation. After adjustment for polyp size the relative risk for bleeding requiring transfusion for caecal snare polypectomy was 13.5 (95%CI 4.5-40.6) and for perforation after caecal non-pedunculated polypectomy was 7.7 (95%CI 1.3-46.1) relative to the distal colon. AE risk after multiple polypectomies was not additive.</p><p><bold>CONCLUSION:</bold> This is the largest study to date focusing on polyp-specific risk factors. We have confirmed that the greatest risk factor for an AE is polyp size. For the first time we have demonstrated a substantial and significantly increased risk for both significant bleeding (requiring transfusion) and perforation specifically from caecal polypectomy per unit polyp size when compared to elsewhere in the colon. Additional polypectomies carry a lesser risk, suggesting that performing multiple polypectomies during the same procedure should maximise benefit whilst minimising harm.</p><p><bold>Contact E-mail Address:</bold><email>matt.rutter@nth.nhs.uk</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Bleeding, colonoscopy performance, Complications, perforation</p></sec><sec><title>OP361 FORCEPS VERSUS SNARE USAGE IN POLYPECTOMIES – ARE WE FOLLOWING THE GUIDELINES?</title><p><bold>M. Britto Arias</bold><sup>1,2,*</sup>, E. Waldmann<sup>1,2</sup>, P. Salzl<sup>1,2</sup>, I. Gessl<sup>1,2</sup>, D. Sallinger<sup>1,2</sup>, M. Trauner<sup>2</sup>, W. Weiss<sup>1</sup>, M. Ferlitsch<sup>1,2</sup></p><p><italic><sup>1</sup>Quality Assurance Working Group, Austrian Society of Gastroenterology and Hepatology (OEGGH), <sup>2</sup>Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University Vienna (Austria) - Department of Internal Medicine III, Vienna, Austria</italic></p><p><bold>INTRODUCTION:</bold> The European guideline for quality assurance in colorectal cancer screening recommends snare resection for all polyps larger than 5 mm. The aim of this study was to assess whether this recommendation is executed in daily clinical practice.</p><p><bold>AIMS&METHODS:</bold> We analyzed resection techniques used for the most malignant polyp of different sizes. Clinical records of 103.592 cancer screening examinations, submitted for quality assurance purposes to the national “quality certificate for screening colonoscopy” were included in the present study.</p><p><bold>RESULTS:</bold> In 36,28% (n=37.593) of colonoscopies polyps were detected; in 34,7% (n=35.949) polyps were resected. 74,9% (n=26.927) were resected using forceps, 16% (n=5.753) using snare and 9% (n=2.659) using both methods. 20 % (n=7.208) of polyps >5 mm were resected with snare, 7,4% (n=1.204) with both methods and 17,25% (n=6.202) with forceps.</p><p>In 36,28% (n=37.593) of colonoscopies polyps were detected; in 34,7% (n=35.949) polyps were resected. 74,9% (n=26.927) were resected using forceps, 16% (n=5.753) using snare and 9% (n=2.659) using both methods. 20 % (n=7.208) of polyps >5 mm were resected with snare, 7,4% (n=1.204) with both methods and 17,25% (n=6.202) with forceps.</p><p>Of all resected polyps between 5-10 mm 8,0% (n=1.814) were resected using snare while in 91,9 % (n=20.725) only forceps was used; in the group of polyps between 10-20 mm 46,8% (n=4.743) were resected using snare and 53,16% (n=5.384) forceps; of the polyps >20 mm 67,12% (n=592) were resected using a snare and 32,8% (n=290) just using forceps.</p><p><bold>CONCLUSION:</bold> In the group of polyps >5mm 46,37% were resected using only forceps. Hence 46,37% of the polypectomies of this group were not resected according to the EU guidelines. This equals 17,25% of all polypectomies. Even though most of these inadequate polypectomies were found in the group of polyps 5-10mm, we would recommend special attention to the matter – especially since 25% of interval carcinomas develop at the site of prior polyp-resection.</p><p><bold>Contact E-mail Address:</bold><email>martha.brittoarias@meduniwien.ac.at</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Forceps polypectomy, Screening colonoscopy, Snare polypectomy</p></sec><sec><title></title><p><bold>WEDNESDAY, OCTOBER 16, 2013 8:30-10:30</bold></p><p><bold>Understanding new technologies: A session for the general gastroenterologist – Hall Oslo</bold></p></sec><sec><title>OP362 FIRST TRIAL OF A WIRELESS ROBOTIC CAPSULE ENDOSCOPE EQUIPPED WITH THERAPEUTIC TOOLS</title><p><bold>H. Ohta</bold><sup>1,*</sup>, S. Katsuki<sup>2</sup>, T. Fujita<sup>2</sup>, Y. Sato<sup>3</sup>, T. Sagawa<sup>3</sup></p><p><italic><sup>1</sup>Gastroenterology, Sapporo Orthopedics and Cardiovascular Hospital, Sapporo, <sup>2</sup>Center of Gastroenterology, Otaru Ekisaikai Hospital, Otaru, <sup>3</sup>Gastroenterology, Hokkaido Cancer Center, Sapporo, Japan</italic></p><p><bold>INTRODUCTION:</bold> Capsule endoscopy (CE) is a good modality for less invasive gastrointestinal screening. We know, however, it has a number of drawbacks such as cost, lack of control, and cannot be used for biopsies or treatment. Therefore we are developing an internet linked robotic capsule endoscopy with multi-functions (iRoboCap).</p><p><bold>AIMS&METHODS: Aim </bold>To overcome the drawbacks mentioned above and become an alternate modality of conventional endoscopies.</p><p><bold>Materials and Methods</bold> The present iRoboCap consisted of two separate units; one was an imaging unit similar to a conventional capsule and the other was a movement control (driving and biopsies) unit. All the parts for imaging, transmission of endoscopic data and batteries were taken from a capsule endoscope (PillCam SB2; Givenimaging, Yoquem Israel) and the movement control unit consisted of DC motors, a receiver of wireless control signals and batteries. While observing the real-time viewer, medical staff used a joystick to navigate the iRoboCap in a phantom and a pig’s stomach and colon via the internet (Control route; joystick--PC or portable device--Internet--Wi-Fi router--control box--iRoboCap).The clipping and biopsy tools were tested in the pig’s stomach and colon.</p><p><bold>RESULTS:</bold> 1) The reaction of the capsule to remote manipulation was quick enough to explore everywhere in the phantom that was filled with water. 2) It was difficult for the capsule to overcome sphincter contraction. 3) The flame rate of SB2 (2/sec.) was not quick enough to observe the GI wall in real time. 4) The battery for propelling the capsule had a lifetime of about 1 hour which was long enough to control the capsule in the stomach and colon. 5) We had to take into account the transmission lag via the internet between images appearing on the real-time viewer and the capsule’s response to manipulation of the joystick. 7) Biopsy specimens were obtained in only half of biopsy trials. 8) The clipping tool successfully attached a 1mm clip each time it was used.</p><p><bold>CONCLUSION:</bold> With further modifications, it might be possible for IRoboCap to become an alternative modality for not only screening endoscopy but also therapeutic endoscopy. At the moment we are trying to add other functions (e.g. injecting or spraying of drugs, cutting and coagulation) to the next generation CE which will be equipped with a PIC-microprocessor.</p><p><bold>Contact E-mail Address:</bold><email>hideohta@true.ocn.ne.jp</email></p><p><bold>Disclosure of Interest</bold>: H. Ohta : None, S. Katsuki : None, T. Fujita : None, Y. Sato : None, T. Sagawa : None</p><p><bold>Keywords:</bold> Navigation of Capsule Endoscope, Robotic Endoscopy, Via the Internet</p></sec><sec><title>OP363 RANDOMIZED CONTROLLED TRIAL: BRIGHT-NBI VS HIGH DEFINITION WHITE LIGHT ENDOSCOPY FOR THE DETECTION OF FOCAL GASTRIC LESIONS</title><p><bold>T. L. Ang</bold><sup>1</sup>, I. Hussain<sup>1,*</sup>, R. Pittayanon<sup>2</sup>, H. H. Shiaw<sup>3</sup>, D. Ang<sup>1</sup>, R. Rerknimitr<sup>2</sup>, K. L. Goh<sup>4</sup></p><p><italic><sup>1</sup>Department of Gastroenterology, Changi General Hospital, Singapore, Singapore, <sup>2</sup>Department of Gastroenterology, Chulalongkorn Hospital, Bangkok, Thailand, <sup>3</sup>Division of Gastroenterology & Hepatology, <sup>4</sup>Department of Gastroenterology, University of Malaya, Kuala Lumpur, Malaysia</italic></p><p><bold>INTRODUCTION:</bold> It is believed that the White light endoscopy (WLE) may miss significant focal gastric lesions (like intestinal metaplasia (IM), dysplasia and early gastric cancer). Althought the current Narrow band imaging (NBI) improves visualization of mucosal details but its use is limited by the dark endoscopic view. The new EXERA III NBI system (Olympus, Tokyo, Japan) with bright illumination and high definition resolution may overcome this problem.</p><p><bold>AIMS&METHODS:</bold> Our aim is to determine whether there was a difference in the detection rate of focal gastric lesions between WLE and NBI using the EXERA III NBI system.</p><p>Three study sites were involved (Singapore, Thailand and Malaysia). Subjects of age 50 years or more who were undergoing upper GI endoscopy were included. Exclusion criteria were 1) active gastrointestinal bleeding; 2) coagulopathy; and/or 3) previous partial gastrectomy. Patients were randomized to either WLE or NBI with permission for interchangeable examination after recording the findings. The presence of focal gastric lesions and the morphology based on the Paris classification were recorded. The histological diagnoses were traced prospectively.</p><p><bold>RESULTS:</bold> A total 421 subjects (WLE: 211; NBI: 210) were examined over 14 months. When compared to WLE, the NBI detected significantly more focal gastric lesions (41.4% vs. 27.5%, p = 0.002) and IM lesions (22.5% vs. 6.6%; p <0.001). With reference to histological diagnoses, the NBI was more sensitive to pick up IM (90.9% vs 57.1%) These cases of IM presented as subtle mucosal abnormalities (morphology: 0_Is: 3.6%; 0_IIa: 65.5%; 0_IIb: 25.5%; 0_IIc: 5.5%). As only 7 cases of gastric cancer were detected, no meaningful analysis concerning its detection rate could be performed.</p><p><bold>CONCLUSION:</bold> NBI was useful for the detection of subtle focal gastric lesions. NBI increased the detection rate of IM compared to WLE.</p><p><bold>REFERENCES:</bold></p><p>1. Ang TL, Fock KM, Teo EK, et al. Gastrointest Endosc 2010; 71:AB202.</p><p>2. Ezoe Y, Muto M, Horimatsu T, et al. Gastrointest Endosc 2010; 71:477-84</p><p>3. Yokoyama A, Inoue H, Minami H. Dig Liver Dis 2010; 42:704-8.</p><p><bold>Contact E-mail Address:</bold><email>Ikram_Hussain@cgh.com.sg</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Bright NBI, Focal gastric lesion, intestinal metaplasia, NBI, upper GI endoscopy NBI</p></sec><sec><title></title><p><bold>WEDNESDAY, OCTOBER 16, 2013 8:30-10:30</bold></p><p><bold>New insights into the pathophysiology of functional GI disorders – Hall 6</bold></p></sec><sec><title>OP363-LB1 EXPLORING THE GENETICS OF IRRITABLE BOWEL SYNDROME: A GWA STUDY IN THE GENERAL POPULATION AND REPLICATION IN MULTI-NATIONAL CASE-CONTROL COHORTS</title><p><bold>W. Ek</bold><sup>1</sup>, S. Ripke<sup>1</sup>, M. Zucchelli<sup>1</sup>, B. Niesler<sup>1</sup>, P. Schmidt<sup>1</sup>, N. Pedersen<sup>1</sup>, P. Magnusson<sup>1</sup>, N. Talley<sup>1</sup>, L. Holliday<sup>1</sup>, L. Houghton<sup>1</sup>, M. Gazouli<sup>1</sup>, G. Karamanolis<sup>1</sup>, M. Barbaro<sup>1</sup>, R. Colucci<sup>1</sup>, G. Assadi<sup>1</sup>, P. Karling<sup>1</sup>, S. Walter<sup>1</sup>, B. Ohlsson<sup>1</sup>, H. Tornblom<sup>1</sup>, F. Bresso<sup>1</sup>, A. Andreasson<sup>1</sup>, A. Dlugosz<sup>1</sup>, M. Simren<sup>1</sup>, L. Agreus<sup>1</sup>, G. Boeckxstaens<sup>1</sup>, M. Bellini<sup>1</sup>, G. Barbara<sup>1</sup>, G. Lindberg<sup>1</sup>, M. Daly<sup>1</sup>, M. Camilleri<sup>1</sup>, M. Wouters<sup>1</sup>, M. D'Amato<sup>1,*</sup></p><p><italic><sup>1</sup>Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden</italic></p><p><bold>INTRODUCTION:</bold> IBS shows genetic predisposition, but no GWAS has yet been attempted. This may be due to the small size of existing patients cohorts and/or the difficulty in defining a common reliable study phenotype. We hypothesize that alternative, powerful approaches may come from the study of large general population samples, by taking advantage of existing epidemiological information to define IBS and related quantitative traits (endophenotypes) based on bowel symptoms/habits data.</p><p><bold>AIMS & METHODS:</bold> We ran a pilot GWAS on Illumina OmniExpress genotype data from 11326 Swedish twins from the Screening Across the Lifespan Twin (SALT) study in relation to GI symptom data recorded for the same individuals. Cases and controls were identified based on a definition of IBS previously reported to show 25% heritability in the very same population. We followed association signals at candidate risk loci in 1718 IBS cases and 1793 asymptomatic controls from clinical centers in Sweden, Belgium, Italy, UK, Greece and USA by targeted Sequenom genotyping. We performed meta-analysis of index GWAS and replication data.</p><p><bold>RESULTS:</bold> Comparison of 534 unrelated IBS singletons with 4932 independent asymptomatic singletons resulted in the identification of 47 independent signals p < 0.0001 associated with IBS in SALT. Based on regional LD plots inspection, 15 of these signals were selected for follow-up, and 2 SNPs from each region were genotyped in the replication cohorts. One locus on chr 7 showed replication for both SNPs in the merged dataset, had same direction of genetic effects on IBS risk in all populations, and reached p = 9.31 x 10<sup>-6</sup> in the meta-analysis (corrected for gender and country of origin). Among other genes, <italic>GRID2IP</italic> maps to this region, and may represent a good causative candidate because of its involvement in glutamate receptor signalling.</p><p><bold>CONCLUSION:</bold> Population-based cohorts with associated genetic and epidemiological data provide good opportunities to study the genetic architecture of IBS and related GI symptoms. The risk signals detected in this study can now be consolidated in additional meta-analyses, which may conclusively determine whether genetic alterations in glutamate receptor signalling pathways impact IBS risk.</p><p><bold>Contact E-mail Address:</bold><email>mauro.damato@ki.se</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> genetics, Irritable bowel syndrome</p></sec><sec><title>OP364 ORIGIN OF ABDOMINAL DISTENSION: IS IT IN THE CHEST AFTER ALL?</title><p><bold>E. Barba</bold><sup>1</sup>, E. Burri<sup>2</sup>, A. Accarino<sup>1,*</sup>, S. Quiroga<sup>3</sup>, E. Monclus<sup>4</sup>, I. Navazo<sup>4</sup>, J. R. Malagelada<sup>1</sup>, F. Azpiroz<sup>1</sup></p><p><italic><sup>1</sup>Digestive System Research Unit, University Hospital Vall d'Hebron, Barcelona, Spain, <sup>2</sup>Internal Medicine, Stadspital Triemli, Zurich, Switzerland, <sup>3</sup>Radiology, University Hospital Vall d'Hebron, <sup>4</sup>ViRVIG-LSI, Universitat Politècnica de Catalunya, Barcelona, Spain</italic></p><p><bold>INTRODUCTION:</bold> It has been previously shown that abdominal distension in patients with functional gut disorders is due to a paradoxical diaphragmatic contraction without major increment in intraabdominal contents (1). Since the abdomen and the thorax form a common cavity (2, 3), we hypothesized that during abdominal distension, diaphragmatic descent, and the consequent increase in lung height, are associated with a compensatory reduction in thoracic cross section, to preserve lung volumes and respiratory function.</p><p><bold>AIMS&METHODS:</bold> To determine whether and in what sense the thorax is implicated in abdominal distension. In 25 patients (23 women, 2 men; 18-64 yrs) with functional intestinal disorders (21 IBS and 4 functional distension) whose predominant complaint was episodic abdominal distension (that developed during daytime and resolved after overnight rest), two abdominal CT scans were performed: one during basal conditions (no distension) and other during an episode of severe abdominal distension.</p><p><bold>RESULTS:</bold> As in previous studies, the increase in girth during distension (3.5±0.3 cm; p<0.001 vs basal) was associated with diaphragmatic descent (12±2 mm; p<0.001 vs basal) and a modest increase of intraabdominal content (444±63 ml; p<0.001 vs basal). Contrary to our hypothesis, during episodes of abdominal distension a marked expansion of the thoracic cavity was observed with increased volume of lung air (485±103 ml; p<0.001 vs basal), which was due not only to the increase in lung height consequent to the diaphragmatic descent, (16±3 mm; p<0.001 vs basal), but also to an elevation of the costal wall (6.2±1.6 mm increase in antero-posterior diameter; p<0.001 vs basal).</p><p><bold>CONCLUSION:</bold> Functional abdominal distension is produced by a sequence of events: a) expansion of the chest with elevation of the costal wall and diaphragmatic descent, b) caudo-ventral displacement of abdominal content, and c) protrusion of the anterior abdominal wall and girth increment; hence, the origin of abdominal distension may be the thorax, rather than the abdomen.</p><p><bold>REFERENCES:</bold></p><p>1. Villoria A,. Azpiroz F, Burri E, Cisternas D, Soldevilla A, Malagelada J-R. Abdomino-phrenic dyssynergia in patients with abdominal bloating and distension<bold>.</bold> Am J Gastroenterol 106:815-819, 2011.</p><p>2. Burri E, Cisternas D, Villoria A, Accarino A, Soldevilla A, Malagelada J-R, Azpiroz F. Accommodation of the abdomen to its content: integrated abdomino-thoracic response. Neurogastroenterol and Mot 24:312-e162, 2012.</p><p>3. Barba, E., Quiroga, S., Accarino, A., Monclus, E., Malagelada, C., Burri, E., Navazo, I., Malagelada, J-R., Azpiroz, F. Mechanisms of abdominal distension in severe intestinal dysmotility: abdomino-thoracic respone to gut retention. Neurogastroenterol and Mot, Neurogastroenterol Motil. 2013 Apr 22. doi: 10.1111/nmo.12128. [Epub ahead of print].</p><p><bold>Contact E-mail Address:</bold><email>azpiroz.fernando@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: E. Barba: None Declared, E. Burri: None Declared, A. Accarino: None Declared, S. Quiroga: None Declared, E. Monclus: None Declared, I. Navazo: None Declared, J. Malagelada Financial support for research from: Given, Shire, Almirall, F. Azpiroz Financial support for research from: Danone, Given, Rotta, Beneo, Shire</p><p><bold>Keywords:</bold> abdominal bloating, abdominal distension, abdominal muscular activity, diaphragmatic function, respiratory function</p></sec><sec><title>OP365 CONTRASTING CHANGES IN SMALL BOWEL WATER CONTENT IN PATIENTS WITH DIARRHOEA :COELIAC DISEASE AND SCLERODERMA VERSUS IBS AND HEALTHY CONTROLS</title><p><bold>C. Lam</bold><sup>1,*</sup>, D. Sanders<sup>2</sup>, P. Lanyon<sup>3</sup>, K. Garsed<sup>4</sup>, S. Foley<sup>5</sup>, S. Pritchard<sup>6</sup>, L. Marciani<sup>1</sup>, C. Hoad<sup>6</sup>, C. Costigan<sup>7</sup>, P. Gowland<sup>6</sup>, R. Spiller<sup>1</sup></p><p><italic><sup>1</sup>NIHR Nottingham Digestive Diseases Biomedical Research Unit, University of Nottingham, Nottingham, <sup>2</sup>Gastroenterology, Royal Hallamshire Hospital and University of Sheffield, Sheffield, <sup>3</sup>Rheumatology, Nottingham University Hospitals Trust, Nottingham, <sup>4</sup>Gastroenterology, Derby Hospitals Foundation Trust, Derby, <sup>5</sup>Gastroenterology, Sherwood Forest Hospitals NHS Foundation Trust, Mansfield, <sup>6</sup>Sir Peter Mansfield Magnetic Resonance Centre, University of Nottingham, <sup>7</sup>Nottingham University Hospitals Trust, Nottingham, United Kingdom</italic></p><p><bold>INTRODUCTION:</bold> We have validated a novel MRI technique to assess small bowel water content. Normal fasting motility patterns clear small bowel contents into the colon thus fasting small bowel water content (SBWC) reflects a balance between secretions/absorption and motility. We hypothesised impaired motility in scleroderma (SCD) and increased secretions in coeliac disease(CD) would increase SBWC while IBS-D would have normal or enhanced motility.</p><p><bold>AIMS&METHODS:</bold> Aim: To compare SBWC in healthy volunteers (HV) with patients with diarrhoea due to irritable bowel syndrome (IBS-D), SCD and CD.</p><p>Methods: Fasting MRI scans were performed on 20 HV, 20 CD, 15 SCD and 26 IBSD patients. Small bowel water content (SBWC) scan was adapted from the magnetic resonance cholangiopancreatography sequence. Colon volumes were measured by manually segmenting each image.</p><p><bold>RESULTS:</bold> (mean ±SD) As shown in Table 1 IBS-D and SCD showed higher bowel frequency. SBWC was significantly increased in CD but not IBS-D. SBWC was non-significantly increased in SCD, p=0.21. SBWC and colonic volumes did not correlate with bowel frequency, consistency nor anxiety though all patients groups were more anxious and depressed compared to HV. 2 CD duodenal biopsies were graded Marsh I and 18 Marsh grade III. Colonic volumes correlated with the severity of Marsh III grading, Spearman’s r=0.6074; p<0.01.</p><p>Table1 :
<table-wrap id="table56-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1">Mean (SD)</th><th rowspan="1" colspan="1">HV</th><th rowspan="1" colspan="1">IBS-D</th><th rowspan="1" colspan="1">Coeliac</th><th rowspan="1" colspan="1">Scleroderma</th><th rowspan="1" colspan="1">P (1 way Anova)* p <0.05 versus HV </th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">N</td><td rowspan="1" colspan="1">20</td><td rowspan="1" colspan="1">26</td><td rowspan="1" colspan="1">20</td><td rowspan="1" colspan="1">15</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">Female:male</td><td rowspan="1" colspan="1">12:8</td><td rowspan="1" colspan="1">17:9</td><td rowspan="1" colspan="1">12:8</td><td rowspan="1" colspan="1">13:2</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">Age (years)</td><td rowspan="1" colspan="1">42.9±15.3</td><td rowspan="1" colspan="1">48.5±11.0</td><td rowspan="1" colspan="1">45.6±14.1</td><td rowspan="1" colspan="1">62.9±12.9*</td><td rowspan="1" colspan="1">0.0002</td></tr><tr><td rowspan="1" colspan="1">Anxiety</td><td rowspan="1" colspan="1">4.53±2.7</td><td rowspan="1" colspan="1">7.65±4.1*</td><td rowspan="1" colspan="1">8.31±3.7*</td><td rowspan="1" colspan="1">6.47±3.7</td><td rowspan="1" colspan="1">0.0209</td></tr><tr><td rowspan="1" colspan="1">Depression</td><td rowspan="1" colspan="1">1.35±1.2</td><td rowspan="1" colspan="1">4.81± 3.3*</td><td rowspan="1" colspan="1">4.85±2.9*</td><td rowspan="1" colspan="1">4.2±3.4*</td><td rowspan="1" colspan="1">0.0005</td></tr><tr><td rowspan="1" colspan="1">SBWC (ml)</td><td rowspan="1" colspan="1">65±43</td><td rowspan="1" colspan="1">51±33</td><td rowspan="1" colspan="1">202±115*</td><td rowspan="1" colspan="1">118±290</td><td rowspan="1" colspan="1">0.0005</td></tr><tr><td rowspan="1" colspan="1">Colonic volume (ml)</td><td rowspan="1" colspan="1">601.4±196.8</td><td rowspan="1" colspan="1">577.1±256.1</td><td rowspan="1" colspan="1">592.8±185.6</td><td rowspan="1" colspan="1">644.3±349.3</td><td rowspan="1" colspan="1">0.9548</td></tr><tr><td rowspan="1" colspan="1">Stool frequency</td><td rowspan="1" colspan="1">1.30±0.5</td><td rowspan="1" colspan="1">2.83±1.4*</td><td rowspan="1" colspan="1">1.58±0.6</td><td rowspan="1" colspan="1">2.867±1.5*</td><td rowspan="1" colspan="1"><0.0001</td></tr><tr><td rowspan="1" colspan="1">Stool consistency</td><td rowspan="1" colspan="1">3.33±0.7</td><td rowspan="1" colspan="1">4.53±1.4*</td><td rowspan="1" colspan="1">4.18±1.2*</td><td rowspan="1" colspan="1">3.331±0.8*</td><td rowspan="1" colspan="1">0.0071</td></tr></tbody></table></table-wrap></p><p><bold>CONCLUSION:</bold> SBWC is significantly increased in coeliac disease compared to healthy subjects. The increased bowel frequency may account for the relative constancy of colonic volumes despite increased ileo-colonic inflow.</p><p><bold>Contact E-mail Address:</bold><email>robin.spiller@nottingham.ac.uk</email></p><p><bold>Disclosure of Interest</bold>: C. Lam: None Declared, D. Sanders: None Declared, P. Lanyon: None Declared, K. Garsed: None Declared, S. Foley Financial support for research from: Financial support from Novartis, Lecture fee(s) from: lecture fee from Shire, S. Pritchard: None Declared, L. Marciani: None Declared, C. Hoad: None Declared, C. Costigan: None Declared, P. Gowland: None Declared, R. Spiller Financial support for research from: research funding from Lesaffre, Ironwood and free drug for clinical trial from Norgine, Consultancy for: Advisory board for Almirall, Alberio, Ironwood, Shire and Prometheus</p><p><bold>Keywords:</bold> Coeliac disease, colonic volume, Irritable bowel syndrome, scleroderma, Small bowel water content</p></sec><sec><title>OP366 INTERFERON-GAMMA INCREASE IN THE MUCOSA OF IRRITABLE BOWEL SYNDROME AND ITS INTERPLAY WITH SEROTONIN METABOLISM AND MUCOSAL PERMEABILITY</title><p><bold>M. R. Barbaro</bold><sup>1,*</sup>, C. Cremon<sup>1</sup>, A. Altimari<sup>2</sup>, M. Fiorentino<sup>2</sup>, L. Zecchi<sup>1</sup>, R. De Giorgio<sup>1</sup>, V. Stanghellini<sup>1</sup>, G. Barbara<sup>1</sup></p><p><italic><sup>1</sup>Department of Medical and Surgical Sciences, <sup>2</sup>Department of Hematology, Oncology and Laboratory Medicine, University of Bologna, Bologna, Italy</italic></p><p><bold>INTRODUCTION:</bold> A variety of peripheral mechanisms may be involved in the pathophysiology of irritable bowel syndrome (IBS). These include alterations in the serotonin metabolism, epithelial permeability, composition of microbiota and immune system. In <italic>vitro</italic> studies demonstrated that interferon-gamma (IFN-γ) enhanced paracellular permeability and decreased serotonin reuptake transporter (SERT) expression.</p><p><bold>AIMS&METHODS:</bold> In this study we assessed the potential role of IFN-γ in IBS. We included a total of 10 healthy controls (HC) and 26 patients with Rome III confirmed IBS. In all cases, we obtained 6 mucosal biopsies from the descending colon (2 for molecular biology and 4 for supernatant collection). Paraffin-embedded colonic biopsies were used to evaluate IFN-γ mRNA expression. Total RNA was extracted from 20 μm slides, retrotranscribed into cDNA and analysed in real-time PCR assays. Enzyme-linked immunosorbent assays (ELISA) were used to evaluate IFN-γ levels both in colonic biopsy homogenates and into supernatants of cultured biopsies. Supernatants of cultured biopsies were used to treat Caco-2 cell line to evaluate their effect on SERT expression level by real-time RT-PCR assays. Supernatants were also used to evaluate their effect on Caco-2 paracellular permeability.</p><p><bold>RESULTS:</bold> IFN-γ mRNA expression was significantly higher in patients with IBS compared to HC (2<sup>-ΔΔCt</sup>=2.57±0.6 <italic>vs</italic> 2<sup>-ΔΔCt</sup>=0.66±0.1; P<0.05). In addition, we showed increased protein levels of IFN-γ in biopsy homogenates of patients with IBS <italic>vs</italic> HC (increase of 48% in IBS-D and 12% in IBS-C <italic>vs</italic> HC; P<0.05). Similarly, we demonstrated a higher concentration of IFN-γ protein in IBS supernatants (increase of 20% in IBS-D and 98% in IBS-C <italic>vs</italic> HC; P<0.05). The treatment of Caco-2 cells with IBS supernatants induced a significant decrease in SERT expression compared to HC supernatants (2<sup>-ΔΔCt</sup>=0.67±0.13 <italic>vs</italic> 1.219±0.2; <italic>P</italic><0.05). IBS supernatants produced an increase in Caco-2 cell permeability. The effects of IBS supernatants on Caco-2 cells were mediated, at least in part, by IFN-γ.</p><p><bold>CONCLUSION:</bold> We demonstrated an increased expression of IFN-γ in the colonic mucosa of patients with IBS. We also showed increased IFN-γ amount both in biopsies and supernatants of patients with IBS. Epithelial permeability was enhanced by IBS supernatants which induced also a reduction of SERT expression, at least in part via IFN-γ. All together, these data suggest a potential role of IFN-γ in IBS pathophysiology.</p><p><bold>Contact E-mail Address:</bold><email>maria.barbaro2@unibo.it</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> interferon gamma, Irritable bowel syndrome, mucosal permeability, serotonin</p></sec><sec><title>OP367 ANALYSIS OF ENDOLUMINAL IMAGES TYPIFIES ABNORMAL INTESTINAL MOTOR BEHAVIOUR IN PATIENTS WITH FUNCTIONAL BOWEL DISORDERS</title><p><bold>C. Malagelada</bold><sup>1,*</sup>, M. Drozdzal<sup>2</sup>, S. Segui<sup>2</sup>, J. Santos<sup>1</sup>, A. Accarino<sup>1</sup>, J.-R. Malagelada<sup>1</sup>, J. Vitrià<sup>2</sup>, P. Radeva<sup>2</sup>, F. Azpiroz<sup>1</sup></p><p><italic><sup>1</sup>Digestive Diseases, Vall d'Hebron Hospital, Barcelona, <sup>2</sup>Computer Vision Center, Bellaterra, Spain</italic></p><p><bold>INTRODUCTION:</bold> In a previous pilot study, endoluminal image analysis based on computer vision and machine learning techniques was used to demonstrate intestinal motor abnormalities in patients with functional bowel disorders (FBD).</p><p><bold>AIMS&METHODS:</bold> Our aim was to expand this preliminary observation in a large population of naïve patients using a capsule with improved optics and a more elaborated diagnostic algorithm.</p><p>The endoscopic capsule (Pillcam SB2, Given Imaging) was administered to 130 patients with FBD (98 irritable bowel syndrome, 12 functional bloating, 11 functional diarrhea, 9 functional constipation) and 134 healthy subjects after an overnight fast. Forty-five minutes after gastric exit, participants were instructed to ingest a liquid meal (Ensure HN; Abbott, Zwolle, The Netherlands; 300 ml, 1 kcal/ml). Using an independent test set (130 FBD patients and 49 healthy volunteers) motility analysis was performed by sequential classifiers, first, to identify cases outside the normal range (defined by a one-class classifier trained on 85 healthy volunteers), and second, to characterize the type of abnormalities. The new program for motility analysis integrates a key dimension that accounts for the temporal relation of frame-to-frame information by sequence analysis.</p><p><bold>RESULTS:</bold> Thirty-two patients (25%) and only 3 healthy subjects were detected as outside the normal range. Based on the motility behaviour, these cases were then classified as hypo or hyperdynamic. As compared to patients with hyperdynamic behaviour, patients with hypodynamic behaviour were characterized by less and shorter sequences of luminal occlusions (15 ± 2 vs 29 ± 3 sequences, respectively; p=0.028 ; 5.6 ± 1.6 vs 3.1 ± 0.3 min long, respectively; p=0.04), short and rhythmically recurrent static periods (4.7 ± 0.7 vs 1.7 ± 0.5 periods , respectively; p=0.014), few sequences of high motion (1.5 ± 0.4 vs 3.7 ± 1.0 sequences, respectively; p=0.012), and more and longer sequences of tunnel view (3.7 ± 0.6 vs 0.7 ± 0.4 sequences, respectively; p=0.009; 8.7 ± 1.0 vs 1.8 ± 1.2 min long, respectively; p=0.003).</p><p><bold>CONCLUSION:</bold> Automated and unbiased analysis of multiple endoluminal parameters and its temporal relationship allows detection of different intestinal motor behaviours in patients with FBD.</p><p><bold>Contact E-mail Address:</bold><email>cmalagelada@vhebron.net</email></p><p><bold>Disclosure of Interest</bold>: C. Malagelada Financial support for research from: Given Imaging, M. Drozdzal Financial support for research from: Given Imaging, S. Segui Financial support for research from: Given Imaging, J. Santos: None Declared, A. Accarino: None Declared, J.-R. Malagelada Financial support for research from: Given Imaging, J. Vitrià Financial support for research from: Given Imaging, P. Radeva Financial support for research from: Given Imaging, F. Azpiroz Financial support for research from: Given Imaging</p><p><bold>Keywords:</bold> Capsule Endoscopy, functional bowel disorders, intestinal motility</p></sec><sec><title>OP368 SYMPTOM-BASED CLUSTERING OF PATIENTS WITH IRRITABLE BOWEL SYNDROME FOLLOWING A COMBINED NUTRIENT AND LACTULOSE CHALLENGE TEST</title><p><bold>B. Le Nevé</bold><sup>1,*</sup>, R. Brazeilles<sup>1</sup>, H. Törnblom<sup>2</sup>, L. Ohman<sup>2</sup>, M. Simren<sup>2</sup></p><p><italic><sup>1</sup>Life Science, Danone Research, Palaiseau, France, <sup>2</sup>Department of Internal Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden</italic></p><p><bold>INTRODUCTION:</bold> We recently demonstrated in a pilot study that a combined nutrient and lactulose challenge test allows symptom-based clustering of patients with irritable bowel syndrome (IBS) unrelated to exhaled gas and Rome III subtype (Le Nevé <italic>et al</italic> Am J Gastro 2013).</p><p><bold>AIMS&METHODS:</bold> The aim was to evaluate the robustness of the lactulose challenge test in identifying subsets of IBS patients based on gastrointestinal (GI) symptom generation in a larger cohort. We included 99 patients with IBS (Rome III) and 38 healthy controls. The fasted subjects were served a test meal consisting in a 400ml liquid breakfast (Nutridrink®, 1.5 kcal/ml) containing 25g lactulose. The severity of GI symptoms, anxiety and depression were evaluated by questionnaires before the test (IBS-SSS, GSRS, HAD, VSI), and eight GI symptoms, the overall level of digestive comfort and the amount of exhaled H<sub>2</sub>/CH<sub>4 </sub>were assessed every 15min during 4h after meal intake. A mapping of the eight GI symptoms was done using a Principal Components Analysis (4h mean score). Independently, a hierarchical cluster analysis was performed on the same parameters to identify GI symptom-based IBS clusters.</p><p><bold>RESULTS:</bold> The 25g lactulose challenge was well tolerated by all subjects and enabled discrimination of IBS from healthy controls according to the symptom response. This challenge also enabled clustering of IBS subjects in two subgroups based mainly on four GI symptoms: pain, bloating, distension and discomfort. Patients in the “High GI symptom group” (n=37; pain: 9.69 [8.47-10.90], bloat: 10.40 [9.40-11.41], dist: 11.12 [10.03-12.20], disc: 12.21 [11.36-13.04]; mean [95% CI]) displayed higher levels of anxiety (9.51 [8.12-10.90] vs. 7.36 [6.28-8.45]; p<0.05) and lower overall digestive comfort (7.71 [6.82-8.60] vs. 12.98 [12.29-13.67] p<0.001) than patients in the “Low GI symptom group” (n=62; pain: 2.33 [1.39-3.27], bloat: 2.99 [2.22-3.78], dist: 3.37 [2.54-4.21], disc: 4.72 [4.08-5.36]; p<0.001). This clustering was independent of the Rome III subtype classification and the amount of exhaled H<sub>2</sub>/CH<sub>4</sub>.</p><p><bold>CONCLUSION:</bold> A test meal containing 25 g of lactulose discriminates IBS patients from healthy controls, and allows clustering of IBS subjects according to their symptom response, independent of Rome III subtypes or the amount of exhaled gas. As shown by two independent studies, the lactulose challenge test appears to be a promising tool to better define postprandial symptoms in IBS and to evaluate the efficacy of new treatment options.</p><p><bold>Contact E-mail Address:</bold><email>boris.le-neve@danone.com</email></p><p><bold>Disclosure of Interest</bold>: B. Le Nevé Other: Boris Le Nevé is employed by Danone Research, R. Brazeilles Other: Rémi Brazeilles is employed by Danone Research, H. Törnblom: None Declared, L. Ohman: None Declared, M. Simren Financial support for research from: Danone Research</p><p><bold>Keywords:</bold> IBS, Pathophysiology</p></sec><sec><title>OP369 MECHANISM OF LACTOSE INTOLERANCE IN IRRITABLE BOWEL SYNDROME: ROLE OF ANXIETY, MUCOSAL IMMUNITY AND VISCERAL HYPERSENSITIVITY</title><p><bold>M. Fox</bold><sup>1,2,*</sup>, J. Yang<sup>3</sup>, Y. Zhu<sup>3</sup>, Y. Long<sup>4</sup>, Y. Cong<sup>3</sup>, H. Chu<sup>3</sup>, N. Dai<sup>3</sup>, M. Fried<sup>1</sup></p><p><italic><sup>1</sup>Division of Gastronenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland, <sup>2</sup>NIHR Nottingham Digestive Diseases Biomedical Research Unit, Nottingham, United Kingdom, <sup>3</sup>Department of Gastroenterology, Sir Run Run Shaw Hospital, <sup>4</sup>Department of Gastroenterology, Sir Run Run Shaw Hospital, Hangzhou, China</italic></p><p><bold>INTRODUCTION:</bold> Many patients with Irritable Bowel Syndrome (IBS) consider that certain foods trigger bloating, diarrhea and other digestive symptoms; however the mechanism underlying "food intolerance" is unknown.</p><p><bold>AIMS&METHODS:</bold> We assessed the role of psychology, mucosal immunity and visceral sensitivity on the development of lactose intolerance (LI) in IBS patients and healthy controls (HCs) with lactase deficiency.</p><p>IBS-D patients meeting Rome III criteria (n=277) and matched HCs (n=64) underwent a 20g lactose hydrogen breath test (LHBT): a validated model of food intolerance (Yang Clin Gastro Hep 2013). Hospital Anxiety and Depression Score was obtained. Hydrogen (H2) gas production was measured by breath test. LI symptoms (bloating, borborygmi, nausea, pain and diarrhea) were recorded using a Lickert scale. An increase in symptom score of >1 on a scale of 0-4 defined LI. Rectal sensitivity was measured by barostat with normal values defined by HCs.</p><p>Additionally, 55 IBS-D patients and 18 HCs underwent ileo-colonoscopy with biopsies obtained from colon and terminal ileum (TI) to quantify mast cells (MCs), T-cells, and enterochromaffin cells (ECC).</p><p><bold>RESULTS:</bold> H2 production was similar in both groups; but LI was more frequent in IBS than HCs (54% vs. 28%, P<0.001) as were individual symptoms including bloating (39% vs. 14%, P<0.001), borborygmi (39% vs. 22%, P=0.010), pain (31% vs. 11%, P = 0.001) and diarrhea (29% vs. 9%, P=0.001). IBS patients with LI were more anxious (p<0.045) and had higher rectal sensitivity (P=0.001) than patients without LI and controls. Multivariate analysis indicated that H2 production in the upper quartile (OR2.2 (95%CI 1.1-4.4), P=0.028) and the presence of visceral hypersensitivity (OR6.6 (1.7-25.0), P=0.005) were associated with total symptom score.</p><p>In those that underwent colonoscopy, IBS patients with LI had increased MCs (p<0.006), T-cells and ECC (both p<0.05) in colonic and TI mucosa compared to IBS patients without LI and HCs. Multivariate analysis indicated that total symptom score was associated with anxiety, mucosal inflammation and hypersensitivity (all r>0.5 and P<0.001).</p><p><bold>CONCLUSION:</bold> Gas production and hypersensitivity to luminal distension both contribute to digestive symptoms after lactose ingestion. IBS-D patients with LI are characterized by anxiety, evidence of mucosal inflammation and visceral hypersensitivity. These results provide insight into the mechanism of food intolerance. The presence of these biomarkers may identify a subgroup of IBS patients likely to respond to dietary management.</p><p><bold>Contact E-mail Address:</bold><email>mark.fox@nottingham.ac.uk</email></p><p><bold>Disclosure of Interest</bold>: M. Fox Financial support for research from: Nestle, J. Yang: None Declared, Y. Zhu: None Declared, Y. Long: None Declared, Y. Cong: None Declared, H. Chu: None Declared, N. Dai: None Declared, M. Fried: None Declared</p><p><bold>Keywords:</bold> Irritable bowel syndrome, lactose intolerance, mucosal inflammation, visceral hypersensitivity</p></sec><sec><title>OP370 GENDER DETERMINES MUCOSAL MACROPHAGE ACTIVITY IN THE HUMAN JEJUNUM: IMPLICATIONS FOR IRRITABLE BOWEL SYNDROME</title><p><bold>C. Frías</bold><sup>1,*</sup>, M. Vicario<sup>1</sup>, M. Pigrau<sup>1</sup>, B. Lobo<sup>1</sup>, E. Salvo-Romero<sup>1</sup>, A. González-Castro<sup>1</sup>, C. Alonso<sup>1</sup>, B. Rodiño-Janeiro<sup>1</sup>, M. Moris<sup>1</sup>, M. D. Castillo<sup>1</sup>, F. Azpiroz<sup>1</sup>, J. Santos<sup>1</sup></p><p><italic><sup>1</sup>Neuro-Immuno-Gastroenterology Group, Digestive Diseases Research Unit, Gastroenterology Department, Hospital General Vall d'Hebron, Vall d' Hebron Research Institute, CIBERehd, Barcelona, Spain</italic></p><p><bold>INTRODUCTION:</bold> Altered intestinal barrier function and mucosal microinflammation are common findings in irritable bowel syndrome (IBS), a highly prevalent functional disorder among women. Effector mast cell and T cells are involved in IBS pathophysiology; however, the role of phagocytes remains unknown.</p><p><bold>AIMS&METHODS:</bold> We aimed at identifying macrophage contribution to IBS. Twenty newly diagnosed diarrhea-predominant IBS (IBS-D, female F n=14) fulfilling Rome III criteria and age-matched healthy (H) participants (H, F n=9) were recruited. One mucosal biopsy was obtained from the jejunum, using the Watson’s capsule. Eosinophils (H&E), mast cells (CD117), T lymphocytes (CD3) and macrophages (CD68) were identified by immunohistochemistry. Mucosal RNA was isolated, submitted to microarray analysis and subsequent biological functions and pathways identification, associated with differential gene expression.</p><p><bold>RESULTS:</bold> Eosinophils, CD117<sup>+</sup>, CD68<sup>+</sup> and CD3<sup>+</sup> infiltrate was similar between H and IBS-D groups. However, in females, the number of CD68<sup>+</sup> was higher in IBS-D compared to H (IBS-D F: 29.0±1.5 n=14; H F: 20.9±1.6 n=7; <italic>P</italic>=0.004). Considering just the H group, females displayed less CD68<sup>+</sup> than males (H F: 20.9±1.6 n=7; H M: 27.2±2.4 n=7; <italic>P</italic>=0.051). Differential gene expression revealed the immunological response as the most altered function in IBS-D, with significant recruitment and activation of monocytes (<italic>P</italic><0.0001), induction and activation of macrophages (<italic>P</italic><0.0001), antigen-presenting and cytotoxic T cells (<italic>P</italic><0.0001). IBS-D group showed significant upregulation of Perforin 1, Chemokine (C-X-C Motif) Receptor 7, CD20 and MHC Class I Polypeptide-Related Sequence A <italic>(PRF1: 1.32; CXCR7: 1.28; MS4A1: 1.23; MICA: 1.23 fold-change ; P<0.05).</italic></p><p><bold>CONCLUSION:</bold> Increased immune activity, specifically macrophage response, features the jejunal mucosa of IBS-D patients. The differences in the number of macrophages in women comparing to men evidence that further studies are needed to clarify gender-dependence in phagocytic activity and whether this mechanism explains increased prevalence of IBS in women.</p><p><bold>Contact E-mail Address:</bold><email>cristina.frias@vhir.org</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> gender , IBS, macrophage</p></sec><sec><title>OP371 FODMAP INTOLERANCE IN IBS: VISUALIZATION BY MAGNETIC RESONANCE IMAGING</title><p><bold>R. M. Undseth</bold><sup>1,*</sup>, A. Berstad<sup>2</sup>, J. Valeur<sup>2</sup></p><p><italic><sup>1</sup>Radiology, <sup>2</sup>Unger-Vetlesens institute, Lovisenberg Diakonale Hospital, Oslo, Norway</italic></p><p><bold>INTRODUCTION:</bold> Postprandial discomfort is commonly reported in patients with Irritable Bowel Syndrome (IBS), and intake of Fermentable Oligo-, Di- and Monosaccharides, and Polyols (FODMAP) may aggravate the symptoms. The mechanisms are unclear, but may involve increased luminal gas production and/or fluid secretion in response to unabsorbed carbohydrates.</p><p><bold>AIMS&METHODS:</bold> Using MRI, employing a method based on Hoad et al. (1), we aimed to visualize the gastrointestinal response to lactulose, a model substance of FODMAP. Patients with IBS according to Rome III criteria (n = 52) and healthy controls (n = 16) underwent a lactulose provocation test, as described previously (2). Abdominal and systemic symptoms, graded 0 to 3, and small bowel water content (SBWC), as measured with MRI, were recorded before (fasting) and 1 hour after ingestion of lactulose 10 gram in 100 ml of water.</p><p><bold>RESULTS:</bold> Lactulose caused significantly more symptoms in IBS patients than in healthy controls (<italic>P</italic> = 0.0004). SBWC increased significanly more in the patient group compared to the control group (<italic>P</italic> = 0.0005). However, neither habitual nor post test symptoms were significantly correlated to SBWC (r = -0, 17, <italic>P</italic> = 0.34).</p><p><bold>CONCLUSION:</bold> Patients with IBS have increased osmotic and/or secretory response to an indigestible, but fermentable carbohydrate (lactulose) compared to healthy controls. The clinical significance of the finding is not clear.</p><p><bold>REFERENCES:</bold></p><p>1. Hoad CL, Marciani L, Totman JJ, Wright J, Bush D, Cox EF, Campbell E, Spiller RC, Gowland. Non-invasive quantification of small bowel water content by MRI: a validation study. Phys Med Biol 2007; 52: 6909-22.</p><p>2. Valeur J, Morken MH, Norin E, Midtvedt T, Berstad A. Carbohydrate intolerance in patients with self-reported food hypersensitivity: comparison of lactulose and glucose. Scand J Gastroenterol 2009; 44: 1416-23.</p><p><bold>Contact E-mail Address:</bold><email>rundseth@hotmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> FODMAP, IBS, MRI</p></sec><sec><title>OP372 PREVALENCE OF IRRITABLE BOWEL SYNDROME-LIKE SYMPTOMS IN ULCERATIVE COLITIS PATIENTS WITH CLINICAL AND ENDOSCOPIC EVIDENCE OF REMISSION: PROSPECTIVE MULTICENTER STUDY</title><p><bold>N. Fukuba</bold><sup>1,*</sup>, S. Ishihara<sup>1</sup>, H. Sonoyama<sup>1</sup>, A. Oka<sup>1</sup>, R. Kusunoki<sup>1</sup>, N. Oshima<sup>1</sup>, I. Moriyama<sup>1</sup>, T. Yuki<sup>2</sup>, K. Kawashima<sup>1,3</sup>, Y. Kushiyama<sup>4</sup>, H. Fujishiro<sup>5</sup>, Y. Kinoshita<sup>1</sup></p><p><italic><sup>1</sup>Department of Internal Medicine II, Shimane university School of Medicine, <sup>2</sup>Division of Gastrointestinal Endoscopy, Shimane University Hospital, Izumo, <sup>3</sup>Department of Internal Medicine, Matsue seikyo hospital, <sup>4</sup>Department of gastroenterology, Matsue red cross hospital, Matsue, <sup>5</sup>Department of gastroenterology, Shimane prefectural central hospital, Izumo, Japan</italic></p><p><bold>INTRODUCTION:</bold> Irritable bowel syndrome (IBS) is a functional intestinal disorder characterized by abdominal pain or discomfort, along with changes in stool frequency and consistency, which reduces quality of life. Previous studies have reported that IBS-like symptoms are often found in ulcerative colitis (UC) patients in remission. In those studies, remission was mainly defined by evaluating clinical symptoms. However, the prevalence of IBS-like symptoms in UC patients with endoscopic evidence of remission shown by mucosal healing remains unknown.</p><p><bold>AIMS&METHODS:</bold> We assessed the prevalence of IBS-like symptoms in UC patients with clinical and endoscopic evidence of remission, and compared the results to healthy controls. For this study, prospectively conducted at 1 university and 3 general hospitals in Japan, 208 UC patients noted to have a good general appearance were enrolled by their physicians. The diagnosis of IBS was evaluated by questionnaire results according to the Rome III criteria. Clinical remission was assessed by clinical activity index (CAI, <4 for at least 6 months), while endoscopic remission was evaluated by endoscopic index (Matts grade ≤2 for at least 3 months).</p><p><bold>RESULTS:</bold> We analyzed 174 patients in remission (mean 49.2 years old), as 34 were excluded for incomplete questionnaire results or non-remission findings, as well as 330 control subjects (mean 47.4 years old). Of the 174 UC patients, 41 (26.1%) had IBS-like symptoms and met the Rome III criteria, which was significantly higher than that of the controls (16/330, 4.8%). In addition, the prevalence rate of IBS-like symptoms in UC patients with endoscopic evidence of remission (Matts grade ≤2) was 25.6%, which was similar to that of those with clinical remission. On the other hand, when endoscopic remission was defined as Matts grade 1, the prevalence rate of IBS-like symptoms was decreased to15.4%, though that rate remained significantly higher than that of the control subjects.</p><p><bold>CONCLUSION:</bold> The prevalence of IBS-like symptoms in UC patients with clinical and endoscopic evidence of remission was significantly higher than that of healthy control subjects. Furthermore, that prevalence rate in patients with complete endoscopic remission (Matts grade 1) was significantly lower than that in patients with clinical remission findings.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Irritable bowel syndrome, remission, Rome III, ulcerative colitis</p></sec><sec><title></title><p><bold>WEDNESDAY, OCTOBER 16, 2013 8:30-10:30</bold></p><p><bold>GORD: From diagnosis to treatment – Hall 9</bold></p></sec><sec><title>OP373 ESOPHAGEAL BASELINE IMPEDANCE VALUES CORRELATE WITH PRESENCE AND SEVERITY OF MICROSCOPIC ESOPHAGITIS IN PATIENTS WITH GASTRO-ESOPHAGEAL REFLUX DISEASE</title><p><bold>E. Savarino</bold><sup>1,*</sup>, N. de Bortoli<sup>2</sup>, M. Furnari<sup>3</sup>, L. Mastracci<sup>4</sup>, V. Savarino<sup>3</sup></p><p><italic><sup>1</sup>Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, <sup>2</sup>Department of Internal Medicine, University of Pisa, Pisa, <sup>3</sup>Department of Internal Medicine, <sup>4</sup>DICMI, Pathologic Division, University of Genoa, Genoa, Italy</italic></p><p><bold>INTRODUCTION:</bold> In patients with Gastro-Esophageal Reflux Disease (GERD) levels of intraluminal baseline impedance (BI) are impaired likely due to reduced mucosal integrity. Microscopic esophagitis (ME) has been associated to tight junction alterations and symptom generation. Moreover, presence of ME has been recently shown to be able to distinguish patients with GERD from those without.</p><p><bold>AIMS&METHODS:</bold> To determine whether levels of BI correlate with presence and severity of ME. We evaluated 104 patients with GERD. During upper endoscopy multiple biopsies were taken at Z-line and 2 cm above it. Basal cell hyperplasia, papillae elongation, dilation of intercellular spaces and eosinophil (Eos) intraepithelial infiltration were measured [0 (absent), 1 (mild or 1=1 Eos), and 2 (marked or 2=>1 eos/HPF)]. A global score was calculated by summing up all the scores and dividing by the number of assessed lesions and was considered positive for ME when >0.35 (range 0-2). Within 3 days from endoscopy, patients underwent impedance-pH testing off- therapy. We evaluated BI values at 3 and 5cm above the LES, during the overnight rest, for at least 30 minutes after excluding swallows and reflux induced changes. Twenty healthy volunteers (HVs; 11F/9M; mean age 44) were also included.</p><p><bold>RESULTS:</bold> We included 20 patients with erosive esophagitis (EE; 11F/9M; mean age 46), 65 with non-erosive reflux disease (NERD; 34F/31M; mean age 46) and 19 with functional heartburn (FH; 11F/8M; mean age 43). ME was more frequent (p<0.001) in EE (95%) and in NERD (75%) than in FH (11%) and in HVs (15%). BI values are shown in the Table. At 3 and 5 cm, patients with ME had lower BI levels compared to patients without ME (1482 vs. 2577 and 1411 vs. 2515; p<0.0001). At both sites, BI levels were lower in EE (p<0.0001) compared to NERD, FH and HVs. Moreover, BI values were lower in NERD (p<0.0001) compared to FH and HVs. No differences were found between FH and HVs (p=0,3324). A negative correlation between BI levels and ME score was found at 3 (r=-0.5449; p<0.0001) and 5cm (r=- 0.5471; p<0.0001) above the LES.
<table-wrap id="table57-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1"></th><th rowspan="1" colspan="1"><bold>EE</bold></th><th rowspan="1" colspan="1"><bold>NERD</bold></th><th rowspan="1" colspan="1"><bold>FH</bold></th><th rowspan="1" colspan="1"><bold>HVs</bold></th><th rowspan="1" colspan="1"><italic>P value</italic></th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">BI Levels at 3cm, Ω (range)</td><td rowspan="1" colspan="1">934 (560- 1660)</td><td rowspan="1" colspan="1">1747 (840- 3120)</td><td rowspan="1" colspan="1"> 3342 (2530- 3860)</td><td rowspan="1" colspan="1">3515 (2950- 4225)</td><td rowspan="1" colspan="1"><0,001</td></tr><tr><td rowspan="1" colspan="1">BI Levels at 5cm, Ω (range)</td><td rowspan="1" colspan="1">897 (580- 1600)</td><td rowspan="1" colspan="1">1682 (770- 3010)</td><td rowspan="1" colspan="1"> 3233 (2465- 3750)</td><td rowspan="1" colspan="1">3404 (2930- 4060)</td><td rowspan="1" colspan="1"><0,001</td></tr></tbody></table></table-wrap></p><p><bold>CONCLUSION:</bold> Esophageal BI values correlate with presence and severity of ME and therefore they can be considered as complementary indexes of impaired mucosal integrity potentially related to symptom generation in GERD. Levels of BI as well as presence of ME may be used to distinguish patients with GERD from those with FH.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> GERD, impedance-pH monitoring, NERD</p></sec><sec><title>OP374 ELECTRICAL STIMULATION THERAPY (EST) OF THE LOWER ESOPHAGEAL SPHINCTER (LES) IS SUCCESSFUL IN TREATING GERD – LONG-TERM TWO YEAR RESULTS.</title><p><bold>L. Rodriguez</bold><sup>1,*</sup>, P. Rodriguez<sup>1</sup>, B. Gomez<sup>1</sup>, M. Galvao<sup>2</sup>, E. Soffer<sup>3</sup>, M. Crowell<sup>4</sup></p><p><italic><sup>1</sup>CCO Obesidad Y Diabetes, Santiago, Chile, <sup>2</sup>Gastro Obeso Center, Sao Paulo, Brazil, <sup>3</sup>University of Southern California, Los Angeles, <sup>4</sup>Mayo Clinic Arizona, Phoenix, United States</italic></p><p><bold>INTRODUCTION:</bold> LES-EST has shown improvement in outcomes patients with GERD at 1 year.</p><p><bold>AIMS&METHODS:</bold> The aim of this open-label human pilot extension trial was to study the safety and efficacy during chronic LES-EST in GERD patients over longer 2-year follow-up.</p><p>We studied GERD patients at least partially responsive to proton pump inhibitors (PPI) and had off-PPI GERD HRQL>20, % 24 hour esophageal pH<4.0 for >5%, hiatal hernia < 3cm and esophagitis < LA Grade C. Bipolar stitch electrodes and an implantable pulse generator (EndoStim BV, the Hague, Netherlands) was implanted using laparoscopy. EST at 20 Hz, 220usec, 3-8mAmp in 30 minutes, 6-12 sessions was delivered starting on day 1 post-implant. Patients are being evaluated using GERD-HRQL, symptom diaries and SF-12, and esophageal pH testing at regular intervals. Stimulation sessions are optimized based on residual symptoms, pH data when available and lead impedance at follow-up.</p><p><bold>RESULTS:</bold> Twenty-five patients (mean age= 53+12 years; men=14) were successfully implanted, 23 agreed to participate in the 2 year extension trial and 21 have completed their 2-year evaluation. At 2-year there was a significant improvement in their median GERD-HRQL on LES-EST compared to both their on-PPI (9 vs. 0, p=0.001) and off-PPI (23.5 vs 0, p<0.001) median GERD-HRQL and their median 24-hour distal esophageal acid exposure (10.1 vs 4.7, p<0.001). 71% patients reported either normalization or at least 50% reduction in their distal esophageal acid exposure. All but two patient reported cessation of regular PPI use (>50% of days with PPI use). There were no implantation- or stimulation-related unanticipated adverse events, or untoward sensation due to stimulation. There was no dysphagia and swallowing function assessed by manometry was also unaffected.</p><p><bold>CONCLUSION:</bold> LES-EST is safe and effective for treating patients with GERD over long-term 2 year duration. There was a significant and sustained improvement in symptoms, esophageal acid exposure and reduction in PPI use. Further, LES-EST is not associated with any GI side-effects or adverse events and can be optimized to individual patient needs.</p><p><bold>Contact E-mail Address:</bold><email>doctor@leonardorodriguez.cl</email></p><p><bold>Disclosure of Interest</bold>: L. Rodriguez Financial support for research from: EndoStim BV, P. Rodriguez Financial support for research from: EndoStim BV, B. Gomez: None Declared, M. Galvao Financial support for research from: EndoStim BV, E. Soffer Consultancy for: EndoStim, M. Crowell Consultancy for: EndoStim</p><p><bold>Keywords:</bold> electrical stimulation, refractory GERD</p></sec><sec><title>OP375 COMPARISON OF CORTICAL RESPONSES BY FUNCTIONAL MAGNETIC RESONANCE IMAGING (FMRI) IN PATIENTS WITH EROSIVE REFLUX DISEASE AND NON EROSIVE REFLUX DISEASE</title><p><bold>S. Yapali</bold><sup>1</sup>, R. Vardar<sup>1</sup>, C. Calli<sup>2</sup>, E. Yildirim<sup>1</sup>, S. Bor<sup>1,*</sup></p><p><italic><sup>1</sup>Gastroenterology, <sup>2</sup>Radiology, Ege University School of Medicine, Izmir, Turkey</italic></p><p><bold>INTRODUCTION:</bold> Esophageal visceral sensation is regulated by complex interactions between the intraluminal stimulus, esophageal receptors, visceral afferent neurons and central perception. The role of cortical response still remains elusive.</p><p><bold>AIMS&METHODS:</bold> The objective of this study is to compare the cortical response to intraesophageal acid exposure by functional magnetic resonance imaging (fMRI) in patients with erosive reflux disease (ERD) and nonerosive reflux disease (NERD).Bernstein test was performed on 81 patients with perfusion of HCL (0.1 mmol/L) and then normal saline into the distal esophagus, of the 34 who experienced acid-induced heartburn, twenty-two right handed patients were enrolled. Patients were divided into 2 groups, 1.ERD (n=11), 2.NERD (n=11). An improved block design model composed of 2 minute baseline phase (Phase-1), followed by 2 minute saline (NaCl) perfusion (Phase-2), acid perfusion phase (Phase-3) divided to (Phase 3a) until the beginning of heartburn and continued on for 2 more minutes (Phase-3b), 2 minute saline perfusion phase (Phase-4). The patient is asked to push the button when heartburn initiates. Imaging was performed on a 3T MR scanner and an echo planar imaging sequence was used (TE= 30 ms, flip angle 90°, matrix 64x64, field of view 192 mm) to obtain 25 transverse slices during fMRI. erfusion (Phase-2). Phase-3b activations with respect to Phase-1 is obtained for each subject. Higher-level (group level) analysis was carried out using mixed effects analysis. The group averages and differences between groups for the contrast of interest were analysed. Z-statistic images were thresholded using clusters of pixels with Z = 1.65 and a corrected cluster significance threshold of p = 0.05.</p><p><bold>RESULTS:</bold> Symptom profile and reflux symptom scores were similar between the two groups.Phase-3b to Phase-1 cortical activation group comparisons showed that inferior frontal gyrus (Z = 2.66), precuneus (Z = 2.38), paracingulate gyrus (Z = 2.15) and orbitofrontal cortex (Z = 2.15) activations were significantly higher among NERD patients compared to ERD group.</p><p><bold>CONCLUSION:</bold> This study performed on a selected group of GERD patients with similar clinical responses to intraesophageal acid perfusion shows that cortical areas associated with pain and awareness of pain show higher level of activation in NERD patients. These findings might be related with the decreased perception thresholds in NERD patients. fMRI studies may contribute to better understanding of visceral hypersensitivity with exclusion of confounding factors, particularly in patients with functional heartburn and hypersensitive esophagus.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> erosive reflux disease, Functional magnetic resonance imaging (fMRI), Gastroesophageal reflux disease(GERD), non erosive reflux disease</p></sec><sec><title>OP376 HISTOLOGY IDENTIFIES PATIENTS WITH GASTROESOPHAGEAL REFLUX DISEASE WHO ARE NOT IDENTIFIED BY PH TESTING OR ENDOSCOPY</title><p><bold>N. Vakil</bold><sup>1,*</sup>, M. Vieth<sup>2</sup>, J. Dent<sup>3</sup>, L. Mastracci<sup>4</sup>, J. Wissmar<sup>5</sup>, B. Wernersson<sup>5</sup>, R. Fiocca<sup>4</sup></p><p><italic><sup>1</sup>University of Wisconsin School of Medicine and Public Health, Madison, United States, <sup>2</sup>Klinikum Bayreuth, Bayreuth, Germany, <sup>3</sup>Royal Adelaide Hospital and University of Adelaide, Adelaide, Australia, <sup>4</sup>University of Genoa, Genoa, Italy, <sup>5</sup>AstraZeneca R&D, Mölndal, Sweden</italic></p><p><bold>INTRODUCTION:</bold> We have shown previously that total epithelial thickness (TET) in the distal esophagus of ≥430 µm correlates significantly with investigation-defined gastroesophageal reflux disease (iGERD).<sup>1</sup> It is not known whether TET adds to the diagnostic yield of endoscopy and pH-metry for iGERD.</p><p><bold>AIMS&METHODS:</bold> We performed a <italic>post hoc</italic> analysis to evaluate the correlation between TET ≥430 µm and individual iGERD markers, and to assess whether the criterion of TET ≥430 µm influences the diagnostic yield for GERD in primary care patients presenting with frequent upper gastrointestinal (GI) symptoms (Diamond study; NCT00291746).<sup>2</sup> Patients were included if they reported upper GI symptoms of any severity on ≥2 days/week for ≥4 weeks and of ≥mild severity on ≥3 days in the week before the study, and had not taken a proton pump inhibitor in the past 2 months. Patients with symptom-defined GERD (sGERD) were identified based on international heartburn/regurgitation frequency/severity criteria,<sup>3</sup> using data from the Reflux Disease Questionnaire completed at study inclusion. iGERD was defined as the presence of ≥1 of: reflux esophagitis (RE; Los Angeles grades A–D); pathological esophageal pH (<4 for >5.5% of the time); positive symptom association probability (SAP ≥95%). TET ≥430 µm at 2.0 cm above the Z-line (3 o’clock position) was added as a novel criterion for GERD.</p><p><bold>RESULTS:</bold> Our analysis included 231 patients from the Diamond study: 37% had pathological esophageal pH, 30% had RE, 16% had a positive SAP and 39% had TET ≥430 µm; 55% had iGERD. TET ≥430 µm correlated significantly with RE, pathological pH and iGERD (all <italic>p</italic><0.005), but not with positive SAP (<italic>p</italic>=1.0). Table 1 gives the specificity/sensitivity of TET ≥430 µm and <430 µm for iGERD and its component markers. Including TET ≥430 µm as a fourth iGERD criterion identified an additional 28 patients (25 of whom met sGERD criteria<sup>3</sup>), increasing the prevalence of iGERD by 22% (from 55% to 67%). <bold>Table 1. </bold>Specificity/sensitivity (%) of TET for iGERD and its component markers
<table-wrap id="table58-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1">TET (µm)</th><th rowspan="1" colspan="1">iGERD</th><th rowspan="1" colspan="1">RE</th><th rowspan="1" colspan="1">Pathological pH</th><th rowspan="1" colspan="1">Positive SAP</th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">≥430</td><td rowspan="1" colspan="1">53.5/68.5</td><td rowspan="1" colspan="1">79.6/44.9</td><td rowspan="1" colspan="1">70.4/48.3</td><td rowspan="1" colspan="1">84.5/15.7</td></tr><tr><td rowspan="1" colspan="1"><430</td><td rowspan="1" colspan="1">31.5/46.5</td><td rowspan="1" colspan="1">55.1/20.4</td><td rowspan="1" colspan="1">51.7/29.6</td><td rowspan="1" colspan="1">84.3/15.5</td></tr></tbody></table></table-wrap></p><p><bold>CONCLUSION:</bold> TET ≥430 µm correlates significantly with RE, pathological pH and iGERD, but not with positive SAP; it increases the diagnostic yield for iGERD. TET ≥430 µm is a clinically useful marker of GERD, particularly in patients with sGERD, which can be misclassified as functional dyspepsia.</p><p><bold>REFERENCES:</bold></p><p>1. Vieth M <italic>et al. Gastroenterology</italic> 2011;140(Suppl 1):S-95. 2. Dent J <italic>et al. Gut</italic> 2010;59:714–21. 3. Vakil N <italic>et al. Am J Gastroenterol</italic> 2006;101:1900–20.</p><p><bold>Contact E-mail Address:</bold><email>nvakil@wisc.edu</email></p><p><bold>Disclosure of Interest</bold>: N. Vakil Consultancy for: AstraZeneca, Ironwood Pharmaceuticals, Orexo, Takeda Pharmaceutical Co. Ltd, Otsuka and Xenoport, Shareholder of: Meridian Bioscience and Orexo, M. Vieth Lecture fee(s) from: AstraZeneca, Falk, Pentax, Olympus, Malesci, Covidien and Shire, J. Dent Consultancy for: AstraZeneca R&D, Mölndal, Sweden, L. Mastracci: None Declared, J. Wissmar Other: Employee of AstraZeneca R&D, Mölndal, Sweden, B. Wernersson Other: Employee of AstraZeneca R&D, Mölndal, Sweden, R. Fiocca: None Declared</p><p><bold>Keywords:</bold> Gastroesophageal reflux disease, histology, sensitivity, specificity, total epithelial thickness</p></sec><sec><title>OP377 PEPSIN IN SALIVA AND GASTROESOPHAGEAL REFLUX MONITORING IN 100 HEALTHY ASYMPTOMATIC SUBJECTS AND 65 PATIENTS WITH SIGNIFICANT HEARTBURN/REGURGITATION</title><p><bold>J. O. Hayat</bold><sup>1,*</sup>, S. Gabieta-Gomez<sup>2</sup>, E. Yazaki<sup>2</sup>, J.-Y. Kang<sup>1</sup>, A. Woodcock<sup>3</sup>, P. Dettmar<sup>3</sup>, J. Mabary<sup>4</sup>, D. Sifrim<sup>2</sup></p><p><italic><sup>1</sup>Dept of Gastroenterology, St.George's University of London, <sup>2</sup>Dept of GI Physiology, Barts and the London School of Medicine and Dentistry, London, <sup>3</sup>Technostics Ltd, Hull, United Kingdom, <sup>4</sup>Sandhill Sci., Colorado, United States</italic></p><p><bold>INTRODUCTION:</bold> Pepsin is a protease originating from pepsinogen secreted into gastric juice from chief cells, found only in the stomach. Its presence in the oesophagus or more proximally suggests gastro-oesophageal reflux (GOR). Several studies have measured pepsin in saliva to determine its value as marker of GOR. Patients with clinically significant heartburn may have GORD, hypersensitive oesophagus or functional heartburn.</p><p><bold>AIMS&METHODS:</bold> The <bold>aim</bold> of this study was to measure pepsin in saliva with objective assessment of GOR by impedance-pH (MII-pH) in a cohort of asymptomatic subjects and consecutive patients with clinically significant heartburn (according to the Montreal definition of GORD).</p><p>100 healthy subjects, age 30.7 y (range 19-55) and 65 pts with +ve Reflux Disease Questionnaire (RDQ) score, age 49.7y (range 25-71) underwent MII-pH monitoring and simultaneous saliva sampling. Subjects collected expectorated saliva on waking, one hour after lunch and dinner. Pepsin was detected using a lateral flow test with two unique monoclonal antibodies to pepsin (Peptest™, RDBiomed Ltd). The cut off value to determine pepsin positivity was 25ng/ml. Pts were divided into 3 phenotypes based on MII-pH results. 1) GORD (increased oesophageal acid exposure time (AET) (10.4 % ± 1.4) and SAP +ve, n=26). 2) Hypersensitive oesophagus (HO)(normal AET and SAP +ve, n=18) and 3) Functional Heartburn (FH)(normal AET and SAP -ve for acid/non-acid reflux, n=12).</p><p><bold>RESULTS:</bold> All healthy subjects selected had normal MII-pH testing. 36/100 normal subjects had at least 1 sample +ve (20% had 1 sample +ve, 12% had 2 samples +ve and 4% had 3 samples +ve). In pepsin +ve samples, the median (25%>75%) pepsin conc. was 118 (64-181)ng/ml. In GORD patients, 21/26 had at least 1 sample +ve (3 patients had 3 samples +ve) and pepsin conc. was 152 (72-250)ng/ml. In HO patients 15/18 had at least 1 sample +ve (4 had 3 samples +ve) and pepsin conc. was 250(74-250)ng/ml. In contrast, only 2/12 FH patients had at least 1 sample +ve and pepsin conc. was 76(67-85)ng/ml. Considering the ability to identify patients with heartburn related to reflux (GORD + HO) Peptest had a sensitivity of 95%, specificity 89%, PPV 97% but a NPV of 57%.</p><p><bold>CONCLUSION:</bold> Pepsin was found in the saliva of a proportion of healthy individuals with no reflux symptoms. Pepsin is significantly more likely to be detected in patients with heartburn related to reflux (SAP +ve) i.e. GORD and HO, (and in higher conc.) than in normal subjects or patients with functional heartburn.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> functional heartburn, gastro-esophageal reflux, hypersensitive esophagus, impedance-pH monitoring, pepsin</p></sec><sec><title>OP378 PHARYNGEAL PH ALONE IS NOT RELIABLE FOR THE DETECTION OF PHARYNGEAL REFLUX EVENTS. A STUDY WITH ESOPHAGEAL AND PHARYNGEAL PH-IMPEDANCE MONITORING</title><p><bold>M. Desjardin</bold><sup>1,*</sup>, S. Roman<sup>2</sup>, S. Bruley Des Varannes<sup>3</sup>, G. Gourcerol<sup>4</sup>, B. Coffin<sup>5</sup>, A. Ropert<sup>6</sup>, F. Mion<sup>2</sup>, F. Zerbib<sup>1</sup>, Groupe Français de Neurogastroentérologie</p><p><italic><sup>1</sup>Gastroenterology , CHU Bordeaux, Bordeaux, <sup>2</sup>Gastroenterology , CHU Lyon, Lyon, <sup>3</sup>IMAD, CHU Nantes, Nantes, <sup>4</sup>Gastroenterology , CHU Rouen, Rouen, <sup>5</sup>Gastroenterology , hôpital Louis Mourier, Colombes, <sup>6</sup>Gastroenterology , CHU Rennes, Rennes, France</italic></p><p><bold>INTRODUCTION:</bold> In clinical practice, the diagnosis of laryngo-pharyngeal reflux (LPR) is challenging. Recently, pharyngeal pH probes and pharyngeal pH-impedance catheters have been developed. The aim of this study was to determine the reliability of pharyngeal pH alone for the detection of pharyngeal reflux events.</p><p><bold>AIMS&METHODS:</bold> We collected ambulatory, 24-hour, pH-impedance recordings from 45 healthy subjects (22 women; mean age, 46.3 years; range, 18–78 years) off therapy using a bifurcated probe that allowed for detection of pharyngeal and esophageal reflux events simultaneously. Impedance measurements were combined with pharyngeal and esophageal pH measurements 1 cm above the upper esophageal sphincter and 5 cm above the lower esophageal sphincter respectively. All pharyngeal pH drops < 4 or < 5 and lasting more than 5 seconds were analyzed for the simultaneous occurrence of pharyngeal reflux (PR), proximal and distal esophageal reflux and swallows according to impedance analysis. Slow pH drifts were deleted from the analysis.</p><p><bold>RESULTS:</bold> Among the 45 recordings<bold>, </bold>256 pharyngeal pH drops <5 were identified; 81.3% of them were associated with a simultaneous esophageal pH drop <5 . Only 7% of the pharyngeal pH drops <5 corresponded to PR. The majority of pharyngeal pH drops <5 were related to swallows (92.6%), and only 10.2% and 13.3% were associated with proximal and distal reflux, respectively. There was no significant difference in the duration of pharyngeal pH drops associated with PR and the others. Among 126 pharyngeal pH drops < 4, 90.5% were associated with a simultaneous esophageal drop . Only 13.5% of pH drops < 4 were related to PR. Most pH drops were related to swallows (89.7%), and 17.5% and 20.6 % were associated with proximal and distal reflux, respectively. There was no significant difference in the duration of pH drops <4 associated with PR and the others</p><p><bold>CONCLUSION:</bold> This study demonstrates that pharyngeal pH alone is not reliable for the detection of pharyngeal reflux and that adding distal esophageal pH analysis is not helpful. The only reliable analysis should take into account impedance patterns demonstrating the presence of a pharyngeal reflux event preceded by a distal and proximal reflux event within the esophagus.</p><p><bold>Contact E-mail Address:</bold><email>frank.zerbib@chu-bordeaux.fr</email></p><p><bold>Disclosure of Interest</bold>: M. Desjardin: None Declared, S. Roman Consultancy for: Given Imaging, S. Bruley Des Varannes Consultancy for: Shire, Alpha Wasserman, Janssen Cilag, Given Imaging, Cephalon, ALmirall, G. Gourcerol Consultancy for: Reckitt Benckiser, B. Coffin Consultancy for: Shire, Cephalon, ALmirall, Abbott, Mundipharma, A. Ropert: None Declared, F. Mion Consultancy for: Shire, ALmirall, Given Imaging, Helioscope, Medtronic, Urogene, F. Zerbib Financial support for research from: Sandhill, Given Imaging, Reckitt Banckiser, , Lecture fee(s) from: Astrazeneca, Sanofi Aventis, Janssen Cilag, Abbott, Consultancy for: Addex, Shire, Almirall</p><p><bold>Keywords:</bold> impedance-pH monitoring, Laryngopharyngeal reflux(LPR), Reflux symptoms</p></sec><sec><title>OP379 ASSESSMENT OF PATIENTS REFERRED FOR GERD EVALUATION: TO CONTINUE OR STOP ACID SUPPRESSANTS BEFORE FUNCTIONAL TESTS?</title><p><bold>D. Ang</bold><sup>1,*</sup>, J. Tack<sup>2</sup></p><p><italic><sup>1</sup>Gastroenterology, Changi General Hospital, Singapore, Singapore, <sup>2</sup>Gastroenterology, KUL, Leuven, Belgium</italic></p><p><bold>INTRODUCTION:</bold> Patients with typical and atypical gastroesophageal reflux symptoms in the presence of a normal gastroscopy and which persist despite proton-pump inhibitor (PPI) therapy are increasingly encountered. Objective assessment with 24 hour pH monitoring, Bilitec and/or multichannel intraluminal impedance (MII-pH) monitoring identifies patients with acid reflux (AR) and/or non-acid reflux (NAR). It remains uncertain if proton pump inhibitors (PPI) should be stopped prior to functional tests.</p><p><bold>AIMS&METHODS:</bold> Aim: To determine the diagnostic yield of all studies performed on and off PPI therapy.Methods: Systematic review of all studies published from January 1996 to December 2012. Data were extracted for patient demographics, symptom profiles, acid exposure times (AET) and symptom index (SI). The prevalence of abnormal oesophageal acid exposure time (AET) and symptom marker based positive symptom index (SI) was compared by chi-square and student t-testing.</p><p><bold>RESULTS:</bold> Between January 1996 and December 2012, 32 studies involving 2925 patients (1130 male, mean [SD] age 50.4[9.9] years) who were evaluated for non-response to PPI therapy whilst on therapy (n=1841) and after PPI washout (n=1084) were identified. These studies included 490 subjects who underwent 24 hour pH study), 65 subjects withpH-bilitec and 2370 subjects who underwent MII-pH. Information on the nature of reflux symptoms was available in 2646 subjects (n=1800 typical symptoms; n=846 atypical symptoms). Thirteen and 11 studies reported elevated esophageal AET in 381 of 1068 (35.7%) patients and 216 of 1062 (20.3%) patients who were studied off and on PPI respectively (p<0.05). A positive SI for AR occurred in 48.5% and 11.9% of patients off and on PPI respectively (p<0.05). A positive SI for NAR occurred in 18.8% and 34.2% of patients off and on PPI respectively (p<0.05). Improved diagnostic yield was observed when patients were studied for AR events off PPI therapy and for NAR events on PPI.</p><p><bold>CONCLUSION:</bold> In GERD patients with insufficient treatment response, improved diagnostic yield was achieved with MII-pH monitoring performed on PPI therapy for evaluation of NAR and off therapy for AR evaluation. Whilst this approach may help direct appropriate therapy, further outcome studies are required.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> ambulatory pH impedance monitoring, GERD symptoms, proton pump inhibitor</p></sec><sec><title>OP380 STW5 REDUCES THE PROINFLAMMATORY SIGNATURE ON TRANSCRIPTOMIC, PROTEOMIC AND HISTOLOGICAL LEVEL IN A RAT MODEL FOR GASTROESOPHAGEAL REFLUX DISEASE</title><p><bold>H. Abdel-Aziz</bold><sup>1,2,*</sup>, D. Weiser<sup>2</sup>, M. T. Khayyal<sup>3</sup>, G. Ulrich-Merzenich<sup>4</sup></p><p><italic><sup>1</sup>Dpt. of Pharmacology, Inst. of Pharm. Chemistry, University of Münster, Münster, <sup>2</sup>Scientific Department, Steigerwald Arzneimittelwerk, Darmstadt, Germany, <sup>3</sup>Pharmacology, Faculty of Pharmacy, Cairo University, Cairo, Egypt, <sup>4</sup>Medizinische Klinik 3, University of Bonn, Bonn, Germany</italic></p><p><bold>INTRODUCTION:</bold> Gastroesophageal reflux disease (GERD) is one of the most common GI-diagnosis. Proton pump inhibitors (PPIs) present the main treatment, but up to 40 % of patients do not achieve adequate symptom control. Therefore the search continues for new therapeutic targets and additional treatment options. STW 5, a multi-component herbal preparation, was shown to relief concomitant reflux symptoms in patients with functional dyspepsia [1] and to prevent inflammation in an acute model of reflux esophagitis (RE) without affecting the pH of the refluxate [2]. Recently, we showed that it also improved macroscopic and histological parameters of esophagitis in a subchronic model of RE in rats, where it down regulated proinflammatory cytokines in the tissue homogenates (proteome profiling) [3].</p><p><bold>AIMS&METHODS:</bold> In the present study, we analyzed in our subchronic model of RE the transcript modulation in the esophageal tissue in an attempt to identify potential therapeutic targets. Rats were pre-treated for 7d either with STW 5 (0.5 or 2 ml/kg) or omeprazole (O). Esophagitis was then induced surgically [4]. Rats were treated for further 10d with STW 5 or O and sacrificed. The esophagi were excised. RNA was isolated from defined tissue areas and transcripts were analyzed by Agilent whole genome microarray (rat). Selected genes were validated by RT-PCR.</p><p><bold>RESULTS:</bold> Well known markers of inflammation and the immune response like IL-6, IL-1 and matrixmetallopeptidases (MMPs) were up-regulated in RE. Even though STW 5 and O down regulated different sets of genes, they showed a common pattern in a number of strongly and highly significantly regulated genes (p<0.0001), including chemokine ligands 4 and 11, G-protein coupled receptor GPR84, the LOX-1 receptor and resistin.</p><p><bold>CONCLUSION:</bold> Since gastric acid does not appear to be the only causative agent in GERD, identifying additional mechanisms involved in the pathogenesis or action of effective drugs may help detect novel therapeutic targets in GERD and pave the way for the development of effective treatment options.</p><p><bold>REFERENCES:</bold></p><p>1. Madisch A; Gut 2007; 56:A336</p><p>2. Abdel-Aziz H et al.; J Pharmacol Sci 2010; 113: 134-142</p><p>3. Abdel-Aziz H et al.; Gastroenterology 2012; 142: S-593</p><p><bold>Contact E-mail Address:</bold><email>heba.abdelaziz@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: H. Abdel-Aziz Other: Employee of Steigerwald Arzneimittelwerk GmbH, D. Weiser Consultancy for: Steigerwald Arzneimittelwerk GmbH, M. Khayyal Financial support for research from: Steigerwald Arzneimittelwerk GmbH, G. Ulrich-Merzenich Financial support for research from: Steigerwald Arzneimittelwerk GmbH</p><p><bold>Keywords:</bold> GERD, Herbal treatment, Inflammation, Protomics, Transcriptomics</p></sec><sec><title>OP381 PRESENCE OF BILE ACIDS AND PEPSIN IN SALIVA AND BRONCHO-ALVEOLAR LAVAGE OF PATIENTS WITH IDIOPATHIC PULMONARY FIBROSIS IS ASSOCIATED WITH INCREASED SEVERITY OF LUNG DISEASE</title><p><bold>E. Savarino</bold><sup>1,*</sup>, P. Zentilin<sup>2</sup>, E. Marabotto<sup>2</sup>, L. Sconfienza<sup>3</sup>, N. de Bortoli<sup>4</sup>, S. Marchi<sup>4</sup>, V. Savarino<sup>2</sup></p><p><italic><sup>1</sup>Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, <sup>2</sup>Department of Internal Medicine, Division of Gastroenterology, University of Genoa, Genoa, <sup>3</sup>Unit of Radiology, IRCCS Policlinico San Donato, Milan, <sup>4</sup>Department of Internal Medicine, Division of Gastroenterology, University of Pisa, Pisa, Italy</italic></p><p><bold>INTRODUCTION:</bold> Recent studies investigated the role of pepsin and bile acids (BAs) in saliva and bronchoalveolar lavage (BAL) of patients with respiratory diseases (i.e. asthma, cystic fibrosis) as specific and sensitive markers of gastro-oesophageal reflux–related pulmonary aspiration. However, no data are available on the role of these markers in patients with idiopathic pulmonary fibrosis (IPF) who are characterized by increased gastroesophageal reflux (up to 85%) and potential aspiration of duodenogastric contents into the lungs.</p><p><bold>AIMS&METHODS:</bold> To assess aspiration in IPF patients by measuring pepsin and BAs in saliva/BAL and to investigate whether their presence correlated with disease severity and pulmonary function tests (PFTs).</p><p>Saliva and BAL samples were collected in 38 and 21 IPF patients, 36 and 21 patients with interstitial lung disease other than IPF (non-IPF patients), 50 healthy volunteers (HVs) and 16 patients undergoing bronchoscopy for other diseases (controls), respectively. All subjects underwent pulmonary high-resolution computed tomography (HRCT) scan and PFTs on the day of saliva/BAL samples collection. BAs and pepsin were measured using two commercial available assays. The presence and severity of pulmonary fibrosis was defined using a previous validated HRCT-score (Best-score). Forced vital capacity (FVC), forced expiratory volume (FEV) and DL<sub>co</sub> curve were measured during PFTs.</p><p><bold>RESULTS:</bold> Patients with IPF had more BAs and pepsin (p<0.001) in BAL (62% and 67%) and saliva (61% and 68%) than non-IPF patients (40% and 40% in BAL, 33% and 36% in saliva) and controls (0% and 0% in BAL) or HVs (0% and 0% in saliva). The concentration of BAs in saliva and BAL was higher (p<0.001) in IPF [3.70 µmol/l and 0.90 µmol/l] than in non-IPF patients [1.5 µmol/l and 0.50 µmol/l]. A good correlation (p<0.001) was found between HRCT score and presence of pepsin and BAs in saliva (r<sup>2</sup>=0.5260 and r<sup>2</sup>=0.4269, respectively) and BAL (r<sup>2</sup>=0.6033 and r<sup>2</sup>=0.4605, respectively). A significant correlation was observed between HRCT score and the concentration of BAs in saliva (r<sup>2</sup>=0.2591, p=0.013) and in BAL (r<sup>2</sup>=0.3843, p=0.024). We failed to find a significant association among presence and concentration of BAs/pepsin in saliva and BAL and abnormalities of lung function parameters (p=ns).</p><p><bold>CONCLUSION:</bold> BAs and pepsin are present in saliva and BAL of more than one-half of patients with IPF, confirming aspiration of duodenogastric contents into the lungs. Their presence as well as their concentration are associated with increased severity of lung fibrosis.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> GERD, Idiopathic Pulmonary Fibrosis, impedance-pH monitoring</p></sec><sec><title></title><p><bold>WEDNESDAY, OCTOBER 16, 2013 8:30-10:30</bold></p><p><bold>Viral hepatitis C – Hall 10</bold></p></sec><sec><title>OP382 HOW OFTEN DO WE „MISS” CHRONIC HEPATITIS C PATIENTS WITH AT LEAST SIGNIFICANT FIBROSIS AND THOSE WITH COMPENSATED CIRRHOSIS BY USING ACOUSTIC RADIATION FORCE IMPULSE ELASTOGRAPHY (ARFI) CUT-OFF VALUES PROPOSED BY META-ANALYSIS ?</title><p><bold>S. Bota</bold><sup>1,*</sup>, I. Sporea<sup>1</sup>, R. Sirli<sup>1</sup>, A. Popescu<sup>1</sup>, M. Danila<sup>1</sup>, O. Gradinaru-Tascau<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology and Hepatology, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania</italic></p><p><bold>INTRODUCTION:</bold> ARFI is a ultrasound elastographic method for non-invasive evaluation of liver fibrosis.</p><p><bold>AIMS&METHODS: Aim</bold>: to evaluate how often we “miss” chronic hepatitis C patients with at least significant fibrosis (F≥2 - which must be treated with specific antiviral therapy) and those with compensated cirrhosis (F=4 - which must immediately be treated with specific antiviral therapy and included in a screening program for hepatocellular carcinoma) by using ARFI cut-off values proposed by meta-analysis.</p><p>METHODS: Our study included 132 patients with chronic hepatitis C evaluated by means of ARFI and liver biopsy-LB (interpreted according to the METAVIR score). Ten liver stiffness (LS) measurements were performed in each patient and a median value was calculated, expressed in meters/second (m/s). Reliable measurements were defined as: median value of 10 LS measurements with a success rate≥60% and an interquartile range interval<30%. For predicting F≥2 and F=4 we used the LS cut-offs proposed in published meta-analysis (1): 1.34 m/s and 1.8 m/s, respectively.</p><p><bold>RESULTS:</bold> Reliable LS measurements by means of ARFI were obtained in 117 patients (87.9%). The classification of liver fibrosis in LB was: F0-5.9%, F1-9.4%, F2-44.5%, F3-28.2% and F4-11.9%.</p><p> In our study, 58 patients (49.6%) had LS values <1.34 m/s; from these 75.8% had F≥2 in LB. From the 59 patients (50.4%) with LS values≥1.34 m/s, only 6.8% had F0 or F1 in LB.</p><p>Also, in our study, 88 patients (75.3%) had LS values <1.8 m/s; from these only 2.2 % had F4 in LB. From the 29 patients (24.7%) with LS values≥1.8 m/s, 41.3% had F4 in LB.</p><p><bold>CONCLUSION:</bold> Similar with Transient Elastography, ARFI had a very good positive predictive value (93.2%) for predicting the presence of significant fibrosis, but the negative predictive value was low (24.2%). So, if the LS value obtained by means of ARFI elastography is at least 1.34 m/s, we can recommend directly antiviral therapy, but if the value is lower than 1.34 m/s a LB should be performed to recover those patients missed by the technique. Also, similar with Transient Elastography, ARFI elastography had a very good negative predictive value (97.8%) for excluding the presence of liver cirrhosis, but the positive predictive value was quite low (41.3%).</p><p><bold>REFERENCES:</bold></p><p>1. Friedrich-Rust et al. J Viral Hepat.2012;19:e212-9</p><p><bold>Contact E-mail Address:</bold><email>bota_simona1982@yahoo.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> ARFI elastography, HCV, liver fibrosis, liver stiffness</p></sec><sec><title>OP383 FREQUENCY OF REGULATORY T CELL AND HCV ANTIGEN SPECIFIC IMMUNE RESPONSE IN RECURRENT HEPATITIS C AFTER LIVER TRANSPLANTATION</title><p><bold>M. Utsumi</bold><sup>1,*</sup>, A. Takaki<sup>2</sup>, K. Koike<sup>2</sup>, Y. Umeda<sup>1</sup>, D. Nobuoka<sup>1</sup>, R. Yoshida<sup>1</sup>, S. Shinoura<sup>1</sup>, H. Sadamori<sup>1</sup>, T. Fujiwara<sup>1</sup>, T. Yagi<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterological Surgery, <sup>2</sup>Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan</italic></p><p><bold>INTRODUCTION:</bold> Regulatory T cells (Treg) and type 1 regulatory T cells (Tr1) could be implicated in HCV recurrence after orthotopic liver transplantation (OLT). These regulatory T cells contribute to hepatitis C virus (HCV) persistence by suppressing HCV-specific T-cell response. In this study, we have sought to examine the frequency of Treg or Tr1 among OLT patients in different condition of post-OLT hepatitis C and evaluate the correlation with frequency of them and HCV specific T cell immune response.</p><p><bold>AIMS&METHODS:</bold> The patients comprised the orthotopic liver transplantation-chronic hepatitis C (CHC) group (<italic>n</italic> = 14), with active post-transplantation hepatitis C (alanine aminotransferase above the upper limit of normal/positive for hepatitis C virus RNA); orthotopic liver transplantation-persistently normal alanine aminotransferase (PNALT) group (<italic>n</italic> = 12), without active post-transplantation hepatitis C (persistently normal alanine aminotransferase/without interferon/ positive for hepatitis C virus RNA); and orthotopic liver transplantation-sustained viral response (SVR) group (<italic>n</italic> = 6), with a sustained post-transplantation viral response through interferon treatment (negative for hepatitis C virus RNA). Also frequency of HCV specific CD4+ T cells secreting IFN-γ was analyzed by enzyme linked immune spot.</p><p><bold>RESULTS:</bold> The results revealed that the frequency of Treg tended to be lower in patients with OLT-SVR than that of patients with OLT-CHC (p=0.068) and frequency of Tr1 in patients with OLT-PNALT was significantly lower than that with OLT-CHC (p=0.001). The frequency of Treg was correlated with HCV-NS3 antigen specific IFN-γ response that had positive relation to HCV clearance.</p><p><bold>CONCLUSION:</bold> Conclusively, regulatory T cells increase in number and diminished hepatitis C virus NS3 antigen-specific response recovers after viral eradication in chronic hepatitis C patients after orthotopic liver transplantation. Reduction in type 1 regulatory T cells correlates with hepatitis control, which may facilitate the control of chronic hepatitis C patients after orthotopic liver transplantation.</p><p><bold>REFERENCES:</bold></p><p>1. Wright TL, Donegan E, Hsu HH, Ferrell L, Lake JR, Kim M, et al. Recurrent and acquired hepatitis C viral infection in liver transplant recipients. Gastroenterology 1992;103:317-322.</p><p>2. Miroux C, Vausselin T, Delhem N. Regulatory T cells in HBV and HCV liver diseases: implication of regulatory T lymphocytes in the control of immune response. Expert Opin Biol Ther 2010;10:1563-1572.</p><p>3. Cabrera R, Tu Z, Xu Y, Firpi RJ, Rosen HR, Liu C, et al. An immunomodulatory role for CD4(+)CD25(+) regulatory T lymphocytes in hepatitis C virus infection. Hepatology 2004;40:1062-1071.</p><p>4. Carpentier A, Conti F, Stenard F, Aoudjehane L, Miroux C, Podevin P, et al. Increased expression of regulatory Tr1 cells in recurrent hepatitis C after liver transplantation. Am J Transplant 2009;9:2102-2112.</p><p>5. Bolacchi F, Sinistro A, Ciaprini C, Demin F, Capozzi M, Carducci FC, et al. Increased hepatitis C virus (HCV)-specific CD4+CD25+ regulatory T lymphocytes and reduced HCV-specific CD4+ T cell response in HCV-infected patients with normal versus abnormal alanine aminotransferase levels. Clin Exp Immunol 2006;144:188-196.</p><p><bold>Contact E-mail Address:</bold><email>masashi11232001@yahoo.co.jp</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> regulatory T cell, Hepatitis C, liver transplantation, Tr1</p></sec><sec><title>OP384 ASSESSMENT OF LIVER STIFFNESS IN PATIENTS WITH HCV-RELATED MIXED CRYOGLOBULINEMIA UNDERGOING RITUXIMAB TREATMENT</title><p><bold>C. Stasi</bold><sup>1,*</sup>, E. Triboli<sup>1</sup>, U. Arena<sup>1</sup>, T. Urraro<sup>1</sup>, A. Petrarca<sup>1</sup>, C. Giannini<sup>1</sup>, G. Laffi<sup>1</sup>, A. L. Zignego<sup>1</sup></p><p><italic><sup>1</sup>Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses MASVE and Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy</italic></p><p><bold>INTRODUCTION:</bold> Mixed Cryoglobulinemia (MC) is a HCV-related lymphoproliferative disorder generally associated with severe liver disease. Clinical manifestations - the so-called MC Syndrome (MCS) - are secondary to a systemic vasculitis of the small vessels. Liver stiffness has been significantly correlated with histopathological stage of fibrosis, with excellent accuracy in distinguishing absent/mild and advanced fibrosis. Moreover, it was influenced by necroinflammatory activity. Rituximab (RTX) is a chimeric monoclonal antibody that bins to the surface of CD-20 B lymphocytes (BL) leading to BL depletion. The BL compartment generally begins to recover 6 months after therapy. A consistent improvement of cirrhotic syndrome was previously observed in MCS patients after RTX treatment.</p><p><bold>AIMS&METHODS:</bold> Aim of this study was to evaluate the changes of liver stiffness following RTX treatment in HCV MCS patients. Fourteen consecutive patients (10 F, 4 M; mean age 60.43±43) with HCV-related chronic hepatitis (n=10) or cirrhosis (n=4) and SCM, eligible for RTX treatment, were prospectively enrolled. Exclusion criteria were: antiviral or immunosuppressive therapies within 6 months; Child-B/C cirrhosis; hepatocellular carcinoma, acute viral hepatitis, HBV or HIV co-infection, metabolic or vascular liver disease, biliary tract disorders; alcohol abuse or hepatotoxic drugs. Intravenous injection of 1 g of RTX was performed at time 0 and 15 days. Assessment of stiffness was carried out by Fibroscan® (Echosens, Paris-France) before treatment, 15 days after the first infusion, and at 1, 3 and 6 months after therapy.</p><p><bold>RESULTS:</bold> All patients were HCV RNA positive. Eleven patients had genotype 1, 2 had genotype 2a/2b and 1 patient had genotype 3. MCS significantly improved during the study, especially during the first 3 months (table 1). The mean stiffness values observed 3 months after treatment were significantly reduced when compared with pre-treatment values (p=0.01). This difference disappeared after 6 months of follow-up. Cytofluorimetric analysis showed a dramatic decrease of CD19+ peripheral blood cells, that started early after anti-CD20 infusion, with the nadir at 3 months after therapy and reconstitution after 6 months.
<table-wrap id="table59-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1">Parameter</th><th rowspan="1" colspan="1">Baseline</th><th rowspan="1" colspan="1">3 months</th><th rowspan="1" colspan="1">P value</th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">Platelets (x10<sup>9</sup> /L)</td><td rowspan="1" colspan="1">145.50±71.22</td><td rowspan="1" colspan="1">163.4±19.89</td><td rowspan="1" colspan="1">p=0.05</td></tr><tr><td rowspan="1" colspan="1">Albumine (g/dL)</td><td rowspan="1" colspan="1">3.82±0.35</td><td rowspan="1" colspan="1">4.05±0.41</td><td rowspan="1" colspan="1">p=0.01</td></tr><tr><td rowspan="1" colspan="1">Mean stiffness (kPa)</td><td rowspan="1" colspan="1">20.44±17.29</td><td rowspan="1" colspan="1">17.00±16.05</td><td rowspan="1" colspan="1">p=0.01</td></tr><tr><td rowspan="1" colspan="1">CD19+ (x10<sup>6</sup>/L)</td><td rowspan="1" colspan="1">124.2±56.15</td><td rowspan="1" colspan="1">38±16.59</td><td rowspan="1" colspan="1">p=0.01</td></tr></tbody></table></table-wrap></p><p><bold>CONCLUSION:</bold> This study, for the first time, shows that RTX-treatment in HCV MCS induces a reduction in liver stiffness that is strictly associated with the B-cell depletion.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> chronic hepatitis C virus (HCV), liver stiffness, mixed cryoglobulinemia , rituximab</p></sec><sec><title>OP385 INCREASED BASELINE PROINFLAMMATORY CYTOKINE PRODUCTION IN CHRONIC HEPATITIS C PATIENTS WITH RAPID VIROLOGICAL RESPONSE TO PEGINTERFERON PLUS RIBAVIRIN</title><p><bold>G. Par</bold><sup>1,*</sup>, L. Szereday<sup>2,3</sup>, T. Berki<sup>4</sup>, L. Palinkas<sup>4</sup>, A. Miseta<sup>5</sup>, A. Vincze<sup>1</sup>, A. Par<sup>1</sup></p><p><italic><sup>1</sup>First Department of Medicine, <sup>2</sup>Department of Medical Microbiology and Immunology, University of Pecs, <sup>3</sup>Janos Szentagothai Research Centre, <sup>4</sup>Department of Immunology and Biotechnology, <sup>5</sup>Department of Laboratory Medicine, University of Pecs, Pecs, Hungary</italic></p><p><bold>INTRODUCTION:</bold> Chronic hepatitis C (CHC) patients achieving rapid virological response (RVR) on PEG-IFN/ribavirin (P/R) therapy have high chance of sustained virological response (SVR). To analyze host immunological factors associated with RVR, viral kinetics, phenotype distribution and Th1/Th2 cytokine production by peripheral blood mononuclear cells (PBMC) were studied prior to and during P/R therapy.</p><p><bold>AIMS&METHODS:</bold> TNF-a, IFN-g, IL-2, IL-6, IL-4 and IL-10 production by PBMC were measured after Toll-like receptor 4 (TLR-4) or phorbol myristate acetate /Ionomycin stimulation in 20 healthy controls and in 50 CHC patients before receiving and during P/R therapy. RVR was achieved by 14, complete early virological response (cEVR) by 19 patients and 17 patients were null-responders (NR).</p><p><bold>RESULTS:</bold> Patients with RVR showed an increased baseline TNF-a and IL-6 production by TLR-4 activated monocytes and increased IFN-g, decreased IL-4 and IL-10 production by lymphocytes compared to non-RVR patients. SVR was also associated with increased baseline TNF-a production and decreased IL-10 levels compared to patients who did not achieve SVR. Baseline IL-2 production was higher in cEVR compared to NR patients. Antiviral treatment increased TNF-a, IL-6 production by monocytes and IFN-g secretion by lymphocytes and decreased IL-4 and IL-10 production by lymphocytes in cEVR compared to NR patients.</p><p><bold>CONCLUSION:</bold> RVR was associated with increased baseline proinflammatory cytokine production by TLR-4 stimulated monocytes and by activated lymphocytes. In null-responders and in patients who did not achieve SVR both TLR-4 sensing function and proinflammatory cytokine production were impaired, suggesting that modulation of TLR activity and controlled induction of inflammatory cytokine production may provide further therapeutic strategy for CHC patients non-responding to P/R treatment.</p><p><bold>Contact E-mail Address:</bold><email>pargabriella@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> cytokine profile, Hepatitis C virus (HCV), rapid virological response</p></sec><sec><title>OP386 CEREBRAL GLUCOSE METABOLISM AND NEUROPSYCHIATRIC SYMPTOMS IN CHRONIC HEPATITIS C PATIENTS WITH ANTIVIRAL THERAPY</title><p><bold>K. Sawara</bold><sup>1,*</sup>, T. Wang<sup>1</sup>, Y. Yoshida<sup>1</sup>, A. Miyasaka<sup>1</sup>, A. Kato<sup>1</sup>, Y. Takikawa<sup>1</sup>, K. Suzuki<sup>1</sup></p><p><italic><sup>1</sup>gastroenterology and hepatology, IWATE MEDICAL UNIVERSITY, Morioka, Japan</italic></p><p><bold>INTRODUCTION:</bold> Antiviral therapy such as Interferon(IFN) therapy is important treatment of chronic hepatitis C patients and widely used in the world. However, adverse effects of the therapy that depression or neuropsychiatric symptoms make it difficult to be completed.</p><p>The aim of study is to evaluate neuropsychiatric symptoms with antiviral therapy and its correlation of effects on cerebral glucose metabolism (CMRglu) in chronic hepatitis C patients and examine how antiviral therapy affects on human brain.</p><p><bold>AIMS&METHODS:</bold> 12patients with chronic hepatitis C undergoing antiviral therapy (Peg IFN α2b,IFN α2b,IFN β plus Ribavirin combination therapy or IFN α monotherapy) were prospectively evaluated neuropsychiatric symptoms by Digit symbol test(DST),Block design test(BDT),Self-rating Depression Scale(SDS) .</p><p>We assessed cerebral glucose metabolism (CMRglu) using [18F] deoxyglucose positron emission tomography (FDG-PET) before and the 8th weeks of therapy and after the therapy.</p><p>On basic science aspect, We examined human astrocytes were exposed to human recombinant IFNs (IFNα2a, IFNα2b, and IFNβ), and the proliferation of cells was measured using the cell count reagent SF and glucose consumption was measured.</p><p><bold>RESULTS:</bold> Compare to before and 8th weeks of therapy, SDS of all patients were worsened. SDS points were 10.9±6.3 points (mean±SD) increased from before the therapy. CMRglu of 6 patients were 1-24% decreased in whole of the brain. CMRglu of 5 patients were 2-37% increased in the whole of the brain. There were no trend of result DST and BDT before and 8th weeks of therapy.</p><p>We examined 7 patients who completed the therapy. Compare to before and after the therapy, SDS of all 7 patients after the therapy were recovered same as much as before the therapy. CMRglu of 5 patients were 11-73% increased in whole of the brain from before the therapy. CMRglu of 1 patient were recovered 93%−100% in whole of the brain from before the therapy. CMRglu of 1 patient were decreased in whole of the brain from before the therapy.</p><p>A physiologically-relevant concentration of IFNα2a and IFNα2b (2IU/ml) significantly decreased the proliferation of human astrocytes by 23% (<italic>p</italic>=0.007) and 13% (<italic>p</italic>=0.02). Treatment with IFNα2a or IFNα2b decreased the glucose consumption in cultured human astrocytes.</p><p><bold>CONCLUSION:</bold> These results suggest that antiviral therapy affects on cerebral glucose metabolism and depression or neuropsychiatric symptoms in chronic hepatitis C patients. Antiviral therapy, especially IFNs affects on cerebral glucose metabolism and that might be involved in proliferation and glucose utilization of human astrocytes. It might be associated with depression or neuropsychiatric symptoms.</p><p><bold>Contact E-mail Address:</bold><email>ikeraw@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> antiviral therapy, cerebral glucose metabolism (CMRglu), human astrocytes, neuropsychiatric symptoms</p></sec><sec><title>OP387 A NEW PROGNOSTIC TEST FOR THE EFFICIENCY OF ANTIVIRAL THERAPY IN ADULTS AND CHILDREN WITH HEPATITIS C VIRUS INFECTION</title><p><bold>A. R. Reizis</bold><sup>1</sup>, O. N. Khokhlova<sup>2,*</sup>, L. V. Serebrovskaya<sup>2</sup></p><p><italic><sup>1</sup>Central Research Institute of Epidemiology, Federal Supervision Servise for Consumer Rights Protection and People,s Welfare, Moscow, Russian Federation, <sup>2</sup>Russian Federal Center AIDS, Central Research Institute of Epidemiology, Federal Supervision Servise for Consumer Rights Protection and People,s Welfare, Moscow, Russian Federation</italic></p><p><bold>INTRODUCTION:</bold> Etiotropic treatment of chronic hepatitis C virus (HCV) infection in adults and children is based on the prolonged administration of recombinant type I interferon (IFN). Reliable prognostic indicators of its efficiency in individual patients are of paramount importance for the choice of optimal therapeutic strategies. Plasmacytoid dendritic cells (pDCs) are major producers of IFN in response to viral infections, and have been proposed to play an important role in the control of HCV infection. Our goal was to test whether the IFN production capacity of pDCs might correlate with and predict the efficiency of antiviral therapy of HCV infection.</p><p><bold>AIMS&METHODS:</bold> We have examined 37 patients with HCV infection (13 children and 24 adults) at different stages of therapy with recombinant IFNa. The pDC population was enumerated by flow cytometry, and in vitro IFN production in the whole blood in response to pDC-specific stimulus unmethylated CpG oligonucleotides was determined by ELISA.</p><p><bold>RESULTS:</bold> We found that IFN therapy strongly increased IFN production by pDCs in the whole blood in both adults and children with HCV. Patients who had eventually achieved a sustained viral response (SVR) showed robust IFN production by pDCs at 12 weeks of therapy (1,558±278 pg/ml in our assay conditions), whereas non-responders showed a significantly (P<0.005) reduced IFN production (69±54 pg/ml). The increase in IFN production capacity at 12 weeks of therapy (>260-fold in adults and >120-fold in children relative to the respective values prior to the therapy) predicted the likelihood of SVR with 96.9% confidence.</p><p><bold>CONCLUSION:</bold> The IFN-producing capacity of pDCs is enhanced by effective antiviral therapy with IFN. Higher levels of IFN production by pDCs correlate with the response to IFN therapy and can serve as a robust early predictor of the successful SVR achievement. These results implicate the stimulation of endogenous IFN production by pDCs as an important mechanism of IFN therapy, and establish a novel test to predict therapy efficiency in HCV patients.</p><p><bold>Contact E-mail Address:</bold><email>x.olia79@mail.ru</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> antiviral therapy , chronic hepatitis C virus (HCV) , Plasmacytoid dendritic cells (pDCs) , Prognostic test</p></sec><sec><title>OP388 THE PREDICTIVE ROLE OF INTERFERON GAMMA INDUCTIBLE PROTEIN-10 FOR VIROLOGICAL RESPONSE IN CHRONIC HEPATITIS C</title><p><bold>D. Crisan</bold><sup>1,*</sup>, C. Radu<sup>1,2</sup>, M. D. Grigorescu<sup>1,2</sup>, D. Damian<sup>1</sup>, P. Szanto<sup>1,2</sup>, A. Cavasi<sup>1,2</sup>, A. Habic<sup>1</sup>, M. Grigorescu<sup>1,2</sup>, First two authors equaly contributed at this study</p><p><italic><sup>1</sup>Regional Institute of Gastroenterology and Hepatology, <sup>2</sup>"Iuliu Hatieganu"University of Medicine and Pharmacy, Cluj-Napoca, Romania</italic></p><p><bold>INTRODUCTION:</bold> Multiple factors contribute to virological response in chronic hepatitis C (CHC). One of them is interferon-gamma inductible protein-10 (IP-10). Its level reflects the status of interferon-stimulated genes (ISGs) which in turn is associated with virological response to antiviral therapy.</p><p><bold>AIMS&METHODS:</bold> The aim of the study was to evaluate the role of serum IP-10 levels on sustained virological response (SVR) and the association of this parameter with insulin resistance (IR), fibrosis and activity.</p><p>One hundred seventy two non-diabetic CHC patients with biopsy proven CHC, genotype 1 were studied. Serum levels of IP-10 were assessed by ELISA method. Insulin resistance (HOMA-IR). stages of fibrosis and degrees of activity were evaluated histologically and by FibroTest and ActiTest(Biopredictive). Area under receiving operating characteristic curve (AUROC). sensibility, specificity, positive predictive value(PPV), negative predictive value(NPV) of IP-10 were assessed.</p><p><bold>RESULTS:</bold> We obtained a cut-off value of 392pg/ml to discriminate between responders and nonresponders. SVR was obtained in 94/172 patients (54.65%) with IP-10 < 392 pg/ml and in 78/172 patients (45.3%) with IP-10 >392pg/ml (p<0.0001). AUROC for SVR was 0.865. with a sensibility of 91.8%. specificity 71.4%. PPV 79.5% and NPV 87.0%. IP-10 < 392 pg/ml was associated with less fibrosis (p<0.0001) and also by FibroTest. An association between IP-10 levels and histologically activity (p=0.004) and ActiTest (p<0.005) was found. In responders patients with lower IP-10 levels, HOMA-IR was lower than nonresponders (p=0.022). In multivariate analysis IP-10 levels and fibrosis stages were independently predictive for SVR.</p><p><bold>CONCLUSION:</bold> The assessment of serum IP-10 level is a predictive factor for SVR and correlates with fibrosis, activity and IR.</p><p><bold>Contact E-mail Address:</bold><email>crisan.dc@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: D. Crisan : none, C. Radu : none, M. D. Grigorescu : none, D. Damian : none, P. Szanto : none, A. Cavasi : none, A. Habic : none, M. Grigorescu : none</p><p><bold>Keywords:</bold> activity, fibrosis, insulin resistance, IP-10, sustained virologic response (SVR)</p></sec><sec><title>OP389 IMPACT OF GENETIC VARIATION IN SR-BI ON HEPATITIS C VIRUS INFECTION</title><p><bold>M. Deest</bold><sup>1</sup>, S. Westhaus<sup>2</sup>, S. Pischke<sup>1</sup>, M. Manns<sup>1</sup>, C. Sarrazin<sup>3</sup>, S. Ciesek<sup>1</sup>, T. Von Hahn<sup>1,2,*</sup></p><p><italic><sup>1</sup>Gastroenterology, Hepatology and Endocrinology, <sup>2</sup>Institute for Molecular Biology, Medizinische Hochschule Hannover, Hannover, <sup>3</sup>Medizinische Klinik 1, Universitaetsklinikum Frankfurt, Frankfurt, Germany</italic></p><p><bold>INTRODUCTION:</bold> The scavenger receptor type B class I (SR-BI) is the physiological receptor for high density lipoproteins (HDL) on hepatocytes. It is also one of four essential hepatitis C virus (HCV) cell surface receptors required for viral entry into hepatocytes. Numerous single-nucleotide polymorphisms (SNPs) have been described in the SCARB1 gene encoding SR-BI. Some of these are known to have a sex-dependent phenotype in the form of altered serum HDL, but their impact on HCV infection is unknown.</p><p><bold>AIMS&METHODS:</bold> We aimed to investigate SCARB1 SNPs with a high likelihood to affect HCV biology. All known SNPs that result in an amino acid exchange in the SR-BI protein (5 SNPs) were subjected to in vitro assays testing their ability to function as HCV receptors. Another four non-coding SNPs that have an allele minor frequency of >1% and had been reported to be associated with a phenotype in humans were investigated in an association study in a cohort of 218 chronically HCV infected patients.</p><p><bold>RESULTS:</bold> In the genetic association part of the study we found the rs5888 and rs3782287 variants to be associated with sustained virologic response (SVR) to dual therapy with interferon and ribavirin in female individuals. Moreover, we found a significant association with altered serum lipids (3 SNPs), transaminase levels (3 SNPs) and APRI score (2 SNPs). All identified associations are currently being retested in a second independent cohort. Among the five coding SNPs, the P297S variant that has recently been reported to be associated with elevated HDL (1) has been found to be fully functional as an HCV receptor. Conversely, the S112F and T175A variants may have mildly reduced HCV receptor function. We currently investigate their impact on HCV inhibition by the compound ITX5061 that inhibits the interaction between HCV and SR-BI and is currently in clinical development.</p><p><bold>CONCLUSION:</bold> Common non-coding variants in SCARB1 modulate serum lipid levels and possibly the clinical course of HCV infection. The P297S variant is fully functional as an HCV receptor while other rare coding variants may result in altered HCV entry.</p><p><bold>REFERENCES:</bold></p><p>1. Vergeer et al. N Engl J Med 2011;364:136-45.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> HDL, Hepatitis C virus, lipid metabolism, Scavenger receptor class B type I, single nucleotide polymorphism</p></sec><sec><title>OP390 LONG-TERM IMPACT OF ANTIVIRAL THERAPY IN THE NATURAL HISTORY OF CHRONIC HEPATITIS C.</title><p><bold>P. Cordero Ruiz</bold><sup>1,*</sup>, I. Carmona Soria<sup>1</sup>, Á. Caunedo Álvarez<sup>1</sup>, J. M. Herrerías Gutiérrez<sup>1</sup>, Á. Vilches Arenas<sup>2</sup></p><p><italic><sup>1</sup>Gastroenterology, Virgen Macarena University Hospital, <sup>2</sup>Preventive Medicine and Public Health, , University of Sevilla, Seville, Spain</italic></p><p><bold>INTRODUCTION:</bold> Many studies have shown that patients with chronic hepatitis C who achieve a sustained virological response (SVR), following antiviral therapy, have lower risk of hepatic decompensation, hepatocellular carcinoma (HCC), liver-related deaths and it is associated to favorable changes in liver histology (1-3)</p><p><bold>AIMS&METHODS:</bold> To compare the rate of clinical events, HCC, all-cause mortality, liver-related mortality and fibrosis, after antiviral therapy among patients with SVR and those non-sustained virological responders (NR) over a long-term follow-up period (16 years). This is an observational, retrospective historical cohort study. One hundred and eighty-two patients with chronic hepatitis C, who had undergone liver biopsy before treatment, with interferon and ribavirina, between 1996 and 2000, from a single Spanish center, were included. All patients were examined with blood test taken for hepatitis C virus detection and clinical outcomes, defined as hepatic decompensation, HCC and death (global and liver-related). Transient elastography (TE) were performed at the end of follow up (between 2010 and 2012).</p><p><bold>RESULTS:</bold> Of 182 patients, 46.7% (n=85) had SVR and 53.3% (n=97) did not. There were no virological relapses during the follow-up period. Twenty seven patients developed hepatic decompensation, 1 patient with SVR and 26 (96.3%) without. Fifteen patients developed HCC, 3 patients with SVR and 12 without (80.0%), 29 patients died, 8 patients with SVR and 21 without (72.4%). Of the 29 deaths, the cause was liver-related in 12 patients, 2 patients with SVR and 10 without (83.3%). Only the adjusted hazard ratio (HR) for time to hepatic decompensation (HR 17.4 (95% CI 2.3-129.0) p=0.005) was significant for NR compared to SVR. Pretreatment liver fibrosis in SVR biopsy was F0/F1/F2 in 84 patients and F3/F4 in 5 patients and in NR was F0/F1/F2 in 75 and F3/F4 in 18 patients. TE was performed in 125 patients (68.7%), 66 patients with SVR and 59 without. At the end of follow-up the ET values showed a different distribution between SVR (Me=6.0 (P25;P75)(4.1;8.1) and NR (Me=10.4 (7.3;16.3) p=0.001. TE was < 7.5 kPa for 15 NR (24.6%), from 7.5 to 9.4 kPa for 9 NR (47.4%), from 9.5 to 14.4 kPa for 19 NR (67.9%) and >14.5 kPa for 16 NR (94.1 %).</p><p><bold>CONCLUSION:</bold> In patients with chronic hepatitis C SVR is long lasting, and it is associated to long-term reduction in clinical events. Although the SVR patients have fewer HCC, all-cause mortality and liver-related mortality than NR, the difference is not significant. TE values are significantly lower in patients with SVR.</p><p><bold>REFERENCES:</bold></p><p>1. Morgan TR, Ghany MG, Kim HY, Snow KK, Shiffman ML, De Santo JL, et al. Outcome of sustained virological responders with histologically advanced chronic hepatitis C. Hepatology. 2010 Sep;52(3):833-44.</p><p>2. George SL, Bacon BR, Brunt EM, Mihindukulasuriya KL, Hoffmann J, Di Bisceglie AM. Clinical, virologic, histologic, and biochemical outcomes after successful HCV therapy: A 5-year follow-up of 150 patients. Hepatology. 2009 Mar;49(3):729-38.</p><p>3. van der Meer AJ, Veldt BJ, Feld JJ, Wedemeyer H, Dufour JF, Lammert F, et al. Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis. JAMA. 2012 Dec 26;308(24):2584-93.</p><p><bold>Contact E-mail Address:</bold><email>rioga_patri@hotmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Chronic hepatitis C, long-term outcomes, sustained virologic response (SVR), Transient elastography</p></sec><sec><title></title><p><bold>WEDNESDAY, OCTOBER 16, 2013 8:30-10:30</bold></p><p><bold>Therapeutic ERCP update – Hall 8</bold></p></sec><sec><title>OP391 ANGLED-TIP GUIDEWIRE ENABLES HIGHER PROCEDURE COMPLETION THAN STRAIGHT-TIP GUIDEWIRE IN ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY: A RANDOMIZED CONTROLLED TRIAL</title><p><bold>O. Inatomi</bold><sup>1,*</sup>, S. Bamba<sup>1</sup>, T. Kanda<sup>1</sup>, Y. Mochizuki<sup>2</sup>, H. Ban<sup>1</sup>, M. Shioya<sup>1</sup>, Y. Saito<sup>2</sup>, A. Andoh<sup>1</sup>, Y. Fujiyama<sup>1</sup></p><p><italic><sup>1</sup>Division of Gastroenterology, <sup>2</sup>Division of Endoscopy, SHIGA UNIVERSITY OF MEDICAL SCIENCE, Otsu, Japan</italic></p><p><bold>INTRODUCTION:</bold> Wire-guided cannulation technique has been widely accepted for endoscopic retrograde cholangiopancreatography (ERCP). Although multiple guidewires are often used based on shape of the papilla or course of the bile duct, the entire procedure can ideally be completed using a single guidewire to reduce cost and avoid complexities of changing guidewires. However, the selection criteria for an optimal guidewire remain controversial. In this study, we conducted a randomized controlled trial that evaluated the utility and safety of using guidewires with different types of tips.</p><p><bold>AIMS&METHODS:</bold> Of the patients who underwent ERCP between June 2011 and December 2012, 225 were enrolled. We used guidewire with one of the two different tips (angled or straight) for the initial approach. We assigned 123 cases to the angled-tip group and 102 cases to the straight-tip group. The primary endpoint was completion rate using a single guidewire. Secondary endpoints were the rates of successful deep cannulation into the bile or pancreatic duct, the incidence of acute pancreatitis and other guidewire-related complications.</p><p><bold>RESULTS:</bold> Completion rate achieved using single guidewire was 85.4% (105/123) in the angled-tip group compared with 73.5% (75/102) in the straight-tip group (p = 0.027). Most frequent reasons for using multiple guidewires were the use of double-guidewire method (17/18; 94.4%) in the angled-tip group and to overcome technical difficulties in seeking the correct orientation for deep cannulation (15/27; 55.6%) in the straight-tip group. There were no significant differences in the final rate of successful deep cannulation, incidence of acute pancreatitis or other complications between the groups.</p><p><bold>CONCLUSION:</bold> In our study, angled guidewire was found to be safe and superior to the straight guidewire for achieving completion of the procedure, without using multiple guidewires. Angled guidewire is suitable to use as the initial guidewire in ERCP.</p><p><bold>Contact E-mail Address:</bold><email>osam@belle.shiga-med.ac.jp</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> ERCP, Wire guided cannulation</p></sec><sec><title>OP392 EMERGING ROLE OF IL-28B GENETICAL POLYMORPHISMS AS PREDISPOSING FACTORS OF BILIARY ANASTOMOTIC STRICTURES IN PATIENTS UNDERGOING ERCP AFTER LIVER TRANSPLANTATION</title><p><bold>S. F. Vadala' di Prampero</bold><sup>1,*</sup>, D. Bitetto<sup>2</sup>, M. Bulajic<sup>1,3</sup>, L. M. Zoratti<sup>1</sup>, P. Toniutto<sup>2</sup>, M. Zilli<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology unit, University Hospital "Santa Maria della Misericordia" Udine, <sup>2</sup>Medical Sciences Clinical and Experimental, Medical Liver Transplantation Unit, Internal Medicine, University of Udine, Udine, Italy, <sup>3</sup>Faculty of Medicine, University of Belgrade, Serbia</italic></p><p><bold>INTRODUCTION:</bold> The main biliary complication following liver transplantation (LT) is biliary anastomotic stricture (BAS). To define possible predisposing factors of BAS appearance we analyzed different demographic and clinical features in patients undergoing ERCP, among which recipient interleukin 28B (IL-28B) rs12979860 C/T polymorphism.</p><p><bold>AIMS&METHODS:</bold> We evaluated 171 consecutive liver transplanted recipients recruited in our Centre from 2004 to 2010 (133 males, median age 56 years), with at least one year of follow-up. All patients with clinical or radiologic suspicion of obstructive jaundice and cholestasis underwent ERCP. The concept of ERCP was based on biliary sphyncterotomy followed by stricture dilation and placement of at least one plastic stent, exchangeable every 3-6 months until the final stricture resolution. IL-28B rs12979860 C/T polymorphisms were genotyped in all recipients using PCR with restriction fragment length polymorphism in DNA samples extracted from whole blood.</p><p><bold>RESULTS:</bold> During post-operative follow-up 40 patients presented BAS. The median number of ERCP per patient was 3, median number of stents inserted per patient per procedure was 1 and median period until stricture resolution was 9 months. Stricture resolution was obtained in 83%. Occurrence of BAS was strongly associated with use of Kehr T tube (12/23 Vs 28/148, p<0.01), with use of cyclosporine as immunosuppressive therapy (18/54 Vs 22/117, p<0.05) and with presence of the C allele of IL-28B polymorphism (C/C 22/71, C/T 16/83, T/T 2/17, p<0.05 for linear trend). The correlation of IL-28B genetic polymorphism and development of BAS was confirmed in cyclosporine treated patients (C/C 10/20 Vs T/* 8/34, p<0.05) but not in those treated by tacrolimus (C/C 12/51 Vs T/* 10/66, p>0.05). Independent predictors of BAS development at logistic regression analysis were the interaction between IL-28B C/C genotype and cyclosporine use (O.R. 4.20, p<0.01), use of Kehr T tube (O.R. 5.46, p<0.01) and donor male gender (O.R. 2.61, p<0.01).</p><p><bold>CONCLUSION:</bold> The defining of recipient IL-28B rs12979860 C/T polymorphisms could represent an emerging role in identifying patients with highly elevated risk of BAS development. This fact could also have a strong impact on choice of more appropriate regimen of treatment of patients undergoing ERCP for BAS post-LT.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> ERCP, Gene polymorphism, post liver transplant biliary strictures, Predictive factors</p></sec><sec><title>OP393 ENDOSCOPIC TREATMENT OF BENIGN BILIARY STRICTURES WITH A REMOVABLE FULLY COVERED SELF-EXPANDABLE METAL STENT: PRELIMINARY DATA FROM A MULTICENTER EUROPEAN STUDY</title><p><bold>A. Schmidt</bold><sup>1,*</sup>, F. Fanelli<sup>2</sup>, F. Fiocca<sup>3</sup>, A. Hoffmeister<sup>4</sup>, M. Kraft<sup>5</sup>, M. Lerch<sup>5</sup>, T. Pickartz<sup>5</sup>, W. van Steenbergen<sup>6</sup>, K. Caca<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology, Klinikum Ludwigsburg, Ludwigsburg, Germany, <sup>2</sup>Interventional Radiology, <sup>3</sup>Gastroenterology, Sapienza University of Rome, Rome, Italy, <sup>4</sup>Gastroenterology, University of Leipzig, Ludwigsburg, <sup>5</sup>Gastroenterology, University of Greifswald, Greifswald, Germany, <sup>6</sup>Gastroenterology, University of Leuven, Leuven, Belgium</italic></p><p><bold>INTRODUCTION:</bold> Endoscopic treatment of benign biliary strictures by using balloon dilatation and insertion of (multiple) plastic stents is effective but requires repeated interventions. Temporary placement of removable fully covered self-expandable metal stents (FCSEMSs) has been reported to be an effective therapy for benign strictures.</p><p><bold>AIMS&METHODS:</bold> The objective of our prospective study at 6 European tertiary care centers is to evaluate the efficacy and safety of this endoscopic treatment. An FCSEMS (GORE® VIABIL® Biliary Endoprosthesis, WL Gore & Associates, Elkton, MD) was implanted in patients with a benign biliary stricture. The devices were scheduled to be removed 9 months later. Patients were followed for an additional 15 months.</p><p><bold>RESULTS:</bold> So far, 36 patients have been enrolled in the study. The biliary stricture was due to chronic pancreatitis in 22 patients, anastomotic stricture in 6, recurrent bile duct stones in 4, iatrogenic bile duct injuries in 2 and other causes (2). Twentyseven of the 36 patients had previously undergone endoscopic treatment. All FCSEMSs were placed successfully, either endoscopically (29) or percutaneously (7) without complications. The stricture resolved immediately after device deployment in 35 patients (97%). Primary stent patency rates were 100 % at 1 month after deployment, 80,0% at 6 months, and 66,4% at 9 months. In 15 patients, the device was removed successfully and without complications at a median (± SD) time of 245 ± 94 days after implantation. In 8 of these 15 patients, removal was done after completion of therapy at 9 months. In the other 7, the device was retrieved earlier because of stent occlusion (3 patients), recurrent cholangitis (1), choledocholithiasis proximal of the stent (1), acute pancreatitis (1) or before resection of the pancreatic head (1). No stent migration was observed. Stricture resolved completely immediately after removal or within a month of removal in 7 of the 15 patients, another five patients had minimal residual stenosis not requiring further treatment. Six-month post-removal follow-up data have so far been obtained in 6 patients; none have had stricture recurrence.</p><p><bold>CONCLUSION:</bold> These preliminary findings indicate that temporary placement of the FCSEMS is a feasible, safe, and effective treatment for benign biliary strictures. The design of the device facilitates easy retrieval even after 9 months. Patient enrollment and follow-up are continuing.</p><p><bold>Contact E-mail Address:</bold><email>arthur.schmidt@kliniken-lb.de</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> biliary stenting, biliary strictures, SEMS, VIABIL</p></sec><sec><title>OP394 PRELIMINARY RESULTS OF A RANDOMIZED STUDY OF MULTIPLE PLASTIC STENTS VERSUS COVERED METALLIC STENT (CSEMS) IN THE TREATMENT OF BILIARY STRICTURE DUE TO CHRONIC PANCREATITIS.</title><p><bold>J. Halttunen</bold><sup>1,*</sup>, C. Haapamäki<sup>1</sup>, M. Udd<sup>1</sup>, O. Lindström<sup>1</sup>, J. Grönroos<sup>2</sup>, A. Saarela<sup>3</sup>, L. Kylänpää<sup>1</sup></p><p><italic><sup>1</sup>Helsinki University Central Hospital, Helsinki, <sup>2</sup>Turku University Central Hospita, Turku, <sup>3</sup>Oulu University Central Hospital, Oulu, Finland</italic></p><p><bold>INTRODUCTION: Background.</bold> The use of covered metallic stents (cSEMS) in benign biliary strictures is not yet established.</p><p><bold>AIMS&METHODS: Materials and methods. </bold>A prospective, multicentre randomized study with 60 patients (54 male) suffering from biliary stricture due to chronic pancreatitis (CP) was started in October 2008. In the first ERCP the biliary stricture was treated with one plastic stent. At randomization 1 to 3 months later, either one cSEMS or 3 plastic stents were inserted. After 3 months, 3 more plastic stents were added and the position of cSEMS was controlled. Six months from randomization all stents were removed. Clinical controls were performed 6 months and 2 years from stent removal.</p><p><bold>RESULTS: Results. </bold>28 patients in the plastic and 24 in the cSEMS group had an alcohol related CP. Prior to the 1st ERCP the mean bilirubin (Bil) levels were (plastic vs. cSEMS) 62 and 103 umol/l, the mean alkaline phosphatase (AFOS) levels were 402 and 567 U/l respectively. The mean stricture lengths were 3 cm in both groups and the mean bile duct diameter above the stricture was 12 and 13 mm, respectively; at the stent removal 7 mm in both groups. Stent migration was seen three times in the plastic group and once in the cSEMS group. The mean follow up time after stent removal until May 2013 is 29 months in the plastic and 27 months in cSEMS groups.</p><p> 59 % of the patients in the plastic and 53 % in the cSEMS group have finished their two-year follow up with a mean Bil 9 and 11 umol/l respectively and the mean AFOS levels 85 and 103 U/l. During follow-up 2 (6 %) recurrent strictures have been found in both groups. During follow-up one patient in the plastic group was operated for pancreatic stent induced duodenal perforation. Two patients in the cSEMS group were operated for suspicion of pancreatic malignancy, the final diagnose being CP. Four patients in the cSEMS group had an episode of cholangitis during the stent treatment. Two patients in the plastic and one in the cSEMS group had cholangitis after stent removal. There has been 6 deaths, two in the plastic group. One early death in the cSEMS group was due to pancreatic cancer. The difference in deaths between the groups is not significant.</p><p><bold>CONCLUSION:</bold> Conclusion</p><p>A six months stenting period either with 6 plastic 10 French stents or with one 10 mm cSEMS seems to produce a fair long term relief of biliary stricture caused by CP. The recurrent stricture rate has remained low in both groups. The low migration rate and the easiness of the insertion would favour the use of cSEMS in the future.</p><p><bold>Contact E-mail Address:</bold><email>jorma.halttunen@hus.fi</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> benign biliary strictures, cSEMS</p></sec><sec><title>OP395 ANALYSIS OF RISK FACTORS FOR POST-ERCP PANCREATITIS IN PATIENTS WHO UNDERWENT PROPHYLACTIC PANCREATIC DUCT STENTING – RESULTS OF A PROSPECTIVE, MULTICENTER, CONTROLLED STUDY</title><p><bold>Z. Dubravcsik</bold><sup>1,*</sup>, A. Szepes<sup>1</sup>, I. Hritz<sup>2</sup>, L. Madácsy<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology and Endoscopy, BÁCS-KISKUN COUNTY HOSPITAL, Kecskemét, <sup>2</sup>Gastroenterology and Endoscopy, Fejér County Szent-György Hospital, Székesfehérvár, Hungary</italic></p><p><bold>INTRODUCTION:</bold> Small caliber pancreatic duct stenting has been accepted and suggested for prevention of post-ERCP pancreatitis (PEP) in the high risk population by the american and european gastrointestinal endoscopic societies. Prophylactic pancreatic stents (PPS) reduce the risk of PEP by 50% in high risk patients, however a subgroup of them still develop PEP.</p><p><bold>AIMS&METHODS:</bold> The aim of the present study was to analyze this subgroup in terms of risk factors, severity of PEP and the consequences of attempted but unsuccessful PPS placement. 237 patients high risk of PEP were considered for PPS placement in 2 Hungarian tertiary referral centers during the past 5 years, and pancreatic stents were successfully placed in 213 cases (90%). PEP was defined based on the Cotton consensus criteria. Cumulative, patient and procedure related risk factors were determined following the guidelines of the ESGE. Univariate analysis was chosen to evaluate risk factors of PEP in patients with PPS.</p><p><bold>RESULTS:</bold> 30 of 213 patients (14.1%) with successful PPS implantation developed PEP (25 mild; 4 moderate; 1 severe), on the contrary in 9 of 24 patients with attempted but failed PPS placement occurred PEP with a significantly higher incidence of 37.5% (3 mild, 5 moderate and 1 severe). Univariate analysis revealed that in patients with successful PPS implantation sphincter of Oddi dysfunction (SOD) was the only significant risk factor for PEP (OR 2.54, CI: 1.1054 to 5.8442, P = 0.0281). Interestingly, in the 24 of 237 patients with attempted but failed PPS placement the procedure related risk factors were significantly higher compared to the 213 patients with successful pancreatic stenting (2.0 vs. 1.53, p=0.026, respectively).</p><p><bold>CONCLUSION:</bold> In 14.1% of patients with high cumulative risk factors PEP developed despite PPS, however in the majority of these cases PEP were mild (83%), therefore in these patients PPS application may also contribute to attenuate the severity of pancreatitis. SOD is the only significant risk factor for PEP after PPS insertion. Attempted but failed PPS placement mainly occurred in more complex ERCP procedures, and it resulted in a significant increase in PEP incidence.</p><p><bold>Contact E-mail Address:</bold><email>dubravcsikzs@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> controlled study, post ERCP pancreatitis, preventive pancreas stent, risk factors</p></sec><sec><title>OP396 ENDOSCOPIC PAPILLARY LARGE BALLOON DILATATION VERSUS REPEAT ENDOSCOPIC SPHINCTEROTOMY FOR THE RECURRENT COMMON BILE DUCT STONES AFTER ENDOSCOPIC SPHINCTEROTOMY</title><p><bold>S. H. Dong</bold><sup>1,*</sup>, J. W. Jeon<sup>1</sup></p><p><italic><sup>1</sup>Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul, Korea, Republic Of</italic></p><p><bold>INTRODUCTION:</bold> There are few studies comparing endoscopic papillary large balloon dilatation (EPLBD: combination of small EST and large balloon dilatation) and repeat endoscopic sphincterotomy (EST) for the removal of recurrent common bile duct (CBD) stones after prior EST.</p><p><bold>AIMS&METHODS:</bold> we conducted this study to compare EPLBD and repeat EST as endoscopic retreatment for recurrent CBD stones occuring in patients with prior EST due to choledocholithiasis. In addition, we analyzed the risk factors for second stone recurrence after endoscopic retreatment. Finally, we investigated whether EPLBD could reduce the second stone recurrence compared with repeat EST.76 subjects of 787 with the history of EST from 2000 to 2010 underwent endoscopic retreatment (EPLBD in 36 and repeat EST in 40) for recurrent CBD stones. We compared the efficacies between EPLBD and repeat EST. In addition, we investigated the risk factors and cumulative recurrence rate for second stone recurrence.</p><p><bold>RESULTS:</bold> There were no significant differences in stone clearance rate and the occurrence of complications between EPLBD and repeat EST. Multivariate analysis identified three risk factors for second stone recurrence; repeat EST (<italic>P</italic>=0.033), CBD of ≥ 15mm (<italic>P</italic>=0.029), and mechanical lithotripsy (<italic>P</italic>=0.029). In cases of CBD of ≥ 15mm, cumulative recurrence rate for second stone recurrence was significantly lower in EPLBD than repeat EST (<italic>P</italic>=0.04).</p><p><bold>CONCLUSION:</bold> EPLBD is considered to be an effective and safe method for the removal of recurrent CBD stones after EST. Moreover, in subjects with CBD of ≥15mm, the cumulative recurrence rate for second stone recurrence was significantly lower in EPLBD than repeat EST.</p><p><bold>Contact E-mail Address:</bold><email>gidrdong@hanmail.net</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Endoscopic papillary large balloon dilatation, endoscopic retreatment, Endoscopic sphincterotomy, Recurrent common bile duct stone</p></sec><sec><title>OP397 CHOLANGIOSCOPY-ASSISTED ELECTROHYDRAULIC LITHOTRIPSY IS HIGHLY EFFECTIVE IN THE MANAGEMENT OF DIFFICULT BILE DUCT STONES</title><p><bold>V. P. K. Lekharaju</bold><sup>1,*</sup>, O. Noorullah<sup>1</sup>, C. Wadsworth<sup>1</sup>, M. Kumar<sup>2</sup>, L. Dwyer<sup>1</sup>, E. Shearer<sup>3</sup>, G. Webster<sup>2</sup>, R. Sturgess<sup>1</sup></p><p><italic><sup>1</sup>Digestive Diseases Unit, AINTREE UNIVERSITY HOSPITAL NHS TRUST, Liverpool, <sup>2</sup>Gastroenterology, University College London Hospital, London, <sup>3</sup>Anaesthesia, AINTREE UNIVERSITY HOSPITAL NHS TRUST, Liverpool, United Kingdom</italic></p><p><bold>INTRODUCTION:</bold> Although conventional endoscopic techniques for removal of stones from biliary tree are effective, they fail in 10% of patients. With introduction of single operator peroral cholangioscope (POC), stone fragmentation under direct visual control has proven to be effective.</p><p><bold>AIMS&METHODS:</bold> To describe the characteristics of patients undergoing POC directed electrohydraulic lithotripsy (POC-EHL) and to evaluate the cost efficacy of POC-EHL in two tertiary Hepatobiliary units in England. Details of patients undergoing POC-EHL at Aintree University Hospital and University College London Hospital were prospectively recorded. Data collected included demographics, number of ERCPs, site of stone, POC-EHL sessions, stone clearance and complications.</p><p><bold>RESULTS:</bold> A total of 103 patients were referred for POC-EHL. There were 27 males (26%) and 76 females (74%). The median age was 62 (20-92) years. 80 (78%) patients were tertiary referrals. 72 (70%) patients had at least two or more endoscopic attempts at stone removal prior to referral for POC-EHL. In six patients POC-EHL was not required because at ERCP prior to POC, the ducts could be cleared with conventional techniques. In seven patients EHL was not attempted due to the size, configuration and quantity of stones. With the knowledge that these patients were fit for cholecystectomy, they were referred for cholecystectomy and bile duct exploration as a one-stage procedure. All POC-EHL sessions were performed under general anaesthesia. Of the 90 patients undergoing POC-EHL 65 (72%) patients needed one POC-EHL session and 14 (16%) required two sessions and 6 (7%) required three sessions for complete stone extraction. In 5/90 (6%) complete stone extraction was not possible despite POC-EHL and these patients were referred for surgery. The sites of stones were common bile duct in 48%, cystic duct and CBD in 20%, cystic duct in 4%, common hepatic duct in 10% and intra-hepatic ducts in 18%. Three patients developed cholangitis post POC-EHL, responding to antimicrobial therapy. Two patients experienced post-procedure bleeding, only one patient required endoscopic intervention. Initial analysis showed a potential cost savings if POC-EHL was performed early.</p><p><bold>CONCLUSION:</bold> On an intention to treat basis, 88% of patients referred for POC-EHL were treated successfully. Successful POC-EHL frequently requires combination with other stone removal techniques including mechanical lithotripsy and large balloon ampullary dilatation. POC-EHL is a safe and highly effective technique in the clearance of refractory biliary stones.</p><p><bold>Contact E-mail Address:</bold><email>pawan.lekharaju@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> cholangioscopy, Choledocholithiasis, ERCP, LITHOTRIPSY</p></sec><sec><title>OP398 ENDOSCOPIC TREATMENT OF PATIENTS WITH MAJOR BILE DUCT INJURY AFTER LAPARASCOPIC CHOLECYSTECTOMY: FACTORS PREDICTING RECURRENCE IN THE LONG TERM</title><p><bold>E. Parlak</bold><sup>1</sup>, S. Dişibeyaz<sup>1,*</sup>, B. Ödemiş<sup>1</sup>, A. S. Köksal<sup>1</sup>, F. Küçükay<sup>2</sup>, N. Şaşmaz<sup>1</sup>, B. Şahin<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology, <sup>2</sup>Radiology, Türkiye Yüksek İhtisas Hospital, Ankara, Turkey</italic></p><p><bold>INTRODUCTION:</bold> Endoscopic treatment is effective in the treatment of patients with bile duct injury after laparascopic cholecystectomy.</p><p><bold>AIMS&METHODS:</bold> The aim of the study is to investigate the long term results of endoscopic treatment, factors predicting the recurrence of the stricture and determine the optimal endoscopic treatment. The study was conducted in patients with major bile duct injury (Strasberg E1-4 and E-5 patients with main bile duct injury) who could be treated with endoscopic biliary stent insertion between January 1995 and September 2011. Patients with minor injury (Luschka and cystic duct leakage), complete transection and aberrant bile duct injury were excluded. In order to determine recurrence only the patients with more than one year of follow-up after stent removal were included. Patients with ongoing stent treatment or less than 1 year of follow-up were excluded.</p><p><bold>RESULTS:</bold> The study group included 156 patients. The median follow-up period after stent removal was 6.5 years (range:1-16.5). Recurrence was seen in 18 patients (11%) after a median duration of 9 months (range:2-96). Multivariant regression analysis revealed that the most important two factors predicting the success of endoscopic treatment were: Rome type treatment (inserting increasing number of stents every 3-4 months) (Odds ratio: 23.8, 95% CI: 1.46-390.7, p:0.026) instead of Amsterdam type treatment (exchange of 2 10F biliary stents every 3-4 months) and dilation of the stricture diameter to at least 76% of the choledoche diameter at the end of stent treatment (Odds ratio: 25.9, 95% CI: 2.46-272.7, p:0.007).</p><p><bold>CONCLUSION:</bold></p><p>Endoscopic treatment is an effective method in the treatment of patients with major bile duct injury after laparascopic cholecystectomy. Inserting multiple stents as much as possible without leaving a scar in the bile ducts should be aimed.</p><p><bold>Contact E-mail Address:</bold><email>koksalas@yahoo.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> biliary injury, cholecystectomy, ERCP, treatment</p></sec><sec><title>OP399 COST CONCERNS SHOULD NOT AFFECT THE CHOICE FOR PLASTIC OR METAL STENT FOR UNRESECTABLE MALIGNANT COMMON BILE DUCT OBSTRUCTION: A RANDOMIZED CONTROLLED TRIAL</title><p><bold>D. Walter</bold><sup>1,*</sup>, F. P. Vleggaar<sup>1</sup>, P. D. Siersema<sup>1</sup>, on behalf of the PLAMET study group</p><p><italic><sup>1</sup>Departement of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, Netherlands</italic></p><p><bold>INTRODUCTION:</bold> Endoscopic stent placement is the procedure of choice for palliation of malignant common bile duct (CBD) obstruction. Although self-expandable metals stents (SEMS) are associated with a longer stent patency compared to plastic stents, they are far more expensive. Until now, no detailed cost analysis comparing treatment with plastic and metal stents have been performed. Aim of this study was to perform a full cost comparison of plastic stent, partially covered SEMS (pcSEMS) and uncovered SEMS (uSEMS) placement for the palliation of CBD obstruction.</p><p><bold>AIMS&METHODS:</bold> Randomized, prospective, multicenter trial in 18 hospitals. In total, 219 patients were randomized to plastic stent (n=73), pcSEMS (n=75) or uSEMS (n=71) placement with stratification for primary stent placement or stent placement after a first recurrent obstruction. Cost comparison included initial costs and costs during follow up. Data on health care use was obtained at 2 weeks and monthly thereafter until death or one year follow-up. Non-parametric bootstrap techniques were used to derive a p-value for the difference in cost distribution.</p><p><bold>RESULTS:</bold> Baseline characteristics were similar between the three groups. Recurrent biliary obstruction occurred in 29 patients (40%) in the plastic stent group, in 10 patients (14%) in the pcSEMS group and in 11 patients (15%) in the uSEMS group. Mean stent patency time was 170 days for plastic stents, 303 days for pcSEMS and 285 days for uSEMS (p<0.05). There was no difference in 3-month (p= 0.77) and overall survival between the groups (p=0.28). Costs for the initial stent placement procedure were significantly lower for plastic stents compared to SEMS (€1,084 vs €1,942; p= 0.001). However, total costs per patient were not significantly different between plastic stents and SEMS (€6,614 vs €7,723, p= 0.13). During follow-up, the main costs driver in both groups were costs for hospitalization (plastic 69% vs SEMS 68%). Total costs for initial medical procedures and reinterventions were not different between the groups (plastic €2,078 vs SEMS €2,434; p= 0.06). In patients with a short survival (≤ 3 months), total costs per patient were also not different between plastic stents and SEMS (€6,796 vs €6,538; p = 0.81). No differences in costs were found between pcSEMS and uSEMS placement.</p><p><bold>CONCLUSION:</bold> Although initial costs are higher for SEMS placement, total costs are not different between plastic stents and SEMS, even in patients with a short survival. Since the clinical outcome with SEMS is favourable and total costs are not different, SEMS placement is recommended in patients with unresectable malignant CBD obstruction.</p><p><bold>Contact E-mail Address:</bold><email>d.walter@umcutrecht.nl</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> costs, malignant biliary obstruction, plastic stent, SEMS</p></sec><sec><title></title><p><bold>WEDNESDAY, OCTOBER 16, 2013 8:30-10:30</bold></p><p><bold>Management of early oesophageal tumours – Salon 11/12</bold></p></sec><sec><title>OP400 A SIMPLIFIED CRITERIA OF NBI MAGNIFIED ENDOSCOPY FINDINGS FOR DIAGNOSING SUPERFICIAL OESOPHAGEAL SQUAMOUS CELL CARCINOMA.</title><p><bold>A. Dobashi</bold><sup>1,*</sup>, K. Goda<sup>1</sup>, K. Sumiyama<sup>1</sup>, H. Toyoizumi<sup>1</sup>, T. Kato<sup>1</sup>, M. Matsushima<sup>2</sup>, H. Tajiri<sup>1,3</sup></p><p><italic><sup>1</sup>Endoscopy, <sup>2</sup>Division of Clinical Epidemiology, <sup>3</sup>Gastroenterology and Hepatology, THE JIKEI UNIVERSITY OF MEDICINE, Tokyo, Japan</italic></p><p><bold>INTRODUCTION:</bold> Diagnostic yields for superficial oesophageal squamous cell carcinoma (SOSCC) including high grade intraepithelial neoplasia by NBI magnified endoscopy (NBI-ME) have been reported to be significantly higher than those by conventional white light endoscopy (CWE). When diagnosing SOSCC by NBI-ME, several diagnostic criteria of NBI-ME have been assessed. That is one of the reasons why NBI-ME is time-consuming procedure and not in widespread use.</p><p><bold>AIMS&METHODS:</bold> The aim of this study was to evaluate whether or not the diagnostic criteria of SOSCC by NBI-ME can be simplified. We performed NBI-ME for 147 patients with present or past history of head and neck or SOSCC between January 2010 and June 2011. We detected 89 lesions (brownish areas > 5 mm in diameter by non-magnified NBI or suspicious lesion of neoplasms by CWE). Two expert endoscopists evaluated whether or not the lesion presented following six findings by NBI-ME in real time, ‘intervascular background coloration’, ‘increasing number of intra-epithelial papillary capillary loops (IPCLs) and well-known four criteria based on morphological changes of IPCL that were proposed by <italic>Inoue et al.</italic>; ‘dilation’, ‘tortuous’, ‘caliber change’, and ‘various forms’. The histology from bite biopsy or endoscopic resection was defined as a gold standard for diagnosis. Minimum criteria of NBI-ME findings for diagnosing SOSCC were determined by means of statistical analysis.</p><p><bold>RESULTS:</bold> The median size of the 89 lesions was 15mm (range; 4 - 100). Forty seven lesions (53%) showed flat (0-IIb) type. Fifty four lesions (65%) were histologically diagnosed as SOSCC and the others as low grade intraepithelial neoplasia or inflammation. The odds ratio of ‘various forms of IPCLs’ for SOSCC was 5.4 (95% CI: 2.0-14.8) by univariate analysis and showed the highest value among the 6 NBI-ME findings. ‘Increasing number of IPCLs’ was statistically determined as the only finding of NBI-ME which improved the diagnostic performance when combined with ‘various forms in IPCLs’ by likelihood ratio test (P<0.05). The area under the curve (AUC) by ROC analysis based on ‘increasing number of IPCLs’ and ‘various forms in IPCLs’ was 0.70 (95% CI: 0.60-0.80). The AUC based on well–known four criteria was 0.73 (95% CI: 0.63-0.84). There were not significant differences between them.</p><p><bold>CONCLUSION:</bold> ‘Increasing number of IPCLs’ and ‘various forms of IPCLs’ might be minimum criteria of NBI-ME findings for diagnosing SOSCC by means of statistical analysis. Further prospective clinical trial will be needed.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> magnifying endoscopy with narrow-band imaging, Oesophageal carcinoma</p></sec><sec><title>OP401 A RANDOMISED TRIAL COMPARING MULTIBAND MUCOSECTOMY AND ER-CAP FOR ENDOSCOPIC PIECEMEAL RESECTION OF EARLY SQUAMOUS NEOPLASIA OF THE ESOPHAGUS</title><p><bold>D. Boerwinkel</bold><sup>1,*</sup>, Y. Zhang<sup>2</sup>, X. Qin<sup>2</sup>, S. He<sup>2</sup>, L. Xue<sup>3</sup>, B. Weusten<sup>1,4</sup>, S. Dawsey<sup>5</sup>, D. Fleischer<sup>6</sup>, L. Dou<sup>2</sup>, Y. Liu<sup>2</sup>, N. Lu<sup>3</sup>, J. Bergman<sup>1</sup>, G. Wang<sup>2</sup></p><p><italic><sup>1</sup>Gastroenterology and hepatology, AMC AMSTERDAM, Amsterdam, Netherlands, <sup>2</sup>Endoscopy, Cancer Institute and Hospital, Chinese Academy of Medical Sciences , <sup>3</sup>Pathology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, China, <sup>4</sup>Gastroenterology and hepatology, St. Antonius Ziekenhuis, Nieuwegein, Netherlands, <sup>5</sup>Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, <sup>6</sup>Gastroenterology and hepatology, Mayo Clinic, Scottsdale, United States</italic></p><p><bold>INTRODUCTION:</bold> Endoscopic Resection (ER) for esophageal highgrade intraepithelial neoplasia (HGIN) or esophageal squamous cell carcinoma (ESCC) is usually performed with the ER-cap technique, which is technically difficult. Multi Band Mucosectomy (MBM) is an ER technique that uses a modified variceal-band ligator for piecemeal resection without submucosal lifting. In China, in certain high-risk areas where ESCC is extremely prevalent and limited endoscopic expertise is available, MBM may be more easily applicable.</p><p><bold>AIMS&METHODS:</bold> We prospectively compared MBM to ER-cap for piecemeal ER of esophageal squamous neoplasia .</p><p>Patients with HGIN or ESCC (size ≥2≤6 cm, ≤2/3 of circumference). Lesions were delineated with electrocoagulation after 1.25% Lugol staining. Patients were randomised to MBM or ER-cap followed by piecemeal resection. Endpoints: complete endoscopic resection (ie complete removal of the lesion including all coagulation markers), procedure time, costs, adverse events, absence of HGIN/ESCC at 3 months follow-up. Calculated sample size: 84 patients.</p><p><bold>RESULTS:</bold> In 88 patients (62 male, mean age 60 yrs) ER was performed with MBM (n=46, 12 ESCC) or ER-cap (n=42, 13 ESCC). There was no difference in size of lesions between groups (5cm vs. 5cm, p=NS; 42% vs. 33% of circumference, p=NS). Endoscopic complete resection was achieved in all lesions. Procedure time was less with MBM (11 vs. 22 minutes, p<0.001), for a median of 5 vs. 4 resections (p=0.03). MBM resulted in smaller (18x12mm vs. 20x15mm; p=NS), thicker (2200 μm vs. 1700μm; p=0.04) resection specimens. No difference in submucosal thickness was observed (900 μm vs. 800 μm; p=NS). Four patients were referred for surgery, based on the ER histology. Total costs of disposables was less for MBM compared to ER-cap ($260 vs. $325, p=0.04).</p><p>No clinically significant bleeding episodes occurred. One perforation was seen after ER-cap, which was treated conservatively. No clinically relevant stenoses were observed.</p><p>At 3 months FU none of the patients demonstrated HGIN/ESCC at the resection site.</p><p><bold>CONCLUSION:</bold> Piecemeal ER of early esophageal squamous neoplasia with MBM is faster and cheaper compared to ER-cap. Both techniques are highly effective and safe. Given its low complexity and costs, MBM may have significant advantages over the ER-cap technique, especially in countries where ESCC is highly prevalent, yet endoscopic expertise and resources are limited.</p><p><bold>Contact E-mail Address:</bold><email>d.f.boerwinkel@amc.uva.nl</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> endoscopic resection, esophageal cancer, esophageal squamous neoplasia</p></sec><sec><title>OP402 CLINICAL EVALUATION OF ENDOSCOPIC SUBMUCOSAL DISSECTION IN EARLY ESOPHAGEAL CANCERS AND DYSPLASIA.</title><p><bold>F. Xu</bold><sup>1</sup>, C. yin<sup>1</sup>, Z. yuan<sup>1</sup>, C. sun<sup>1</sup>, R. shi<sup>1,*</sup>, S. yang<sup>1</sup>, L. yu<sup>1</sup></p><p><italic><sup>1</sup>Jiangsu province hospital, nanjing, China</italic></p><p><bold>INTRODUCTION:</bold> Today,more attention were paid to endoscopic treatment for early gastrointestinal cancer,and the endoscopic submucosal dissection (ESD) has been widely accepted by medical workers for the efficacy and less trauma. However , compared with early gastric cancer and dysplasia<bold>,</bold> ESD in esophageal requires higher operating techniques, because of the difference of anatomical structures and organizational characteristics between them. Therefore, we reported the treatment, efficacy, complications and follow-up of 176 patients, who suffering from early esophageal cancers or dysplasia, in order to discuss the application value and safety and to understand exhaustive the advantages, risks and precautions of ESD for the treatment of early esophageal cancers and dysplasia.</p><p><bold>AIMS&METHODS:</bold> 176 patients with early esophageal cancer and dysplasia who underwent ESD were selected from February 2009 to July 2012, lesions were confined to the mucous layer and the submucosa by ultrasound, and lymph node metastasis was excluded by Chest CT examination. To observe and compare the circumstance of surgery and treatment, complications, efficacy of postoperative follow-up, and so on.</p><p><bold>RESULTS:</bold> Among the 176 cases, average operation time of ESD for 56 cases of low-grade intraepithelial neoplasia(LEIGN), 80 cases of High-grade intraepithelial neoplasia(HGIEN) and 40 cases of early esophageal cancer are respectively 62 min, 72 min and 86 min, and the average diameter of three groups were respectively 4.3cm,5.0cm and 5.7cm. Chest pain in 80 patients (45.5%), bleeding in 2 cases (1.1%) , perforation in 3 cases (1.7%), esophageal stricture in 15 cases(8.5%), bellyache in 17cases (9.6%) and fever in 15 case (8.5%) were observed postoperation, None case was observed for other complications. 125 cases completed the follow-up investion, with a median follow-up time of 14 months (1-39 months), among which residual lesions were occured in 11 patients (6.3%), two of which LEIGN, six was HEIGN, three was early esophageal cancer and two cases of recurrence(4%).101 cases were proceeded for a 2 months postoperative review, with healing rate of 100% (101/101). 79 cases were proceeded for 6 months postoperative review with two cases of local recurrence, wound healing rate of 100% (79/79). 52 cases completed were proceeded for 12 months postoperative review with one cases of local recurrence, wound healing rate of 100% (52/52) .</p><p><bold>CONCLUSION:</bold> ESD could excise early esophageal cancer and precancerous lesions as en bloc, provide complete pathologic data and reduce recurrence and complication. ESD was not only a safe and effective therapeutic method but also a good diagnostic methodfor early esophageal cancer and dysplasia.</p><p><bold>REFERENCES:</bold></p><p>1. Gotoda T. The estimation using a large number of cases.Gastric Cancer.2000,3:219-225.</p><p>2. Ishihara R, Lishi H, Takeuchi Y, Kato M, Yamamoto S, Yamamoto S, et al. Local recurrence of large squamous-cell carcinoma of the esophagus after endoscopic resection. Gastrointest Endosc 2008;67:799-804.</p><p>3. Takizawa K,Oda I,Gotoda T.Routine coagulation of visible vesels may prevent delayed bleeding after endoscopic submucosal dissection—an analysis of risk factors.Endoscopy,2008,40:179-183.</p><p>4. Higashiyama, M.Oka, S.Tanaka, S.et al.Risk factors for bleeding after endoscopic submucosal dissection of gastric epithelial neoplasm.Dig Endosc.2011,23(4):290-295.</p><p>5. Ono S, Fujishiro M, Niimi O, Goto O, Kodashima S, Yamamichi N, et al. Predictors of postoperative stricture after esophageal endoscopic submucosal dissection for superficial squamous cell neoplasms. Endoscopy 2009;41:661-5.</p><p><bold>Contact E-mail Address:</bold><email>xufangyuan0326@q26.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Diagnosis, Early esophageal cancer and precancerous lesion, Endoscopic submucosal dissection, Treatment</p></sec><sec><title>OP403 SUBMUCOSAL TUNNELING ENDOSCOPIC RESECTION FOR SUBMUCOSAL TUMORS OF THE ESOPHAGOGASTRIC JUNCTION ORIGINATING FROM THE MUSCULARIS PROPRIA LAYER: A FEASIBILITY STUDY</title><p><bold>M.-D. Xu</bold><sup>1,*</sup>, X.-Y. wang<sup>1</sup>, P.-H. Zhou<sup>1</sup>, L.-Q. Yao<sup>1</sup>, Q.-L. Li<sup>1</sup>, Y.-Q. Zhang<sup>1</sup>, W.-F. Chen<sup>1</sup>, Y.-S. Zhong<sup>1</sup></p><p><italic><sup>1</sup>Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China</italic></p><p><bold>INTRODUCTION:</bold> The esophagogastric junction (EGJ) is a difficult location for endoscopic resection due to its narrow lumen and sharp angle. Potential increased risks of perforation and mediastinal infection exist, especially for submucosal tumors (SMTs) originating from the muscularis propria (MP) layer<sup>1</sup>. Inspired by natural orifice endoscopic transluminal surgery (NOTES) and peroral endoscopic myotomy (POEM)<sup>2</sup>, We previously demonstrated the safety and efficacy of submucosal tunneling endoscopic resection (STER) for upper GI SMTs<sup>3</sup> but the feasibility of STER for the removal of SMTs at the EGJ requires systematic investigation.</p><p><bold>AIMS&METHODS:</bold> We included 76 consecutive patients with SMT of the EGJ originating from the MP layer who were treated with STER between July 2009 and January 2013. Main outcome measurements of the STER including complications, en bloc resection rate and local recurrence were assessed. We aim to evaluate the clinical impact of STER for the removal of SMTs at the EGJ.</p><p><bold>RESULTS:</bold> Of the 76 SMTs originating from MP layer, The mean diameter of the lesions in treated patients was 21.5 mm (range, 6-35 mm).The mean procedure time was 47 minutes (range, 15-120 minutes). The en bloc resection rate was 100% (76/76). The pathological diagnoses included leiomyomas (n = 61, 80.3%), GI stromal tumors (GIST) (n = 10, 13.1%), intramuscular lipoma (n = 1, 1.3%), granular cell tumor (n = 1, 1.3%) schwannoma (n = 3, 4.0%). No delayed hemorrhage or severe adverse events occurred in any of the 76 patients following STER. No local recurrence and distant metastasis occurred during 24 months’ follow-up. Less subcutaneous emphysema and pneumomediastinum absorption time (p = 0.005) occurred with CO2 vs. air insufflations.</p><p><bold>CONCLUSION:</bold> In our 2-year feasibility study, it showed that STER was safe and effective, provided accurate histopathologic evaluation, and was curative for SMTs of the deep MP layers at the EGJ. Furthermore, it expanded the indications for tunnel endoscopy. CO2 gas insufflation is recommended.</p><p><bold>REFERENCES:</bold></p><p>1. Lee IL, Lin PY, Tung SY, et al. Endoscopic submucosal dissection for the treatment of intraluminal gastric subepithelial tumors originating from the muscularis propria layer. Endoscopy 2006;38:1024-8.</p><p>2. Inoue H, Minami H, Kobayashi Y, et al. Peroral endoscopic myotomy (POEM) for esophageal achalasia. Endoscopy 2010;42:265-71.</p><p>3. Xu MD, Cai MY, Zhou PH, et al. Submucosal tunneling endoscopic resection: a new technique for treating upper GI submucosal tumors originating from the muscularis propria layer (with videos). Gastrointest Endosc 2012; 75:195-9.</p><p><bold>Contact E-mail Address:</bold><email>xumeidong@yahoo.com.cn</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> submucosal tumors, esophagogastric junction, Submucosal tunneling endoscopic resection</p></sec><sec><title>OP404 THE FREQUENCY OF LYMPH-NODE METASTASIS IN EARLY ADENOCARCINOMA (EAC) OF THE ESOPHAGUS INVADING THE SUBMUCOSAL LAYER (PT1B): RESULTS FROM A LARGE PROSPECTIVE SERIES OF ENDOSCOPICALLY AND SURGICALLY TREATED PATIENTS</title><p><bold>H. Manner</bold><sup>1,*</sup>, J. Wetzka<sup>1</sup>, O. Pech<sup>2</sup>, A. May<sup>1</sup>, A. Behrens<sup>1</sup>, M. Pauthner<sup>3</sup>, D. Lorenz<sup>3</sup>, M. Vieth<sup>4</sup>, M. Stolte<sup>5</sup>, C. Ell<sup>1</sup></p><p><italic><sup>1</sup>Department of Internal Medicine II, HSK Hospital Wiesbaden, Wiesbaden, <sup>2</sup>St. John of God Hospital, Regensburg, <sup>3</sup>Dept. of Surgery, HSK Hospital Wiesbaden, Wiesbaden, <sup>4</sup>Bayreuth Hospital, Bayreuth, <sup>5</sup>Klinikum Kulmbach, Kulmbach, Germany</italic></p><p><bold>INTRODUCTION:</bold> The rate of lymph-node (LN) metastasis in pT1b EAC has been analyzed in a number of retrospective series from surgical centers. However, data are controversial. Also, data from larger series from patients having been treated endoscopically and surgically have not yet been reported.</p><p><bold>AIMS&METHODS:</bold> The aim of the present study was to analyze the rate of LN metastasis in a large prospective series of patients treated by endosopic resection or eosphagectomy.</p><p>A total of 230 patients with suspicion of (endoscopic ultrasound, EUS) or histologically confirmed diagnosis (endoscopic resection/esophagectomy) of a submucosal EAC (pT1b) were referred to the Department of Internal Medicine II of the HSK Hospital Wiesbaden during a 14-yr-period. These patients either underwent endoscopic treatment with a curative or palliative intent or were referred to surgery (mainly surgical department of HSK Hospital Wiesbaden). Patients were included into a prospective database.</p><p>The rate of LN metastasis was analyzed retrospectively, depending on the relative depth of tumor invasion into the submucosa (pT1b sm1-sm2-sm3), and on histological risk patterns for LN metastasis (low-risk (LR) patients: G1-2, L0, V0; high-risk (HR) patients: G3, L1, V1; at least one factor required for classification into high-risk group). The size of the tumor (≤2 cm or >2 cm) was not taken into consideration during analysis.</p><p>The diagnosis of LN metastasis was made either by EUS in the endoscopically treated patients (follow-up at least 24 months, EUS performed in regular intervals), or by histopathological work-up of the surgical resection specimen.</p><p><bold>RESULTS:</bold> In 166/230 patients, the relative depth of submucosal invasion as well as the histological risk patterns were completely evaluable.</p><p>The rate of LN metastasis was as follows: sm1 LR 1/72 (1.4%), sm1 HR 2/26 (7.7%), sm2 LR 2/12 (16.7%), sm2 HR 5/14 (35.7%), sm3 LR 1/6 (16.7%), sm3 HR 13/36 (36.1%).</p><p><bold>CONCLUSION:</bold> According to this so far largest series on the rate of LN metastasis in pT1b EAC, the LN rate in sm1 low-risk lesions was lower than the mortality rate of surgery which is known to be 2-5%. Therefore, endoscopic treatment may be used as an alternative to esophageal resection in this subgroup of pT1b patients. Further studies will have to clarify whether sm2 low-risk lesions with a limited size may also be candidates for endoscopic resection.</p><p><bold>Contact E-mail Address:</bold><email>HSManner@gmx.de</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> BARRETT´S ESOPHAGUS, Barrett's neoplasia, early adenocarcinoma of the esophagus, lymph node metastases </p></sec><sec><title>OP405 COMPARISON OF ENDOSCOPIC PIECEMEAL MUCOSAL RESECTION (EPMR) AND ENDOSCOPIC SUBMUCOSAL DISSECTION (ESD) FOR SUPERFICIAL ESOPHAGEAL LESION LARGER THAN 15 MM</title><p><bold>Q.-L. Li</bold><sup>1,1</sup>, P.-H. Zhou<sup>1,*</sup>, M.-J. He<sup>1</sup>, M.-D. Xu<sup>1</sup>, L.-Q. Yao<sup>1</sup></p><p><italic><sup>1</sup>Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China</italic></p><p><bold>INTRODUCTION:</bold> Because neither en bloc resection nor assessment of the resection margin could be obtained in endoscopic piecemeal mucosal resection (EPMR) for large esophageal lesion, the boundary of each snare becomes the potential recurrence origin theoretically. Endoscopic submucosal dissection (ESD) is now being increasingly used for these tumors because of high curative resection rate. However, the technical difficulty of ESD repeatedly been shown to be associated with higher complication rate.</p><p><bold>AIMS&METHODS:</bold> From September 2009 to August 2011, 63 patients with esophageal lesion ≥ 15mm underwent EPMR, while 198 patients underwent ESD. Patient characteristics, procedure time, complications (bleeding, perforation, and stricture), local recurrence and distant metastases were compared between ESD and EPMR. Logistic multivariate analysis was used to analyze the independent factors for en-bloc resection, local recurrence and severe complications in ESD group.</p><p><bold>RESULTS:</bold> The tumor size was significant larger in ESD group compared with EPMR group (3.02 ± 1.13mm vs. 2.66 ± 0.95mm, <italic>P</italic> = 0.021), and the procedure time was longer (70.4±32.8min vs. 50.8±28.3min, <italic>P </italic>< 0.001). The local recurrence rate was higher in EPMR group than that in ESD group (11.5% vs. 3.7%, <italic>P</italic> = 0.023), although both groups obtained the same tumor-free rate of deep margins (<italic>P</italic> > 0.05). The incidence of severe short-term complications, including severe bleeding and perforation, were with no significant difference (both P > 0.05). Esophageal stricture happened much more frequently in EPMR group (ESD vs. EPMR, 6.2% vs. 23.0%, <italic>P </italic>< 0.001), probably due to the larger circumferential mucosal defect in EPMR group (<italic>P </italic>< 0.001). The rate of en bloc resection and curative resection were 100% and 96.0% in ESD group, respectively. Local recurrence after ESD was significantly related to tumor size (95%C.I. 1.127-4.388, <italic>P </italic>= 0.021), while the procedure time (95%C.I. 1.197-21.506, <italic>P </italic>=0.028), tumor size (95%C.I. 1.045-2.748, <italic>P </italic>= 0.033), and percentage of the circumferential mucosal defect (95%C.I. 1.002-1.041, <italic>P </italic>= 0.028) were independent risk factors for postoperative stricture.</p><p><bold>CONCLUSION:</bold> ESD was found to be superior to EPMR for large superficial esophageal lesions because of lower local recurrence rate and acceptable complications. The present study also provided useful information for predicting risks for incomplete resection, local recurrence and severe complications in esophageal ESD.</p><p><bold>Contact E-mail Address:</bold><email>zhou.pinghong@zs-hospital.sh.cn</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> endoscopic piecemeal mucosal resection, endoscopic submucosal dissection (ESD), superficial esophageal lesion</p></sec><sec><title>OP406 ENDOSCOPIC RESECTION FOLLOWED BY STEPWISE ENDOSCOPIC BARRETT'S ABLATION FOR EARLY NEOPLASIA IN BARRETT'S OESOPHAGUS</title><p><bold>N. Fernandopulle</bold><sup>1</sup>, G. Horgan<sup>1</sup>, A. A. Bailey<sup>1</sup>, R. Marshall<sup>2</sup>, B. Sgromo<sup>2</sup>, N. Maynard<sup>2</sup>, B. Braden<sup>1,*</sup></p><p><italic><sup>1</sup>Translational Gastroenterology Unit, <sup>2</sup>Department of Surgery, OXFORD UNIVERSITY HOSPITALS TRUST, Oxford, United Kingdom</italic></p><p><bold>INTRODUCTION:</bold> Endoscopic mucosal resection (EMR) followed by radiofrequency ablation (RFA) is now considered standard treatment for high grade dysplasia (HGD) and intramucosal cancer in Barrett’s oesophagus. Complete ablation of the Barrett’s epithelium is recommended to reduce the risk of metachronous neoplasia. However, RFA is an expensive treatment modality often requiring repeat procedures and further endoscopic surveillance thereafter. RFA might not be necessary in all patients.</p><p><bold>AIMS&METHODS:</bold> The aim of the study is to assess the outcome of EMR without RFA in regard to the length of the Barrett’s oesophagus.</p><p>We analysed our database of oesophageal EMR procedures performed for HGD or early cancer from 2008 to 2012. Patients’ demographics, Barrett’s length, histology, number of procedures, remission and complication rates were assessed. EMR was performed using band ligation mucosectomy with maximal two resections per session. Patients were followed up endoscopically in 3 monthly intervals and EMR was repeated as required. When no dysplasia was found within a year, follow-up intervals were increased to 6 months.</p><p><bold>RESULTS:</bold> 64 patients underwent EMR for HGD (20) or early oesophageal cancer (44) in Barrett’s oesophagus. 149 EMR procedures were performed. 48 patients were male (75%), mean age was 71 years (range 30-87). 20 patients (31%) with submucosal or deeper infiltration or poor differentiation in the EMR specimen underwent surgery/chemotherapy or were conservatively managed depending on patient’s fitness, comorbidities and choice.</p><p>Mean follow-up of the remaining 44 patients was 23 month (range 1-55). Remission of dysplasia and neoplasia was achieved in 97.9%. Stepwise EMR during follow up resulted in complete ablation of Barrett’s epithelium in 18 patients (40%) in mean of 4 sessions. All patients with complete endoscopic Barrett’s ablation had an initial maximal Barrett lengths < 3 cm. 12 patients with long Barrett’s (>5cm) received RFA, 7 others are still awaiting the procedure. The overall complication rate was low (6.7 %) including one stricture after RFA (0.7 %), no perforation, 8 procedural (5.3 %, thereof none Hb relevant) and one delayed bleeding (0.7%). All complications were managed endoscopically.</p><p><bold>CONCLUSION:</bold> EMR is a safe procedure which can achieve remission of early oesophageal neoplasia. In short segment Barrett’s oesophagus it can also result in complete ablation of Barrett’s epithelium. Stepwise endoscopic resection for Barrett's ablation has a low complication rate when performed with maximal two ligation resections in 3 monthly follow-up intervals.</p><p><bold>Contact E-mail Address:</bold><email>braden@em.uni-frankfurt.de</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Band ligation, Barrett’s esophageal cancer, EMR, high grade dysplasia, radio frequency ablation</p></sec><sec><title>OP407 CLINICOPATHOLOGIC FEATURES AND OUTCOME OF BARRETT’S ADENOCARCINOMAS RESECTED BY ENDOSCOPIC SUBMUCOSAL DISSECTION</title><p><bold>S. Oka</bold><sup>1,*</sup>, S. Tanaka<sup>1</sup>, K. Kagemoto<sup>2</sup>, Y. Urabe<sup>2</sup>, Y. Sanomura<sup>1</sup>, S. Yoshida<sup>1</sup>, K. Arihiro<sup>3</sup>, K. Chayama<sup>2</sup></p><p><italic><sup>1</sup>Endoscopy, <sup>2</sup>Gastroenterology and Metabolism, <sup>3</sup>Pathology, Hiroshima University Hospital, Hiroshima, Japan</italic></p><p><bold>INTRODUCTION:</bold> Recently in Japan, Barrett’s adenocarcinomas (BAs) are discovered at an early stage because of advances in diagnostic techniques, and are resected by endoscopic submucosal dissection (ESD). However, there are few reports on the efficacy and safety of ESD for BA.</p><p><bold>AIMS&METHODS:</bold> The aim of this study is to conduct a retrospective analysis of clinicopathologic features and outcomes of BAs resected by ESD. Twenty BAs in18 patients (16 males, median age 61 years [45-80]) were resected by ESD at Hiroshima University Hospital between April 2006 and December 2012. We investigated the clinicopathologic features of BAs and outcome of ESD.</p><p><bold>RESULTS:</bold> Eighteen lesions (90%) developed from SSBE, and 2 lesions (10%) from LSBE (12%). Locations (o’clock direction) of BA were as follows: 0-3 o’clock; 13 lesions (65%), 3-6 o’clock; 3 lesions (15%), 6-9 o’clock; 2 lesions (10%) and 9-12 o’clock; 2 lesions (10%). Median tumor size was 15mm (5-60 mm). Macroscopic types of BA were as follows: depressed; 11 lesions (55%), flat elevated; 8 lesions (40%), and protruded; 1 lesion (5%). The colors of BA were as follows: reddish; 18 lesions (90%) and same as background; 2 lesions (10%). The magnifying NBI findings of BA were irregular of both surface pattern and vascular pattern in all lesions. Endoscopic en-bloc resection rate was 100% (20/20), and histological en bloc resection rate was 85% (17/20). Median procedure time was 85 minutes (range, 30-210 minutes). Delayed bleeding occurred in 1 case, and no perforation occurred. Stenosis after ESD was cured conservatively by balloon dilatation in 4 cases. The histology of BE was as follows: well differentiated; 15 lesions (75%), moderately differentiated; 4 lesions (20%), and poorly differentiated; 1 lesion (5%). The depth of invasion was as follows: lamina propria; 4 lesions (20%), muscularis mucosa; 8 lesions (40%) and submucosa; 8 lesions (40%). Additional surgical resection after ESD was performed in 7 cases, and there were no residual tumors and lymph node metastasis. There was no recurrent tumor, however, 1 metachronous adenocarcinoma occurred in 11 patients with follow-up (median period after ESD, 42 months).</p><p><bold>CONCLUSION:</bold> ESD for early stage BA appears to be a safe and effective treatment as a total excisional biopsy.</p><p><bold>Contact E-mail Address:</bold><email>oka4683@hiroshima-u.ac.jp</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Barrett's neoplasia, ESD, NBI, outcome</p></sec><sec><title>OP408 OUTCOME OF ENDOSCOPIC SUBMUCOSAL DISSECTION FOR SUBMUCOSAL INVADED ESOPHAGEAL SQUAMOUS CELL CARCINOMA</title><p><bold>A. Takahashi</bold><sup>1,*</sup>, T. Oyama<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology, SAKU CENTRAL HOSPITAL, Nagano, Japan</italic></p><p><bold>INTRODUCTION:</bold> Standard therapy of submucosal invaded esophageal squamous cell carcinoma (ESCC) is esophagectomy. However, esophagectomy is an invasive therapy, and it is difficult to treat poor risk patient by esophagectomy. Endoscopic submucosal dissection (ESD) is a minimal invasive therapy, and ESD or ESD + chemo radio therapy (CRT) could be an alternative therapy. However, those outcomes are unknown.</p><p><bold>AIMS&METHODS:</bold> The aim of this study is to investigate the outcome of SM2 ESCC treated by ESD and Esophagectomy.</p><p>23 patients treated by ESD and 11 patients treated by esophagectomy from January 2000 to December 2009 were enrolled into this retrospective study. The patients who underwent surgery after neo adjuvant chemotherapy were excluded. The median age was 71 (54-82) and 65 (44-91) years, male/female was 19/4 and 11/0, respectively. The follow up period was 61 (27-148) and 65 (44-91) months. Ce/Ut/Mt/Lt/Ae was 4/3/9/7/1 and 0/0/3/5/3 respectively. 0-I/0-IIa/IIb/IIc was 4/3/1/15 and 2/3/0/6, respectively.</p><p><bold>RESULTS:</bold> 1. The median diameter of lesion was 29 (8-73) mm in ESD and 35 (14-50) mm in esophagectomy.</p><p>2. En-bloc resection rate and R0 resection rate were 96% (22/23) and 91% (21/23).</p><p>3. Local recurrence rate was 0%.</p><p>4. Lymph node metastasis (LNM) was found in 4 of 11 (36%) esophagectomy, and 1 of 23 (4%) ESD.</p><p>5. Distant metastasis was 0% in both groups.</p><p>6. Prognosis: ESD group: 12 patients were treated by additional therapy (AT) (CRT 11 and RT 1), and 11 patients were followed up without AT because of patient’s condition. Only 1 patient was died of ESCC at 23 months after ESD. The patient was treated by ESD + CRT, and LNM was found outside of radiation field at 12 months after ESD. Other patients are alive without recurrence. 4 patients were died of other disease.</p><p> Esophagectomy group: No patient was died of ESCC. 1 patient was died of other disease.</p><p><bold>CONCLUSION:</bold> The outcome of ESD + CRT is excellent. Therefore, that could be an alternative treatment for SM2 ESCC.</p><p><bold>Contact E-mail Address:</bold><email>aurevoireurope@yahoo.co.jp</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> endoscopic submucosal dissection, esophageal squamous cell carcinoma</p></sec><sec><title></title><p><bold>WEDNESDAY, OCTOBER 16, 2013 8:30-10:30</bold></p><p><bold>Unravelling new pathways in IBD pathogenesis – Roof Garden</bold></p></sec><sec><title>OP409 HIGH FAT DIET ACCELERATES PATHOGENESIS OF MURINE CROHN'S DISEASE LIKE ILEITIS INDEPENDENTLY OF OBESITY</title><p><bold>L. Gruber</bold><sup>1,2,*</sup>, S. Kisling<sup>1</sup>, J. Fiamoncini<sup>3</sup>, S. May<sup>1</sup>, D. Haller<sup>1,2</sup></p><p><italic><sup>1</sup>Chair of Nutrition and Immunology, <sup>2</sup>Biofunctionality Unit, ZIEL - Research Center for Nutrition and Food Sciences, Technische Universität München, Freising, Germany, <sup>3</sup>University of São Paulo, São Paulo, Brazil</italic></p><p><bold>INTRODUCTION:</bold> Obesity has been associated with a more severe disease course in inflammatory bowel disease (IBD) and epidemiological data recently identified dietary fats but not obesity as risk factor for the development of IBD. Crohn’s disease is one of the two major IBD phenotypes and mostly affects the terminal ileum. Despite recent observations that high fat diets (HFD) impair intestinal barrier functions and drive pathobiont selection relevant for chronic inflammation in the colon, mechanisms of HFD in the pathogenesis of Crohn’s disease are not known. The aim of this study was to characterize the effect of HFD on the development of chronic ileal inflammation in a murine model of Crohn’s disease-like ileitis.</p><p><bold>AIMS&METHODS:</bold> TNF<sup>ΔARE/WT </sup>mice and wildtype C57BL/6 littermates were fed a HFD (palm oil based, 48%kJ from fat) compared to control diet (12%kJ) for different durations. Intestinal pathology and metabolic parameters (glucose tolerance, mesenteric tissue weight and adipocyte size) were assessed. Intestinal barrier integrity was characterized at different levels including polyethylene glycol (PEG) translocation, endotoxin in portal vein and cellular markers of barrier function. Inflammatory activation of epithelial cells as well as immune cell infiltration into ileal tissue were determined and related to luminal factors.</p><p><bold>RESULTS:</bold> HFD aggravated ileal inflammation in early phase, but did not induce significant overweight or typical metabolic disorders in TNF<sup>ΔARE/WT</sup>. Expression of the tight junction protein Occludin was markedly reduced in the ileal epithelium of HFD mice independently of inflammation, and translocation of endotoxin was increased. Epithelial cells showed enhanced expression of inflammation-related activation markers, along with recruitment of CD11c<sup>+</sup> dendritic cells via CCL20, and Th17 biased lymphocyte infiltration into the ileal lamina propria. Accordingly, <italic>in vitro</italic> studies emphasized that both dendritic cell recruitment and Th17-commitment are driven by luminal factors.</p><p><bold>CONCLUSION:</bold> HFD feeding, independently of obesity, accelerated disease onset of small intestinal inflammation in the Crohn’s disease-relevant mouse model TNF<sup>ΔARE/WT </sup>through mechanisms that involve increased intestinal permeability and altered luminal factors, leading to enhanced dendritic cell recruitment and promoted Th17 immune responses.</p><p><bold>Contact E-mail Address:</bold><email>dirk.haller@tum.de</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> crohn's disease, dendritic cells, fat, Inflammatory bowel disease (IBD), Nutrition, Obesity</p></sec><sec><title>OP410 BEYOND FIGHT OR FLIGHT: REGULATION OF INTESTINAL TH17 LYMPHOCYTES BY SYMPATHETIC NERVOUS SYSTEM</title><p><bold>S. Dhawan</bold><sup>1,*</sup>, J. Duarte<sup>1</sup>, F. Hilbers<sup>1</sup>, C. Verseijden<sup>1</sup>, W. de Jonge<sup>1</sup></p><p><italic><sup>1</sup>Tytgat Institute for Liver and Intestinal Research, ACADEMIC MEDICAL CENTRE, AMSTERDAM, Amsterdam, Netherlands</italic></p><p><bold>INTRODUCTION:</bold> The vagal nerve is put forward as a regulator of immune homeostasis in the gut, however parasympathetic (vagal) and sympathetic (adrenergic) systems work in tandem to modulate innate immune responses. Many types of non-neuronal immune cell populations in the gut can produce neurotransmitters and function as cells that relay neuro-immune signalling.In this study we characterize the cholinergic T cell populations in the intestine and identify the factors dictating their cholinergic phenotype.</p><p><bold>AIMS&METHODS:</bold> To identify acetylcholine-producing T cells in the intestine, we used ChAT(BAC)-EGFP mice, which express eGFP under the control of transcriptional regulatory elements for ChAT, and VACht, enzymes that catalyze the biosynthesis and secretion of acetylcholine. Bone marrow derived dendritic cells (BMDC) were loaded with ovalbumin and matured by overnight LPS (100ng/ml) stimulation. Adrenergic receptor agonist, Norepinephrine (NE), was tested at concentrations of 1nM - 10µM against vehicle. Ovalbumin specific CD4+ CD62L+ T cells were used in an antigen specific skewing assay.</p><p>CD45+CD4+ cells were isolated from small intestine and colon and analysed by flow cytometry. Furthermore, we isolated intestinal CD4+, CCR6+ (IL-17) and CXCR3+ (IFN-g) ChAT+cells by enzymatic digestion and cell sorting, and assessed gene transcription by qPCR.</p><p><bold>RESULTS:</bold> Flow cytometry revealed that ChAT<sup>+</sup> cells were 31.80±1.78 % and 31.20±3.11 % of total CD4<sup>+</sup> T cells in the peyer’s patches and MLNs respectively, indicating a small subset of memory T cells express ChAT. In addition, (2.1% and 3.8%) of CD4<sup>+ </sup>T cells were ChAT-positivein the colon and the ileum respectively.In vitro, ChAT+ T cells were induced after adrenergic receptor activation of DCs in a dose dependent fashion (veh: 3.07±2.3%; NE 1µM: 18.37±9.6 %). This increase was specific to Th17 cells because it was due to an increase in the Tcell pool that produced IL-17 (veh: 3.07±2.31 %; 18.37±6.37 %). No significant differences were observed in Th1 or Th2 cells (Th1; veh: 14.01±6.03 % NE 1µM: 12.43±4.5 %). Although NE lead to a significant induction of T<sub>reg</sub> cells (veh: 9.6±7.6%; NE 1 µM 27.35±7.99%), there was no change in Treg ChAT (veh: 4.07±2.22 %; NE 1 µM 3.42±2.96 %).</p><p>In addition, CCR6+ CXCR3+ ChAT positive cells were observed to express increased IL-17 (2.2 fold), IL-22 (43 fold) and ROR-γ (21 fold) transcripts compared to CCR6+ CXCR3+ ChAT negative cells.</p><p><bold>CONCLUSION:</bold> In conclusion, our data provides new evidence of ChAT+ T cells in the intestine, which (1) respond to sympathetic input by upregulating acetylcholine producing capacity, and (2) seem to be a subset of Th17 Tcells that play a key role in regulating the innate immune system.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> cytokines, Dendritic cell, Innate Immunity, mucosal inflammation, t cells</p></sec><sec><title>OP411 IDENTIFICATION OF TSG-6 AS A KEY FACTOR IN MEDIATING THE THERAPEUTIC EFFECTS OF MESENCHYMAL STEM CELLS FOR EXPERIMENTAL COLITIS TREATMENT</title><p><bold>E. Sala</bold><sup>1</sup>, M. Genua<sup>1</sup>, V. Arena<sup>2</sup>, A. Anselmo<sup>3</sup>, S. D’Alessio<sup>1</sup>, A. Gandelli<sup>1</sup>, C. Tacconi<sup>1</sup>, A. Malesci<sup>1</sup>, S. Danese<sup>1</sup>, S. Vetrano<sup>1,*</sup></p><p><italic><sup>1</sup>Division of Gastroenterology, Humanitas Clinical and Research Center, Rozzano, Milan, rozzano, <sup>2</sup>Department of Pathology, , Catholic University of Rome, Rome, <sup>3</sup>Department of Immunology, Humanitas Clinical and Research Center, Rozzano, Milan, rozzano, Italy</italic></p><p><bold>INTRODUCTION:</bold> Mesenchymal stem cells (MSCs) have been candidate as therapeutic treatment for several immune diseases including IBD.Although most of beneficial effects are explained by MSC engrafting at the site of tissue injury with modulation of inflammatory reactions, we have demonstrated that MSC gut-homing is not relevant for exerting their immunomodulatory effects in the treatment of colitis, but rather these effects could be mediated by paracrine factors</p><p><bold>AIMS&METHODS:</bold> Aim of this study was to identify the potential MSC-derived soluble factor involved in the resolution of intestinal inflammation.The expression of a panel of candidate genes encoding MSC-derived paracrine factors was analyzed in murine MSCs by RT-PCR. MSCs were isolated from bone marrow of wild type (WT) or TSG-6 KO mice. Colitis was induced in mice by 3% DSS treatment for 10 days. At day 5 of colitic induction WT mice were treated intraperitoneally with a single injection of 3x106 WT or TSG-6 MSC-derived cells, or in alternative with 5 daily injections of recombinant murine TNFα-stimulating gene protein 6 (rTSG-6) each of 4 μg.Body weight, disease activity index (DAI) and survival rate were monitored daily and the damage of colonic mucosa was evaluated by endoscopic and histological scores. Levels of TSG-6, IL-6, and IFN-γ, were measured in serum and in mucosal extracts by ELISA, while mucosal infiltration of leukocytes was examined by FACS</p><p><bold>RESULTS:</bold> The screening of MSC-derived paracrine factors showed an elevated expression of both mRNA and protein TSG-6, with 7-fold of increase (p<0,01) than other factors. increase of serum TSG-6 was found in colitic mice treated with WT MSC after 72 h of injection compared to control mice treated with saline. rTSG-6 treatment improved survival rate and colitis by reducing markedly both systemic and mucosal levels of IL-6, IFN-γ, neutrophil infiltration.Surprisingly, after 10 days of DSS treatment, rTSG-6 injected mice appeared healthy and vital and displayed reduced colon inflammation compared to saline injected mice, as demonstrated by endoscopic and histological analysis. In contrast, MSCs derived from TSG-6 KO mice did not have any therapeutic effect in experimental colitis</p><p><bold>CONCLUSION:</bold> Overall, our data demonstrate that MSCs ameliorate colitis mediating the release of a multipotent anti-inflammatory protein TSG-6, rather than their engraftment in the colon.The identification of TSG-6 as a key factor in the therapeutic efficacy of MSCs could pave the way for an alternative approach to MSC-based therapy for the treatment of IBD</p><p><bold>Contact E-mail Address:</bold><email>stefania.vetrano@humanitasresearch.it</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> DSS-induced colitis, Inflammatory bowel disease (IBD), mesenchymal stem cells, , TSG-6</p></sec><sec><title>OP412 ANTI-INFLAMMATORY EFFECTS OF ALTERED GP130 STAT3 SIGNALING AND THE ROLE OF MYELOID-DERIVED SUPPRESSOR CELLS IN DSS INDUCED COLITIS</title><p><bold>J. Däbritz</bold><sup>1,*</sup>, H. V. Chalinor<sup>1</sup>, T. R. Menheniott<sup>1</sup>, A. S. Giraud<sup>1</sup>, L. M. Judd<sup>1</sup></p><p><italic><sup>1</sup>Gastrointestinal Research in Inflammation & Pathology, Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Australia</italic></p><p><bold>INTRODUCTION:</bold> STAT3 regulates the expansion of myeloid-derived suppressor cells (MDSC) during inflammation, infection and cancer. The gp130757FF (FF) mouse has an induced single base pair mutation at position 757 of gp130 that impairs activation of downstream Ras/MAPK/ERK signalling. This results in hyper-activation of oncogene STAT3, with the development of gastric tumours but also protection from DSS-induced colitis.</p><p><bold>AIMS&METHODS:</bold> This study determined a mechanism for this protection and compared this to mice with mutated myeloid derived cells that are unable to express STAT3. gp130757FF (FF), LysMCre/STAT3Flox (MCreSTAT3) and appropriate wild type (WT) mice were treated with 3% DSS in drinking water for 6 days, 3 days recovery without DSS, then euthanized. Colons were removed for histological, mRNA and protein analysis as well as isolation of lamina propria mononuclear cells (LPMC) and intraepithelial lymphocytes (IEL). Cell populations from spleen (SPL), mesenteric lymph nodes (MLN), LPMC, and IEL were characterized by flow cytometry for subpopulations of MDSC, dendritic cells (DC), monocytes, macrophages, and granulocytes. Antibodies included anti-mouse CD11b, CD11c, Ly6C, Ly6G, CD49 and F4/80.</p><p><bold>RESULTS:</bold> FF mice were protected from DSS-induced colitis compared to WT mice. Expression of pro-inflammatory cytokines which are induced in WT mice with DSS-induced colitis (e. g. IL-6, IL-17, IL-1β, IFNγ) were either unchanged or significantly impaired in the FF mouse. Likewise, expression of cytokines with a cytoprotective role in the colon (IL-19, IL-33) were modestly elevated in WT mice, but markedly increased in FF mice following DSS treatment. DSS-induced colitis resulted in a comparable increase in DC, monocytes/ macrophages and granulocytes in LPMC and IEL of WT mice and FF mice. MDSC are not increased in SPL and MLN of WT mice during T-cell independent colitis. However, DSS treatment of WT mice resulted in a marked increase in MDSC in IEL and LPMC. Interestingly, the frequency of granulocytic MDSC was further increased in LPMC and IEL of FF mice. MCreSTAT3 mice were not resistant to colitis and showed no change or even a decrease in the frequency of MDSC in LPMC or IEL compared to wildtype mice.</p><p><bold>CONCLUSION:</bold> Here we show that a mechanism for resistance to DSS-induced colitis in gp130FF mice is via increased expression of IL-19 and IL-33, and reduced expression of pro-inflammatory markers, and the marked increase in MDSC in the colon. The protective effects can be blocked, when STAT3 is specifically deleted from myeloid cells, which underpins the potential role of MDSC as a new immune regulatory pathway in inflammatory bowel disease.</p><p><bold>Contact E-mail Address:</bold><email>jan.dabritz@mcri.edu.au</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Experimental colitis, inflammatory bowel disease</p></sec><sec><title>OP413 DISTINCT GENE EXPRESSION PROFILES ARE ASSOCIATED WITH INDUCTION OF FIBROSIS AND WITH ADDITIONAL RECOVERY IN CHRONIC DSS COLITIS</title><p><bold>C. Breynaert</bold><sup>1,2,*</sup>, I. Arijs<sup>1,3</sup>, J. Van der Goten<sup>1,3</sup>, L. Van Lommel<sup>3</sup>, J. Cremer<sup>1,2</sup>, F. Schuit<sup>3</sup>, M. Ferrante<sup>1</sup>, S. Vermeire<sup>1</sup>, P. Rutgeerts<sup>1</sup>, J. Ceuppens<sup>2</sup>, G. Van Assche<sup>1</sup></p><p><italic><sup>1</sup>Translational Research Center for Gastrointestinal Disorders (TARGID), <sup>2</sup>Laboratory of Clinical Immunology, <sup>3</sup>Gene Expression Unit, KU Leuven, Leuven, Belgium</italic></p><p><bold>INTRODUCTION:</bold> Colonic gene expression profiles in different phases of inflammation and fibrosis might help to elucidate the molecular pathways of tissue remodeling. To date the transcriptomics of colonic gene expression in a chronic murine model of IBD have not been studied.</p><p><bold>AIMS&METHODS:</bold> The aim of this study was to study the effect of additional recovery on fibrosis and colonic gene expression in a chronic murine DSS model. Chronic relapsing colonic inflammation was induced in C57BL6 mice using 2 cycles of 1 week of DSS administration followed by a recovery period of 2 weeks with drinking water (2 cycles). The effect of prolonged recovery was studied by adding an additional 3 weeks recovery period after the 2 cycles of DSS. Total RNA, extracted from snap frozen colon (n=5/group), was used to analyze the mRNA expression via Affymetrix Mouse Gene 1.0 ST arrays. Data were analyzed with Bioconductor software.</p><p><bold>RESULTS:</bold> Martius-Scarlett-Blue staining showed abundant collagen deposition in the (sub)mucosa after 2 cycles of DSS. After prolonged recovery, there was a lower degree of fibrosis (p<0.001). In 2-cycles DSS colitis, the top 10 significantly upregulated genes (fold discovery rate<5%, >2-fold change) vs. controls were <italic>REG3G, REG3B, CLCA4, CXCL9, KHDC1, WFDC18, IDO1, PLA2G2A, NOS2</italic> and <italic>IL1B</italic>. After additional recovery, the top 10 significantly upregulated genes vs. controls were <italic>PPBP, REG3G, REG3B, KRT5, KRT6A, KRT4, KRT13, DAPL1, PSCA </italic>and<italic> LTF</italic>. To study the impact of recovery on gene expression unrelated to the degree of chronicity, we identified all significantly upregulated genes after additional recovery compared to 2 cycles DSS colitis followed by immediate sacrifice. As compared to controls, we identified 376 significantly upregulated genes after 2 cycles of DSS with additional recovery. Of these 376 genes, 255 were also upregulated after 2 cycles of DSS while 90 genes were uniquely upregulated after additional recovery. Eight of these genes coded for keratins (<italic>KRT4, KRT5, KRT6, KRT13, KRT14, KRT16, KRT17, KRT84</italic>) and 5 of these keratin genes were in the top 15 significantly upregulated genes.</p><p><bold>CONCLUSION:</bold> Prolonged recovery after DSS induced chronic murine colitis is associated with specific gene expression profiles pointing to activation of molecular pathways for healing and repair. This opens perspectives to identify therapeutic targets specific for avoiding intestinal fibrosis.</p><p><bold>Contact E-mail Address:</bold><email>Christine.Breynaert@med.kuleuven.be</email></p><p><bold>Disclosure of Interest</bold>: C. Breynaert Financial support for research from: Agency for Innovation by Science and Technology in Flanders (IWT), Broad Medical Research Program of the Broad Foundation (IBD-0319R), I. Arijs Financial support for research from: Postdoctoral grant of the Foundation for Scientific Research Flanders, FWO Vlaanderen, J. Van der Goten: None Declared, L. Van Lommel: None Declared, J. Cremer: None Declared, F. Schuit: None Declared, M. Ferrante Financial support for research from: Janssen Biologics, Lecture fee(s) from: Merck, Tillotts, Ferring, Abbott, Consultancy for: Abbott, Merck, Janssen Biologics, S. Vermeire Financial support for research from: UCB Pharma, MSD, Abbvie, Foundation for Scientific Research Flanders, FWO Vlaanderen, Lecture fee(s) from: Abbvie, Merck, Ferring, UCB Pharma, Centocor, Consultancy for: UCB Pharma, AstraZeneca, Ferring, Abbvie, Merck, Ferring, Shire, Pfizer, P. Rutgeerts Financial support for research from: UCB Pharma, Abbvie, Janssen Biologics, Merck, Prometheus, Lecture fee(s) from: Abbvie, Merck, Consultancy for: Amgen, Merck, UCB Pharma, Genentech, BMS, Abbvie, Janssen Biologics, Millenium, Neovacs, Actogenics, Prometheus, J. Ceuppens: None Declared, G. Van Assche Financial support for research from: Abbvie, Ferring, Foundation for Scientific Research Flanders, FWO Vlaanderen, Broad Medical Research Program of the Broad Foundation (IBD-0319R), Lecture fee(s) from: Janssen-Cilag, Merck, Abbvie, Consultancy for: PDL BioPharma, UCB Pharma, Sanofi-Aventis, Abbvie, Ferring; Novartis, , Biogen Idec, Janssen Biologics, NovoNordisk, Zealand Pharma A/S, Millenium/Takeda, Shire, Novartis, BMS</p><p><bold>Keywords:</bold> DSS, Fibrosis, Microarray, Tissue repair </p></sec><sec><title>OP414 IL-22-MEDIATED ANTIMICROBIAL RESPONSE IS REGULATED BY HES1 VIA STAT3-DEPENDENT TRANSCRIPTION IN HUMAN INTESTINAL EPITHELIAL CELLS</title><p><bold>R. Okamoto</bold><sup>1,*</sup>, T. Murano<sup>1</sup>, H. Shimizu<sup>1</sup>, G. Ito<sup>1</sup>, S. Fujii<sup>1</sup>, T. Nakata<sup>1</sup>, K. Tsuchiya<sup>1</sup>, T. Nakamura<sup>1</sup>, M. Watanabe<sup>1</sup></p><p><italic><sup>1</sup>Tokyo Medical and Dental University, Tokyo, Japan</italic></p><p><bold>INTRODUCTION:</bold> Notch signaling plays an essential role in proliferation and differentiation of intestinal epithelial cells (IECs). We have previously shown that Notch-Hes1 signaling is up-regulated in the inflamed mucosa of ulcerative colitis (UC), and thereby plays an indispensable role in tissue regeneration. However, whether Notch-Hes1 signaling can interact with the inflammatory cytokine signals, and regulate immune responses of IECs, has never been described.</p><p><bold>AIMS&METHODS:</bold> In this study, we investigated whether any interaction between Notch-Hes1 and IL-22/IL-22R pathway may exist in IECs, and thereby contribute to regeneration of the intestinal epithelia in IBD. Notch-Hes1 pathway was activated by forced expression of Hes1, in LS174T or DLD1 cells. IL-22/IL-22R pathway was activated in those cells by addition of recombinant human IL-22. Under concomitant activation of these two pathways, activity of RBP-J-dependent or STAT3-dependent transcription was measured by reporter assays. Phosphorylation of STAT3 was examined by immunoblot analysis, and expressions of downstream target genes were analyzed by quantitative RT-PCR and ELISA.</p><p><bold>RESULTS:</bold> Upon concomitant activation of Notch-Hes1 and IL-22/IL-22R pathway, no significant interaction was observed in RBP-J-dependent transcription. In sharp contrast, STAT3-dependent transcription was significantly up-regulated by activation of both Notch-Hes1 and IL-22/IL-22R pathway, compared to IL-22/IL-22R pathway alone. Such an additional effect on STAT3-dependent transcription was mediated by Hes1, as forced expression of Hes1 in addition to IL-22 up-regulated STAT3-dependent transcription up to 230 folds, whereas IL-22 alone up-regulated its activity up to 20 folds. Consistently, in response to IL-22, phosphorylation of STAT3 at Tyr705 could be maintained at a high level for a significantly extended period of time by forced expression of Hes1. Quantitative RT-PCR analysis showed that such a co-operation between Hes1 and IL-22/IL-22R pathway not only enhanced STAT3 dependent transcriptional activity, but also further enhanced expression of its target genes, such as REG1A, REG3A and REG3G. Conversely, reduction of Hes1 protein level by a γ-secretase inhibitor significantly down-regulated the induction of those genes in IECs, resulting in markedly poor response to IL-22.</p><p><bold>CONCLUSION:</bold> Our present findings add a new aspect in molecular function of Hes1, which can interact with cytokine signals and regulate the immune response of IECs, and thus further emphasizes the importance of Hes1 expression in the inflamed colonic environment.</p><p><bold>Contact E-mail Address:</bold><email>rokamoto.gast@tmd.ac.jp</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Hes1, IL-22, STAT3, ulcerative colitis</p></sec><sec><title>OP415 FECAL LIPOCALIN2 REFLECTS COLONIC INFLAMMATION IN MURINE COLITIS MODEL: A POSSIBLE ROLE OF MEASURING FECAL LIPOCALIN2 AS A BIOMARKER OF IBD</title><p><bold>T. Toyonaga</bold><sup>1,*</sup>, H. Nakase<sup>2</sup>, N. Minami<sup>2</sup>, S. Yamada<sup>2</sup>, Y. Honzawa<sup>2</sup>, T. Yoshino<sup>2</sup>, M. Matsuura<sup>2</sup>, K. Okazaki<sup>1</sup>, T. Chiba<sup>2</sup></p><p><italic><sup>1</sup>Gastroenterology & Hepatology, Kansai Medical University, Hirakata, <sup>2</sup>Gastroenterology & Hepatology, Kyoto University, Kyoto, Japan</italic></p><p><bold>INTRODUCTION:</bold> Inflammatory bowel diseases (IBD) are chronic and relapsing-remitting immune-mediated disorders, which are required to keep medical treatments throughout life. Therefore, the development of non-invasive modalities for monitoring of colonic inflammation such as calprotectin is important for the management of patients with IBD. Neutrophil gelatinase-associated lipocalin (NGAL), also known as Lipocalin2 (Lcn2) was originally identified as a component of neutrophil granules, but also expressed in the epithelial cells in response to inflammatory signals. Although it was reported that Lcn2 protects against several inflammatory diseases, little is known about the role of Lcn2 in the pathogenesis of IBD.</p><p><bold>AIMS&METHODS:</bold> The aim of this study is to evaluate the role of Lcn2 in colonic inflammation of an immune-mediated colitis model, Interleukin-10 knockout (IL-10 KO) mouse. We examined Lcn2 expressing cells in the colonic tissues of C57BL/6(WT) and IL-10 KO mice by immunohistochemistry (IHC). Serial changes of Lcn2 expression in the colonic tissues of both mice were assessed by quantitative real-time PCR, and fecal levels of Lcn2 (fecal Lcn2) were quantified by enzyme-linked immunosorbent assay (ELISA). Also, we analyzed the correlation between fecal Lcn2 and histologic inflammation of IL-10 KO mice. Lcn2 secretion from colonic epithelial cells stimulated with lipopolisaccharides (LPS) was examined by ELISA using a murine colonic epithelial cell line, Colon-26.</p><p><bold>RESULTS:</bold> (1) IHC revealed that Lcn2 was mainly expressed in the intestinal epithelial cells in IL-10 KO mice, whereas Gr-1, CD3, CD11b, CD11c, CD45R, and aSMA-positive cells were negative for Lcn2. (2) Despite no findings of obvious colonic inflammation at 4 weeks after birth of IL-10 KO mice, increased gene expression of Lcn2 was observed in IL-10 KO mice in comparison with WT mice. Of note, the level of fecal Lcn2 in IL-10 KO mice was significantly higher than that of control mice at 4 weeks (452.4 ng/g <italic>vs</italic> 4.7 ng/g, <italic>p</italic><0.05). Moreover, there was a significant correlation between fecal Lcn2 and histological colitis score of IL-10 KO mice throughout observation period. (3) Stimulation with LPS (100 ng/mL) increased the production of Lcn2 from Colon-26 cells compared to that of non-stimulated Colon-26 cells (6639.5 pg/mL <italic>vs</italic> 243.6 pg/mL, p<0.05).</p><p><bold>CONCLUSION:</bold> Our data demonstrated that expression of Lcn2 in epithelial cells, rather than immune cells, could play an important role in the colonic inflammation. In addition, measurement of fecal Lcn2 might a novel biomarker for monitoring colonic inflammation in human IBD.</p><p><bold>Contact E-mail Address:</bold><email>toyo.necco@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> inflammatory bowel disease, Lipocalin2</p></sec><sec><title>OP416 HUMAN INTESTINAL DENDRITIC CELLS DRIVE T-CELL DYSFUNCTION IN ULCERATIVE COLITIS: THE ARYL HYDROCARBON RECEPTOR AS A THERAPEUTIC TARGET</title><p><bold>E. R. Mann</bold><sup>1,2,*</sup>, D. Bernardo<sup>1</sup>, H. O. Al-Hassi<sup>1</sup>, J. Landy<sup>3</sup>, S. Peake<sup>3</sup>, R. Man<sup>1</sup>, H. Spranger<sup>3</sup>, T. Elliott<sup>3</sup>, S. Sarkar<sup>1</sup>, N. Yassin<sup>1</sup>, G.-H. Lee<sup>1</sup>, S. Knight<sup>1</sup>, A. Hart<sup>1</sup></p><p><italic><sup>1</sup>Imperial College London, Harrow, United Kingdom, <sup>2</sup>Johns Hopkins Medicine, Baltimore, United States, <sup>3</sup>St. Mark's Hospital, Harrow, United Kingdom</italic></p><p><bold>INTRODUCTION:</bold> Intestinal immune homeostasis is mediated by dendritic cells (DC), which are unique in their ability to drive primary T-cell responses (immunogenic or tolerogenic), and imprint specific homing properties on T-cells. The aryl hydrocarbon receptor (AhR) is a transcription factor which modulates intestinal inflammation; in mice, AhR activation at intestinal sites results in amelioration of colitis in an IL-22-dependent manner. However, gut DC had yet to be characterised for AhR expression in any species. Furthermore, immunological factors driving pathology in human ulcerative colitis (UC) are poorly understood. Gut DC in particular are poorly characterised in humans.</p><p><bold>AIMS&METHODS:</bold> We aimed to characterise human gut DC for AhR expression and to compare the function of gut DC from UC patients (UC-DC) and healthy controls (control-DC). Control-DC and UC-DC were isolated from colonic biopsies, conditioned +/- specific AhR agonist 6-formylindolo(3,2-b)carbazole (FICZ), and characterised by flow cytometry or used to stimulate T-cell responses <italic>in vitro.</italic></p><p><bold>RESULTS:</bold> Human gut DC expressed AhR; expression was restricted on UC-DC. An increased proportion of UC-DC were CD11c<sup>-</sup> (non-myeloid) compared to control-DC, whereas there was a loss of CD103<sup>+</sup>CCR7<sup>+</sup> DC (“tolerogenic” gut DC in mice) from the UC gut. UC-DC exhibited an enhanced capacity to generate gut-specific T-cells (expressing gut-homing molecules β7 and CCR9, but negative for skin-homing markers CLA and CCR4). Furthermore, UC-DC reduced IFNγ and IL-22 production by T-cells, whilst enhancing T-cell production of IL-4. Activation of AhR on gut DC via FICZ conditioning enhanced their ability to drive IL-22, IL-17 and TGFβ production by T-cells that they stimulated.</p><p><bold>CONCLUSION:</bold> This is the first study to demonstrate that dysregulated T-cell function in human UC is driven by intestinal dendritic cells, and that human gut DC express AhR. UC-DC skew T-cell responses towards Th2 responses with the loss of IL-22 likely to contribute to epithelial barrier damage in UC. In mice, gut DC ability to drive intestinal immune tolerance is governed by myeloid CD103<sup>+</sup>CCR7<sup>+ </sup>DC; the loss of CD103<sup>+</sup>CCR7<sup>+</sup> and AhR<sup>+</sup> DC in UC is likely to account for disrupted mucosal homeostasis in the UC gut. Increased generation of gut-homing T-cells in UC is likely to contribute to T-cell infiltration at inflamed sites. Targeting AhR for therapeutic purposes may result in increased epithelial barrier repair and restoration of intestinal homeostasis.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> cytokines, dendritic cells, T-cells, ulcerative colitis</p></sec><sec><title>OP417 THE GCN2/EIF2ALPHA/ATF4 SIGNALING PATHWAY IS NECESSARY FOR AUTOPHAGY RESPONSE TO INFECTION WITH CROHN’S DISEASE-ASSOCIATED ADHERENT-INVASIVE ESCHERICHIA COLI</title><p><bold>H. T. T. Nguyen</bold><sup>1,*</sup>, J. Carrière<sup>1</sup>, G. Dalmasso<sup>1</sup>, A.-C. Maurin<sup>2</sup>, A. Bruhat<sup>2</sup>, A. Darfeuille-Michaud<sup>1</sup></p><p><italic><sup>1</sup>UMR 1071 Inserm, University of Auvergne, Clermont-Ferrand, <sup>2</sup>Human Nutrition Unit, INRA, Theix, France</italic></p><p><bold>INTRODUCTION:</bold> Crohn′s disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract, of which the etiology involves environmental, genetic and microbial factors. Our group and others have shown a high prevalence of the invasive <italic>E. coli </italic>strains, designated adherent-invasive <italic>E. coli </italic>(AIEC), in the intestinal mucosa of CD patients. Upon AIEC infection, autophagy is induced in host cells to restrain the replication of the bacteria. The signaling pathway inducing autophagy response to AIEC infection, however, remains unknown.</p><p><bold>AIMS&METHODS:</bold> Here, we investigated the role of the GCN2/eIF2α/ATF4 pathway in such mechanism. Intestinal epithelial cells (IECs) were infected with the AIEC reference strain LF82, a non-pathogenic K12 or the commensal<italic> E. coli</italic> HS strain. Activation of the GCN2/eIF2α/ATF4 pathway was assessed by Western blot and qRT-PCR analyses. Autophagy was assessed by Western blot analysis and immunofluorescent labelling of LC3 and p62. The number of intracellular bacteria was determined by a bacterial invasion assay and confocal microscopy.</p><p><bold>RESULTS:</bold> We found that infection of IECs with AIEC LF82, but not with K12 or <italic>E. coli</italic> HS, increased the levels of phospho-GCN2, phospho-eIF2α and enhanced ATF4 protein expression. The later consequently led to upregulated mRNA expression levels of target genes of ATF4, such as <italic>ASNS</italic>, <italic>TRB3</italic>, <italic>GLYT</italic>, <italic>CHOP</italic>, <italic>ATF3</italic>, and autophagy genes (<italic>MAP1LC3B</italic>, <italic>p62</italic>). Intracellular multiplication of AIEC was increased in GCN2<sup>-/-</sup> and ATF4<sup>-/-</sup> mouse embryonic fibroblasts (MEFs) compared with that in wild type MEFs as determined by bacterial invasion assay and confocal microscopy using a LF82-GFP strain. These results were validated <italic>in vivo</italic> using GCN2 knockout mice and a model of AIEC infection that we previously established. AIEC infection induced a stronger pro-inflammatory response in GCN2<sup>-/-</sup> and ATF4<sup>-/-</sup> MEFs than in wild type MEFs, and in GCN2 knockout mice versus wild type mice. Autophagy induction in response to infection, assessed by Western blot and immunofluorescent analyses of LC3 levels, was decreased in GCN2<sup>-/-</sup> and ATF4<sup>-/-</sup> MEFs compared with wild type MEFs.</p><p><bold>CONCLUSION:</bold> Our study shows that upon AIEC infection, the GCN2/eIF2α/ATF4 signaling pathway is activated in host cells, which is served as a host defense mechanism to induce a functional autophagy-mediated control of AIEC intracellular replication.</p><p><bold>Contact E-mail Address:</bold><email>hang.nguyen@udamail.fr</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> adherent-invasive E. coli, autophagy, Crohn's disease</p></sec><sec><title></title><p><bold>WEDNESDAY, OCTOBER 16, 2013 11:00-12:30</bold></p><p><bold>Oesophageal motility disorders and eosinophilic oesophagitis – Hall 9</bold></p></sec><sec><title>OP421 TREATMENT OF EOSINOPHILIC ESOPHAGITIS WITH THE CRTH2-ANTAGONIST OC000459: A NOVEL THERAPEUTIC PRINCIPLE</title><p><bold>A. Straumann</bold><sup>1,*</sup>, C. Bussmann<sup>2</sup>, L. P. Collins<sup>3</sup>, R. Pettipher<sup>3</sup>, M. Hunter<sup>3</sup>, J. Steiner<sup>3</sup>, H.-U. Simon<sup>4</sup></p><p><italic><sup>1</sup>Swiss EoE Research Network, Olten, <sup>2</sup>Patology Viollier, Basel, Switzerland, <sup>3</sup>Oxagen Ldt, Middletown, United Kingdom, <sup>4</sup>Pharmacology University of Berne, Bern, Switzerland</italic></p><p><bold>INTRODUCTION:</bold> Eosinophilic esophagitis (EoE) is a Th2-type inflammatory disease of the esophagus, characterized clinically by symptoms related to esophageal dysfunction and histologically by an eosinophil-predominant inflammation. CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells) is a receptor expressed by Th2 cells and eosinophils, which mediates chemotaxis and activation of these cells in response to prostaglandin D<sub>2</sub>, a key prostanoid in allergic responses. OC000459 is a selective and orally bioavailable CRTH2 antagonist, which blocks the ability of PGD<sub>2</sub> to recruit and activate Th2 cells and eosinophils with proven efficacy in asthma. OC000459 is therefore expected to suppress tissue inflammation associated with EoE. The purpose of this study was to evaluate the efficacy and safety of an OC000459 monotherapy in adult patients with active EoE.</p><p><bold>AIMS&METHODS:</bold> In this randomized, double-blind, placebo-controlled trial 26 adult patients (m/f = 22/4; mean age 41 yrs, range 22-69 yrs) with active (≥20 eos/hpf and symptoms), corticosteroid-dependent and/or -resistant EoE were treated either with 100 mg OC000459 (n=14) or placebo (n=12) twice daily for 8 weeks. Pre- and post-treatment disease-activity was assessed clinically, endoscopically, histologically and via biomarkers. The primary endpoint was the reduction of the esophageal eosinophil infiltration.</p><p><bold>RESULTS:</bold> After an 8-week treatment of active EoE with OC000459, the mean eosinophil number decreased from 114.7 to 74.2 eos/hpf, whereas under placebo, no reduction was observed (from 102.8 to 99.4 eos/hpf) (p=0.159). The effect of OC000459 was more pronounced in the proximal (64% reduction, p=0.131) than in the distal esophagus (16% reduction, p=0.667). The global assessment of disease activity decreased under OC000459 from 7.1 to 5.2 pts, whereas the reduction was less in the placebo group (from 6.7 to 5.8, p=0.424). The endoscopic appearance decreased under OC000459 from 6.3 to 5.5 and increased under placebo from 5.5 to 5.8 pts (p=0.118). In spite of these differences, the symptom score decreased in both OC000459 (from to 16.5 to 8.8 pts) and placebo (from 16.7 to 9.8 pts) groups equally (p=0.989). The treatment was well tolerated and no serious adverse events occurred.</p><p><bold>CONCLUSION:</bold> This study demonstrates that 1) treatment with the CRTH2-antagonist OC000459 exerts a moderate anti-inflammatory effect in adult patients with active EoE; 2) the effect is more pronounced in the proximal than in the distal esophagus and; 3) treatment with OC000459 is well tolerated.</p><p><bold>Disclosure of Interest</bold>: A. Straumann Financial support for research from: Oxagen Ldt sponsoring the study, Consultancy for: Oxagen, Pfizer, Actelion, GASK, Novartis, Shareholder of: Roche, Novartis, C. Bussmann Financial support for research from: Study Sponsor, L. P. Collins Other: Employed by Study Sponsor, R. Pettipher Other: Employed by Study Sponsor, M. Hunter Other: Employed by Study Sponsor, J. Steiner Consultancy for: for Study Monitoring , H.-U. Simon: None Declared</p><p><bold>Keywords:</bold> CRTH2 Antagonist, RCT, TH2 Type Inflammation</p></sec><sec><title>OP422 PROTON PUMP INHIBITOR-RESPONSIVE OESOPHAGEAL EOSINOPHILIA CORRELATES WITH DOWNREGULATION OF EOTAXIN-3 AND TH2 CYTOKINES</title><p><bold>J. Molina-Infante</bold><sup>1,*</sup>, M. D. Rivas<sup>2</sup>, G. Vinagre-Rodriguez<sup>1</sup>, M. Hernandez-Alonso<sup>1</sup>, B. Perez-Gallardo<sup>1</sup>, C. Dueñas-Sadornil<sup>1</sup>, J. M. Mateos-Rodriguez<sup>1</sup>, M. Fernandez-Bermejo<sup>1</sup>, P. Robledo-Andres<sup>1</sup>, R. Bañares<sup>3</sup>, J. Zamorano<sup>2</sup></p><p><italic><sup>1</sup>Gastroenterology, <sup>2</sup>Research Unit, Hospital San Pedro de Alcantara, Caceres, <sup>3</sup>Hepatology, Hospital Gregorio Marañon, Madrid, Spain</italic></p><p><bold>INTRODUCTION:</bold> Proton pump inhibitor-responsive oesophageal eosinophilia (PPI-REE) is a recently described phenotype distinct from eosinophilic oesophagitis (EoE), but not neccesarily a manifestation of gastro-oesophageal reflux disease. The underlying mechanism remains unknown.</p><p><bold>AIMS&METHODS:</bold> To address baseline eotaxin-3 and Th2 cytokine expression profile in patients with suspected EoE, to characterize the course of cytokines after systematic PPI therapy and to evaluate the cytokine profile outcome in PPI-REE after PPI therapy compared to that in EoE patients after topical steroids. In consecutive adult patients with dysphagia/food impaction and esophageal eosinophilia > 15 eo/HPF, eotaxin-3, IL-13 and IL-5 were tested in distal and proximal biopsies, at baseline and after PPI therapy for 8 weeks (omeprazole 40 mg twice daily). PPI-REE was defined by symptomatic remission and < 15 eo/HPF in both distal and proximal esophagus. EoE patients (> 15 eo/HPF on high-dose PPI therapy) were offered rescue therapy with topical steroids (swallowed fluticasone nasal drops 400 µg bid) for 6 weeks.</p><p><bold>RESULTS: :</bold> 47 patients were included and reevaluated on PPI therapy. 23/47 patients (46%) had PPI-REE (15/44 (30%) complete and 8/47 (16%) partial). No differences were observed between PPI-REE and EoE patients regarding demographics (age 32 <italic>vs.</italic> 31.5, p 0.98), symptoms (dysphagia/food impaction 89% vs. 93%, p 0.7), endoscopic findings (reflux esophagitis 16% vs. 23%, p 0.39 or esophageal eosinophilia degree neither at distal (54.9 vs. 68.5, p 0.22) nor at proximal esophagus (44.9 vs. 63.1, p 0.12). Baseline molecular characteristics were indistinguishable between PPI-REE and EoE at distal [eotaxin-3, 0.72 vs. 0.54 (p 0.44), IL-13, 0,012 vs. 0.017 (p 0.86) and IL-5, 0.021 vs. 0.039 (p 0.22)] and proximal esophagus [eotaxin-3, 0.46 vs. 0.78 (p 0.23), IL-13, 0.008 vs. 0.012 (p 0.33) and IL-5, 0.016 vs. 0.071 (p 0.08)]. 14/24 EoE patients were given steroids, of whom 11 (78%) achieved complete histological remission. PPI therapy significantly downregulated eotaxin-3, IL-13 and IL-5 levels in both distal and proximal esophagus in PPI-REE patients in a similar way to that seen in EoE patients after topical steroids.</p><p><bold>CONCLUSION:</bold> PPI-REE is a cytokine-mediated entity, with baseline overexpression of eotaxin-3/Th2 cytokines indistinguishable from EoE. PPI therapy downregulates these molecular markers in PPI-REE patients in a similar way to that seen in EoE after topical steroids.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Eosinophilic esophagitis, Gastroesophageal reflux disease(GERD), proton pump inhibitor</p></sec><sec><title>OP423 PER-ORAL ENDOSCOPIC MYOTOMY (POEM) IN ELDERLY PATIENTS WITH ACHALASIA: PECULIARITIES AND OUTCOME</title><p><bold>H. Sato</bold><sup>1,*</sup>, H. Inoue<sup>1</sup>, H. Ikeda<sup>1</sup>, E. Grace, R. Santi<sup>1</sup>, R. Maselli<sup>1</sup>, A. Yoshida<sup>1</sup>, M. Onimaru<sup>1</sup>, S.-E. Kudo<sup>1</sup></p><p><italic><sup>1</sup>Digestive Disease Center, Showa University, Northern Yokohama Hospital, Yokohama , Japan</italic></p><p><bold>INTRODUCTION:</bold> Peroral endoscopic myotomy (POEM) has been developed as one of the best treatment options for esophageal achalasia. The study aim is to evaluate the efficacy and safety of POEM in elderly patients.</p><p><bold>AIMS&METHODS:</bold> From September 2008 to March 2013, a total of 362 patients (M/F 154/208, mean age 43 years) underwent POEM at Showa University Northern Yokohama Hospital. Patients ≧ 65 years old (n=55) were the intended subjects of this study. Data regarding demographic profile, performance status (PS), type of achalasia (sigmoid or non-sigmoid), previous treatment for achalasia, clinical course, pre- and post-POEM Eckardt score, manometry findings, and treatment outcomes including duration of hospitalization and occurrence of complications were collected and analyzed. POEM was performed following the technique described earlier.</p><p><bold>RESULTS:</bold> A total of 55 patients were included in this study. Mean duration of symptoms was 12.9 years. Twenty-two, 22 (40%) had pneumatic balloon dilation while 2 (3.6%) had Heller’s myotomy prior to POEM. Pre-existing comorbidity particularly cardiovascular disease was seen in 5 (9.1%) of patients. Twelve, 12 (21.8%) were taking anticoagulant medications. Although majority (78.2%) of patients have non-sigmoid type achalasia, sigmoid type was seen in 12 (21.8%) of cases. Evidence of pneumonia was seen on baseline CT scan in 35 (63.6%) which can be attributed to chronic aspiration due to achalasia. Six, 6 (10.9%) patients had PS of 2, however, none have deterioration of PS score after POEM. Mucosal perforation occurred in 2 (3.6%) which was successfully closed by endoscopic clipping. No serious life-threatening complications were encountered.</p><p>A significant reduction in the baseline LES pressure was seen post-operatively (24.8 vs. 14.2 mmHg, p<.001). Significant symptom reduction was achieved in 53 (96.4%) of patients (pre-op Eckardt score 5 vs. post-op Eckardt score 0, p<.001) except in two patients: one with severe submucosal fibrosis precluded complete myotomy, and the other failed to follow-up.</p><p><bold>CONCLUSION:</bold> POEM is effective and safe even for elderly patients, and considered to be positively recommended to the patients with long term history, recurrence or persistence of symptoms after other treatments (i.e. balloon dilatation, botulinum injection, Heller myotomy). Continuing follow up is needed to determine long term outcomes.</p><p><bold>REFERENCES:</bold></p><p>1. Inoue H, Minami H, Kobayashi Y, et al. Peroral endoscopic myotomy (POEM) for esophageal achalasia. Endoscopy. 2010 Apr; 42(4):265-71</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Achalasia, Elderly, Peroral endoscopic myotomy</p></sec><sec><title>OP424 MULTIPLE RAPID SWALLOWING DURING HIGH RESOLUTION MANOMETRY: LOW OR HIGH VOLUME?</title><p><bold>A. Elvevi</bold><sup>1,*</sup>, A. Mauro<sup>1</sup>, D. Pugliese<sup>1</sup>, I. Bravi<sup>1</sup>, D. Conte<sup>1</sup>, R. Penagini<sup>1</sup></p><p><italic><sup>1</sup>Gastrointestinal Unit 2, Università degli Studi and Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico., Milan, Italy</italic></p><p><bold>INTRODUCTION:</bold> Addition of multiple rapid swallowing (MRS) to oesophageal manometry studies has been suggested, in order to further assess oesophageal function. Different MRS protocols have been proposed.</p><p><bold>AIMS&METHODS:</bold> Aim of our study was to compare low and high volume MRS. Fifteen healthy subjects (5 men, 28; 22-31 yrs), 20 consecutive patients with oesophageal symptoms (10 men, 56; 28-73 yrs), all with normal or hypotensive peristalsis and 2 of them having oesophagogastric (OG) junction outflow obstruction (4s IRP >15 mmHg) , and 11 achalasia patients after successful pneumatic dilation (7 men, 59; 54-69 yrs, n= 3 type 1, n= 4 type 2 and n= 4 with restored peristalsis), performed eight 5ml single swallows (SS), two 10ml (low volume) MRS and one 200ml (high volume) MRS. The three groups had similar basal intraoesophageal basal pressure, -4 (-7 to –3), -4 (-8 to –2) and –5 (-8 to –2) mmHg respectively. Analysis during MRS: 1) presence of motor inhibition, i.e. no pressure wave > 20mmHg in the distal oesophageal body. 2) OG pressure gradient in the last 5s of MRS. 3) 4s integrated relaxation pressure of the lower oesophageal sphincter (4s IRP). Analysis after MRS: 1) presence of after contraction, i.e. pressure wave > 20 mmHg in the distal oesophageal body. 2) distal contractile integral (DCI) of the after contraction, expressed as % change of DCI after SS.</p><p><bold>RESULTS:</bold> (median; IQR): see table.
<table-wrap id="table60-2050640613502899" position="float"><label>Table</label><caption><p>OP424</p></caption><table frame="hsides" rules="groups"><thead align="left"><tr><th colspan="2" rowspan="1"></th><th colspan="2" rowspan="1"><bold>Healthy subjects (HS)</bold></th><th colspan="2" rowspan="1"><bold>Symptomatic patients</bold></th><th colspan="2" rowspan="1"><bold>Achalasia patients </bold>§</th></tr></thead><tbody align="left"><tr><td colspan="2" rowspan="1"><bold>MRS Volume</bold></td><td rowspan="1" colspan="1">Low</td><td rowspan="1" colspan="1">High</td><td rowspan="1" colspan="1">Low</td><td rowspan="1" colspan="1">High</td><td rowspan="1" colspan="1">Low</td><td rowspan="1" colspan="1">High</td></tr><tr><td rowspan="3" colspan="1"><bold>During MRS </bold></td><td rowspan="1" colspan="1"><bold>Motor inhibition </bold>(n° of pts)</td><td rowspan="1" colspan="1">14/15</td><td rowspan="1" colspan="1">15/15</td><td rowspan="1" colspan="1">13/20</td><td rowspan="1" colspan="1">13/20</td><td rowspan="1" colspan="1">9/11</td><td rowspan="1" colspan="1">2/11†</td></tr><tr><td rowspan="1" colspan="1"><bold>OG pressure gradient </bold>(mmHg)</td><td rowspan="1" colspan="1">- 0.5;-1.4 to 0.0</td><td rowspan="1" colspan="1">1.0;1.0 to 3.0†</td><td rowspan="1" colspan="1">-3.0;-6.0 to 2.0</td><td rowspan="1" colspan="1">1.0;0.5 to 4.0†</td><td rowspan="1" colspan="1">-0.5;-1.9 to 2.9</td><td rowspan="1" colspan="1">9.0;5.5 to 12†‡</td></tr><tr><td rowspan="1" colspan="1"><bold>4s IRP</bold>(mmHg)</td><td rowspan="1" colspan="1">1.5;0.3 to 2.0</td><td rowspan="1" colspan="1">2.0;0.5 to 2.9</td><td rowspan="1" colspan="1">2.1;-0.6 to 6.1</td><td rowspan="1" colspan="1">0.9;-0.9 to 3.4†</td><td rowspan="1" colspan="1">5.9;3.3 to 7.0*</td><td rowspan="1" colspan="1">5.3;1.4 to 6.3‡</td></tr><tr><td rowspan="2" colspan="1"><bold>After MRS</bold></td><td rowspan="1" colspan="1"><bold>After contraction </bold>(n° of pts)</td><td rowspan="1" colspan="1">15/15</td><td rowspan="1" colspan="1">10/15†</td><td rowspan="1" colspan="1">17/20</td><td rowspan="1" colspan="1">4/20†</td><td rowspan="1" colspan="1">4/4</td><td rowspan="1" colspan="1">2/4</td></tr><tr><td rowspan="1" colspan="1"><bold>Change of DCI with reference to SS </bold>(%)</td><td rowspan="1" colspan="1">96%;15 to 127</td><td rowspan="1" colspan="1">-41%;-100 to 14†</td><td rowspan="1" colspan="1">-7%;-19 to 57*</td><td rowspan="1" colspan="1">-100%;-100 to -25†</td><td rowspan="1" colspan="1">49%;-22 to 136</td><td rowspan="1" colspan="1">-88%;-100 to 305</td></tr></tbody></table></table-wrap></p><p>† p<0.05 vs low volume MRS; * p<0.05 vs HS; ‡ p < 0.01 vs HS and symptomatic patients. § only 4 patients with peristalsis analysed after MRS.</p><p><bold>CONCLUSION:</bold> Both types of MRS evaluate motor inhibition and its alteration in symptomatic patients. Low volume but not high volume MRS evaluates the “motor reserve” of the oesophagus, as assessed by presence and strength of the after contraction. High volume MRS identifies patients with increased resistance to outflow, who markedly increase their OG pressure gradient during high volume MRS only. Both low and high volume MRS should be used in routine clinical practice.</p><p><bold>Contact E-mail Address:</bold><email>alessandra.elvevi@policlinico.mi.it</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Achalasia, High resolution manometry, Multiple rapid swallowing, Oesophageal motility</p></sec><sec><title>OP425 HIGH-RESOLUTION ESOPHAGEAL MANOMETRY: CHICAGO CLASSIFICATION… MADE RIDICULOUSLY SIMPLE</title><p><bold>M. Herzig</bold><sup>1,*</sup>, R. Tutuian<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology and Hepatology, Universitiy clinic for visceral surgery and medicine, Inselspital, Bern, Bern, Switzerland</italic></p><p><bold>INTRODUCTION:</bold> High-resolution manometry (HRM) is currently the gold standard in evaluating esophageal motility. The most recently proposed HRM classification system (Chicago classification) incorporates novel metrics and defines achalasia (including 3 subtypes), esophago-gastric junction (EGJ) outflow obstruction, motility disoders (including spasm, jackhammer esophagus and absent peristalsis) and peristaltic abnormalities (including rapid contractions, hypertensive peristalsis, weak peristalsis with large/small breaks and frequent failed peristalsis) making normal motility a finding of exclusion. While widely promoted, the advantages of the Chicago over the conventional classification (Spechler and Castell in 2001) haven’t been systematically analyzed.</p><p><bold>AIMS&METHODS:</bold> The aims of the study were to evaluate how conventional manometric findings “translate” into the Chicago classification and present a simplified understanding on the HRM classification system.</p><p>In a retrospective analysis of prospectively collected data at our institution from 03/2009 to 05/2012 we classified each manometry recording according to the conventional manometric criteria (Spechler & Castell Gut 2001) and HRM criteria (Bredenoord et al NGM 2012). We excluded patients who underwent previous treatments in the region of the EGJ (i.e. fundoplication, bariatric surgery, pneumatic dilatation, myotomies) and recordings with less than 7 evaluable swallows.</p><p><bold>RESULTS:</bold> Of 629 investigations 524 (83%) fulfilled inclusion/exclusion criteria. Of 49 patients with achalasia by conventional criteria 13 (26%) fulfilled the HRM criteria for achalasia, 22 (45%) for aperistalsis (IRP <15mmHg), and 14 (29%) for esophageal spasms (IRP <15mmHg). Of 146 patients with normal conventional manometry 2 (1%) had hypertensive peristalsis, 16 (11%) small peristaltic breaks and 128 (88%) normal manometry by HRM criteria.</p><p><bold>CONCLUSION:</bold> Diagnosis of achalasia should be made primarily on failed peristalsis, setting a cut-off for IRP may lead to missing the diagnosis in some patients. The agreement between the two classification systems regarding normal manometry is very high. Grouping motility abnormalities as low amplitude, high amplitude and discoordinated peristalsis may help make the HRM classification system easier to use in clinical practice.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Classification model, esophageal motility disorders </p></sec><sec><title>OP426 THE RESPONSE TO MULTIPLE RAPID SWALLOWS DURING HIGH-RESOLUTION MANOMETRY PREDICTS OESOPHAGEAL EMPTYING IN ACHALASIA PATIENTS</title><p><bold>F. A. M. Ponds</bold><sup>1,*</sup>, A. J. Smout<sup>1</sup>, A. J. Bredenoord<sup>1</sup></p><p><italic><sup>1</sup>Department of Gastroenterology and Hepatology, Academic Medical Centre Amsterdam, Amsterdam, Netherlands</italic></p><p><bold>INTRODUCTION:</bold> The timed barium oesophagography makes it possible to measure oesophageal emptying in achalasia patients, which is considered to be a relevant parameter in the management of these patients. However, it exposes patients to ionizing radiation. It has been suggested that the incorporation of multiple rapid swallows (MRS) during high-resolution manometry (HRM) may serve as an additional oesophageal function test.</p><p><bold>AIMS&METHODS:</bold> The aim of our study was to investigate whether the response to MRS can predict oesophageal emptying in achalasia patients. 18 treated and 10 untreated patients (14 males; mean age 45.4 ± 2.7) with achalasia underwent HRM in supine position. After 10 regular wet swallows MRS was performed by rapidly drinking 200 ml of water with a straw. All patients subsequently underwent a timed barium oesophagography with radiographs taken at 0, 1, 2 and 5 minutes after drinking 200 ml of barium in upright position. The response to MRS was evaluated by measuring the oesophageal body pressurization during the last 5 seconds of the MRS.</p><p><bold>RESULTS:</bold> Achalasia type I was observed in 12 patients (42.9%), achalasia type II in another 12 patients (42.9%) and 4 patients were classified as achalasia type III (13.4%). The IRP during regular wet swallows was 17.2 mmHg (9.7- 28.3) (median (IQR)) and baseline LOS pressure was 14.5 mmHg (8.5-26.7). The barium height at 5 minutes was 2.4 cm (0-5.7). The median oesophageal body pressurization during MRS was 22.5 mmHg (11.8-32.5). Oesophageal body pressurization was correlated with oesophageal emptying on timed barium oesophagography at all time points (T0: r=0.495; P <.01, T1: r=0.541; P <.01, T2: r=0.543; P <.01, T5: r=0.681; P <.01) and also with the IRP during regular wet swallows (r=0.784; P <.01). A weak correlation between the oesophageal body pressurization and the maximum width of the oesophagus during timed barium oesophagography was found (r=0.389; P <.05). Oesophageal body pressurization was significantly higher in type II achalasia compared to subtype I (28.5 (16.8-40.3) vs 15.5 (11-20.8) mmHg, P <.05) and higher in the untreated patients compared to the treated patients (34 (25-50) vs 15.5 (10.8-24.3) mmHg, P <.05). Of the treated patients, 5 were asymptomatic. The oesophageal body pressurization of these patients was substantially lower (14 (9-15.5) mmHg) compared to untreated patients (34 (25-50) mmHg) and symptomatic treated patients (20 (11-25) mmHg).</p><p><bold>CONCLUSION:</bold> The response to MRS correlates very well with oesophageal emptying as measured with a timed barium oesophagography and provides additional information to regular HRM. We propose to add this simple and inexpensive test to each HRM procedure in achalasia patients.</p><p><bold>Contact E-mail Address:</bold><email>f.a.ponds@amc.uva.nl</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Achalasia, High-resolution manometry, Multiple rapid swallows, Oesophageal emptying, Timed barium oesophagography </p></sec><sec><title></title><p><bold>WEDNESDAY, OCTOBER 16, 2013 11:00-12:30</bold></p><p><bold>Capsule endoscopy: From mouth to anus – Hall 10</bold></p></sec><sec><title>OP427 RISK FACTORS FOR SMALL BOWEL MUCOSAL BREAKS IN LOW-DOSE ASPIRIN USERS: DATA FROM A PROSPECTIVE MULTICENTER REGISTRY</title><p><bold>H. Endo</bold><sup>1</sup>, E. Sakai<sup>1,*</sup>, R. Taniguchi<sup>2</sup>, T. Kessoku<sup>3</sup>, A. Ezuka<sup>4</sup>, H. Kawamura<sup>5</sup>, T. Higurashi<sup>1</sup>, H. Ohkubo<sup>1</sup>, E. Yamada<sup>1</sup>, H. Takahashi<sup>1</sup>, T. Sakaguchi<sup>3</sup>, Y. Hata<sup>2</sup>, H. Nagase<sup>4</sup>, A. Nakajima<sup>1</sup></p><p><italic><sup>1</sup>Yokohama City University Hospital, Yokohama, <sup>2</sup>Chigasaki Municipal Hospital, Chigasaki, <sup>3</sup>Hiratsuka City Hospital, Hiratsuka, <sup>4</sup>Yokohama Rosai Hospital, Yokohama, <sup>5</sup>Odawara Municipal Hospital, Odawara, Japan</italic></p><p><bold>INTRODUCTION:</bold> Identification of the risk factors is important for developing appropriate management strategies to prevent gastrointestinal injury in patients taking low-dose aspirin. However, few studies have reported on the risk factors for small bowel injury among low-dose aspirin users.</p><p><bold>AIMS&METHODS:</bold> Our aim was to evaluate the risk factors for small bowel mucosal breaks in chronic low-dose aspirin users. Capsule endoscopy data were collected prospectively. A total of 156 low-dose aspirin users who underwent capsule endoscopy were enrolled in this study from five institutions. Any identified small bowel mucosal breaks were classified into erosions or ulcers. Risk factors for erosions and ulcers were assessed using logistic regression analysis.</p><p><bold>RESULTS:</bold> Data of 152 patients (104 males and 48 females; mean age 70.9 years) were included in the analysis. Of these patients, there were 94 (61.8%) patients with at least 1 erosion, and 42 (27.6%) patients with at least 1 ulcer. Univariate analysis identified only one factor associated with the presence of small bowel erosions, namely, the use of thienopyridine (<italic>P</italic>=0.01), whereas both use of enteric-coated aspirin (<italic>P</italic>=0.04) and PPI (<italic>P</italic>=0.001) were identified as significant risk factors for the presence of small bowel ulcers. Multivariate analysis identified PPI (odds ratio 3.48; 95% confidence interval, 1.50-8.09, <italic>P</italic>=0.04) as an independent risk factor for the presence of ulcers.</p><p><bold>CONCLUSION:</bold> PPI use can exacerbate the small bowel injury in chronic low-dose aspirin users. It is necessary for clinicians to recognize this dilemma of PPI therapy, and novel means for the treatment of aspirin-induced gastroenteropathy are urgently needed.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> capsule endoscopy, low-dose aspirin, small bowel ulcerative lesions</p></sec><sec><title>OP428 ASSESSMENT OF SMALL BOWEL POLYPS IN PEUTZ-JEGHERS SYNDROME: SHOULD MR ENTEROGRAPHY BE THE FIRST LINE SURVEILLANCE MODALITY RATHER THAN CAPSULE ENDOSCOPY?</title><p><bold>R. Rameshshanker</bold><sup>1,*</sup>, A. O'Rourke<sup>1</sup>, J. Butcher<sup>1</sup>, R. Phillips<sup>2</sup>, S. Clark<sup>2</sup>, C. Fraser<sup>1</sup></p><p><italic><sup>1</sup>Wolfson Endoscopy Unit, <sup>2</sup>Polyposis registry, St Mark's Hospital, Harrow, United Kingdom</italic></p><p><bold>INTRODUCTION:</bold> Peutz-Jeghers syndrome (PJS) causes multiple hamartomatous polyp formation throughout the gastrointestinal tract. Large polyps within the small bowel (SB) may cause complications and morbidity including obstruction, bleeding, an increased risk of cancer and post surgical adhesional disease. Regular surveillance and removal of large polyps are important to prevent complications from occurring.</p><p><bold>AIMS&METHODS:</bold> The aim of our study was to assess the utility of SB capsule endoscopy (SBCE) compared with MR enterography (MRE) for the detection of small bowel PJS polyps.</p><p>We performed a retrospective review of all adult PJS patients under the care of the St Mark’s Polyposis Registry between 2006-2012. Participants’ MRE and SBCE findings, enteroscopy reports and case notes were reviewed. Polyps >10mm were regarded as clinically relevant. Large polyps (>15mm) resected at push enteroscopy (PE), double balloon enteroscopy (DBE) or intraoperative enteroscopy (IOE) were correlated in terms of size, location, number and need for resection with both MRE and SBCE findings.</p><p><bold>RESULTS:</bold> 83 patients (median age 38yrs, 60% female) were included. SBCE was performed in 76 patients, either alone (n=29) or prior to MRE (n=47). Reasons for MRE post SBCE were: previous study involvement (n=19), post-polypectomy reassessment (n=10), persistent symptoms (n=9) and confirmation of significant polyp findings (n=9). MRE was performed in 54 patients, either alone (n=7) or with SBCE (n=47). There was no significant difference between patients in whom >10mm polyps were detected (40 vs. 43 for SBCE and MRE, respectively; <italic>p</italic> = 0.52). In 6 patients, large polyps (>15mm) not detected at SBCE, were identified at MRE. Endoscopic removal of large polyps was performed in 36 patients. 18 patients did not require polypectomy. DBE’s were incomplete due to failure of deep intubation in 7 patients (19%) but 4 of these patients subsequently underwent laparoscopic assisted DBE and successful polypectomy. Concordance with DBE findings for polyp size for SBCE vs. MRE was 61% and 79%, respectively (p=0.18). Concordance with DBE findings for polyp location for SBCE vs. MRE was 79% and 92%, respectively (p=0.76).</p><p><bold>CONCLUSION:</bold> MRE appears at least as effective as the current iteration of SBCE for small-bowel polyp surveillance in adults with PJS. MRE may be less prone to missing large polyps and more accurate in polyp size assessment and localisation and in post -polypectomy reassessment of the SB.</p><p><bold>Contact E-mail Address:</bold><email>rameshshan777@yahoo.co.uk</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Capsule Endoscopy, MR enterography, Peutz-Jeghers Syndrome</p></sec><sec><title>OP429 PROSPECTIVE RANDOMIZED COMPARISON BETWEEN AXIAL AND LATERAL VIEWING CAPSULE ENDOSCOPY SYSTEMS IN PATIENTS WITH OBSCURE DIGESTIVE BLEEDING.</title><p><bold>M. Pioche</bold><sup>1,*</sup> on behalf of SFED, , G. Vanbiervliet<sup>2</sup> on behalf of SFED, , P. Jacob<sup>3</sup>, C. Duburque<sup>4</sup> on behalf of SFED, , R. Gincul<sup>5</sup> on behalf of SFED, , B. Filoche<sup>4</sup> on behalf of SFED, , J. Daudet<sup>3</sup> on behalf of SFED, , J. Filippi<sup>2</sup> on behalf of SFED, , J.-C. Saurin<sup>5</sup> on behalf of SFED and Société Française d'endoscopie digestive (SFED)</p><p><italic><sup>1</sup>Endoscopy, Hôpital Edouard Herriot, Lyon, <sup>2</sup>Gastroenterology, Hôpital de L'archet 2, Nice, <sup>3</sup>Gastroenterology, Polyclinique du Grand Sud, Nîmes, <sup>4</sup>Gastroenterology, Hôpital Saint-Philibert, Lille, <sup>5</sup>Gastroenterology, Hôpital Edouard Herriot, Lyon, France</italic></p><p><bold>INTRODUCTION:</bold> Videocapsule is recommended as the first exploration in obscure digestive bleeding. Given Pillcam SB2Ò efficiency is widely reported. The CapsovisionÒ capsule, with four cameras all around, allows to explore small bowel with a 360 degrees lateral viewing. This system does not include a recording system so the capsule has to be returned by the patient after expulsion to download the film.</p><p><bold>AIMS&METHODS:</bold> To evaluate diagnostic concordance (kappa value) between PillCam SB2â and Capsovisionâ capsules performed in the same patients. Prospective comparative study in 4 french reference endoscopy units. 73 consecutive patients ingested at 1 hour interval the two capsules in randomized order.</p><p><bold>RESULTS:</bold> There were 13 technical issues (11 CapsovisionÒ, 2 PillCam SB2Ò). Among the 60 patients analysable, a concordant positive and negative diagnosis was obtained in 23 (38.3%) and 27 patients (45.0%) respectively. Concordance was good with a k value of 0.63 in analysable patients, with 46.7% diagnosis with CapsoCam® versus 48.3% with PillCam® SB2Ò. Capsovision® and Pillcam SB2® procedures identified 81.8 % (27/33) and 84.8% (28/33) of positive patients respectively with no significant difference (p = 0.791). In a per lesion analysis, Capsovision® capsule detected significantly more lesions (108 vs 85 lesions, p=0.001). Reading time was longer in Capsovisionâ procedures with 32.0 versus 26.2 min with PillCam SB2® (p=0.002).</p><p><bold>CONCLUSION:</bold> This study shows comparable efficiency of the Capsovision® and PillCam SB2® capsule system regarding the diagnostic yield and image quality.</p><p><bold>Contact E-mail Address:</bold><email>mathieu.pioche@chu-lyon.fr</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> capsule endoscopy, Small Bowel</p></sec><sec><title>OP430 WHY SHOULD WE STILL USE CAPSULE ENDOSCOPY IN INFLAMMATORY BOWEL DISEASES?</title><p><bold>L. Marquez</bold><sup>1,*</sup>, À. Cañas<sup>1</sup>, S. Bacchiddu<sup>1</sup>, A. Peláez<sup>2</sup>, J. M. Dedeu<sup>3</sup>, M. A. Álvarez<sup>3</sup>, I. Ordás<sup>2</sup>, E. Ricart<sup>2</sup>, A. Jauregui<sup>2</sup>, A. Ramirez<sup>2</sup>, J. Llach<sup>2</sup>, J. Panés<sup>2</sup>, M. Andreu<sup>1</sup>, B. González<sup>2</sup></p><p><italic><sup>1</sup>Digestive Department. Gastroenterology Unit., Hospital del Mar, <sup>2</sup>Gastroenterology Department. Endoscopy Unit, Hospital Clinic, <sup>3</sup>Digestive Department. Endoscopy Unit., Hospital del Mar, Barcelona, Spain</italic></p><p><bold>INTRODUCTION:</bold> Capsule endoscopy (CE) has been described as a useful tool in the diagnosis of patients with inflammatory bowel diseases (IBD).</p><p><bold>AIMS&METHODS:</bold> To analyze the impact of CE on the diagnosis and management of suspected or established IBD.</p><p>We included patients referred to Hospital del Mar and Hospital Clinic (Barcelona, Spain) between 2007 and 2012 for a CE, because of (group A)suspected IBD according to ICCE criteria or (group B) established IBD presenting new symptoms or for initial extension assessment. For group B, Harvey-Bradshaw activity index (H-B), CRP and VSG were recorded, and CE findings were described using Lewis score and CECDAI. New explorations and therapy changes motivated by CE findings were analyzed, as well as correlation between endoscopic indexes, H-B and CRP/VSG (Spearman correlation, Mann-Withney and Kruskall Wallis tests).</p><p><bold>RESULTS:</bold> 262 CE were performed in 242 patients (median age of diagnosis 31 yrs, 61.5% females). 11 CE were excluded for incomplete register or poor bowel cleaning. Group A included 63 cases and group B 188 cases (157 Crohn’s disease (CD) and 31 ulcerative colitis (UC)). Overall, CE findings lead to a new diagnose in 42.9% cases: 38.1% in group A (21 CD, 3 other diagnostics) and 4.8% in group B (9 CD, all patients with a previous diagnose of UC). In group B in 30.3% cases a new extension of CD was described according to Montreal classification:mainly L1+L4 (26), L3+L4 (10), L2+L4 (5) and L3 (8).</p><p>In both groups, CE results indicated new explorations in 26% cases: 11 colonoscopies, 11 MRI and 9 enteroscopies.</p><p>Regarding new treatments, in group A new treatments were started in 33.9% cases (7 cases 5-ASA, 4 systemic steroids, 5 local steroids, 2 azathioprine, 1 anti-TNF, 1 stop previous treatment); in group B a switch in treatment was performed in 40.4% cases (2 5-ASA, 17 systemic steroids, 25 azathioprine, 3 methotrexate, 18 antiTNF, 13 stop previous treatments).</p><p>Both capsule scores showed a good correlation coefficient (0.944, p<0.001).There were no statistically significant correlations between CE indexes and H-B, VSG and PCR values. Lewis score seems to have a better correlation with H-B when referring to mild symptoms (p 0.33).</p><p><bold>CONCLUSION:</bold> CE is a useful tool not only to diagnose new IBD cases, but also to optimize treatments in a significant group of IBD patients. As previously reported, new CE score indexes have not a good correlation with clinical and analytical data.</p><p><bold>Contact E-mail Address:</bold><email>lmarquez@parcdesalutmar.cat</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Capsule endoscopy, inflammatory bowel disease</p></sec><sec><title>OP431 COLON CAPSULE ENDOSCOPY VERSUS CT-COLONOGRAPHY IN THE EVALUATION OF PATIENTS WITH INCOMPLETE TRADITIONAL COLONOSCOPY: A PROSPECTIVE COMPARATIVE TRIAL</title><p><bold>C. Spada</bold><sup>1,*</sup>, C. Hassan<sup>1</sup>, B. Barbaro<sup>2</sup>, F. Iafrate<sup>3</sup>, P. Cesaro<sup>1</sup>, L. Petruzziello<sup>1</sup>, L. Minelli Grazioli<sup>1</sup>, M. Iannitti<sup>3</sup>, M. Salsano<sup>2</sup>, G. Alvaro<sup>2</sup>, A. Laghi<sup>3</sup>, L. Bonomo<sup>2</sup>, G. Costamagna<sup>1</sup></p><p><italic><sup>1</sup>Digestive Endoscopy Unit, <sup>2</sup>Radiology, Catholic University, <sup>3</sup>Radiology, Università La Sapienza, Rome, Italy</italic></p><p><bold>INTRODUCTION:</bold> Optical Colonoscopy (OC) may be incomplete in 4-25% of patients (pts). In such cases, complementary tests (CT-Colonography [CTC], barium enema, colonoscopy using different endoscopes or sedation) are indicated to complete colonic inspection. Colon-Capsule-Endoscopy (CCE) (PillCam Colon, Given Imaging, Israel) was shown to be feasible to complement incomplete OC.</p><p><bold>AIMS&METHODS:</bold> Aims: to compare CCE and CTC completeness and accuracy in pts with incomplete OC. In this prospective, blinded trial were enrolled pts aged 18-75 yrs referred for OC as indicated for any reason, in which OC was incomplete. Pts underwent CCE and CTC on the same day following the standard regimen of prep for CCE with inclusion of sodium-amidotrizoate and meglumine-amidotrizoate (Gastrografin, Bayer). CTC was performed after CCE excretion or latest 10-12 hrs post ingestion. CCE and CTC were defined complete when they visualized colonic segments not explored by OC. To evaluate the incremental value of CCE and CTC, efficacy analysis was performed considering significant findings (polyps/masses≥6mm) in segments not visualized at 1st OC. In case of significant findings and/or discrepancies a 2nd OC (gold standard) was performed.</p><p><bold>RESULTS:</bold> 100 pts (34M) were enrolled. 2 pts refused CTC because of air insufflation and were excluded from efficacy analysis. CCE and CTC were able to complete colonic evaluation in 98% of pts. CCE and/or CTC detected at least a significant finding in 20 pts. In detail, in 6 pts at least a polyp≥6mm was detected by both CCE and CTC and confirmed by second OC. In 13 pts, CCE only detected at least a polyp≥6mm confirmed by second OC in 12. In 1 pt a polyp≥6mm was detected by CTC only and not found during second OC. Significant difference was found between yield of the 2 modalities for polyps≥6mm (p≤0.029). Accuracy for polyps ≥6mm and ≥10mm is reported in Table.
<table-wrap id="table61-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1"></th><th rowspan="1" colspan="1"></th><th rowspan="1" colspan="1">CCE</th><th rowspan="1" colspan="1">CTC</th></tr></thead><tbody align="left"><tr><td rowspan="4" colspan="1">Polyps≥6mm</td><td rowspan="1" colspan="1">Sensitivity (%)</td><td rowspan="1" colspan="1">100 (CI 86-100)</td><td rowspan="1" colspan="1">35 (CI 19-41)</td></tr><tr><td rowspan="1" colspan="1">Specificity (%)</td><td rowspan="1" colspan="1">91 (CI 67-91)</td><td rowspan="1" colspan="1">92 (CI 71-100)</td></tr><tr><td rowspan="1" colspan="1">PPV (%)</td><td rowspan="1" colspan="1">95 (CI 82-95)</td><td rowspan="1" colspan="1">86 (CI 46-99)</td></tr><tr><td rowspan="1" colspan="1">NPV (%)</td><td rowspan="1" colspan="1">100 (74-100)</td><td rowspan="1" colspan="1">52 (40-56)</td></tr><tr><td rowspan="4" colspan="1">Polyps≥10 mm</td><td rowspan="1" colspan="1">Sensitivity (%)</td><td rowspan="1" colspan="1">100 (CI 60-100)</td><td rowspan="1" colspan="1">67 (CI 30-67)</td></tr><tr><td rowspan="1" colspan="1">Specificity (%)</td><td rowspan="1" colspan="1">96 (CI 86-96)</td><td rowspan="1" colspan="1">100 (CI 91-100)</td></tr><tr><td rowspan="1" colspan="1">PPV (%)</td><td rowspan="1" colspan="1">86 (CI 51-86)</td><td rowspan="1" colspan="1">100 (44-100)</td></tr><tr><td rowspan="1" colspan="1">NPV (%)</td><td rowspan="1" colspan="1">100 (89-100)</td><td rowspan="1" colspan="1">92 (CI 84-92)</td></tr></tbody></table></table-wrap></p><p>CCE cleansing was adequate in 83% of pts. CTC procedure was adequate in 88% of pts.</p><p><bold>CONCLUSION:</bold> Results of the present study suggest that both CCE and CTC are effective to complete incomplete OC, but CCE diagnostic yield is significantly higher than CTC for significant polyps.</p><p><bold>Contact E-mail Address:</bold><email>cristianospada@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: C. Spada Lecture fee(s) from: Given Imaging, Consultancy for: Given Imaging, C. Hassan Lecture fee(s) from: Given Imaging, Consultancy for: Given Imaging, B. Barbaro: None Declared, F. Iafrate: None Declared, P. Cesaro: None Declared, L. Petruzziello: None Declared, L. Minelli Grazioli: None Declared, M. Iannitti: None Declared, M. Salsano: None Declared, G. Alvaro: None Declared, A. Laghi: None Declared, L. Bonomo: None Declared, G. Costamagna Financial support for research from: Given Imaging, Lecture fee(s) from: Given Imaging, Consultancy for: Given Imaging</p><p><bold>Keywords:</bold> colon capsule endoscopy, CT-colonography, Incomplete colonoscopy</p></sec><sec><title>OP432 FLAT COLORECTAL LESIONS AT PILLCAM COLON CAPSULE ENDOSCOPY</title><p><bold>C. Spada</bold><sup>1,*</sup>, C. Hassan<sup>1</sup>, S. Adler<sup>2</sup>, P. Cesaro<sup>1</sup>, L. Petruzziello<sup>1</sup>, L. Minelli Grazioli<sup>1</sup>, G. Costamagna<sup>1</sup></p><p><italic><sup>1</sup>Digestive Endoscopy Unit, Catholic University, Rome, Italy, <sup>2</sup>Division of Gastroenterology, Bikur Holim Hospital, Jerusalem, Israel</italic></p><p><bold>INTRODUCTION:</bold> flat lesions have gained special attention because they were noted to have a higher risk of being cancerous than polypoid lesions. Studies performed in Western populations indicate a prevalence ranging between 5% and 25%. These lesions in some circumstances are difficult to detect and may be easily missed at optical colonoscopy (OC). Colon Capsule Endoscopy (CCE) was proven to be accurate to detect significant findings (i.e. polyps ≥6mm) with a sensitivity and specificity for polyps ≥10mm of 88% and 89-95%, respectively. The ability of CCE to detect flat colonic lesions is unknown since no specific studies in this setting are available.</p><p><bold>AIMS&METHODS:</bold> Aim of this study was to primarily evaluate the ability of CCE in diagnosing flat colonic lesions. This is a retrospective evaluation of patients enrolled in prospective comparative trials that used the OC as gold standard. Patients underwent CCE following the standard regimen of preparation for CCE. OC was performed after CCE excretion or, latest, in the following days. Paris classification was adopted to classify polyps for both OC and CCE. Accuracy (i.e. sensitivity and specificity) was assessed for CCE, considering the OC as gold standard.</p><p><bold>RESULTS:</bold> 27 polyps ≥6mm were detected by OC in 16 pts (11F, mean age 63,5 yrs). According to Paris classification, 15 out of 27 polyps (55,5%) were classified as IIA lesions (i.e. non-polypoid-superficial, elevated lesions). 12 out of 27 polyps (44,5%) were classified as IS lesions (i.e. polypoid-protruded, sessile lesions). Twenty-five polyps were detected by CCE. According to Paris classification, 24 out of 25 polyps (96%) were classified as polypoid lesions and 1 (4%) as non-polypoid lesion. CCE failed to detect 3 lesions (2 IIA and 1 IS lesions). In one patient CCE visualized an 11 mm flat lesion that was not confirmed by OC. Interestingly, all the non-polypoid-superficial-elevated lesions (IIA) detected by OC, were classified as polypoid-protruded-sessile lesions by CCE. Per-polyp sensitivity and specificity of CCE for flat lesions were 90% and 96%, respectively.</p><p><bold>CONCLUSION:</bold> Preliminary results suggest that CCE can detect flat lesions with high accuracy. Paris classification does not seem applicable to CCE, since non-polypoid lesions detected by OC usually look like protruding lesions by CCE.</p><p><bold>Contact E-mail Address:</bold><email>cristianospada@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: C. Spada Lecture fee(s) from: Given Imaging, Consultancy for: Given Imaging, C. Hassan Lecture fee(s) from: Given Imaging, Consultancy for: Given Imaging, S. Adler Lecture fee(s) from: Given Imaging, Consultancy for: Given Imaging, P. Cesaro: None Declared, L. Petruzziello: None Declared, L. Minelli Grazioli: None Declared, G. Costamagna Financial support for research from: Given Imaging, Lecture fee(s) from: Given Imaging, Consultancy for: Given Imaging</p><p><bold>Keywords:</bold> colon capsule endoscopy, Flat colonic lesion </p></sec><sec><title></title><p><bold>WEDNESDAY, OCTOBER 16, 2013 11:00-12:30</bold></p><p><bold>Management issues in pancreatic and biliary cancers – Hall 8</bold></p></sec><sec><title>OP433 PREOPERATIVE CHARACTERISTICS OF PATIENTS WITH PRESUMED PANCREATIC CANCER BUT ULTIMATELY BENIGN DISEASE: A MULTICENTER SERIES OF 344 PANCREATODUODENECTOMIES</title><p><bold>A. Gerritsen</bold><sup>1,2,*</sup>, I. Q. Molenaar<sup>1</sup>, T. L. Bollen<sup>3</sup>, C. Y. Nio<sup>4</sup>, M. G. Dijkgraaf<sup>5</sup>, H. C. van Santvoort<sup>1</sup>, G. J. Offerhaus<sup>6</sup>, E. Sieders<sup>7</sup>, K. P. de Jong<sup>7</sup>, R. M. van Dam<sup>8</sup>, E. van der Harst<sup>9</sup>, H. van Goor<sup>10</sup>, B. van Ramshorst<sup>11</sup>, B. A. Bonsing<sup>12</sup>, I. H. de Hingh<sup>13</sup>, M. F. Gerhards<sup>14</sup>, C. H. van Eijck<sup>15</sup>, D. J. Gouma<sup>2</sup>, I. H. Borel Rinkes<sup>1</sup>, O. R. Busch<sup>2</sup>, M. G. Besselink<sup>2</sup> and the Dutch Pancreatic Cancer Group</p><p><italic><sup>1</sup>Surgery, UMC, Utrecht, <sup>2</sup>Surgery, AMC, Amsterdam, <sup>3</sup>Radiology, St Antonius Hospital , Nieuwegein, <sup>4</sup>Radiology, <sup>5</sup>Biostatistics and Clinical Epidemiology, AMC, Amsterdam, <sup>6</sup>Pathology, UMC, Utrecht, <sup>7</sup>Surgery, UMCG, Groningen, <sup>8</sup>Surgery, MUMC, Maastricht, <sup>9</sup>Surgery, Maasstad Ziekenhuis, Rotterdam, <sup>10</sup>Surgery, UMC St Radboud, Nijmegen, <sup>11</sup>Surgery, St Antonius Hospital, Nieuwegein, <sup>12</sup>Surgery, LUMC, Leiden, <sup>13</sup>Surgery, Catherina Hospital, Eindhoven, <sup>14</sup>Surgery, OLVG, Amsterdam, <sup>15</sup>Surgery, Erasmus MC, Rotterdam, Netherlands</italic></p><p><bold>INTRODUCTION:</bold> Differentiation between malignant and benign pancreatic tumours can be difficult. Consequently, a proportion of patients undergoing pancreatoduodenectomy for suspected malignancy will ultimately have benign disease. A predictive model might prevent unnecessary pancreatoduodenectomies in a subgroup of these patients.</p><p><bold>AIMS&METHODS:</bold> To compare preoperative clinical and imaging characteristics of patients with unexpected benign pathology after pancreatoduodenectomy with those of patients with confirmed (pre)malignant disease.</p><p>We performed a multicenter retrospective cohort study in 1629 consecutive patients undergoing pancreatoduodenectomy for suspected malignancy between 2003 and 2010. Preoperative characteristics were compared in a 1:3 benign: malignant ratio. Malignant cases were randomly selected from the entire cohort. A multivariable logistic regression prediction model was constructed to predict benign disease.</p><p><bold>RESULTS:</bold> 107 patients (6.7%) had unexpected benign disease after pancreatoduodenectomy. 86 fulfilled the inclusion criteria and were compared to 258 patients with (pre)malignant disease. Patients with benign disease presented less frequently with jaundice (60% vs. 80%, P<0.01), pancreatic mass (54% vs. 70%, P=0.03), double duct sign on CT (27% vs. 52%, P=0.01) or EUS (22% vs. 51%, P=0.02), but more often with pain (56% vs. 38%, P=0.04). In a prediction model using these clinical and CT parameters, only 27% of patients with benign disease were correctly predicted and 6% of patients with malignant disease were missed.</p><p><bold>CONCLUSION:</bold> Nearly 7% of patients undergoing pancreatoduodenectomy for suspected malignancy were ultimately diagnosed with benign disease. Although some preoperative clinical and imaging signs might indicate absence of malignancy, their discriminatory value is not sufficient for clinical use.</p><p><bold>Contact E-mail Address:</bold><email>a.gerritsen@pancreasparel.nl</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> clinical characteristics, Computed tomography, EUS, Pancreatic Cancer, pancreatitis, pancreatoduodenectomy</p></sec><sec><title>OP434 THE DIAGNOSTIC VALUE OF ABDOMINAL DRAINAGE IN THE INDIVIDUAL RISK ASSESSMENT OF PANCREATIC FISTULA FOLLOWING PANCREATICODUODENECTOMY</title><p><bold>C. Ansorge</bold><sup>1,*</sup>, E. Rangelova<sup>1</sup>, J. Blomberg<sup>1</sup>, M. del Chiaro<sup>1</sup>, L. Lundell<sup>1</sup>, R. Segersvärd<sup>1</sup></p><p><italic><sup>1</sup>Department of Surgical Gastroenterology, Karolinska University Hospital, Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden</italic></p><p><bold>INTRODUCTION:</bold> Pancreaticoduodenectomy (PD) remains the conceptual fundament for curative-intent treatment of malignant diseases confined to the pancreatic head, distal bile duct and periampullary region of the duodenum. Due to uncertain therapeutic value, the use of prophylactic abdominal drainage following PD is controversial (1). However, the diagnosis of postoperative pancreatic fistula (POPF), the predominate cause of PD-associated morbidity, is based on amylase levels in drain output according to the ISGPF definition (2). The aim of the present study was to assess the POPF-predictive value of drain pancreatic amylase (DPA), plasma pancreatic amylase (PPA) and serum C-reactive protein (CRP) in a POPF-risk stratified PD cohort.</p><p><bold>AIMS&METHODS:</bold> Prospective cohort study of 315 standardized PDs with prophylactic drainage 2008-2012. DPA, PPA and CRP were obtained daily. Differences between the study groups with clinically-relevant POPF (ISGPF-B/C) and without (non-POPF/ISGPF-A) were evaluated. ROC analyses were performed for the POPF-predictive values of DPA, PPA and CRP. Risk profiles for clinically-relevant POPF were constituted and related to the intraoperative pancreatic risk assessmen (i.e. the assessment of pancreatic texture and main duct diameter, 3).</p><p><bold>RESULTS:</bold> Fifty-nine patients (19%) had clinically-relevant POPF. CRP, PPA and DPA levels for postoperative day (POD) 1-3 differed significantly between the study groups. The POPF-predictive value of DPA (POD 1: 1322 U/L; OR 25; POD 2: 314 U/L, OR 35) was superior to that of PPA (OR 14/16), especially when combined with CRP (POD 3: 202 mg/L; OR 17). A model of DPA and CRP predicted 90% of the cases correctly (OR 44). Patients with intra-operatively classified low-risk glands had negligible POPF-risks (specificity 99%, OR 65).</p><p><bold>CONCLUSION:</bold> The intraoperative pancreatic risk assessment represents a mandatory component of the PD procedure and offers a platform for reliably predicting the risk of developing postoperative pancreatic fistula. In patients with low POPF risk, the use of prophylactic abdominal drainage does not offer any additional diagnostic value. In patients with intermediate or high POPF risks, a diagnostic model based on cut-off levels of serum C-reactive protein and drain pancreatic amylase could serve as a predictive marker for the subsequent development of clinically relevant pancreatic fistula formation.</p><p><bold>REFERENCES:</bold></p><p>1. Correa-Gallego C, Brennan MF, D'Angelica M, et al. Operative Drainage Following Pancreatic Resection: Analysis of 1122 Patients Resected Over 5 Years at a Single Institution. Ann Surg 2013.</p><p>2. Bassi C, Dervenis C, Butturini G, et al. Postoperative pancreatic fistula: an international study group (ISGPF) definition. Surgery 2005; 138(1):8-13.</p><p>3. Ansorge C, Strommer L, Andren-Sandberg A, et al. Structured intraoperative assessment of pancreatic gland characteristics in predicting complications after pancreaticoduodenectomy. The British journal of surgery 2012; 99(8):1076-82.</p><p><bold>Contact E-mail Address:</bold><email>christoph.ansorge@karolinska.se</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> drain output, pancreatic amylase, pancreaticoduodenectomy, postoperative complications</p></sec><sec><title>OP435 INFLUENCE OF MICROSCOPICALLY POSITIVE RESECTION MARGINS ON ≥5-YEAR SURVIVAL AFTER RESECTION OF PANCREATIC DUCTAL ADENOCARCINOMA</title><p><bold>Y. Hamada</bold><sup>1,*</sup>, K. Maeshiro<sup>2</sup>, Y. Nakayama<sup>3</sup></p><p><italic><sup>1</sup>Pathology, Fukuoka University, Fukuoka, <sup>2</sup>Chubu Tokushukai Hospital, Okinawa, <sup>3</sup>Kyushu Medical Center, Fukuoka, Japan</italic></p><p><bold>INTRODUCTION:</bold> The impact of microscopically positive resection margins (R1) on surgical outcomes has been vague. Although some researchers have shown R1 to have important prognostic significance, others have not. Based on long-term follow-up data, 24% of 5-year survivors had positive margins after pancreatic carcinoma resection. However, there are very few articles describing >5-year survival after pancreatic resection. The aim of this study was to evaluate the prognostic influence of R1 and R0 (negative margins) on ≥5-year survival after resection of pancreatic ductal adenocarcinoma.</p><p><bold>AIMS&METHODS:</bold> A case-control study of 271 patients with pancreatic ductal adenocarcinoma who underwent pancreatic resection between 1991 and 2007 at Fukuoka University (Fukuoka, Japan) was performed. Of the 271 patients, 33 were actual 5-year survivors, and the overall 5-year survival rate was 12.2%. The observation period was 61 to 288 months (5.1–24.0 years). Clinicopathological data were retrospectively analysed according to the Japan Pancreatic Society classification of pancreatic carcinoma. Tissue samples were fixed in 10% formalin, and each tumour was then cut into 3- to 4-mm slices and embedded in paraffin. R1 status was defined by the British Royal College of Pathology as the presence of tumour tissue ≤1 mm from a circumferential margin surface of the resected pancreatic tissue.</p><p><bold>RESULTS:</bold> The R1 and R0 groups comprised 14 and 19 of the 33 patients, respectively. A significantly higher number of female patients was present in the R1 group than in the R0 group. The R0 group tended to show a significantly weaker relationship between the R status and stage than the R1 group. Multivariate analysis showed that the R status was an independent prognostic marker (p = 0.0071), and Kaplan–Meier curves showed that >5-year survivors in the R1 group had significantly worse prognoses than did those in the R0 group (p = 0.002). Of the 14 patients in the R1 group, 12 died of local recurrence.</p><p><bold>CONCLUSION:</bold> Among patients surviving >5 years after pancreatic resection, the prognosis of R1 patients was poor and almost all died of local recurrence. Surgeons and pathologists should be aware of the status of the pancreatic cut margin.</p><p><bold>REFERENCES:</bold></p><p>1. Ferrone CR, Pieretti-Vanmarcke, R, Bloom, JP, et al. Pancreatic ductal adenocarcinoma: Long-term survival does not equal cure. Surgery 152; S43-49: 2012</p><p>2. Schnelldorfer T, Ware al, Sarr MG, et al. Long-term survival after pancreatoduodenectomy for pancreatic adenocarcinoma Is cure possible? Ann Surg 247; 456-462: 2008</p><p>3. Verbeke CS, Leitch D, Menon KV, et al. Pedefining the R1 resection in pancreatic cancer Br J Surg 93; 1232-1237: 2006</p><p><bold>Contact E-mail Address:</bold><email>yoshihiro42@me.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> long-term follow up, pancreatic cancer, R1 resection</p></sec><sec><title>OP436 AN EARLY ORAL FEEDING STRATEGY AFTER PANCREATODUODENECTOMY ENHANCES RECOVERY WITHOUT INCREASING MORBIDITY</title><p><bold>A. Gerritsen</bold><sup>1,*</sup>, R. A. Wennink<sup>1</sup>, M. G. Besselink<sup>1,2</sup>, H. C. van Santvoort<sup>1</sup>, D. S. Tseng<sup>1</sup>, E. Steenhagen<sup>3</sup>, I. H. Borel Rinkes<sup>1</sup>, I. Q. Molenaar<sup>1</sup></p><p><italic><sup>1</sup>Department of Surgery, University Medical Center Utrecht, Utrecht, <sup>2</sup>Department of Surgery, Academic Medical Center, Amsterdam, <sup>3</sup>Department of Dietetics, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands</italic></p><p><bold>INTRODUCTION:</bold> Delayed gastric emptying (DGE), necessitating nutritional support, is a frequent complication after pancreatoduodenectomy (PD). Data on the optimal routine feeding strategy after PD are lacking.</p><p><bold>AIMS&METHODS:</bold> The aim of this study was to evaluate whether the introduction of an early oral feeding strategy with on demand nasojejunal tube (NJT) feeding after PD improved outcomes as compared to routine NJT feeding.</p><p>A monocenter cohort study was performed in 102 consecutive patients undergoing PD. In period 1 (June 2010-September 2011, n=51) the routine postoperative feeding strategy was NJT feeding (historical controls). This changed to early oral feeding with on demand NJT feeding in period 2 (January-December 2012, n=51; consecutive prospective cohort). The oral feeding strategy consisted of protocolized resumption of oral intake starting on the day of surgery, a NJT was only placed in case of severe preoperative malnutrition (MUST≥2) or when oral intake was insufficient (<50% of daily required caloric/protein intake) on postoperative day 7, supervised by a dietitian. Analysis was by intention-to-treat.</p><p><bold>RESULTS:</bold> Groups were comparable for baseline characteristics. In period 1, 98% (n=50) of patients received NJT feeding versus 53% (n=27) in period 2 (becuase of insufficient intake, n=20, or preoperative malnutrition, n=7). The time to resumption of adequate oral intake (primary outcome) significantly decreased with early oral feeding (12 vs. 9 days, P=0.01) as well as hospital stay (18 vs. 13 days, P=0.01), especially in patients with an uncomplicated postoperative course (primary outcome: 11 vs. 6 days, P=0.01, and hospital stay: 15 vs. 9 days, P=0.01 respectively) whereas no differences were seen in patients who developed DGE. There was no difference in the incidence of Clavien-Dindo≥3 complications (47% vs. 45%, P=0.84), DGE (31% vs. 35%, P=0.67), pancreatic fistula (12% vs. 12%, P=>0.99), postoperative haemorrhage (12% vs. 10%, P=0.75) and mortality (6% vs. 2%, P=0.61) between the groups.</p><p><bold>CONCLUSION:</bold> The introduction of an early oral feeding strategy, with on demand NJT feeding, after PD reduced the time to resumption of adequate oral intake and length of hospital stay, without negative impact on overall morbidity, DGE or pancreatic fistula.</p><p><bold>Contact E-mail Address:</bold><email>agerritsen-9@umcutrecht.nl</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Enteral Nutrition, nasojejunal tube feeding, Oral feeding, pancreas, pancreatoduodenectomy, surgery</p></sec><sec><title>OP437 IMPACT OF OPTICAL BIOPSY ON MANAGEMENT OF PATIENTS WITH BILIARY STRICTURES: INTERIM RESULTS OF A MULTICENTER STUDY</title><p><bold>A. Slivka</bold><sup>1,*</sup>, P. Jamidar<sup>2</sup>, I. Gan<sup>3</sup>, M. Giovannini<sup>4</sup>, F. Caillol<sup>4</sup>, G. Costamagna<sup>5</sup>, P. Cesaro<sup>5</sup>, M. Kahaleh<sup>6</sup></p><p><italic><sup>1</sup>University of Pittsburgh Medical Center, Pittsburgh, <sup>2</sup>Yale New Haven Hospital, Yale, <sup>3</sup>Virginia Mason Medical Center, Seattle, United States, <sup>4</sup>Institut Paoli Calmettes, Marseille, France, <sup>5</sup>Policlinico Agostino Gemelli / Univ. Cattolica Del Sacro Cuore, Roma, Italy, <sup>6</sup>New York Presbyterian Weill Cornell Medical Center, New York, United States</italic></p><p><bold>INTRODUCTION:</bold> Accurate differential diagnosis of indeterminate biliary stricture presents a clinical problem owing to the low sensitivity of tissue sampling. Probe based confocal laser endomicroscopy (pCLE) has been shown to accurately differentiate benign from malignant strictures in real time during ongoing ERCP procedure, with a sensitivity of 98%.</p><p><bold>AIMS&METHODS:</bold> This study presents the interim analysis of an ongoing international multicentric trial (FOCUS, NCT01392274) aimed at evaluating the impact of pCLE on the management of patients with indeterminate biliary stricture. Initial performance and impact on the subsequent patient workup will be presented.</p><p>Patients presenting with indeterminate biliary strictures are currently enrolled in 6 international centers (2 european, 4 US) and undergoing pCLE procedure during standard ERCP. For each patient, the following information is collected prospectively and evaluated in a sequential fashion: #1: clinical history + ERCP impression;#2: pCLE information, #3: histology/cytology results. At each stage the investigator is asked to provide a presumptive diagnosis as well as a patient management recommendation.</p><p><bold>RESULTS:</bold> 36 cases with a final diagnosis have been accumulated at this time 34 malignant proven by surgery or positive tissue sampling; 2 benign proven by surgery)</p><p>32 patients (31 malignant, 1 benign) were accurately diagnosed based on the clinical information and ERCP impression, pCLE accurately diagnosed the same 32 patients, whereas tissue sampling (combination of brush cytology and biopsy) would have missed 5 malignant patients. In 100% of the cases where physicians felt confident to immediately proceed with patient management, patient management based on clinical history and ERCP impression (n=7) and pCLE impression (n=10) were identical to decision making once tissue sample returned.</p><p><bold>CONCLUSION:</bold> This is the first study evaluating the impact of pCLE on management of patients with biliary strictures. A high preponderance of cancer is expected in this interim analysis based on study design. Clinical impression and pCLE outperform tissue sampling and optical biopsy has the potential to improve clinical decision making for difficult cases by reducing the work-up algorithm.</p><p><bold>Contact E-mail Address:</bold><email>slivax@upmc.edu</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> endomicroscopy, MANAGEMENT, strictures</p></sec><sec><title>OP438 PATTERNS OF RECURRENCE AFTER R0 RESECTION OF GALLBLADDER CANCER: ANALYSIS OF PATIENTS UNDERGOING LYMPH NODE DISSECTION OF THE HEPATODUODENAL LIGAMENT WITHOUT ROUTINE EXTRAHEPATIC BILE DUCT RESECTION.</title><p><bold>J. K. Wiggers</bold><sup>1,*</sup>, B. Groot Koerkamp<sup>1</sup>, O. Busch<sup>1</sup>, D. Gouma<sup>1</sup>, T. van Gulik<sup>1</sup></p><p><italic><sup>1</sup>Surgery, Academic Medical Centre, Amsterdam, Netherlands</italic></p><p><bold>INTRODUCTION:</bold> The routine use of extrahepatic bile duct resection along with lymph node dissection of the hepatoduodenal ligament (LnHDL) in patients with gallbladder cancer is controversial.(<italic>Nishio 2011)</italic></p><p><bold>AIMS&METHODS:</bold> The aim of this study was to analyse patterns of recurrence in patients who underwent radical resection of gallbladder cancer without extrahepatic bile duct resection. This analysis included 64 patients who had undergone explorative laparotomy for gallbladder carcinoma between 1993 – 2012 at a single centre. Patients with resectable disease and no tumour infiltration beyond the cystic duct underwent cholecystectomy in combination with excision of the gallbladder fossa (segm4/5); LnHDL for tumors stage T1b and higher; and partial liver or duodenal resection when indicated. Extrahepatic bile duct resection was only used in case of tumor infiltration beyond the cystic duct.</p><p><bold>RESULTS:</bold> Thirty-six patients (56%) underwent resection at laparotomy. Twenty-five patients (39%) underwent R0 resection with LnHDL, but no extrahepatic bile duct resection (tumor stage T1b in 5 patients; T2 in 16; T3 in 3; and T4 in 1). The median number of lymph nodes harvested from the hepatoduodenal ligament in these patients was 3 (range, 1 – 11). Nine patients developed recurrent disease after a median of 15 months (range, 3 – 25): Isolated disease at the hepatic resection margin in 2 patients, and distant disease in 7 patients. Sixteen patients remained disease-free at median follow-up of 32 months (range, 10 – 164).</p><p><bold>CONCLUSION:</bold> The majority of patients develop distant metastatic disease as initial pattern of recurrence after R0 resection of gallbladder carcinoma. No patients developed isolated recurrent disease in the hepatoduodenal ligament, suggesting that extrahepatic bile duct resection has no additional value over lymph node dissection alone of the hepatoduodenal ligament.</p><p><bold>REFERENCES:</bold></p><p>1. Nishio H, Ebata T, Yokoyama Y, Igami T, Sugawara G, Nagino M. Gallbladder cancer involving the extrahepatic bile duct is worthy of resection. Ann Surg 2011.253(5):953-60.</p><p><bold>Contact E-mail Address:</bold><email>j.k.wiggers@amc.nl</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> gallbladder cancer, lymph node dissection, lymph node metastases</p></sec><sec><title></title><p><bold>WEDNESDAY, OCTOBER 16, 2013 11:00-12:30</bold></p><p><bold>Colorectal cancer: Back to the basics – Salon 11/12</bold></p></sec><sec><title>OP439 ER STRESS DEPLETES APC MUTANT INTESTINAL EPITHELIAL STEM CELLS DOWNSTREAM OF NUCLEAR BETA-CATENIN</title><p><bold>J. F. Van Lidth De Jeude</bold><sup>1,*</sup>, M. C. Wielenga<sup>1</sup>, A. S. Lee<sup>2</sup>, V. Muncan<sup>1</sup>, G. R. van den Brink<sup>1</sup>, J. Heijmans<sup>1</sup></p><p><italic><sup>1</sup>Tytgat institute for Liver and Intestinal Research, Amsterdam, Netherlands, <sup>2</sup>Department of Biochemistry and Molecular Biology, USC/Norris Comprehensive Center, Los Angeles, United States</italic></p><p><bold>INTRODUCTION:</bold> Wnt signalling drives self-renewal of intestinal epithelial stem cells (ISCs) through activation of β-catenin. Hyperactivation of Wnt signalling causes stem cell expansion and constitutes a first step in development of colorectal cancer. In contrast, we have previously shown that endoplasmic reticulum (ER) stress signalling causes loss of self-renewal capacity in ISCs, but how these two functionally opposite pathways interact remains elusive. By deletion of ER stress repressor gene <italic>Grp78</italic>, we investigate effects of ER stress on ISCs that lack the Wnt gatekeeper gene <italic>Apc </italic>and thus exhibit hyperactive Wnt signalling.</p><p><bold>AIMS&METHODS:</bold> To validate knockout of <italic>Grp78</italic> as a model of ER stress we generated organoids of intestinal epithelium from <italic>Grp78<sup>fl/fl</sup></italic> mice and analysed gene expression using Illumina arrays. For <italic>in vivo</italic> studies we used inducible <italic>Villin<sup>CreERT2</sup>-Apc<sup>fl/fl</sup>-Grp78<sup>fl/fl</sup></italic> mice in which simultaneous deletion of <italic>Apc</italic> and <italic>Grp78</italic> resulted in hyperactivation of Wnt signalling and concomitant ER stress.</p><p><bold>RESULTS:</bold> Analysis of <italic>Grp78<sup>fl/fl</sup></italic> organoids showed robust upregulation of a panel of ER stress markers, conforming <italic>Grp78</italic> deletion as a bona fide model for the study on ER stress. Deletion of <italic>Apc</italic> from mouse intestinal epithelium resulted in accumulation of nuclear β-catenin, hyperproliferation, crypt enlargement and crypt fissioning 3 days post induction (p.i.). Induction of ER stress in <italic>Apc</italic> mutant epithelium by combined deletion of <italic>Apc</italic> and <italic>Grp78</italic>, resulted in marked (41%) reduction of BrdU<sup>+</sup> cells indicating halted proliferation at day 3 p.i. (<italic>P</italic> < 0.001). Additionally, crypts were taken over by <italic>Grp78</italic> proficient, wild type cells, indicating loss of self-renewal capacity. While loss of the hyperproliferative phenotype and self-renewal capacity occurred, cells in <italic>Apc-Grp78</italic> double mutant crypts maintained nuclear localization of β-catenin.</p><p><bold>CONCLUSION:</bold> Homozygous deletion of <italic>Apc</italic> results in a known hyperproliferative phenotype and ultimately tumor formation. We show that concomitant depletion of <italic>Apc</italic> and <italic>Grp78</italic> results in abrogation of this phenotype while maintaining nuclear localization of β-catenin, the hallmark of activated Wnt signalling. Thus, ER stress mediated stem cell loss is dominant over hyperactivation of the Wnt signalling pathway and may interfere with stemness downstream of β-catenin. These results highlight a role for ER stress as a potential target in development of novel cancer therapy.</p><p><bold>Contact E-mail Address:</bold><email>j.f.vanlidthdejeude@amc.uva.nl</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> ER stress, intestinal stem cells, mouse model, Proliferation, Unfolded Protein Response, Wnt signaling pathway</p></sec><sec><title>OP440 REPORT AND ANALYSIS OF LYNCH SYNDROME ASSOCIATED GENETIC VARIATIONS REPORTED BY THE FRENCH UMD MMR –MLH1/MSH2/MSH6 DATABASE</title><p><bold>P. Grandval</bold><sup>1,*</sup>, A. fabre<sup>2</sup>, P. gaildrat<sup>3</sup>, P. gaildrat<sup>3</sup>, S. Baert-Desurmont<sup>4</sup>, M. P. buisine<sup>5</sup>, A. ferrari<sup>6</sup>, Q. wang<sup>7</sup>, C. beroud<sup>8</sup>, S. olschwang<sup>2</sup></p><p><italic><sup>1</sup>gastroenterology, <sup>2</sup>CHU TIMONE, marseille, <sup>3</sup>Inserm UMR 1079, <sup>4</sup>genetic department, rouen, <sup>5</sup>Centre de biologie et pathologie, lille, <sup>6</sup>Centre de biologie et pathologie, <sup>7</sup>Plateforme de recherche translationnelle, centre leon berard, lyon, <sup>8</sup>inserm umr s 910, marseille, France</italic></p><p><bold>INTRODUCTION:</bold> Lynch syndrome is an inherited disease caused by a constitutional mutation of MLH1, MSH2 and MSH6 genes, who are involved in DNA misappariement (MMR). The French laboratories network who perform genetic analysis has injected a total of 7047 genetic variants in Lynch syndrome suspected individuals since 1995. The aim of our study was to propose a classification and a description of the 707 variants of uncertain significance (VUS).</p><p><bold>AIMS&METHODS:</bold> Three groups of parameters were systematically collected: i) <italic>in silico</italic> prediction (splicing analyses, conservation level, SIFT and UMD-Predictor estimates; ii) specific clinico-pathological and biological parameters provided by the network contributors (cosegregation analyses, clinical phenotype according to the enlarged Amsterdam criteria, MMR function status in tumor cells by genotyping and immunohistochemistry analysis, splicing analysis using a splicing reporter minigene and RT-PCR in case of anomaly, transcription-translation assays when VUS involve the Kozak or 5’UTR sequences, concurrent variations within all analyzed MMR genes); iii) public data such research papers and online databases (functional protein assays, allele frequencies).The international 5 class classification was systematically applied after critical analysis of each VUS characterization.</p><p><bold>RESULTS:</bold> All the information’s were inserted in the French database and are on line at <ext-link ext-link-type="uri" xlink:href="www.umd.be/MLH1/">www.umd.be/MLH1/</ext-link>, <ext-link ext-link-type="uri" xlink:href="www.umd.be/MSH2/et">www.umd.be/MSH2/ et</ext-link><ext-link ext-link-type="uri" xlink:href="www.umd.be/MSH6/">www.umd.be/MSH6/</ext-link>. A decisional tree was elaborated, and applied for each variant. 370 VUS among 707 could be characterized as class 1 (neutral) for 181 and 2 (probably neutral) for 80, which are not responsible for Lynch syndrome. 55 VUS were classified as class 5 (causal) and 54 as class 4 (probably causal), which are highly suspected to lead Lynch syndrome. The remaining 337 are classified as class 3, as long as no available functional assays can demonstrate their pathogenicity.</p><p><bold>CONCLUSION:</bold> Our algorithm allows us a classification of 370 new MMR gene variant, actually available for the scientific community in the French MMR database, which is regularly updated. Only class 5 can be used for genetic counseling.</p><p><bold>Contact E-mail Address:</bold><email>philippe.grandval@ap-hm.fr</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> classification, LYNCH SYNDROME AND VARIANTS </p></sec><sec><title>OP441 BACTERIAL GENOTOXIN COLIBACTIN PROMOTES COLON TUMOR GROWTH BY MODIFYING TUMOR MICROENVIRONMENT</title><p><bold>A. Cougnoux</bold><sup>1</sup>, G. Dalmasso<sup>1,*</sup>, R. Martinez<sup>2</sup>, E. Buc<sup>1,3</sup>, J. Delmas<sup>1,3</sup>, L. Gibold<sup>1,3</sup>, P. Sauvanet<sup>1</sup>, C. Darcha<sup>3</sup>, P. Déchelotte<sup>3</sup>, M. Bonnet<sup>1</sup>, D. Pezet<sup>1,3</sup>, H. Wodrich<sup>2</sup>, A. Darfeuille-Michaud<sup>1,3</sup>, R. Bonnet<sup>1,3</sup></p><p><italic><sup>1</sup>M2iSH, Inserm UMR 1071, INRA Usc 2018, University of Auvergne, Clermont-Ferrand, <sup>2</sup>MFP, CNRS UMR 5234, University of Bordeaux, Bordeaux, <sup>3</sup>Medicine, Centre Hospitalier Universitaire, Clermont-Ferrand, France</italic></p><p><bold>INTRODUCTION:</bold> Microbiota is thought to play a critical role in colorectal cancer (CRC). Most of mucosa-associated <italic>Escherichia coli</italic> isolated from CRC harbor the <italic>pks</italic> genomic island (<italic>pks</italic>+ <italic>E. coli</italic>) responsible for the synthesis of colibactin, a genotoxic compound able to induce DNA damage. It was recently showed that <italic>pks</italic>+ <italic>E. coli</italic> increased tumor incidence in a colitis-associated cancer mouse model.</p><p><bold>AIMS&METHODS:</bold> Our aim was to investigate the mechanisms involved in <italic>pks</italic>+ <italic>E. coli</italic>-induced carcinogenesis. Conditioned media derived from infected HCT116 intestinal epithelial cells were used to stimulate the growth of uninfected cells. Importance of growth factors was assessed using neutralizing antibodies <italic>in vitro</italic> and in a xenograft model. Signaling pathways activated by <italic>pks</italic>+ <italic>E. coli</italic> were investigated by qRT-PCR and Western blot. Results were validated using human biopsies isolated from tumor colonized by <italic>pks</italic>+ or <italic>pks</italic>- <italic>E. coli</italic>.</p><p><bold>RESULTS:</bold> A transient contact of HCT116 cells with <italic>pks</italic>+ <italic>E. coli</italic> increased tumor growth in a mouse xenograft model. Conditioned media derived from <italic>pks</italic>+ <italic>E. coli</italic>-infected cells stimulated the growth of uninfected cells. Growth was sustained by cellular senescence, which is accompanied by production of HGF. Neutralization of HGF abolished <italic>pks</italic>+ pro-proliferative effect. Cellular senescence is known to be driven by post-translational modifications involving SUMO proteins. We observed that <italic>pks</italic>+ <italic>E. coli</italic>-infected cells displayed a modified pattern of SUMO-conjugated proteins correlated with a decrease of SENP1 expression, a key protein involved in the control of the SUMOylation process. Over-expression of SENP1 abolished <italic>pks</italic>+ <italic>E. coli</italic>-induced alteration of protein SUMOylation as well as cellular senescence. Using bioinformatics and molecular approaches, we found that SENP1 expression is directly regulated by microRNA-20a-5p. Anti-miR-20a-5p inhibited <italic>pks</italic>+ <italic>E. coli</italic>-mediated (i) drop of SENP1 expression, (ii) cellular senescence as well as (iii) cell proliferation. Finally, we found that human tumor colonized by <italic>pks</italic>+ <italic>E. coli</italic> expressed significantly higher level of HFG and miR-20a-5p compared to tumor colonized by <italic>pks</italic>- <italic>E. coli</italic>. SENP1 expression was significantly decreased in tumors colonized with <italic>pks</italic>+ <italic>E. coli</italic>.</p><p><bold>CONCLUSION:</bold> Our results suggest that colibactin-producing bacteria modulate the tumor microenvironment and favor the emergence of senescent cells, which promote tumor growth by the secretion of growth factors.</p><p><bold>Contact E-mail Address:</bold><email>guillaume.dalmasso@udamail.fr</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> colibactin, Colorectal Cancer, Escherichia coli, microRNA, pks, Senescence</p></sec><sec><title>OP442 INFLAMMATION INCREASES NOTCH1 ACTIVITY IN COLORECTAL CANCER CELLS AND IS COUNTERACTED BY EICOSAPENTAENOIC ACID-FREE FATTY ACID.</title><p><bold>C. Fazio</bold><sup>1,*</sup>, G. Piazzi<sup>1</sup>, P. Vitaglione<sup>2</sup>, V. Fogliano<sup>2</sup>, A. Munarini<sup>1</sup>, A. Prossomariti<sup>1</sup>, L. D'Angelo<sup>1</sup>, M. Napolitano<sup>3</sup>, A. Belluzzi<sup>4</sup>, F. Bazzoli<sup>1</sup>, L. Ricciardiello<sup>1</sup></p><p><italic><sup>1</sup>Department of Medical and Surgical Sciences, University of Bologna, Bologna, <sup>2</sup>Department of Food Science, University of Naples “Federico II”, Portici (Naples), <sup>3</sup>Department of Surgical and Medical Sciences, University of Bologna, <sup>4</sup>Gastroenterology Unit, S.Orsola-Malpighi Hospital, Bologna, Italy</italic></p><p><bold>INTRODUCTION:</bold> The link between inflammation and colorectal cancer (CRC) is well established, and inflammatory cells in the lamina propria, including macrophages, are critical for cancer initiation and progression. Notch signalling has a pivotal role in colorectal carcinogenesis. Eicosapentaenoic acid free fatty acid (EPA), a ω-3 polyunsaturated fatty acid, has been demonstrated to be protective toward CRC in preclinical and clinical models.</p><p><bold>AIMS&METHODS:</bold> The aim of this study was to evaluate whether Notch1 can be activated by inflammatory stimuli through STAT3-Jagged1 in CRC cells, and whether this mechanism could be counteracted by EPA (SLA Pharma UK). A cytokine-enriched conditioned media (CM) was obtained from THP-1 cells after differentiation into macrophages. CM was applied to untreated and EPA-treated HT29 cells. Cytokine levels in the CM, fatty acids incorporation and cell adhesion of HT29, were tested. Cells were also treated with either IL-6 or IL-8. Levels of Notch1 intracellular domain (NICD), Jagged1, STAT3 and pSTAT3 were quantified by western blotting. Gene expression of Jagged1 and Notch1 downstream targets NRARP and HATH1, were evaluated by Real-Time PCR. HT29 stably silenced for Notch-1 were tested as well.</p><p><bold>RESULTS:</bold> CM treatment increased cellular adhesion of HT29 up to 90% and this phenomenon was paired by a strong activation of pSTAT3, increased expressions of Jagged1 and NICD. Stimulation of HT29 with either IL-6 or IL-8 led to a lower activation of Jagged1 and NICD compared to the CM-treated counterparts. The activation of Notch1 caused up-regulation of NRARP and down-regulation of HATH1. This effect was less pronounced in Notch1-silenced HT29, while the expression of Jagged1 remained unchanged. Interestingly, a three-day pre-treatment with non-cytotoxic concentration of EPA counteracted the CM-driven increases of Jagged1, NICD and pSTAT3. Finally, EPA effects on Notch1 were supported by a concordant modulation of its downstream targets NRARP and HATH1.</p><p><bold>CONCLUSION:</bold> The inflammatory microenvironment is a stronger activator of Notch1 signalling in CRC cells compared to the effect of each single inflammatory cytokine, and pre-treatment with non-cytotoxic concentrations of EPA counteracts this effect. Our data suggest a possible new mechanism of action of EPA as chemopreventive agent in CRC through inhibition of Notch1 signalling.</p><p><bold>Disclosure of Interest</bold>: C. Fazio: None Declared, G. Piazzi: None Declared, P. Vitaglione: None Declared, V. Fogliano: None Declared, A. Munarini: None Declared, A. Prossomariti: None Declared, L. D'Angelo: None Declared, M. Napolitano: None Declared, A. Belluzzi: None Declared, F. Bazzoli: None Declared, L. Ricciardiello Financial support for research from: SLA Pharma</p><p><bold>Keywords:</bold> chemoprevention, inflammation, notch pathway, Omega-3 fatty acid</p></sec><sec><title>OP443 ROLE FOR HEPCIDIN IN OBESITY DRIVEN COLORECTAL TUMORIGENESIS</title><p><bold>E. Shawcross</bold><sup>1</sup>, A. Chauhan<sup>1,*</sup>, T. Iqbal<sup>1</sup>, C. Tselepsis<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology, University Of Birmingham Queen Elizabeth Hospital, Birmingham, United Kingdom</italic></p><p><bold>INTRODUCTION:</bold> While there is a strong association between obesity and colon cancer, the underlying molecular and cellular mechanisms are unclear. Accumulating evidence suggests a critical role for adipose hormones; leptin and IL-6. Both IL-6 and leptin induce hepcidin expression in obesity. A constitutively high hepcidin expression in obesity may result in dysregulated iron metabolism with high intracellular and low serum iron. High intracellular iron has been shown via wnt signalling to mediate colorectal cancer (CRC).</p><p><bold>AIMS&METHODS:</bold> We aim to investigate the role of adipose cytokines and hepcidin in mediating CRC both in vivo and in vitro in malignant cell lines. Serum samples from 163 patients attending for colonoscopy as part of the national colorectal screening programme were obtained and leptin, IL6 and hepcidin levels measured. 73 of these patients were confirmed as having colonic neoplasia. Using tissue extracted from the greater omentum of patients undergoing surgery for CRC, we isolated and cultured human adipocytes. The differentiated adipocyte secretome (DAS) was collected and used to challenge colorectal cancer cell line SW480 in the presence or absence of leptin, IL-6 and hepcidin inhibitors. Viability and proliferation assays were then conducted on the SW480 cell lines.</p><p><bold>RESULTS:</bold> A positive correlation was found between hepcidin and leptin in patients with cancer. Antibody arrays and ELISA confirmed the presence of adipokines in the DAS and elevated levels of leptin (29 fold), IL-6 (12 fold) and hepcidin (3 fold). Co-incubation of SW480 cells with DAS increased cellular viability and proliferation, both of which reverted to control levels with IL-6, leptin or hepcidin blockade. These results were replicated on stimulating SW480 cells sequentially with IL6, leptin or hepcidin. Colonocyte challenge with IL6 or Leptin enhanced Hepcidin production. A hepcidin antagonist, blocked IL-6 and Leptin mediated increases in colonocyte viability and proliferation.</p><p><bold>CONCLUSION:</bold> We provide the first demonstration that hepcidin is produced by adipocytes and has a important role in obesity mediated carcinogenesis. The importance of hepcidin in colonocyte fate is further highlighted by our finding that a hepcidin antagonist abolished IL6 and leptin mediated increases in cell viability and proliferation. This is the first time the observation has been made in tissue that does not endogenously express hepcidin. Taken in conjunction with the positive correlation between hepcidin and leptin in neoplasia, we predict that systemic IL6 and leptin production in obese patients drives local tumoural hepcidin production, thus driving carcinogenesis.</p><p><bold>REFERENCES:</bold></p><p>1. Brookes et al. A role for iron in Wnt signalling. Oncogene. 2006 Feb 7;27(7):966-75.</p><p>2. Larsson SC et al. Obesity and colon and rectal cancer risk: a meta-analysis of prospective studies. Am J Clin Nutr. 2007;86:556-65.</p><p>3. Moghaddam A et al. Obesity and risk of colorectal cancer: A meta-analysis. Cancer Epidemiol Biomarkers Prev, 2007. 16(12): p. 2533-47. Considine et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med. 1996 Feb 1;334(5):292-5.</p><p>4. Stattin P et al. Obesity and colon cancer: does leptin provide a link? Int J Cancer. 2004;109:149-52.</p><p><bold>Contact E-mail Address:</bold><email>abhichauhan@mac.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Colorectal cancer, hepcidin, IL-6, leptin, obesity</p></sec><sec><title>OP444 COLON CANCER STEM CELL PROLIFERATION AND TUMOUR GROWTH ARE PROMOTED BY NITRIC OXIDE SYNTHASE-2</title><p><bold>M. A. Puglisi</bold><sup>1,*</sup>, V. Tesori<sup>1</sup>, L. Ricci-Vitiani<sup>2</sup>, E. Giorda<sup>3</sup>, R. Carsetti<sup>3</sup>, A. Cittadini<sup>4</sup>, G. B. Gasbarrini<sup>5</sup>, G. Pani<sup>4</sup>, A. Gasbarrini<sup>1</sup></p><p><italic><sup>1</sup>Internal Medicine and Gastroenterology, GEMELLI HOSPITAL, <sup>2</sup>Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità , <sup>3</sup>Cytofluorimetry Laboratory, Bambino Gesù Pediatric Hospital, <sup>4</sup>Institute of General Pathology, GEMELLI HOSPITAL, ROME, <sup>5</sup>Medical Research Foundation , ONLUS, Bologna, Italy</italic></p><p><bold>INTRODUCTION:</bold> Chronic inflammation represents a leading cause of neoplastic transformation in many human cancers and especially in colon cancer (CC), in part due to tumor promotion by Nitric Oxide (NO) generated at inflammatory sites. It has also been suggested that high NO synthesis, secondary to inducibile NOS (iNOS) expression, is a distinctive feature of “cancer stem cells” (CSC), a small subset of cells with self-renewal capacity, that may be identified by the expression of the CD133 surface marker.</p><p><bold>AIMS&METHODS:</bold> Aim of this study was to explore the contribution of NO in the definition of CSC features in colon cancer.</p><p>The production of intracellular NO was assayed using the 4,5-diaminofluorescein diacetate (DAF-2DA) detection system. Cells were sorted from five human colon CSC lines obtained from tumor tissues and from four established human CC cell lines (CaCo-2,HCT-116, Lovo and HT29), on the basis of their level of DAF-2DA (NO<sup>“high”</sup>and NO<sup>“low”</sup>) by FACS-sorter and aseptically recovered. We compared the tumorigenic potential of NO<sup>“high”</sup> cells respect the NO<sup>“low”</sup> cell by <italic>in vitro</italic> and <italic>in vivo </italic>assay</p><p><bold>RESULTS:</bold> We observed that NO<sup>“high”</sup>cells displayed higher expression level of iNOS and stem cell markers (CD133, LGR5, BMI, TWIST and SNAIL) than NO<sup>“low”</sup>cells. In vitro assay showed that NO<sup>“high”</sup>cells displayed a significantly greater capacity to give rise to colonies in soft agar and a higher invasive and proliferative capacity than NO<sup>“low”</sup>cells. Moreover, we inoculated the two cell fractions in nude mice and we observed that tumors derived from NO<sup>high </sup>cells were markedly larger and more vascularized than those formed by NO<sup>low</sup>cells. We hypothesized that the NO<sup>”high”</sup> cells are the true CSC, while cells with lower production of NO may be more committed progenitor cells. Interestingly, we observed that NO<sup>“high”</sup>cells treated with the highly selective iNOS inhibitor, 1400W, showed a significant reduction of their tumorigenic ability, confirming that iNOS is critical for NO production in colon CSC.</p><p><bold>CONCLUSION:</bold> These studies are relevant, since they provide the first demonstration that NO synthesis, secondary to high iNOS expression, is a distinctive feature of colon CSC relative to non-CSC, and in the long run, these data will hopefully serve as an impetus for evaluation of iNOS-directed therapies as a component of multimodal treatment regimens for human CC.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> cancer stem cell, colon cancer, inducible NO-synthase, nitric oxide</p></sec><sec><title></title><p><bold>WEDNESDAY, OCTOBER 16, 2013 11:00-12:30</bold></p><p><bold>Optimizing clinical outcomes in IBD – Roof Garden</bold></p></sec><sec><title>OP445 RANDOMIZED CONTROLLED TRIAL COMPARING SETON REMOVAL ALONE OR IN ASSOCIATION WITH ANAL FISTULA PLUG IN FISTULISING ANO-PERINEAL CROHN’S DISEASE</title><p><bold>A. Senejoux</bold><sup>1,*</sup>, L. Siproudhis<sup>2</sup>, L. Abramowitz<sup>3</sup>, N. Munoz-Bongrand<sup>4</sup>, K. Desseaux<sup>5</sup>, G. Bouguen<sup>2</sup>, A. Bourreille<sup>6</sup>, O. Dewit<sup>7</sup>, C. Stefanescu<sup>1</sup>, G. Vernier<sup>8</sup>, E. Louis<sup>9</sup>, J. C. Grimaud<sup>10</sup>, B. Godart<sup>11</sup>, G. Savoye<sup>12</sup>, X. Hebuterne<sup>13</sup>, P. Bauer<sup>14</sup>, M. Nachury<sup>15</sup>, D. Laharie<sup>16</sup>, S. Chevret<sup>5</sup>, Y. Bouhnik<sup>1</sup> on behalf of GETAID</p><p><italic><sup>1</sup>CHU Beaujon, Clichy, <sup>2</sup>CHU Rennes, Rennes, <sup>3</sup>CHU Bichat, <sup>4</sup>CHU Saint Louis, <sup>5</sup>Université Paris VII, Paris, <sup>6</sup>CHU Nantes, Nantes, France, <sup>7</sup>Clinique Universitaire Saint-Luc, Bruxelles, Belgium, <sup>8</sup>CHU Claude Huriez, Lille, France, <sup>9</sup>Hopital Sart Tilman, Liège, Belgium, <sup>10</sup>CHU Marseille, Marseille, <sup>11</sup>CHU Tours, Tours, <sup>12</sup>CHU Rouen, Rouen, <sup>13</sup>CHU Nice, Nice, <sup>14</sup>Hopital Diaconesses, Paris, <sup>15</sup>CHU Lille, Lille, <sup>16</sup>CHU Bordeaux, Bordeaux, France</italic></p><p><bold>INTRODUCTION:</bold> Anal fistula plug (AFP) is a bioabsorbable bioprosthesis made of lyophilized porcine intestinal submucosa used for patients with ano-perineal fistula. No controlled data is available with AFP in fistulising ano-perineal Crohn’s disease (FAP-CD).</p><p><bold>AIMS&METHODS:</bold> The aim of our study was to assess efficacy and safety of AFP in FAP-CD (ClinicalTrials.gov No.2008-A00122-53). It was a multicenter, open-label, randomized controlled trial comparing seton removal alone or with AFP insertion in CD patients with non or mildly active luminal disease (CDAI≤250) having at least one ano-perineal fistula tract drained for more than one month. Patients with abscess (collection ≥ 3 mm on magnetic resonance) or recto-vaginal fistulas were excluded. Setons were removed at baseline in all patients, and randomization was stratified according to AGA classification in simple or complex fistulas. The primary end point was fistula closure at week 12, defined by the absence of any draining or perianal pain, and abscess. Analysis was made on an intent-to-treat basis.</p><p><bold>RESULTS:</bold> From June 2008 to December 2011, 106 patients from 15 centers have been randomized either to AFP (n=54) or control group (n=52); there were 68 women; median age: 34 years [interquartile range: 26-43]; median fistula duration: 23 months [10-53]; median CDAI at baseline: 81 [45-135].</p><p>Fistula closure was achieved in 17/54 (31.5%) patients in the AFP group and in 12/52 (23.1%) in the control group at week 12. No interaction in treatment effect with complexity stratum was found, with fistula closure in 5/15 patients with complex fistula and in 12/39 patients with simple fistula in AFPs, as compared to 2/13 and 10/39 in controls (P= 0.52 by the Breslow-Day homogeneity test). No evidence of increased prevalence of patients with at least one adverse events was found (17/54, 32% vs. 8/52, 15% in the controls; p= 0.07).</p><p><bold>CONCLUSION:</bold> Anal fistula plug in combination with seton removal doesn’t seem more effective than seton removal alone to achieve ano-perineal fistula closure in patients with CD.</p><p><bold>Contact E-mail Address:</bold><email>yoram.bouhnik@gmail.com</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> anal fistula plug, anoperineal fistula, Crohn’s disease, randomised controlled trial</p></sec><sec><title>OP446 COMPOSITE REMISSION MEASURES IN EARLY CROHN’S DISEASE: A POST-HOC ANALYSIS OF THE SONIC TRIAL</title><p><bold>J. F. Colombel</bold><sup>1,*</sup>, W. Reinisch<sup>2</sup>, G. Mantzaris<sup>3</sup>, A. Kornbluth<sup>4</sup>, A. Oortwijn<sup>5</sup>, G. S. Bevelander<sup>6</sup>, F. Cornillie<sup>5</sup>, W. J. Sandborn<sup>7</sup></p><p><italic><sup>1</sup>Centre Hospitalier Universitaire de Lille, Lille, France, <sup>2</sup>University Hospital Vienna, Vienna, Austria, <sup>3</sup>Evangelismos Hospital, Athens, Greece, <sup>4</sup>Mount Sinai Medical Center, New York, United States, <sup>5</sup>Janssen Biologics BV, Leiden, Netherlands, <sup>6</sup>Janssen Biologics BV, Leiden, <sup>7</sup>University of California San Diego, La Jolla, United States</italic></p><p><bold>INTRODUCTION:</bold> Treatment goals in CD are evolving. Treatment targets now include clinical remission (CR; CDAI<150), mucosal healing (MH), and biological remission such as normalization of CRP<sup>1,2</sup>.<sub>.</sub> In addition, early treatment leads to better outcomes<sup>3</sup>.</p><p><bold>AIMS&METHODS:</bold> This post-hoc analysis of SONIC evaluated different composite remission measures at wk26. SONIC included 508 CD-pts naïve to immunomodulators and biologics<sup>3</sup>. This analysis included 188pts (median disease duration of 2.3yrs) who had evidence of mucosal ulcerations at baseline (BL), ileocolonoscopy and evaluable CDAI scores, CRP and ileocolonoscopies at BL <italic>and</italic> wk26. Composite remission measures were evaluated as follows: CR and MH (defined as absence of mucosal ulceration at wk26), CR and MH and CRP normalization (CRP<sub>norm</sub>; defined as CRP<0.8mg/dL), MH and CRP<sub>norm</sub> ,CR and CRP<sub>norm.</sub></p><p><bold>RESULTS:</bold> Overall, 136/188 pts (72.3%) were in clinical remission and 90/188 pts (47.9%) achieved MH (0 ulcers) at wk26. The composite measure of clinical remission and MH was achieved by 72/188 pts(38.3%). Among those pts with elevated CRP(118/188 pts;CRP≥0.8mg/dL) at BL, 38/118 pts(32.2%) achieved clinical remission, MH <italic>and </italic>CRP normalization. The combination of IFX+AZA showed higher composite remission measures ranging from 52.3% to 63.3% vs IFX (32.3%>51.2%) or AZA(12.9%>29%) alone.While IFX monotherapy showed numerically higher composite remission measures vs AZA alone,all composite outcomes for IFX+AZA were significantly higher vs AZA alone(Table).A significantly greater proportion of IFX+AZA-treated pts achieved the composite remission measures which included MH vs IFX alone.</p><p><bold>Table: Clinical remission and composite remission measures at wk26 in SONIC**</bold></p><p>* Fisher Exact Test (two-tailed)**This analysis takes into account CR. Note that the primary endpoint of SONIC was corticosteroid free clinical remission at wk26</p><p><bold>CONCLUSION:</bold> Combination therapy with IFX + AZA showed to be more effective in achieving various composite remission measures, especially when MH is included, compared to treatment with AZA or IFX alone.
<table-wrap id="table62-2050640613502899" position="float"><label>Table</label><caption><p>OP446</p></caption><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1"></th><th rowspan="1" colspan="1">AZA (n=54)</th><th rowspan="1" colspan="1">IFX (n=62)</th><th rowspan="1" colspan="1">IFX+AZA (n=72)</th><th rowspan="1" colspan="1">P-value* IFX+AZA vs. AZA</th><th rowspan="1" colspan="1">P-value* IFX vs. AZA</th><th rowspan="1" colspan="1">P-value* IFX+AZA vs. IFX</th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">CR (N=188)</td><td rowspan="1" colspan="1">57.4% (31/54)</td><td rowspan="1" colspan="1">75.8% (47/62)</td><td rowspan="1" colspan="1">80.6% (58/72)</td><td rowspan="1" colspan="1">0.006</td><td rowspan="1" colspan="1">0.047</td><td rowspan="1" colspan="1">0.534</td></tr><tr><td rowspan="1" colspan="1">CR + MH (N=188)</td><td rowspan="1" colspan="1">20.4% (11/54)</td><td rowspan="1" colspan="1">32.3% (20/62)</td><td rowspan="1" colspan="1">56.9% (41/72)</td><td rowspan="1" colspan="1"><0.001</td><td rowspan="1" colspan="1">0.207</td><td rowspan="1" colspan="1">0.005</td></tr><tr><td rowspan="1" colspan="1">CR + MH +CRP<sub>norm</sub> (N=118)</td><td rowspan="1" colspan="1">12.9%(4/31)</td><td rowspan="1" colspan="1">25.6%(11/43)</td><td rowspan="1" colspan="1">52.3%(23/44)</td><td rowspan="1" colspan="1"><0.001</td><td rowspan="1" colspan="1">0.245</td><td rowspan="1" colspan="1">0.015</td></tr><tr><td rowspan="1" colspan="1">MH + CRP<sub>norm</sub> (N=118)</td><td rowspan="1" colspan="1">19.4%(6/31)</td><td rowspan="1" colspan="1">30.2% (13/43)</td><td rowspan="1" colspan="1">56.8%25/44)</td><td rowspan="1" colspan="1">0.002</td><td rowspan="1" colspan="1">0.419</td><td rowspan="1" colspan="1">0.017</td></tr><tr><td rowspan="1" colspan="1">CR + CRP<sub>norm</sub> (N=118)</td><td rowspan="1" colspan="1">29.0% (9/31)</td><td rowspan="1" colspan="1">51.2%(22/43)</td><td rowspan="1" colspan="1">63.6%(28/44)</td><td rowspan="1" colspan="1">0.005</td><td rowspan="1" colspan="1">0.094</td><td rowspan="1" colspan="1">0.282</td></tr></tbody></table></table-wrap></p><p><bold>REFERENCES:</bold></p><p>1. Zallot C. and Peyrin-Biroulet L. Deep Remission in Inflammatory Bowel Disease: Looking Beyond Symptoms. <italic>Curr. Gasteroenterol. Rep.</italic> 2013;15:315</p><p>2. Colombel JF., Louis E., Peyrin-Biroulet L., Sanborn WJ. and Panaccione R. Deep Remission: a New Concept? <italic>Dig Dis</italic> 2012; 30 (suppl 3): 107-111</p><p>3. Colombel JF., Sandborn WJ., Reinisch W. et al. Infliximab, Azathioprine, or Combination Therapy for Crohn’s Disease. <italic>N Engl J Med</italic> 2010;362:1383-95</p><p><bold>Contact E-mail Address:</bold><email>FCornill@its.jnj.com</email></p><p><bold>Disclosure of Interest</bold>: J. Colombel Financial support for research from: Janssen, W. Reinisch Financial support for research from: Janssen, G. Mantzaris Financial support for research from: Janssen, A. Kornbluth Financial support for research from: Janssen, A. Oortwijn Other: Janssen employee, G. Bevelander Other: Janssen employee, F. Cornillie Other: Janssen employee, W. Sandborn Financial support for research from: Janssen</p><p><bold>Keywords:</bold> Crohn's disease, Infliximab, SONIC</p></sec><sec><title>OP447 COMPARISON OF EFFICACY AND TOLERANCE OF TWO MAINTENANCE REGIMENS WITH ADALIMUMAB IN PATIENTS WITH MODERATE TO SEVERE CROHN’S DISEASE.</title><p><bold>J. Filippi</bold><sup>1,*</sup>, D. Agrefilo<sup>1</sup>, E. Fontas<sup>2</sup>, X. Hébuterne<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology and clinical nutrition, Archet 2 Hospital, <sup>2</sup>Clinical research department, Cimiez Hospital, Nice, France</italic></p><p><bold>INTRODUCTION:</bold> In adult patients with Crohn’s disease (CD), the induction regimen commonly used with adalimumab (ADA) is 160 mg at week 0 (w0) and 80 mg at w2, followed by a maintenance regimen of 40 mg every other week (eow). In situations of partial response or loss of response, the interval between injections can be shortened to one week, or the dose can be increased to 80 mg eow. It has been shown in the literature that 30% of patients require such optimization. The aim of this study was to assess the efficacy and safety of a systematic maintenance optimization of the dose (80 mg eow), in comparison with the classical regimen (40 mg eow).</p><p><bold>AIMS&METHODS:</bold> This monocentric, retrospective study was based on the ADA prescribing practices of two physicians implicated in the management of CD patients: one using the classical (CLA) dose (160 mg w0, 80 mg w2 and 40 mg eow), the other using the systematic optimized (OPT) dose (160 mg w0 and 80 eow). Outpatients with moderate to severe CD, treated with ADA and followed every three months between 2007 and 2011, were studied. Baseline characteristics, efficacy and tolerance of the two regimens were assessed. Results are expressed as percentage and median. Comparisons were performed using Chi-square tests for qualitative parameters, exact Fisher tests (for small sample size) and Mann-Whitney tests for quantitative parameters.</p><p><bold>RESULTS:</bold> A total of 84 patients (39 CLA and 45 OPT) were analyzed. Baseline characteristics were similar between the two groups. In the CLA and OPT groups, 30.8% and 28.9% of patients had concomitant immunosuppressive drugs, 33.3% and 46.7% of patients were on second line of anti TNF alpha therapy and at baseline, the median Harvey Bradshaw Index (HBI) was 11.6 and 10.7, respectively (NS). At 3, 6, 9 and 12 months, the steroid-free remission (HBI<4) rates were 66.7%, 65.8%, 59% and 40.7% in the CLA group and 84.4%, 84.2%, 82% and 81.3% in the OPT group respectively (p=0.05 at months 3 and 6, p=0.01 at month 9 and p=0.001 at month 12). During follow-up, treatment optimization was required in 64.1% of CLA patients versus 13.3% of OPT patients (p<0.0001); in 31.1% of patients in the OPT group it was possible to taper the maintenance regimen to 40 mg eow. There was no significant difference concerning the occurrence of side effects (tumor, dermatological, infectious, and rheumatic) between groups.</p><p><bold>CONCLUSION:</bold> In moderate to severe CD patients, maintenance treatment with ADA optimized at 80 mg eow appears to be more effective than the standard regimen, with a similar tolerance. These results should be confirmed by a prospective controlled study.</p><p><bold>Contact E-mail Address:</bold><email>filippi.j@chu-nice.fr</email></p><p><bold>Disclosure of Interest</bold>: J. Filippi Lecture fee(s) from: Abbott, Ferring, MSD, Norgine, Consultancy for: Abbott, Astellas Pharma, D. Agrefilo: None Declared, E. Fontas: None Declared, X. Hébuterne Lecture fee(s) from: Abbott, Ferring, Fresenius-Kabi, MSD, Norgine, Nutricia, Consultancy for: Abbott, Fresenius-Kabi, Nestlé</p><p><bold>Keywords:</bold> adalimumab, anti TNF therapy, Crohn's disease</p></sec><sec><title>OP448 RESIDUAL ADALIMUMAB TROUGH LEVELS ARE ASSOCIATED WITH CLINICAL REMISSION AND MUCOSAL HEALING IN IBD.</title><p><bold>X. Roblin</bold><sup>1,*</sup>, M. Rinaudo<sup>1</sup>, H. marotte<sup>1</sup>, E. Del Tedesco<sup>1</sup>, J. M. phelip<sup>1</sup>, L. Peyrin-Biroulet<sup>2</sup>, S. paul<sup>1</sup></p><p><italic><sup>1</sup>university of saint etienne, saint etienne, <sup>2</sup>CHU Nancy, Nancy, France</italic></p><p><bold>INTRODUCTION:</bold> Few data have been reported on the impact of residual adalimumab trough levels, antibodies against adalimumab (ADAb) and clinical response in IBD. In addition, there is no data on the impact of these assays on mucosal healing (MH). The aim of our study was to investigate whether there was a relationship between residual adalimumab trough levels and ADAb regarding the clinical response in IBD patients and also to search for a link between these rates and the presence of MH.</p><p><bold>AIMS&METHODS:</bold> This is a trans sectional study that included any patient with IBD under ADA maintenance therapy and for who we have the patient record clinical activity, endoscopy score, residual adalimumab trough levels and ADAb during the same period. Clinical remission was defined for Crohn by a CDAI <150 and for Ulcerative Colitis (UC) with a Mayo score <4. MH was defined as a Mayo endoscopic score mayo <2 for UC and by the disappearance of ulceration in Crohn patients. Residual adalimumab trough levels and ADAb were measured with the Premium Lisa-Tracker assay (Theradiag, France) in blind of the clinical datas.</p><p><bold>RESULTS:</bold> 40 patients under ADA maintenance (or 40mg per day during 14 days or 40mg / 7j) were included (mean age: 42 + / - 13 years, sex ratio M / F: 1.6). Among the 22 patients with Crohn disease (13 L1), seven had clinical remission (31%). MH was reported in 8 cases (36%). 18 patients had a UC (E3 14) and were in clinical remission in 33% of cases (N: 6) and mucosal healing in 8 cases (44%). Adalimumab rates observed were 4.9 µg/ml (1.9-6 µg/ml) and ADAb rate of 4.6 ng/ml (0.9 to 6.8 ng/ml)). Seven patients had ADAb levels > 10 ng/ml and none of them had MH. Median of residual adalimumab trough levels were significantly higher in patients with clinical remission (7.1 vs 4.1 µg/ml, p=0.012). Similarly, residual adalimumab trough levels were also significantly higher in patients with mucosal healing (7.4 vs 3.9 µg/ml, p=0.0053). These results were the same whatever the type of IBD. On multivariate analysis, two independent factors are associated with healing mucosa (trough levels of ADA (RR : 0.62, 95%CI: 0.40-0.94;p=0.026) and disease duration (RR : 0.82, 95%CI: 0.68-0.97; p=0.026). The ADAb median were identical regardless the presence or the absence of clinical remission or MH.</p><p><bold>CONCLUSION:</bold> Residual adalimumab trough levels were significantly higher in cases of clinical remission and mucosal healing presence in IBD patients under adalimumab treatment. Rates of ADAb levels are negative predictors of MH.</p><p><bold>Disclosure of Interest</bold>: X. Roblin Consultancy for: Abbott, Theradiag, M. Rinaudo: None Declared, H. marotte: None Declared, E. Del Tedesco: None Declared, J. M. phelip: None Declared, L. Peyrin-Biroulet: None Declared, S. paul: None Declared</p><p><bold>Keywords:</bold> adalimumab, IBD, mucosal healing, trough levels</p></sec><sec><title>OP449 THE CLINICAL SIGNIFICANCE OF ANTIBODY TO INFLIXIMAB FORMATION IN INFLAMATORY BOWEL DISEASE PATIENTS ON INFLIXIMAB MAINTENANCE</title><p><bold>H. Awadie</bold><sup>1,*</sup>, H. Bar Yoseph<sup>1</sup>, S. Ben Horin<sup>2</sup>, Y. Chowers<sup>1</sup>, M. Waterman<sup>3</sup></p><p><italic><sup>1</sup>Gastroenterology, Rambam Health Care Campus, Haifa, <sup>2</sup>Gastroenterology, Sheba Medical Center, Tel Aviv, <sup>3</sup>Gastroenterology, Rambam Health Care Campus&The B. Rappaport Faculty of Medicine – The Technion, Haifa, Israel</italic></p><p><bold>INTRODUCTION:</bold> Infliximab therapy in patients with inflammatory bowel disease (IBD) is highly effective though up to 40% of patients lose response to infliximab. Antibodies to infliximab (ATI) formation, occurs in 6-17% of patients on scheduled infliximab maintenance therapy and are associated with loss of response. The aim of our study is to assess the clinical significance of ATI formation in IBD patients on maintenance therapy with infliximab</p><p><bold>AIMS&METHODS:</bold> Infliximab (IFX) trough levels and ATI at trough were prospectively determined in IBD patients on maintenance infliximab (IFX) therapy, using anti lambda chain enzyme linked immunosorbent assay (ELISA). Only patients on IFX maintenance therapy with at least 3 ATI tests were included. Patients were divided according to ATI levels into two groups: sustained negative (<1 mcg/ml) ATI levels (LATI), and fluctuating ATI (FATI) levels (at least one sample with ATI < 1 and at least one >1mcg/ml). Meticulous retrospective chart review was performed to assess clinical response - defined as stable dosing of IFX and no change in therapy alongside with physician's note on patient's good clinical status. Statistical analysis comparing FATI to LATI was performed using student's t-test for continuous variables and Chi square for categorical variables. A two-tailed p-value≤0.05 was considered significant</p><p><bold>RESULTS:</bold> Forty-eight IBD patients with available clinical data and serum samples were included. Twenty five patients had sustained low ATI levels and 23 patients had fluctuating ATI levels. Both groups were similar in IBD subtype distribution (CD in 73.9% and 60% of FATI and LATI groups, respectively), mean age at last follow-up (37 vs. 43 years), mean serum albumin levels (4.2 VS. 3.9 gr/dl), rates of concomitant immunomodulator therapy (82% and 80%), and mean trough serum IFX levels (3.3 vs. 4.6 mcg/ml) in FATI and LATI groups, respectively. There were similar rates of clinical response (64% vs. 76%), and mean serum C-reactive protein levels (9.4 vs. 8.5 mg/dl, ULN=5) in the FATI and LATI groups. Subgroup analysis looking specifically at clinical response in the FATI and LATI according to IBD subtype, showed similar response rates in UC (33% vs. 40%, respectively) and in CD (76% vs. 100%, respectively)</p><p><bold>CONCLUSION:</bold> IBD patients on scheduled infliximab maintenance with fluctuating ATI formation pattern have similar rates of clinical response and remission compared with patients without ATI</p><p><bold>Contact E-mail Address:</bold><email>h_awadie@rambam.health.gov.il</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> antibodies to infliximab, inflamatory bowel disease, biological therapy</p></sec><sec><title>OP450 ASSOCIATION BETWEEN THIOPURINES METABOLITES LEVELS AND CLINICAL REMISSION IN IBD PATIENTS : AN UPDATED META-ANALYSIS</title><p><bold>A. moreau</bold><sup>1</sup>, S. laporte<sup>1</sup>, E. deltedesco<sup>1</sup>, S. paul<sup>1</sup>, J. M. phelip<sup>1</sup>, L. peyrin-biroulet<sup>2</sup>, X. Roblin<sup>1,*</sup></p><p><italic><sup>1</sup>university of saint etienne, saint etienne, <sup>2</sup>CHU Nancy, Nancy, France</italic></p><p><bold>INTRODUCTION:</bold> A first meta-analysis, published in 2006, support the association between thiopurines metabolites levels (6-thioguanine nucleotides or 6-TGN) and clinical remission. This meta-analysis has pooled the results of 6 studies (N = 518 patients). Since then, several studies have been published and some of them present conflicting conclusions. Therefore, an update of this first meta-analysis has been performed.</p><p><bold>AIMS&METHODS:</bold> A systematic search was performed up to July 2012. The primary goal was to assess the association between thiopurines metabolites levels and clinical remission in IBD patients. Secondary objectives were to evaluate whether or not the association was influenced by differences in study design such as the presence of a selection and/or information bias (misclassification by differences in disease activity scores, metabolites concentration assays). A Mantel-Haenszel pooled risk estimate provide a measure of that association. The Cochran <italic>Q </italic>test and the <italic>I</italic>2 statistic were used to evaluate heterogeneity between studies. Two different softwares were used for all statistical analysis (Revman® and R).</p><p><bold>RESULTS:</bold> A total of 20 studies were included in this meta-analysis (N=2405 patients). When studying datas with a cut-off level of 230 pmol / 8.10<sup>8</sup> RBC (N= 2234 patients), the pooled OR was 2.09 (95% CI, 1.53-2.87, p<.00001). Visual inspection of funnel plot asymmetry and statistical asymmetry tests were also performed. Neither showed indication of publication bias. A sensitivity analysis was conducted and showed no significant difference in the overall OR with removal of any individual study.</p><p><bold>CONCLUSION:</bold> This meta-analysis reassert the utility of using cut-off levels of thiopurines metabolites for the monitoring of IBD patients. The results of the cumulative meta-analysis are univocals and representative: the OR stabilizes with time and it clearly demonstrates the inutility to perform any more studies to establish the association between thiopurines metabolites levels and clinical remission in IBD patients.</p><p><bold>REFERENCES:</bold></p><p>1. Association of 6-thioguanine nucleotide levels and inflammatory bowel disease activity: a meta analysis<bold>.</bold> OstermanMT, Kundu R, Lichtenstein GR, Lewis JD. <italic>Gastroenterology</italic>. 2006 Apr;130(4):1047-53.</p><p><bold>Contact E-mail Address:</bold><email>xavier.roblin@chu-st-etienne.fr</email></p><p><bold>Disclosure of Interest</bold>: A. moreau: None Declared, S. laporte: None Declared, E. deltedesco: None Declared, S. paul: None Declared, J. M. phelip: None Declared, L. peyrin-biroulet: None Declared, X. Roblin Consultancy for: HAC Pharma</p><p><bold>Keywords:</bold> azathioprine, IBD, thioguanine nucleotides</p></sec><sec><title></title><p><bold>WEDNESDAY, OCTOBER 16, 2013 14:00-15:30</bold></p><p><bold>GI Surgery: What's new in 2013? – Hall 6</bold></p></sec><sec><title>OP451 RECURRENCES AFTER ENDOSCOPIC STENTING AS TREATMENT FOR ACUTE MALIGNANT COLONIC OBSTRUCTION IN THE DUTCH STENT-IN 2 TRIAL .</title><p><bold>D. A. Sloothaak</bold><sup>1,*</sup>, M. W. van der Berg<sup>2</sup>, M. G. Dijkgraaf<sup>3</sup>, P. Fockens<sup>2</sup>, P. J. Tanis<sup>1</sup>, J. W. van Hooft<sup>2</sup>, W. A. Bemelman<sup>1</sup> and collaborative Dutch Stent-In study group</p><p><italic><sup>1</sup>Surgery, <sup>2</sup>Gastroenterology and Hepatology, <sup>3</sup> Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center Amsterdam, Amsterdam, Netherlands</italic></p><p><bold>INTRODUCTION:</bold> The Stent-in-2 trial randomised patients with acute malignant colonic obstructions between treatment with endoscopic stent as a bridge to elective surgery and emergency surgery. The rate of clinical and subclinical stent related tumour perforations was unexpectedly high. Potential oncological consequences of these (sub)clinical perforations are not clear.</p><p><bold>AIMS&METHODS:</bold> The aim of our study was to compared the risk of cancer recurrence after endoscopic stenting for acute malignant colonic obstructions to that of emergency surgery. Medical charts from eligible patients of the Stent-in-2 trial (n=97), with proven malignancy of the obstructing tumour and potential curable disease (n=58), were reviewed. Data was collected about adjuvant treatment, cancer recurrence and survival. We calculated the 5 year overall, and locoregional recurrence rates and used a competing risk analysis to explore differences in the cumulative incidence of recurrence. Patients in the stent group with a (sub)clinical perforation (n=6) were identified for a subgroup analysis.</p><p><bold>RESULTS:</bold> Emergency surgery was performed in 32 (55%) patients and endoscopic stenting as a bridge to surgery in 26 (45%) patients. Patient, and tumour characteristics and the use of adjuvant chemotherapy were comparable between the two groups. The median follow up was 38 months (IQR 18-44) in the emergency surgery group and 36 months (IQR 34-49) in the stent group. The 5 year overall recurrence rate was 25% (n=8) and 42% (n=11), respectively (p=0.027). The locoregional recurrence rate was 9% (n=3) and 19% (n=5), respectively (p=0.052). The cumulative incidence of overall recurrences in patients with a (sub)clinical stent related perforation was 83% [CI95% 58-100] which was significantly increased compared to patients who underwent emergency surgery or stenting without perforation (26% [CI95% 14-47], 34% [CI95% 18-65], respectively, p = 0.0072). The cumulative incidence of locoregional recurrences within 5 years was also increased in patients with a (sub)clinical stent related perforation (50% [CI95% 22-100], 11% [CI95% 3-41], 10 [CI95% 3-28], respectively, p = 0.053).</p><p><bold>CONCLUSION:</bold> Although the small number of patients in our study can be considered as a limitation, our results relate to a prospective cohort with a low risk of allocation bias. Clinical and subclinical perforations after endoscopic stenting for malignant colonic obstructions seem to be associated with an increased risk of recurrent disease.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> colon cancer, Stenting</p></sec><sec><title>OP452 SIMPLIFYING ENDOSCOPIC EN-BLOC-RESECTION OF LARGE LESIONS BY COMBINING A NEW INSTRUMENT AND A SPECIAL REGARD TO THE IMPEDANCE OF SUBMUCOSAL INJECTION SOLUTIONS</title><p><bold>N. Al-Dayaa</bold><sup>1,*</sup>, N. Quaas<sup>1</sup>, M. Lösle<sup>1,2</sup>, K. E. Grund<sup>1,2</sup></p><p><italic><sup>1</sup>Surgical Endoscopy, Department of General, Visceral and Transplant Surgery, University Hospital, Tübingen, <sup>2</sup>supported by: Federal Ministry of Economics and Technology based on a resolution of the Bundestag, Berlin, Germany</italic></p><p><bold>INTRODUCTION:</bold> Till today the removal of large (Ø >20 mm) and difficult lesions is a great challenge for high-frequency (HF) surgery. New instruments and injection solutions have been developed to decrease the complication rates and to facilitate the resection. However the correlation between HF-parameters (alternating current, alternating voltage and impedance) and the cutting result is not in focus of these developments. Previous results led to the conclusion that a high impedance of the tissue is essential for the removal of large lesions in the gastrointestinal tract.</p><p><bold>AIMS&METHODS:</bold> In large lesions the contact surface of the snare is bigger than in small lesions which results in a lower impedance. A low impedance can cause problems with the HF-surgical cutting process, so our aim was to increase the impedance by developing a new instrument and finding a submucosal injection solution with few electrolytes.</p><p>We compared the impedance (RF-impedance-meter, f. 100 kHz) of snares with wires of varying lengths in a standard solution for submucosal injection (0,9% saline) and during the resection of imitated lesions (Ø 20 mm) in isolated porcine stomachs.</p><p>With standardized electrodes (gold probes 1mm/15mm) we measured the impedance (RF-impedance-meter, f. 100 kHz) of various solutions isolated and after injection of 3 ml into the submucosa of isolated porcine stomachs. Following solutions were tested: 0,9% saline, 4% gelatine, 6% hydroxyethyl starch, 10% glycerol/5% fructose in 0,9% saline and 10% glucose solution.</p><p><bold>RESULTS:</bold> The measuring of the impedance with varying cutting-wires in 0,9% saline solution showed an exponential increase of the impedance during reduction of the length of the wire. During the resection the impedance showed a mean increase by 175% by varying the length of the wire from 30 mm to 10 mm.</p><p>The 10% glucose solution had a significantly (p < 0,001) higher impedance (plus 53-156%) than the other submucosal injection solutions. The other tested solutions showed no significant difference in the impedance compared to 0,9% saline solution.</p><p><bold>CONCLUSION:</bold> For the first time we investigated the differences in the impedance concerning the length of the cutting-wire and various submucosal injection solutions. We developed a new instrument with a partially insulated snare-wire so the cutting part of the wire is very short (15 mm). This instrument in combination with an optimal injection solution with fewer electrolytes opens up new possibilities for the expansion and improvement of conventional resection techniques (polypectomy and EMR) and as an alternative to ESD.</p><p><bold>Contact E-mail Address:</bold><email>chir.endo@uni-tuebingen.de</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> EMR, HF-Surgery, Large Lesions, Submucosal Injection Solution</p></sec><sec><title></title><p><bold>WEDNESDAY, OCTOBER 16, 2013 14:00-15:30</bold></p><p><bold>Nutrition: From the nursery to the nursing home – Hall 10</bold></p></sec><sec><title>OP453 VIOLATIONS TO THE ESPGHAN PEDIATRIC GUIDELINES FOR ACUTE GASTROENTERITIS IN 11 EUROPEAN COUNTRIES</title><p><bold>E. Nicastro</bold><sup>1,*</sup>, I. Liguoro<sup>1</sup>, A. Lo Vecchio<sup>1</sup>, A. Chmielewska<sup>2</sup>, M. Pieścik<sup>2</sup>, C. De Bruyn<sup>3</sup>, J. Dolinsek<sup>4</sup>, E. Doroshina<sup>5</sup>, S. Fessatou<sup>6</sup>, T. L. Pop<sup>7</sup>, C. Prell<sup>8</sup>, M. Tabbers<sup>9</sup>, M. Tavares<sup>10</sup>, P. Urenden<sup>11</sup>, A. Guarino<sup>12</sup> and the Tutorial European Electronic Network on Acute Gastroenteritis (TEEN-AGE) working group</p><p><italic><sup>1</sup>Department of Translational Medical Sciences, Pediatric Area, University Federico II, Naples, Italy, <sup>2</sup>2nd Department of Pediatrics, The Medical University of Warsaw, Warsaw, Poland, <sup>3</sup>CDB Universitair Ziekenhuis Brussel Kinderen, Vrije Universiteit Brussel, Brussels, Belgium, <sup>4</sup>University Medical Centre, Maribor, Slovenia, <sup>5</sup>Russian Medical Postgraduate Academy, Moscow, Russian Federation, <sup>6</sup>First Department of Pediatrics, Athens Children's Hospital “P. & A. Kyriakou”, Athens, Greece, <sup>7</sup>"Iuliu Hatieganu" University of Medicine and Pharmacy,, Cluj-Napoca, Romania, <sup>8</sup>Division of Paediatric Gastroenterology & Hepatology, University of Munich Medical Center, Munich, Germany, <sup>9</sup>Emma's Children's Hospital Academic Medical Centre, Amsterdam, Netherlands, <sup>10</sup>Department of Pediatrics, Hospital Sao Joao, Porto, Portugal, <sup>11</sup>Department of Pediatrics, Marmara University, Istanbul, Turkey, <sup>12</sup>Department of Translational Medical Sciences, University Federico II, Naples, Italy</italic></p><p><bold>INTRODUCTION:</bold> The Tutorial European Electronic Network on Acute gastroenteritis (TEEN-AGE) is a project of implementation of ESPGHAN/ESPID pediatric guidelines for acute gastroenteritis (AGE) in Europe through an e-learning course hosted by the UEG platform (1).</p><p><bold>AIMS&METHODS:</bold> We aimed at investigating the adherence to AGE guidelines in in- and out-patients < 5 years. Patients’ data were collected by the physicians participating in the network before the e-learning course and loaded in a CRF available on the UEG website.</p><p><bold>RESULTS:</bold> We enrolled 278 children (143 boys, mean age 23±16 months), 184 in- and 94 out-patients. Only 39.4% of the outpatients and 51% of the inpatients received oral rehydration solution (ORS) at home. Among the inpatients, 120/184 (65.2%) presented more than 3 episodes of vomiting/24 hors. Physicians reported a dehydration > 5% in 100/184 (54.3%) of the children. Severe dehydration and ORS failure were the reasons for admission in 39.2% and 30.9% of cases, respectively. Only 63.6% of hospitalized children needed IV rehydration and in only 16.8% a weight gain > 5% was observed at discharge, indicating a low rate of severely dehydrated children among those who were hospitalized. Inappropriate changes in diet were done in 30.9% of the outpatients and in 33.7% of the inpatients. All the inpatients and 46.8% of the outpatients underwent laboratory investigations, while stool culture were done in 53.3% (inpatients) and 16% (outpatients) of cases, respectively.</p><p><bold>CONCLUSION:</bold> Unnecessary, invasive and expensive interventions were commonly observed in clinical management of AGE, including an excess of admissions with low rate of intravenous rehydration and the negligible difference of weight between admission and discharge. Unnecessary investigation were also prescribed. The second phase of the TEEN-AGE will aim at reducing the violations to the guidelines recommendations through the e-learning implementation.</p><p><bold>REFERENCES:</bold></p><p>1. <ext-link ext-link-type="uri" xlink:href="http://www.e-learning.ueg.eu/courses/course-summary.html?eprs%5Br%5D=18362">http://www.e-learning.ueg.eu/courses/course-summary.html?eprs%5Br%5D=18362</ext-link></p><p><bold>Contact E-mail Address:</bold><email>emanuele.nicastro@unina.it</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> children, e-learning, ESPGHAN guidelines, gastroenteritis</p></sec><sec><title>OP454 EFFICACY AND ADVERSE EVENTS OF LAPAROSCOPIC GASTROSTOMY PLACEMENTS IN CHILDREN: RESULTS OF A LARGE COHORT STUDY</title><p><bold>J. Franken</bold><sup>1</sup>, F. A. Mauritz<sup>1,2,*</sup>, D. C. van der Zee<sup>1</sup>, M. Y. van Herwaarden-Lindeboom<sup>1</sup></p><p><italic><sup>1</sup>Pediatric Surgery, Wilhelmina Children's Hospital, University Medical Center Utrecht, <sup>2</sup>Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, Netherlands</italic></p><p><bold>INTRODUCTION:</bold> The placement of a gastrostomy tube is an established treatment to provide enteral feeding directly via the stomach. Available data on long-term outcomes of a laparoscopic gastrostomy (LAG) with regard to the efficacy and adverse events, specifically gastroesophageal reflux (GER) are limited. Furthermore, some studies advocate the routine use of preoperative 24-hour pH monitoring to predict postoperative GER symptoms; however, this predictive value is under debate.</p><p><bold>AIMS&METHODS:</bold> The aim of this study is to evaluate long-term efficacy and adverse events after LAG. A retrospective observational cohort study was performed including all 300 patients that underwent LAG between January 2004 and December 2011. The median age at the time of operation was 2.66 years (IQR 1.28 – 7.44). The majority of patients (75.0%) were neurologically impaired. Endpoints for efficacy were successful feeding and weight-for-length and length-for-age z-scores and endpoints to evaluate adverse events were complications, reinterventions and GER symptoms.</p><p><bold>RESULTS:</bold> After a median follow-up of 2.63 years (IQR 1.07 – 4.77), feeding through the gastrostomy was successful in 255 patients (95.9%). Weight-for-length z-scores had significantly increased after operation compared to preoperative measures (-0,98SDS to -0,26SDS; p<0.0005). Length-for-age z-score remained similar (p=0.695). Major complications, such as stomach wall dehiscence and intraoperative bleeding were seen in 6 patients (2.0%). Minor complications, mainly hypergranulation, leakage, wound infection and early catherer dislodgement were encountered in 221 patients (74.0%). A total number of 48 reinterventions was needed to treat complications. In 28.2% of patients with preoperative GER, reflux symptoms dissolved after operation. However, de novo postoperative GER symptoms were present in 34.2% (p=0.824). Preoperative 24-hour pH monitoring was performed in 180 patients (60%). The sensitivity and specificity of the preoperative 24-hour pH monitoring to identify patient with postoperative reflux symptoms were respectively 17.5% and 76.9%.</p><p><bold>CONCLUSION:</bold> LAG placement in children leads to successful feeding in 96% of patients and is associated with a low risk of developing serious adverse events; however, minor complications were very frequently encountered. Contrary to the results of previous studies, the incidence of GER symptoms does not increase after LAG and preoperative 24-hour pH monitoring is not a reliable tool to accurately predict postoperative GER symptoms, since a large percentage of patients with postoperative GER symptoms have negative preoperative pH measurements.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> children, enteral feeding, gastroesophageal reflux, laparoscopic gastrostomy</p></sec><sec><title>OP455 ETHANOL AND TAUROLIDINE LINE LOCKS FOR THE REDUCTION AND TREATMENT OF CATHETER RELATED BLOOD STREAM INFECTIONS IN PAEDIATRIC INTESTINAL FAILURE: A SYSTEMATIC REVIEW AND META-ANALYSIS</title><p><bold>P. Henderson</bold><sup>1</sup>, R. Tayler<sup>2</sup>, D. C. Wilson<sup>1</sup>, A. Barclay<sup>2,*</sup></p><p><italic><sup>1</sup>Child Life and Health, University of Edinburgh, Edinburgh, <sup>2</sup>Paediatric Gastroenterology , RHSC, Glasgow , United Kingdom</italic></p><p><bold>INTRODUCTION:</bold> Paediatric intestinal failure (PIF: dependency on parental nutrition (PN) for ≥28 days) requires a central venous catheter (CVC) for PN administration, with significant morbidity and mortality associated with catheter-related blood stream infection (CRBSI). Studies suggest that specialised line locks containing ethanol or taurolidine may significantly reduce CRSBI for PIF.</p><p><bold>AIMS&METHODS:</bold> Our aim was systematically review the evidence for effectiveness of ethanol and taurolidine line locks in the prevention or treatment of CRBSI in PIF. Systematic retrieval of data from studies of PIF was obtained (PN >28 days, age <18yr). Electronic searches of the Cochrane Library, MEDLINE (1946 –April 2013) and PubMed (to April 2013) were made using keyword and MeSH terms 'Intestinal failure', 'child' , 'ethanol locks' and 'taurolidine locks'. Hand searches were also performed. Two authors independently assessed the level of evidence (EL) using SIGN methodology (<ext-link ext-link-type="uri" xlink:href="www.sign.ac.uk">www.sign.ac.uk</ext-link>). Outcome measures were the reduction in rates of CRBSI or eradication of CRBSI with rates expressed per 1000 CVC days; a meta-analysis was also performed using RevMan</p><p><bold>RESULTS:</bold><table-wrap id="table63-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1">Study</th><th rowspan="1" colspan="1">EL</th><th rowspan="1" colspan="1">Rx Group</th><th rowspan="1" colspan="1">Intervention</th><th rowspan="1" colspan="1">Reduction in CRBSI per 1000 CVC days</th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">Jones</td><td rowspan="1" colspan="1">2-</td><td rowspan="1" colspan="1">23</td><td rowspan="1" colspan="1">70% ethanol</td><td rowspan="1" colspan="1">9.9 to 2.1</td></tr><tr><td rowspan="1" colspan="1">Wales</td><td rowspan="1" colspan="1">2-</td><td rowspan="1" colspan="1">10</td><td rowspan="1" colspan="1">70% ethanol</td><td rowspan="1" colspan="1">10.2 to 0.3</td></tr><tr><td rowspan="1" colspan="1">Blackwood</td><td rowspan="1" colspan="1">3</td><td rowspan="1" colspan="1">2</td><td rowspan="1" colspan="1">70% ethanol</td><td rowspan="1" colspan="1">-</td></tr><tr><td rowspan="1" colspan="1">Cober</td><td rowspan="1" colspan="1">2-</td><td rowspan="1" colspan="1">15</td><td rowspan="1" colspan="1">70% ethanol</td><td rowspan="1" colspan="1">7.9 to 0.5</td></tr><tr><td rowspan="1" colspan="1">Onland</td><td rowspan="1" colspan="1">3</td><td rowspan="1" colspan="1">9</td><td rowspan="1" colspan="1">70% ethanol</td><td rowspan="1" colspan="1">-</td></tr><tr><td rowspan="1" colspan="1">Mouw</td><td rowspan="1" colspan="1">2-</td><td rowspan="1" colspan="1">5</td><td rowspan="1" colspan="1">70% ethanol</td><td rowspan="1" colspan="1">11.5 to 2.3</td></tr><tr><td rowspan="1" colspan="1">McGrath</td><td rowspan="1" colspan="1">3</td><td rowspan="1" colspan="1">7</td><td rowspan="1" colspan="1">70% ethanol</td><td rowspan="1" colspan="1">-</td></tr><tr><td rowspan="1" colspan="1">Chu</td><td rowspan="1" colspan="1">2-</td><td rowspan="1" colspan="1">19</td><td rowspan="1" colspan="1">Taurolidine</td><td rowspan="1" colspan="1">8.6 to 1.2</td></tr><tr><td rowspan="1" colspan="1">Pieroni 2013</td><td rowspan="1" colspan="1">2-</td><td rowspan="1" colspan="1">20</td><td rowspan="1" colspan="1">70% ethanol</td><td rowspan="1" colspan="1">9.8 to 2.7</td></tr></tbody></table></table-wrap></p><p>The search strategy yielded 3142967 hits. Combination searches using 'intestinal failure' and 'Child' reduced this to 2993. 15 studies were read in detail; five were excluded due to containing purely adult data or where data on PIF alone could not be extracted. Ten studies were included in our review, six of CRBSI prevention and four of CRSBI treatment. 8 studies used ethanol alone and 1 reported taurolidine use (Table; 2 studies by Pieroni reported duplicate data, only the later one is shown). Four studies reported success in prevention of recurrent line sepsis. 2 thrombotic episodes were reported. A meta-analysis of the five studies reported ethanol locks for CRBSI prevention demonstrated a reduction in CRBSI by 7.47 events (95% CI 5.86-9.08) per 1000 catheter days.</p><p><bold>CONCLUSION:</bold> Although data for the use of ethanol line locks are limited and of poor methodological quality (and thus of lower EL), ethanol locks appear to be an effective therapy in CRBSI prevention and treatment. With only one study of taurolidine locks, no clear conclusions can be made. Well designed studies are warranted to compare these two treatments.</p><p><bold>Contact E-mail Address:</bold><email>andrew.barclay@ggc.scot.nhs.uk</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> central line sepsis , intestinal failure , parenteral nutrition</p></sec><sec><title>OP456 DOES INSERTION OF A GASTROSTOMY CONFER ANY QUALITY OF LIFE BENEFIT TO EITHER PATIENTS OR THEIR CARERS?</title><p><bold>M. Kurien</bold><sup>1,*</sup>, M. E. McAlindon<sup>1</sup>, J. Grant<sup>1</sup>, E. F. Wong<sup>1</sup>, A. Johnston<sup>1</sup>, B. Hoeroldt<sup>2</sup>, K. L. Dear<sup>3</sup>, D. S. Sanders<sup>1</sup></p><p><italic><sup>1</sup>Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield, <sup>2</sup>Department of Gastroenterology, Rotherham District General Hospital, Rotherham, <sup>3</sup>Department of Gastroenterology, Chesterfield Royal Hospital, Chesterfield, United Kingdom</italic></p><p><bold>INTRODUCTION:</bold> Gastrostomy feeding is an effective means of providing enteral nutrition to patients who have functionally normal gastrointestinal tracts but who cannot meet their nutritional requirements because of an inadequate oral intake. Whilst improvements in outcome measures such as nutritional status and mortality have been demonstrated in certain patients undergoing gastrostomy insertion, there remains a paucity of work evaluating another important health outcome measure, which is health related quality of life (HRQoL). Furthermore no previous study has looked at the impact on carers’ HRQoL when considering all referral indications for gastrostomy. This prospective, multicenter study evaluates HRQoL in both gastrostomy patients and their carers, with comparisons made with a population control group.</p><p><bold>AIMS&METHODS:</bold> 61 patients (mean age 68 years) and 58 carers (mean age 65 years) were prospectively recruited from 4 hospitals in South Yorkshire between Feb-Dec 2012. All individuals had HRQoL evaluated prior to gastrostomy insertion, with repeated measurements undertaken at 3 months. Assessment was undertaken using EQ-5D, a validated assessment tool and preferential measure used by NICE, producing scores between 0 for dead and 1 for perfect health. Findings were then compared with a separate cohort of population controls (n=419), to determine if differences existed in HRQoL. Non-parametric statistical analysis was undertaken using a Wilcoxon Rank test to compare longitudinal paired EQ-5D scores, and a Mann-Whitney test to compare EQ-5D scores between groups, with p values <0.05 considered significant.</p><p><bold>RESULTS:</bold> 61 gastrostomy patients have been assessed to date. Of these, 3 died prior the 3 month reassessment post insertion. No significant change was shown in mean EQ-5D scores in either the gastrostomy patients (0.74 versus 0.73, p=0.11) or their carers (0.96 versus 0.97, p=0.30) at 3 months following gastrostomy insertion. When compared to population controls, carers had comparable scores to the population controls unlike the gastrostomy patients who had significantly lower mean EQ-5D scores (0.73 versus 0.94, p<0.0001).</p><p><bold>CONCLUSION:</bold> This study demonstrates that HRQoL does not significantly improve for patients or their carers following gastrostomy insertion. Given that gastrostomy feeding has no positive effect on HRQoL, questions must be raised as to the merits of this intervention if it only serves to improve physiological outcomes.</p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Gastrostomy, Nutrition</p></sec><sec><title>OP457 ASSESSING LEVELS OF PAIN AND ANXIETY AFTER PEG INSERTION IN BOTH COMMUNICATIVE AND NON-COMMUNICATIVE PATIENTS</title><p><bold>P. Oppong</bold><sup>1</sup>, S. Cochrane<sup>1,*</sup>, N. Pitts<sup>1</sup>, V. Chudleigh<sup>2</sup>, S. Lewis<sup>1</sup></p><p><italic><sup>1</sup>Gastroenterology, <sup>2</sup>Dietetics, Derriford Hospital, Plymouth, United Kingdom</italic></p><p><bold>INTRODUCTION:</bold> Abdominal pain following percutaneous endoscopic gastrostomy (PEG) placement is considered to be secondary to a chemical peritonitis. However, the prevalence and degree of severity of pain is poorly characterised. Abdominal pain following liver biopsy is strongly linked to preprocedural anxiety levels<sup>1</sup>. We assessed abdominal pain and anxiety associated with PEG placement.</p><p><bold>AIMS&METHODS:</bold> A prospective questionnaire assessed patient anxiety and abdominal pain 1 hour (h) pre PEG placement, 1h post and 24h post using a 10-point Likert scale. The questionnaire was completed by the patient where possible or clinician if not. Abdominal pain was assessed by examination at 1h post procedure. 24h post procedure complications and analgesia requirements were recorded. Patients’ Mini Mental Score (MMSE, 0-30) and Barthel index (0-20) were completed.</p><p><bold>RESULTS:</bold> 70 consecutive patients (M:F 45:25) median age 61.5 (19-94) were assessed. The commonest indications were head and neck malignancies (44%) and stroke (11%). First pass rate was 97%, with no clinical complications recorded.</p><p> Mean (StD), MMSE, Barthel, anxiety and pain scores
<table-wrap id="table64-2050640613502899" position="float"><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1"></th><th rowspan="1" colspan="1"><bold>MMSE</bold></th><th rowspan="1" colspan="1"><bold>Barthel</bold></th><th colspan="3" rowspan="1"><hr></hr><bold>Anxiety</bold></th><th colspan="3" rowspan="1"><hr></hr><bold>Pain</bold></th></tr><tr><th rowspan="1" colspan="1"><bold>Assessment</bold></th><th rowspan="1" colspan="1"></th><th rowspan="1" colspan="1"></th><th rowspan="1" colspan="1"><bold>Pre</bold></th><th rowspan="1" colspan="1"><bold>1h post</bold></th><th rowspan="1" colspan="1"><bold>24h post</bold></th><th rowspan="1" colspan="1"><bold>Pre</bold></th><th rowspan="1" colspan="1"><bold>1h post</bold></th><th rowspan="1" colspan="1"><bold>24h post</bold></th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1">Patient n=49</td><td rowspan="1" colspan="1">28.1 (6.4)</td><td rowspan="1" colspan="1">17.8 (5.0)</td><td rowspan="1" colspan="1">3.5 (3.2)</td><td rowspan="1" colspan="1">1.7 (2.3)</td><td rowspan="1" colspan="1">2.8 (2.9)</td><td rowspan="1" colspan="1">0.1 (0.3)</td><td rowspan="1" colspan="1">2.0 (2.3)</td><td rowspan="1" colspan="1">3.4 (2.9)</td></tr><tr><td rowspan="1" colspan="1">Clinician n=21</td><td rowspan="1" colspan="1">6.2 (9.6)</td><td rowspan="1" colspan="1">3.2 (4.3)</td><td rowspan="1" colspan="1">0.3 (0.7)</td><td rowspan="1" colspan="1">0.1 (0.2)</td><td rowspan="1" colspan="1">0.2 (0.7)</td><td rowspan="1" colspan="1">0 (0)</td><td rowspan="1" colspan="1">0 (0)</td><td rowspan="1" colspan="1">0.1 (0.7)</td></tr><tr><td rowspan="1" colspan="1">Combined n=70</td><td rowspan="1" colspan="1">21.6 (12.6)</td><td rowspan="1" colspan="1">13.4 (8.3)</td><td rowspan="1" colspan="1">2.5 (3.0)</td><td rowspan="1" colspan="1">1.2 (2.0)</td><td rowspan="1" colspan="1">2 (2.8)</td><td rowspan="1" colspan="1">0 (0.3)</td><td rowspan="1" colspan="1">1.4 (2.1)</td><td rowspan="1" colspan="1">2.5 (2.9)</td></tr></tbody></table></table-wrap></p><p>24 self-reporting patients had a pain score of 1-3 at 1h post placement and 20 at 24h. 3 patients reported a pain score of 7-10 at 1h and 7 at 24h. 21/49 self-reporting patients and 0/21 non self-reporting had PEG site and/or general abdominal tenderness on clinical examination at 1h.</p><p>Pain post PEG placement was noted in only 1 clinician-assessed patient. This was at 24h. 50.7% of patients took analgesia at 24 hours post procedure (all self-reporting). Regression showed no relationship between pre placement anxiety and post placement pain.</p><p><bold>CONCLUSION:</bold> Pain at 1h post PEG placement was common in self-reporting patients and usually mild. By 24h, 41% reported moderate to severe pain, often taking analgesia. Preprocedural anxiety did not predict post procedural pain. Clinician assessment at 1h and 24h where patients could not self assess failed to identify pain. After PEG placement patients should be offered advice on pain and given access to analgesia. It is likely that pain is not identified in debilitated patients and clinicians need to be more alert to its possible presence.</p><p><bold>REFERENCES:</bold></p><p>1. Riley T. Predictors of pain medication use after percutaneous liver biopsy. <italic>Digest Dis Sci</italic> 2002;47:2151-53</p><p><bold>Contact E-mail Address:</bold><email>sjl@doctors.org.uk</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Pain, Percutaneous endoscopic gastrostomy</p></sec><sec><title>OP458 OPEN LABEL, RANDOMIZED INTERNATIONAL MULTICENTRE STUDY OF THE IMPACT OF DIET ON ‘INFLAMM-AGEING’, OXIDATIVE STRESS AND GUT MICROBIOTA IN ELDERLY PEOPLE (RISTOMED): BENEFITS OF DIETARY ADVICE ALONE OR IN CONJUNCTION WITH VSL#3® PROBIOTIC.</title><p><bold>L. Valentini</bold><sup>1,*</sup>, A. Pinto<sup>2</sup>, I. Bourdel-Marchasson<sup>3</sup>, R. Ostan<sup>4</sup>, P. Brigidi<sup>5</sup>, S. Turroni<sup>5</sup>, S. Hrelia<sup>6</sup>, P. Hrelia<sup>7</sup>, F. Buccolini<sup>8</sup>, C. Franceschi<sup>4</sup>, H. Lochs<sup>1,9</sup></p><p><italic><sup>1</sup>Dept Gastroenterology and Hepatology, Charité-Universitätsmedizin Berlin, CCM, Berlin, Germany, <sup>2</sup>Experimental Medicine Department, Sapienza University of Rome, Rome, Italy, <sup>3</sup>Pole de Gerontologie Clinique, Xavier Arnozan Hospital, Bordeaux, France, <sup>4</sup>Department of Experimental, Diagnostic and Specialty Medicine, <sup>5</sup>Department of Pharmacy and Biotechnology, <sup>6</sup>Dept Life Quality Studies, <sup>7</sup>Dept Pharmacy and Biotechnologies, Alma mater Studiorum University of Bologna, Bologna, <sup>8</sup>R&D, VoxNet CEO, Rome, Italy, <sup>9</sup>Rectorate, Medical University of Innsbruck, Innsbruck, Austria</italic></p><p><bold>INTRODUCTION:</bold> Aging is associated with a phenomenon termed ‘inflamm-aging’, which is characterised by chronic, low-grade pro-inflammatory conditions leading to long-term tissue damage. Reducing chronic low-grade inflammation may be a way to prevent or reduce the severity of age-related diseases. It has been proposed that the age-related changes in gut microbiota, associated with an increase in systemic inflammation may also contribute to the progression of disease and frailty in the elderly. Evidence exists that inflammation, oxidative stress and gut microbiota are influenced by diet or nutraceutical dietary supplements.</p><p><bold>AIMS&METHODS:</bold> To assess the impact of a personalized diet, with or without the addition of VSL#3® probiotic blend, on markers of inflammation, oxidative stress and gut microbiota in elderly individuals. Open label, randomized multicentre study. Setting: Community. Primary endpoint: baseline change in hsCRP (high-sensitivity C-reactive protein). As a part of a larger study, 62 participants were randomized to follow a personalized diet created through a web-based platform (RISTOMED) and optimized to reduce inflammation and oxidative stress, either with or without supplementation with VSL#3®, for 8 weeks.</p><p><bold>RESULTS:</bold> There was no significant change in hsCRP amount in either study arm. However, a subgroup of 17 participants were classified as having high inflammation at baseline, and hsCRP fell significantly in this group (p=0.022). VSL#3® plus diet, but not diet alone, was associated with a significant reduction in homocysteine levels and increases in folate (p<0.01) and vitamin B12 (p=0.03). No significant changes from baseline in total antioxidant activity or gut microbiota composition were observed.</p><p><bold>CONCLUSION:</bold> The RISTOMED diet may reduce inflammation in elderly people with basal high inflammatory status. Addition of VSL#3® was associated with increased folate and vitamin B12 concentrations and significant reduction of homocysteine levels in all participants regardless of inflammatory status. Combined supplementation of VSL#3 with a proper diet may potentially reduce aging-related risks associated with high homocysteine and reduced folate and vitamin B12 levels.</p><p><bold>REFERENCES:</bold></p><p>1. ClinicalTrials.gov: NCT01069445 – NCT01179789</p><p><bold>Contact E-mail Address:</bold><email>luzia.valentini@charite.de</email></p><p><bold>Disclosure of Interest</bold>: None Declared</p><p><bold>Keywords:</bold> Aging, Diet, Gut microbiota, low grade inflammation, oxidative stress, VSL#3 probiotic</p></sec></body></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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