Re-epithelialization of the prostatic urethra after two-micron laser resection of the prostate
Identifieur interne : 000052 ( Pmc/Corpus ); précédent : 000051; suivant : 000053Re-epithelialization of the prostatic urethra after two-micron laser resection of the prostate
Auteurs : Guang-Heng Luo ; Hong Liu ; Lei Luo ; Jun Liu ; Xiu-Shu Yang ; Yan-Dong Wang ; Zhao-Lin Sun ; Shu-Jie XiaSource :
- Asian Journal of Andrology [ 1008-682X ] ; 2015.
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DOI: 10.4103/1008-682X.154993
PubMed: 26178394
PubMed Central: 4736348
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Re-epithelialization of the prostatic urethra after two-micron laser resection of the prostate</title><author><name sortKey="Luo, Guang Heng" sort="Luo, Guang Heng" uniqKey="Luo G" first="Guang-Heng" last="Luo">Guang-Heng Luo</name><affiliation><nlm:aff id="aff1">Department of Urology Surgery, Guizhou Province People's Hospital, Guiyang, China</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">Department of Urology Surgery, Institute of Urology, Shanghai JiaoTong University, Shanghai, China</nlm:aff></affiliation></author><author><name sortKey="Liu, Hong" sort="Liu, Hong" uniqKey="Liu H" first="Hong" last="Liu">Hong Liu</name><affiliation><nlm:aff id="aff3">Department of Physiology, North Sichuan Medical College, Nanchong, China</nlm:aff></affiliation></author><author><name sortKey="Luo, Lei" sort="Luo, Lei" uniqKey="Luo L" first="Lei" last="Luo">Lei Luo</name><affiliation><nlm:aff id="aff4">Department of Research and Education, Guizhou Province People's Hospital, Guiyang, China</nlm:aff></affiliation></author><author><name sortKey="Liu, Jun" sort="Liu, Jun" uniqKey="Liu J" first="Jun" last="Liu">Jun Liu</name><affiliation><nlm:aff id="aff2">Department of Urology Surgery, Institute of Urology, Shanghai JiaoTong University, Shanghai, China</nlm:aff></affiliation></author><author><name sortKey="Yang, Xiu Shu" sort="Yang, Xiu Shu" uniqKey="Yang X" first="Xiu-Shu" last="Yang">Xiu-Shu Yang</name><affiliation><nlm:aff id="aff2">Department of Urology Surgery, Institute of Urology, Shanghai JiaoTong University, Shanghai, China</nlm:aff></affiliation></author><author><name sortKey="Wang, Yan Dong" sort="Wang, Yan Dong" uniqKey="Wang Y" first="Yan-Dong" last="Wang">Yan-Dong Wang</name><affiliation><nlm:aff id="aff2">Department of Urology Surgery, Institute of Urology, Shanghai JiaoTong University, Shanghai, China</nlm:aff></affiliation></author><author><name sortKey="Sun, Zhao Lin" sort="Sun, Zhao Lin" uniqKey="Sun Z" first="Zhao-Lin" last="Sun">Zhao-Lin Sun</name><affiliation><nlm:aff id="aff1">Department of Urology Surgery, Guizhou Province People's Hospital, Guiyang, China</nlm:aff></affiliation></author><author><name sortKey="Xia, Shu Jie" sort="Xia, Shu Jie" uniqKey="Xia S" first="Shu-Jie" last="Xia">Shu-Jie Xia</name><affiliation><nlm:aff id="aff2">Department of Urology Surgery, Institute of Urology, Shanghai JiaoTong University, Shanghai, China</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26178394</idno><idno type="pmc">4736348</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4736348</idno><idno type="RBID">PMC:4736348</idno><idno type="doi">10.4103/1008-682X.154993</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000052</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000052</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Re-epithelialization of the prostatic urethra after two-micron laser resection of the prostate</title><author><name sortKey="Luo, Guang Heng" sort="Luo, Guang Heng" uniqKey="Luo G" first="Guang-Heng" last="Luo">Guang-Heng Luo</name><affiliation><nlm:aff id="aff1">Department of Urology Surgery, Guizhou Province People's Hospital, Guiyang, China</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">Department of Urology Surgery, Institute of Urology, Shanghai JiaoTong University, Shanghai, China</nlm:aff></affiliation></author><author><name sortKey="Liu, Hong" sort="Liu, Hong" uniqKey="Liu H" first="Hong" last="Liu">Hong Liu</name><affiliation><nlm:aff id="aff3">Department of Physiology, North Sichuan Medical College, Nanchong, China</nlm:aff></affiliation></author><author><name sortKey="Luo, Lei" sort="Luo, Lei" uniqKey="Luo L" first="Lei" last="Luo">Lei Luo</name><affiliation><nlm:aff id="aff4">Department of Research and Education, Guizhou Province People's Hospital, Guiyang, China</nlm:aff></affiliation></author><author><name sortKey="Liu, Jun" sort="Liu, Jun" uniqKey="Liu J" first="Jun" last="Liu">Jun Liu</name><affiliation><nlm:aff id="aff2">Department of Urology Surgery, Institute of Urology, Shanghai JiaoTong University, Shanghai, China</nlm:aff></affiliation></author><author><name sortKey="Yang, Xiu Shu" sort="Yang, Xiu Shu" uniqKey="Yang X" first="Xiu-Shu" last="Yang">Xiu-Shu Yang</name><affiliation><nlm:aff id="aff2">Department of Urology Surgery, Institute of Urology, Shanghai JiaoTong University, Shanghai, China</nlm:aff></affiliation></author><author><name sortKey="Wang, Yan Dong" sort="Wang, Yan Dong" uniqKey="Wang Y" first="Yan-Dong" last="Wang">Yan-Dong Wang</name><affiliation><nlm:aff id="aff2">Department of Urology Surgery, Institute of Urology, Shanghai JiaoTong University, Shanghai, China</nlm:aff></affiliation></author><author><name sortKey="Sun, Zhao Lin" sort="Sun, Zhao Lin" uniqKey="Sun Z" first="Zhao-Lin" last="Sun">Zhao-Lin Sun</name><affiliation><nlm:aff id="aff1">Department of Urology Surgery, Guizhou Province People's Hospital, Guiyang, China</nlm:aff></affiliation></author><author><name sortKey="Xia, Shu Jie" sort="Xia, Shu Jie" uniqKey="Xia S" first="Shu-Jie" last="Xia">Shu-Jie Xia</name><affiliation><nlm:aff id="aff2">Department of Urology Surgery, Institute of Urology, Shanghai JiaoTong University, Shanghai, China</nlm:aff></affiliation></author></analytic><series><title level="j">Asian Journal of Andrology</title><idno type="ISSN">1008-682X</idno><idno type="eISSN">1745-7262</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Alan, Jw" uniqKey="Alan J">JW 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Asian J Androl</journal-id><journal-id journal-id-type="iso-abbrev">Asian J. Androl</journal-id><journal-id journal-id-type="publisher-id">AJA</journal-id><journal-title-group><journal-title>Asian Journal of Andrology</journal-title></journal-title-group><issn pub-type="ppub">1008-682X</issn><issn pub-type="epub">1745-7262</issn><publisher><publisher-name>Medknow Publications & Media Pvt Ltd</publisher-name><publisher-loc>India</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">26178394</article-id><article-id pub-id-type="pmc">4736348</article-id><article-id pub-id-type="publisher-id">AJA-18-151</article-id><article-id pub-id-type="doi">10.4103/1008-682X.154993</article-id><article-categories><subj-group subj-group-type="heading"><subject>Letter to the Editor</subject></subj-group></article-categories><title-group><article-title>Re-epithelialization of the prostatic urethra after two-micron laser resection of the prostate</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Luo</surname><given-names>Guang-Heng</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="corresp" rid="fn">*</xref></contrib><contrib contrib-type="author"><name><surname>Liu</surname><given-names>Hong</given-names></name><xref ref-type="aff" rid="aff3">3</xref><xref ref-type="corresp" rid="fn">*</xref></contrib><contrib contrib-type="author"><name><surname>Luo</surname><given-names>Lei</given-names></name><xref ref-type="aff" rid="aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Liu</surname><given-names>Jun</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Yang</surname><given-names>Xiu-Shu</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Wang</surname><given-names>Yan-Dong</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Sun</surname><given-names>Zhao-Lin</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Xia</surname><given-names>Shu-Jie</given-names></name><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="corresp" rid="cor1"></xref></contrib></contrib-group><aff id="aff1"><label>1</label>Department of Urology Surgery, Guizhou Province People's Hospital, Guiyang, China</aff><aff id="aff2"><label>2</label>Department of Urology Surgery, Institute of Urology, Shanghai JiaoTong University, Shanghai, China</aff><aff id="aff3"><label>3</label>Department of Physiology, North Sichuan Medical College, Nanchong, China</aff><aff id="aff4"><label>4</label>Department of Research and Education, Guizhou Province People's Hospital, Guiyang, China</aff><author-notes><fn id="fn"><label>*</label><p>These authors contributed equally to this work.</p></fn><corresp id="cor1">Correspondence: Dr. SJ Xia (<email xlink:href="xiashujie7710@hotmail.com">xiashujie7710@hotmail.com</email>)
</corresp></author-notes><pub-date pub-type="ppub"><season>Jan-Feb</season><year>2016</year></pub-date><pub-date pub-type="epub"><day>14</day><month>7</month><year>2015</year></pub-date><volume>18</volume><issue>1</issue><fpage>151</fpage><lpage>153</lpage><history><date date-type="received"><day>09</day><month>10</month><year>2014</year></date><date date-type="rev-recd"><day>05</day><month>12</month><year>2014</year></date><date date-type="accepted"><day>24</day><month>3</month><year>2015</year></date></history><permissions><copyright-statement>Copyright: © Asian Journal of Andrology</copyright-statement><copyright-year>2016</copyright-year><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc-sa/3.0"><license-p>This is an open access article distributed under the terms of the Creative Commons Attribution NonCommercial ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non commercially, as long as the author is credited and the new creations are licensed under the identical terms.</license-p></license></permissions></article-meta></front><body><p>Dear Editor,</p><p>Benign prostatic hyperplasia (BPH) is the most common genitourinary tract disease in elderly males.<xref rid="ref1" ref-type="bibr">1</xref> The two-micron laser combines the advantages of efficient resection and rapid vaporization, resulting in high-performance resection and excellent hemostasis in resection of the prostate adenoma, which makes it an effective and promising modality in BPH treatment.<xref rid="ref2" ref-type="bibr">2</xref> However, severe edema and necrosis of the remaining prostatic tissue after vaporesection of the prostatic adenoma may cause severe irritative and/or obstructive symptoms and may even result in the need for a second operation. Rapid wound re-epithelialization in the prostatic urethra can, however, reduce the incidence of postoperative complications after transurethral resection of the prostate (TURP).<xref rid="ref1" ref-type="bibr">1</xref></p><p>It is generally considered that re-epithelialization of the prostatic urethra after TURP initiates from normal epithelial cells of the bladder neck, which proliferate and differentiate to seal the wounds. Nevertheless, Orihuela <italic>et al</italic>.<xref rid="ref3" ref-type="bibr">3</xref> demonstrated that it was the germinal epithelium in the remaining prostatic glands and ducts that dominated the healing process; however, the exact healing mechanism at the molecular level remains unknown.</p><p>Stem cells are defined as undifferentiated cells that can self-renew and differentiate. To date, stem cells have been detected in individuals at all development stages as well as in multiple organs and tissues of adults.<xref rid="ref4" ref-type="bibr">4</xref><xref rid="ref5" ref-type="bibr">5</xref><xref rid="ref6" ref-type="bibr">6</xref> Azuma <italic>et al</italic>.<xref rid="ref7" ref-type="bibr">7</xref> grafted matrigel containing freshly isolated epithelial and interstitial cells from adult prostate subcutaneously into the flank of nude mice, and prostatic duct-like structures were observed. Kyprianou and Isaacs<xref rid="ref8" ref-type="bibr">8</xref> found a rapid reduction in the total prostate volume due to programmed death of androgen-dependent prostatic epithelial cells, with only basal cells surviving in castrated mice. However, this trend was reversed, and the prostate restored in size and function upon testosterone administration. The study suggested that the basal-cell layer contains stem cells are responsible for the development, maturation and function of the prostate. Thus, we tried to investigate the mechanism of re-epithelialization of the prostatic urethra after transurethral two-micron laser resection of the prostate (TmLRP) in a canine model by focusing on the healing process, epithelial origin of the prostatic urethra, and the role of basal-cell-layer-related stem cells.</p><p>Thirty adult cross-breed male dogs (age 5–7 years; weight 18–22 kg) were established a model of TmLRP using the RevoLixTM 2-μm laser device (the wavelength 2.013 μm, and an energy of 70 W) after anesthetized with an intraperitoneal administration of 10% chloral hydrate (0.3 ml per 100 g). The animals were taken biopsies from the bladder neck, prostatic urethra, and urethral mucosa in the verumontanum (prostate apex) under the cystoscopy and postoperation after TmLRP. Also, specimens were examined using hematoxylin-eosin staining and immunohistochemistry.</p><p>Under the cystoscopy, no normal mucosa of the prostatic urethra remained, and the wounds had a burnt-like appearance after TmLRP. At day 3, no epithelia covering the wounds. At day 5 to day 10, from small numbers of scattered insular epithelial-cell clusters to thin layers of epithelial cells were observed covering the wounds. There was still no evidence of epithelial migration from the bladder neck or proximal end of the verumontanum. After 2 to 8 weeks, the wounds were completely covered by integral epithelia and had become redder. There were clear boundaries between newly formed epithelia and those of the bladder neck and proximal end of the verumontanum (data not shown).</p><p>Compared with normal specimens (<xref ref-type="fig" rid="F1"><bold>Figure 1a</bold></xref>), isolated epithelial cells were scattered in the surface of the necrotic tissues at day 3 (<xref ref-type="fig" rid="F1"><bold>Figure 1b</bold></xref>). At day 5, overlying insular epithelial cell clusters were found (<xref ref-type="fig" rid="F1"><bold>Figure 1c</bold></xref>). At day 7, Punctate and lamellar epithelial cells were observed overlying the surface of the necrotic tissues (<xref ref-type="fig" rid="F1"><bold>Figure 1d</bold></xref>). At day 10, the wounds were covered with a thin layer of irregularly arranged epithelial cells of variable shape and size (<xref ref-type="fig" rid="F1"><bold>Figure 1e</bold></xref>). Two to four weeks after surgery, the wounds were covered with an overlying epithelium with a varying number of cell layers from 2 or 3 layers to 6−8 layers (<bold>Figure <xref ref-type="fig" rid="F1">1f</xref> and <xref ref-type="fig" rid="F1">1g</xref></bold>). After 8 weeks, the prostatic urethra was covered by a mature epithelium consisting of cells with polarity (<xref ref-type="fig" rid="F1"><bold>Figure 1h</bold></xref>).</p><fig id="F1" position="float"><label>Figure 1</label><caption><p>Epithelium of the prostatic urethra by H and E staining and expression levels of Ups and p63 in urotheliums of the prostatic urethra (×400). (<bold>a</bold>) Preoperative epithelium of the prostatic urethra by H and E staining; (<bold>b</bold>) 3 days after TmLRP by H and E staining; (<bold>c</bold>) 5 days after TmLRP by H and E staining; (<bold>d</bold>) 7 days after TmLRP by H and E staining; (<bold>e</bold>) 10 days after TmLRP by H and E staining; (<bold>f</bold>) 2 weeks after TmLRP by H and E staining; (<bold>g</bold>) 4 weeks after TmLRP by H and E staining; (<bold>h</bold>) 8 weeks after TmLRP by H and E staining; (<bold>i</bold>) expression levels of Ups in preoperative epithelium of the prostatic urethra; expression levels of Ups in 3 (<bold>j</bold>), 5 (<bold>k</bold>), 7 (<bold>l</bold>), 10 (<bold>m</bold>) days, 2 weeks (<bold>n</bold>), 4 weeks (<bold>o</bold>), 8 weeks (<bold>p</bold>) after TmLRP; (<bold>q</bold>) expression levels of p63 in preoperative epithelium of the prostatic urethra; expression levels of p63 in 3 (<bold>r</bold>), 5 (<bold>s</bold>), 7 (<bold>t</bold>), 10 (<bold>u</bold>) days, 2 weeks (<bold>v</bold>), 4 weeks (<bold>w</bold>), 8 weeks (<bold>x</bold>) after TmLRP.</p></caption><graphic xlink:href="AJA-18-151-g001"></graphic></fig><p>Compared with normal specimens (<xref ref-type="fig" rid="F1"><bold>Figure 1i</bold></xref>), UPs were positively stained in the cytoplasm of urothelial cells. Our results showed a few scattered UPs-positive cells distributed in the surfaces of the remaining prostatic tissues 3 days after TmLRP (<xref ref-type="fig" rid="F1"><bold>Figure 1j</bold></xref>). After 5 and 7 days, the UPs started appearing in the borders of the tubular and follicular cells (<bold>Figure <xref ref-type="fig" rid="F1">1k</xref> and <xref ref-type="fig" rid="F1">1l</xref></bold>), while at day 10, a layer of UPs emerged in the wound surface (<xref ref-type="fig" rid="F1"><bold>Figure 1m</bold></xref>). Complete urothelia with a polar nature formed from 2 to 8 weeks, which were generally UPs positive, particularly in the umbrella cell layers (<bold>Figure <xref ref-type="fig" rid="F1">1n</xref>–<xref ref-type="fig" rid="F1">1p</xref></bold>).</p><p>Compared with normal specimens (<xref ref-type="fig" rid="F1"><bold>Figure 1q</bold></xref>), there were no p63-positive cells in the wounds at day 3 (<xref ref-type="fig" rid="F1"><bold>Figure 1r</bold></xref>). However, scattered p63-positive cells were visible at day 5 (<xref ref-type="fig" rid="F1"><bold>Figure 1s</bold></xref>). p63-positive cells were insularly distributed and associated with cells of the remaining prostatic tissue, which also expressed p63 protein at day 7 (<xref ref-type="fig" rid="F1"><bold>Figure 1t</bold></xref>). At day 10, insular cell clusters developed a continuous monolayer covering the surface of the wound (<xref ref-type="fig" rid="F1"><bold>Figure 1u</bold></xref>). Two weeks after surgery, a basal cell layer formed in the newly developed urothelium and the basal cells displayed p63-protein expression (<xref ref-type="fig" rid="F1"><bold>Figure 1v</bold></xref>)). p63-positive basal cells were continuous and an integral part of the basal layer of the well-differentiated newly formed urothelium 8 weeks after surgery (<bold>Figure <xref ref-type="fig" rid="F1">1w</xref> and <xref ref-type="fig" rid="F1">1x</xref></bold>).</p><p>Re-epithelialization is the key to the healing process of the prostatic urethra after TURP in patients with BPH. During the whole healing process in the present study, we found no evidence of epithelial migration from the bladder neck or proximal end of verumontanum to the wounds. These results suggest that re-epithelialization may not occur by migration of epithelia from the bladder neck or proximal end of the verumontanum, rather the remaining prostatic tissues may be an important cellular source for the re-epithelialization of the prostatic urethra. Also, our results suggested that p63-positive basal cells in the remaining prostatic tissues may participate in the re-epithelialization process of the prostatic urethra.</p><sec id="sec1-1"><title>AUTHOR CONTRIBUTIONS</title><p>LL, HL and GHL conceived the study, established the design, and performed the experimental work. SJX and JL participated in the establishment of the canine model. XSY participated in the immunohistochemistry work. YDW and ZLS participated in the data analysis and provided critical comments on the study design and manuscript. LL drafted this manuscript. All authors read and approved the final manuscript.</p></sec><sec id="sec1-2"><title>COMPETING INTERESTS</title><p>All authors declare no competing interests.</p></sec></body><back><ack><title>ACKNOWLEDGMENTS</title><p>This study was supported by the Natural Science Foundation of China (81260119) and the Guizhou Science and Technology Agency Fund ([2012]4013; SZ2012[3077]; SY2011[3024]; LS2011[020]).</p></ack><ref-list><title>REFERENCES</title><ref id="ref1"><label>1</label><element-citation publication-type="book"><person-group person-group-type="author"><name><surname>Alan</surname><given-names>JW</given-names></name></person-group><article-title>Development, molecular biology, and physiology of the prostate. 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