Intercostobrachial Nerves as a Novel Anatomic Landmark for Dividing the Axillary Space in Lymph Node Dissection
Identifieur interne : 003E90 ( Pmc/Corpus ); précédent : 003E89; suivant : 003E91Intercostobrachial Nerves as a Novel Anatomic Landmark for Dividing the Axillary Space in Lymph Node Dissection
Auteurs : Jianyi Li ; Yang Zhang ; Wenhai Zhang ; Shi Jia ; Xi Gu ; Yan Ma ; Dan LiSource :
- ISRN Oncology [ 2090-5661 ] ; 2013.
Abstract
Url:
DOI: 10.1155/2013/279013
PubMed: 23401796
PubMed Central: 3563178
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PMC:3563178Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Intercostobrachial Nerves as a Novel Anatomic Landmark for Dividing the Axillary Space in Lymph Node Dissection</title>
<author><name sortKey="Li, Jianyi" sort="Li, Jianyi" uniqKey="Li J" first="Jianyi" last="Li">Jianyi Li</name>
<affiliation><nlm:aff id="I1">Department of Breast Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China</nlm:aff>
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<author><name sortKey="Zhang, Yang" sort="Zhang, Yang" uniqKey="Zhang Y" first="Yang" last="Zhang">Yang Zhang</name>
<affiliation><nlm:aff id="I1">Department of Breast Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Zhang, Wenhai" sort="Zhang, Wenhai" uniqKey="Zhang W" first="Wenhai" last="Zhang">Wenhai Zhang</name>
<affiliation><nlm:aff id="I1">Department of Breast Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China</nlm:aff>
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<author><name sortKey="Jia, Shi" sort="Jia, Shi" uniqKey="Jia S" first="Shi" last="Jia">Shi Jia</name>
<affiliation><nlm:aff id="I1">Department of Breast Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China</nlm:aff>
</affiliation>
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<author><name sortKey="Gu, Xi" sort="Gu, Xi" uniqKey="Gu X" first="Xi" last="Gu">Xi Gu</name>
<affiliation><nlm:aff id="I1">Department of Breast Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China</nlm:aff>
</affiliation>
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<author><name sortKey="Ma, Yan" sort="Ma, Yan" uniqKey="Ma Y" first="Yan" last="Ma">Yan Ma</name>
<affiliation><nlm:aff id="I2">Ultrasound Diagnosis Center, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Li, Dan" sort="Li, Dan" uniqKey="Li D" first="Dan" last="Li">Dan Li</name>
<affiliation><nlm:aff id="I3">Pathological Diagnosis Center, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China</nlm:aff>
</affiliation>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Intercostobrachial Nerves as a Novel Anatomic Landmark for Dividing the Axillary Space in Lymph Node Dissection</title>
<author><name sortKey="Li, Jianyi" sort="Li, Jianyi" uniqKey="Li J" first="Jianyi" last="Li">Jianyi Li</name>
<affiliation><nlm:aff id="I1">Department of Breast Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Zhang, Yang" sort="Zhang, Yang" uniqKey="Zhang Y" first="Yang" last="Zhang">Yang Zhang</name>
<affiliation><nlm:aff id="I1">Department of Breast Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Zhang, Wenhai" sort="Zhang, Wenhai" uniqKey="Zhang W" first="Wenhai" last="Zhang">Wenhai Zhang</name>
<affiliation><nlm:aff id="I1">Department of Breast Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Jia, Shi" sort="Jia, Shi" uniqKey="Jia S" first="Shi" last="Jia">Shi Jia</name>
<affiliation><nlm:aff id="I1">Department of Breast Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Gu, Xi" sort="Gu, Xi" uniqKey="Gu X" first="Xi" last="Gu">Xi Gu</name>
<affiliation><nlm:aff id="I1">Department of Breast Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ma, Yan" sort="Ma, Yan" uniqKey="Ma Y" first="Yan" last="Ma">Yan Ma</name>
<affiliation><nlm:aff id="I2">Ultrasound Diagnosis Center, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Li, Dan" sort="Li, Dan" uniqKey="Li D" first="Dan" last="Li">Dan Li</name>
<affiliation><nlm:aff id="I3">Pathological Diagnosis Center, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China</nlm:aff>
</affiliation>
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</analytic>
<series><title level="j">ISRN Oncology</title>
<idno type="ISSN">2090-5661</idno>
<idno type="eISSN">2090-567X</idno>
<imprint><date when="2013">2013</date>
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<front><div type="abstract" xml:lang="en"><p><italic>Purpose</italic>
. Our aim was to assess the feasibility of using the intercostobrachial nerves (ICBNs) as a possible new anatomic landmark for axillaries lymph node dissection in breast cancer patients. <italic>Background Data Summary</italic>
. The preservation of ICBN is now an accepted procedure in this type of dissection; however, it could be improved further to reduce the number of postoperative complications. The axillary space is divided into lower and upper parts by the ICBN—a thorough investigation of the metastasis patterns in lymph nodes found in this area could supply new information leading to such improvements. <italic>Methods</italic>
. Seventy-two breast cancer patients, all about to undergo lymph node dissection and with sentinel lymph nodes identified, were included in this trial. The lymph nodes were collected in two groups, from lower and upper axillary spaces, relative to the intercostobrachial nerves. The first group was further subdivided into sentinel (SLN) and nonsentinel (non-SLN) nodes. All lymph nodes were tested to detect macro- and micrometastasis. <italic>Results</italic>
. All the sentinel lymph nodes were found under the intercostobrachial nerves; more than 10 lymph nodes were located in that space. Moreover, when lymph nodes macrometastasize or micrometastasize above the intercostobrachial nerves, we also observe metastasis-positive nodes under the nerves; when the lower group nodes show no metastasis, the upper group is also metastasis free. <italic>Conclusions</italic>
. Our results show that the intercostobrachial nerves are good candidates for a new anatomic landmark to be used in lymph node dissection procedure.</p>
</div>
</front>
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<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">ISRN Oncol</journal-id>
<journal-id journal-id-type="iso-abbrev">ISRN Oncol</journal-id>
<journal-id journal-id-type="publisher-id">ISRN.ONCOLOGY</journal-id>
<journal-title-group><journal-title>ISRN Oncology</journal-title>
</journal-title-group>
<issn pub-type="ppub">2090-5661</issn>
<issn pub-type="epub">2090-567X</issn>
<publisher><publisher-name>Hindawi Publishing Corporation</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">23401796</article-id>
<article-id pub-id-type="pmc">3563178</article-id>
<article-id pub-id-type="doi">10.1155/2013/279013</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Clinical Study</subject>
</subj-group>
</article-categories>
<title-group><article-title>Intercostobrachial Nerves as a Novel Anatomic Landmark for Dividing the Axillary Space in Lymph Node Dissection</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Li</surname>
<given-names>Jianyi</given-names>
</name>
<xref ref-type="aff" rid="I1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zhang</surname>
<given-names>Yang</given-names>
</name>
<xref ref-type="aff" rid="I1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zhang</surname>
<given-names>Wenhai</given-names>
</name>
<xref ref-type="aff" rid="I1"><sup>1</sup>
</xref>
<xref ref-type="corresp" rid="cor1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Jia</surname>
<given-names>Shi</given-names>
</name>
<xref ref-type="aff" rid="I1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Gu</surname>
<given-names>Xi</given-names>
</name>
<xref ref-type="aff" rid="I1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ma</surname>
<given-names>Yan</given-names>
</name>
<xref ref-type="aff" rid="I2"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Li</surname>
<given-names>Dan</given-names>
</name>
<xref ref-type="aff" rid="I3"><sup>3</sup>
</xref>
</contrib>
</contrib-group>
<aff id="I1"><sup>1</sup>
Department of Breast Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China</aff>
<aff id="I2"><sup>2</sup>
Ultrasound Diagnosis Center, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China</aff>
<aff id="I3"><sup>3</sup>
Pathological Diagnosis Center, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China</aff>
<author-notes><corresp id="cor1">*Wenhai Zhang: <email>sjbreast@sina.com</email>
</corresp>
<fn fn-type="other"><p>Academic Editors: B. Comin-Anduix, L. Saragoni, K. Sonoda, and Y. Yamamoto</p>
</fn>
</author-notes>
<pub-date pub-type="collection"><year>2013</year>
</pub-date>
<pub-date pub-type="epub"><day>20</day>
<month>1</month>
<year>2013</year>
</pub-date>
<volume>2013</volume>
<elocation-id>279013</elocation-id>
<history><date date-type="received"><day>9</day>
<month>11</month>
<year>2012</year>
</date>
<date date-type="accepted"><day>16</day>
<month>12</month>
<year>2012</year>
</date>
</history>
<permissions><copyright-statement>Copyright © 2013 Jianyi Li et al.</copyright-statement>
<copyright-year>2013</copyright-year>
<license xlink:href="https://creativecommons.org/licenses/by/3.0/"><license-p>This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
</license>
</permissions>
<abstract><p><italic>Purpose</italic>
. Our aim was to assess the feasibility of using the intercostobrachial nerves (ICBNs) as a possible new anatomic landmark for axillaries lymph node dissection in breast cancer patients. <italic>Background Data Summary</italic>
. The preservation of ICBN is now an accepted procedure in this type of dissection; however, it could be improved further to reduce the number of postoperative complications. The axillary space is divided into lower and upper parts by the ICBN—a thorough investigation of the metastasis patterns in lymph nodes found in this area could supply new information leading to such improvements. <italic>Methods</italic>
. Seventy-two breast cancer patients, all about to undergo lymph node dissection and with sentinel lymph nodes identified, were included in this trial. The lymph nodes were collected in two groups, from lower and upper axillary spaces, relative to the intercostobrachial nerves. The first group was further subdivided into sentinel (SLN) and nonsentinel (non-SLN) nodes. All lymph nodes were tested to detect macro- and micrometastasis. <italic>Results</italic>
. All the sentinel lymph nodes were found under the intercostobrachial nerves; more than 10 lymph nodes were located in that space. Moreover, when lymph nodes macrometastasize or micrometastasize above the intercostobrachial nerves, we also observe metastasis-positive nodes under the nerves; when the lower group nodes show no metastasis, the upper group is also metastasis free. <italic>Conclusions</italic>
. Our results show that the intercostobrachial nerves are good candidates for a new anatomic landmark to be used in lymph node dissection procedure.</p>
</abstract>
</article-meta>
</front>
<body><sec id="sec1"><title>1. Introduction</title>
<p>The axillary lymph node (ALN) status represents one of the most important prognostic factors in breast cancer patients and determines, among other parameters, the type of subsequent adjuvant treatment [<xref rid="B1" ref-type="bibr">1</xref>
, <xref rid="B2" ref-type="bibr">2</xref>
]. Lymph nodes in axillary space are traditionally divided into 3 groups by pectoralis minor (level I, level II, and level III), according to the rule of lymph nodes metastasis [<xref rid="B3" ref-type="bibr">3</xref>
]. It is the accepted basic principle for axillary lymph node dissection (ALND) of breast cancer that lymph nodes should be extracted from level I to level III, step by step [<xref rid="B4" ref-type="bibr">4</xref>
]. The postoperative risk of arm lymphedema increases with the increasing axillary space level during the dissection [<xref rid="B5" ref-type="bibr">5</xref>
]. On the other hand, the necessity of intercostobrachial nerves (ICBNs) preservation is now accepted by the surgeons and has become the standard procedure in such dissections, reducing the postoperative skin numbness and loss of feeling in the upper arm [<xref rid="B6" ref-type="bibr">6</xref>
]. The ICBN is nearly parallel to the axillary vein, at the distance of about 1.5 cm [<xref rid="B7" ref-type="bibr">7</xref>
]. It naturally divides the axillary space into the lower and upper parts. The upper part includes level III, a large part of level II, and a small part of level I; if the tissue between the ICBN and axillary vein is preserved, the postoperative lymphedema of arm should be prevented. Therefore, it would be useful to decide whether ICBN could serve as the anatomic landmark for dividing the axillary lymph nodes into groups, with a practical application in mind. In the current study, the data of 72 patients with breast cancer are analyzed to identify the feasibility of such assignment and potential clinical significance of ICBN in dividing the axillary space. The relationship between lymph node metastasis and ICBN, the number of nodes under the ICBN, and the relationship between sentinel nodes and ICBN is also examined.</p>
</sec>
<sec id="sec2"><title>2. Patients and Methods</title>
<sec id="sec2.1"><title>2.1. Patients</title>
<p>Between July 2009 and May 2010, a total of 86 patients with breast cancer, about to undergo the axillary lymph node dissection in Shengjing Hospital (SJHCMU), were enrolled in this study. Inclusion criteria for the study were (1) infiltrating duct carcinoma (IDC) identified by a pathologist, (2) no prior history of breast cancer or other malignancies, (3) no neoadjuvant therapy, (4) no pregnancy, (5) sentinel lymph nodes (SLNs) identified using methylene blue dye (MBD). Fourteen patients did not meet the criteria and were therefore excluded; seventy-two patients met the inclusions criteria. All the patients agreed to the axillary lymph node dissection (ALND) and signed the Informed Consent Sheet, even if the SLN was negative (as judged by using the frozen section method intraoperatively). All the lymph nodes dissections were performed by the same surgical team of China Medical University affiliated Shengjing Hospital (SJHCMU). The study was approved by the Local Ethics Committee.</p>
</sec>
<sec id="sec2.2"><title>2.2. Lymph Nodes Groups and Operative Techniques</title>
<p>Sentinel lymph node mapping was performed using methylene blue dye (MBD), as described previously [<xref rid="B8" ref-type="bibr">8</xref>
]. Briefly, 3-4 mL MBD (1.25 mg/mL) was injected into tumor bed and areola of breast 15 minutes before the dissection. If the tumor was located in the outer quadrant, two-thirds of the dose of MBD was injected into tumor bed, and one-third into areola of breast; the dosage was distributed the other way round for tumors located in the inner quadrant. All the patients underwent ALND according to the principle of level I to level III dissection, but the lymph nodes were divided into three groups, as described earlier. All the blue staining nodes were identified as sentinel nodes (SLNs, <xref ref-type="fig" rid="fig1">Figure 1</xref>
). Nodes defined as non-SLNs were located under the intercostobrachial nerves and did not show blue staining. All the nodes above the ICBN were assigned to the upper lymph node group. This last group included a small part of level I, a large part of level II, and level III. Because there were no blue staining nodes above the intercostobrachial nerves, the SLN and non-SLN constituted the lower lymph node group. The clearance of lower nodes' group has to be defined to preserve the ICBN, a large part of long thoracic and thoracodorsal nerves under the ICBN (<xref ref-type="fig" rid="fig2">Figure 2</xref>
).</p>
</sec>
<sec id="sec2.3"><title>2.3. Examination of Lymph Nodes Pathology</title>
<p>The frozen sections of SLN were routinely used intraoperatively to determine which level should be dissected. The patients with SLN macrometastases in frozen sections underwent immediately level II or level III dissection; others, without SLN macrometastasis, were submitted to level I or level II axillary lymph node dissection. The extracted lymphatic tissue was formalin fixed and embedded in paraffin for histological analysis. The tissue was then examined using step sectioning at a cutting interval of 250 <italic>μ</italic>
m. Step sections were stained with hematoxylin & eosin (H&E). If no carcinoma cells were detected in the nodes, immunohistochemistry with cytokeratin antibody CK-22 (Santa Cruz, CA, USA), using a standard immunoperoxidase method (ABC Elite kit), was performed [<xref rid="B9" ref-type="bibr">9</xref>
]. Micrometastasis was defined as tumor of the size exceeding 0.2 mm and less than or equal to 2 mm in diameter, according to the American Joint Committee of Cancer (AJCC) classification. Hence, isolated tumor cells or tumor cell clusters measuring less than or equal to 0.2 mm in diameter did not meet the definition of micrometastases. Therefore, the patients with such clusters were considered as micrometastasis negative. All the previous analysis was performed by a pathologist from the Breast Group of Pathology Diagnosis Center of SJHCMU.</p>
</sec>
<sec id="sec2.4"><title>2.4. Statistical Analysis</title>
<p>The data are represented by the mean values or the frequency tables, depending on the data type. Statistical analysis was performed using SPSS 17.0 (SPSS, Chicago, IL, USA).</p>
</sec>
</sec>
<sec id="sec3"><title>3. Results</title>
<p>From July 2009 to May 2010, the sentinel node biopsies were performed on 86 breast cancer patients. The overall SLN identification rate was 95.3% (82/86). Fourteen patients did not meet the inclusion criteria for this study because four patients have not been SLN stained by MBD, and ten patients' tumors were not infiltrating duct carcinoma, as judged by the postoperative pathological diagnosis (<xref ref-type="fig" rid="fig3">Figure 3</xref>
). The characteristics of the 72 patients are listed in <xref ref-type="table" rid="tab1">Table 1</xref>
. The median age was 49 years (range 33–72). The median tumor size was 1.9 mm (range 0.9–5.5). About half of the tumors were located in the outer-upper quadrant of breast. The preoperative axillary assessment was performed using 3 methods: palpation, Doppler ultrasound, and molybdenum target photography (MTP). If the lymph node tumescence was identified by any one of these methods, the axillary nodes were considered to be positive preoperatively; about 40% of patients were found to have metastatic lymph nodes.</p>
<p>The blue staining nodes were not detected above ICBN in any of the patients. The nodes below the nerves were divided into SLN and non-SLN groups; the lymph node numbers in each group are shown in <xref ref-type="table" rid="tab2">Table 2</xref>
. The total number of axillary space lymph nodes examined was 1503: 232 SLNs, 685 non-SLNs, and 586 upper group lymph nodes. The average number of axillary lymph nodes per patient was 20.94; 3.22 in SLN group, 9.51 in non-SLN group, and 8.14 in the upper group. The mean for lower group nodes' number was 12.74, which exceeds the required number of 10 and is, therefore, sufficient for assessing the axillary node status.</p>
<p>All the lymph nodes collected were formalin fixed and embedded in paraffin for histological analysis. The number of patients with macrometastasis-positive (LN+) and macrometastasis-negative (LN−) nodes in different groups is shown in <xref ref-type="table" rid="tab3">Table 3</xref>
. There were 19 patients with one macrometastasis node in non-SLN subgroup, 15 showing metastasis in SLN subgroup, and 3 in upper LN group. <xref ref-type="table" rid="tab4"> Table 4</xref>
contains the data for the individual patients with macrometastasis, identified using H&E. Metastasis in non-SLN and upper group nodes was found in one case (<sup>#</sup>
), in three cases we see metastasis in non-SLN group only (*), and two patients show metastasis positive nodes in all the groups (<sup>§</sup>
). In the remaining 13 metastasis cases, the positive nodes were found in the lower space groups. To summarize, in patients with metastasis-negative lower nodes, the upper group nodes were also metastasis free; in cases with the upper metastasized nodes, the lower nodes showed positive staining as well. Within the lower space node group, in cases with the positive-staining SLN, the non-SLN subgroup was also positive.</p>
<p>All the macrometastasis-negative nodes were stained with CK-22 to detect micrometastasis; the results are shown in <xref ref-type="table" rid="tab5">Table 5</xref>
. There were 24 patients with micrometastasis nodes in non-SLN group, 12 patients showed metastasis in SLN group, and 3 in the upper group.</p>
<p><xref ref-type="table" rid="tab6">Table 6</xref>
shows the results for individual patients where micrometastasis positive nodes were identified by CK-22 staining in at least one of the node groups. We found micrometastasis in nodes from all three groups in one patient only (<sup>#</sup>
) and micrometastasis limited to sentinel nodes also in one patient (<sup>¥</sup>
). In two cases, we found positive nodes in both non-SLN group and upper node group (*). In 10 cases, there were positive-staining nodes in SLN and non-SLN groups (<sup>§</sup>
); only non-SLN group positives were discovered in other 10 patients (<sup>$</sup>
).</p>
<p>In most cases, the upper group nodes do not show micrometastasis. In cases where it does occur, metastasis-positive nodes are also found in one of the lower space node groups.</p>
</sec>
<sec id="sec4"><title>4. Discussion</title>
<p>According to Lloyd's study of skip metastases in lymph nodes (1989), the problems associated with axillary lymph node dissection in breast cancer should be all but solved [<xref rid="B3" ref-type="bibr">3</xref>
]. It has been long accepted by most surgeons that ALND should precede from level I to level III, step by step, according to the results of SLN biopsy, and that 10 lymph nodes should be obtained from the axillary space [<xref rid="B10" ref-type="bibr">10</xref>
, <xref rid="B11" ref-type="bibr">11</xref>
]. However, the arm lymphedema still remains an important and not uncommon postoperative complication, and there are no effective measures to deal with this problem [<xref rid="B12" ref-type="bibr">12</xref>
]. A meta-analysis suggested that mastectomy, extent of axillary dissection, radiation therapy, and presence of positive nodes can all increase the risk of developing arm lymphedema after breast cancer treatment [<xref rid="B13" ref-type="bibr">13</xref>
]. Some existing studies show that the increased incidence of lymphedema is associated with the extent and degree of ALND, more than with any other factor [<xref rid="B14" ref-type="bibr">14</xref>
]. McLaughlin's study suggests that the lymphedema incidence can be reduced from 16% to 5% by using sentinel node biopsy, while more than 16% of patients after ALND (level I to level III) suffer from arm lymphedema [<xref rid="B15" ref-type="bibr">15</xref>
]. Therefore, the question of what constitutes an adequate axillary dissection in breast cancer treatment still remains largely unanswered. On the other hand, the procedure of ICBN preservation provides a new potential anatomic landmark in axillary lymph node dissection. It has been reported that in 86% of cases, ICBN is found in the second intercostals space in axillary [<xref rid="B16" ref-type="bibr">16</xref>
]. In the current study, we found intercostobrachial nerves easily in that location, in all cases. Should ICBN's location vary, the pectoralis minor branch of thoracoacromial artery (PMBTA) can substitute ICBN as anatomic landmark (<xref ref-type="fig" rid="fig4">Figure 4</xref>
). The technique of ICBN preservation is accepted by the majority of surgeons and easily followed; so, from the practical point of view, there should be no problems in utilizing those nerves as a new landmark for dividing the axillary space. The results displayed in <xref ref-type="table" rid="tab2">Table 2</xref>
show that sentinel lymph nodes are always located under the ICBN, and the number (12.74) of lymph nodes under ICBN exceeds 10. Some reports suggest that the sentinel nodes are always located near the lateral thoracic artery [<xref rid="B17" ref-type="bibr">17</xref>
]. In our study, the number of non-SLNs, also in the lower node group, is 9.51, which is close to 10. In general, it can be assumed that if there are some SLNs located under ICBN, the number of lower group nodes will exceed 10. This means that enough lymph nodes can be obtained under the ICBN to assess axillary node status. Goldberg considers that there is no correlation between number of lymph nodes removed and change in the upper extremity circumference or incidence of lymphedema. His data suggest that other factors, such as the global disruption of the lymphatic channels during axillary lymph node dissection, play a larger role in development of lymphedema than does the number of nodes removed [<xref rid="B18" ref-type="bibr">18</xref>
].</p>
<p>In summary, taking into account our results, we could formulate two interesting rules for lymph node metastasis in lower and upper groups in axillary space divided by ICBN. If the lower group nodes are negative by H&E and CK-22 staining, the upper nodes are also negative (Tables <xref ref-type="table" rid="tab3">3</xref>
and <xref ref-type="table" rid="tab5">5</xref>
); if the upper group nodes are positive by H&E and CK-22 staining, the lower nodes are positive too (Tables <xref ref-type="table" rid="tab4">4</xref>
and <xref ref-type="table" rid="tab6">6</xref>
). Although skip metastasis had been identified in some previous studies, we did not detect any evidence of skip metastasis in the current analysis, possibly because of a small number of cases [<xref rid="B19" ref-type="bibr">19</xref>
]. The results suggest that the lymph node metastases progress from lower to upper and from outer to inner areas, stepwise, and the probability of skip metastasis might be quite low. This rule for lymph node metastases can be probably applied only to infiltrating duct carcinoma; other cancers or sarcomas should be investigated separately. Most surgeons agree that the destruction of lymph vessel draining in the arm during ALND procedure is the main reason of postoperative lymphedema [<xref rid="B20" ref-type="bibr">20</xref>
]. Existing studies suggest that the lymph draining in the arm is closely associated with axillary vein [<xref rid="B21" ref-type="bibr">21</xref>
]. If the lymphatic and fatty tissues between ICBN and axillary vein could be preserved, the postoperative arm lymphedema would be prevented in most cases. Therefore, it is of a potential clinical significance that the axillary space can be considered, for practical purposes, subdivided by ICBN. Long-term follow-up studies should show that preservation of tissue above the ICBN can substantially reduce or even completely prevent the postoperational arm lymphedema. If the outer margin of pectoralis minor is replaced by ICBN as the anatomic landmark between level I and level II, the new level I in ALND procedure for early stage breast cancer can be defined with sufficient number of lymph nodes to assess the axillary lymph node status. At the same time, the lymph vessel draining in the arm will not be disturbed, avoiding the postoperational lymphedema complications. This, of course, can be only confirmed by thorough, long-term follow-up studies.</p>
</sec>
</body>
<back><ack><title>Conflict of Interests</title>
<p>J. Li and other coauthors have no conflict of interests.</p>
</ack>
<ack><title>Authors' Contribution</title>
<p>J. Li and W. Zhang contributed equally to this work. J. Li and W. Zhang designed the research; J. Li, Y. Zhang, S. Jia and X. Gu performed the research; Y. Ma evaluated axillary lymph nodes by ultrasound before operation; D. Li performed the pathological diagnosis; J. Li, Y. Zhang, and S. Jia analyzed the data; J. Li, Y. Zhang, and W. Zhang wrote the paper.</p>
</ack>
<ack><title>Acknowledgments</title>
<p>The funding for this study was provided by the Science and Technology Foundation of Shenyang City, no. 1091142-9-02. The design, execution, and analysis of the study are the sole responsibility of the authors.</p>
</ack>
<glossary><title>Abbreviations</title>
<def-list><def-item><term>ICBNs:</term>
<def><p>Intercostobrachial nerves</p>
</def>
</def-item>
<def-item><term>ALND:</term>
<def><p> Axillary lymph node dissection</p>
</def>
</def-item>
<def-item><term>LNs:</term>
<def><p> Lymph nodes</p>
</def>
</def-item>
<def-item><term>SLN:</term>
<def><p> Sentinel lymph node</p>
</def>
</def-item>
<def-item><term>MBD:</term>
<def><p> Methylene blue dye</p>
</def>
</def-item>
<def-item><term>H&E:</term>
<def><p> Hematoxylin and eosin</p>
</def>
</def-item>
<def-item><term>CK-22:</term>
<def><p> Cytokeratin-22</p>
</def>
</def-item>
<def-item><term>ALN:</term>
<def><p> Axillary lymph node</p>
</def>
</def-item>
<def-item><term>SJHCMU:</term>
<def><p>Shengjing Hospital of China Medical University</p>
</def>
</def-item>
<def-item><term>IDC:</term>
<def><p> Infiltrating duct carcinoma</p>
</def>
</def-item>
<def-item><term>AJCC:</term>
<def><p> American Joint Committee of Cancer</p>
</def>
</def-item>
<def-item><term>MTP:</term>
<def><p> Molybdenum target photograph</p>
</def>
</def-item>
<def-item><term>PMBTA:</term>
<def><p> Pectoralis minor branch of thoracoacromial artery.</p>
</def>
</def-item>
</def-list>
</glossary>
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<floats-group><fig id="fig1" orientation="portrait" position="float"><label>Figure 1</label>
<caption><p>It is considered SLN; those blue LNs are stained by MBD, and there are two SLNs under the ICBN and besides the outer margin of pectoralis minor. Those LNs belong to lower LNs and level I.</p>
</caption>
<graphic xlink:href="ISRN.ONCOLOGY2013-279013.001"></graphic>
</fig>
<fig id="fig2" orientation="portrait" position="float"><label>Figure 2</label>
<caption><p>The extent of dissection under the ICBN. The ICBN was revealed completely in axillary space, and the LNs adjoined with ICBN belonged to the lower LNs. It was necessary to reveal and reserve the long thoracic and thoracodorsal nerves in the operation.</p>
</caption>
<graphic xlink:href="ISRN.ONCOLOGY2013-279013.002"></graphic>
</fig>
<fig id="fig3" orientation="portrait" position="float"><label>Figure 3</label>
<caption><p>72 patients have accomplished follow chart.</p>
</caption>
<graphic xlink:href="ISRN.ONCOLOGY2013-279013.003"></graphic>
</fig>
<fig id="fig4" orientation="portrait" position="float"><label>Figure 4</label>
<caption><p>The PMBTA is located at the outer margin of pectoralis minor, and it seems to be vertical to ICBN and axillary vein. The vertical dimension from axillary vein to PMBTA is about 1.5 cm.</p>
</caption>
<graphic xlink:href="ISRN.ONCOLOGY2013-279013.004"></graphic>
</fig>
<table-wrap id="tab1" orientation="portrait" position="float"><label>Table 1</label>
<caption><p>Characteristics of patients with breast cancer (<italic>n</italic>
= 72).</p>
</caption>
<table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="1" colspan="1">Parameters</th>
<th align="center" rowspan="1" colspan="1">Number</th>
<th align="center" rowspan="1" colspan="1">Percent</th>
</tr>
</thead>
<tbody><tr><td align="left" rowspan="1" colspan="1">Age (years)</td>
<td align="center" rowspan="1" colspan="1"> </td>
<td align="center" rowspan="1" colspan="1"> </td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Median</td>
<td align="center" rowspan="1" colspan="1">49</td>
<td align="center" rowspan="1" colspan="1"> </td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Range</td>
<td align="center" rowspan="1" colspan="1">(33–72)</td>
<td align="center" rowspan="1" colspan="1"> </td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Tumor size (cm)</td>
<td align="center" rowspan="1" colspan="1"> </td>
<td align="center" rowspan="1" colspan="1"> </td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Median</td>
<td align="center" rowspan="1" colspan="1">1.9</td>
<td align="center" rowspan="1" colspan="1"> </td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Range</td>
<td align="center" rowspan="1" colspan="1">(0.9–5.5)</td>
<td align="center" rowspan="1" colspan="1"> </td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Quadrant</td>
<td align="center" rowspan="1" colspan="1"> </td>
<td align="center" rowspan="1" colspan="1"> </td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Areolar</td>
<td align="center" rowspan="1" colspan="1">2</td>
<td align="center" rowspan="1" colspan="1">2.8</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Outer upper</td>
<td align="center" rowspan="1" colspan="1">37</td>
<td align="center" rowspan="1" colspan="1">51.4</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Outer lower</td>
<td align="center" rowspan="1" colspan="1">15</td>
<td align="center" rowspan="1" colspan="1">20.8</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Inner lower</td>
<td align="center" rowspan="1" colspan="1">7</td>
<td align="center" rowspan="1" colspan="1">9.7</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Inner upper</td>
<td align="center" rowspan="1" colspan="1">11</td>
<td align="center" rowspan="1" colspan="1">15.3</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Operation</td>
<td align="center" rowspan="1" colspan="1"> </td>
<td align="center" rowspan="1" colspan="1"> </td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Mastectomy</td>
<td align="center" rowspan="1" colspan="1">61</td>
<td align="center" rowspan="1" colspan="1">84.7</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Tumorectomy</td>
<td align="center" rowspan="1" colspan="1">11</td>
<td align="center" rowspan="1" colspan="1">15.3</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Axillary assessment</td>
<td align="center" rowspan="1" colspan="1"> </td>
<td align="center" rowspan="1" colspan="1"> </td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Positive</td>
<td align="center" rowspan="1" colspan="1">29</td>
<td align="center" rowspan="1" colspan="1">40.3</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Negative</td>
<td align="center" rowspan="1" colspan="1">43</td>
<td align="center" rowspan="1" colspan="1">59.7</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Histological grading</td>
<td align="center" rowspan="1" colspan="1"> </td>
<td align="center" rowspan="1" colspan="1"> </td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> G1</td>
<td align="center" rowspan="1" colspan="1">17</td>
<td align="center" rowspan="1" colspan="1">23.6</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> G2</td>
<td align="center" rowspan="1" colspan="1">45</td>
<td align="center" rowspan="1" colspan="1">62.5</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> G3</td>
<td align="center" rowspan="1" colspan="1">10</td>
<td align="center" rowspan="1" colspan="1">13.9</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Estrogen receptor status</td>
<td align="center" rowspan="1" colspan="1"> </td>
<td align="center" rowspan="1" colspan="1"> </td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Positive</td>
<td align="center" rowspan="1" colspan="1">37</td>
<td align="center" rowspan="1" colspan="1">51.4</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Negative</td>
<td align="center" rowspan="1" colspan="1">35</td>
<td align="center" rowspan="1" colspan="1">48.6</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Progesteron receptor status</td>
<td align="center" rowspan="1" colspan="1"> </td>
<td align="center" rowspan="1" colspan="1"> </td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Positive</td>
<td align="center" rowspan="1" colspan="1">31</td>
<td align="center" rowspan="1" colspan="1">43.1</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Negative</td>
<td align="center" rowspan="1" colspan="1">41</td>
<td align="center" rowspan="1" colspan="1">56.9</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Her2 receptor status</td>
<td align="center" rowspan="1" colspan="1"> </td>
<td align="center" rowspan="1" colspan="1"> </td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Positive</td>
<td align="center" rowspan="1" colspan="1">28</td>
<td align="center" rowspan="1" colspan="1">38.9</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Negative</td>
<td align="center" rowspan="1" colspan="1">44</td>
<td align="center" rowspan="1" colspan="1">61.1</td>
</tr>
</tbody>
</table>
</table-wrap>
<table-wrap id="tab2" orientation="portrait" position="float"><label>Table 2</label>
<caption><p>Lymph node numbers in different node groups.</p>
</caption>
<table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="2" colspan="1"> </th>
<th colspan="3" align="center" rowspan="1">Lower LN</th>
<th align="center" rowspan="1" colspan="1">Upper LN group</th>
<th align="center" rowspan="1" colspan="1">Total</th>
</tr>
<tr><th align="center" rowspan="1" colspan="1">SLN</th>
<th align="center" rowspan="1" colspan="1">Non-SLN</th>
<th align="center" rowspan="1" colspan="1">SLN + non-SLN</th>
</tr>
</thead>
<tbody><tr><td align="left" rowspan="1" colspan="1">Sum of LN</td>
<td align="center" rowspan="1" colspan="1">232</td>
<td align="center" rowspan="1" colspan="1">685</td>
<td align="center" rowspan="1" colspan="1">917</td>
<td align="center" rowspan="1" colspan="1">586</td>
<td align="center" rowspan="1" colspan="1">1503</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Mean number of nodes per patient</td>
<td align="center" rowspan="1" colspan="1">3.22 ± 1.47</td>
<td align="center" rowspan="1" colspan="1">9.51 ± 3.34</td>
<td align="center" rowspan="1" colspan="1">12.74 ± 3.50</td>
<td align="center" rowspan="1" colspan="1">8.14 ± 3.20</td>
<td align="center" rowspan="1" colspan="1">20.94 ± 4.83</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn><p>SLN: sentinel lymph nodes group; non-SLN: nonsentinel lymph nodes group.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="tab3" orientation="portrait" position="float"><label>Table 3</label>
<caption><p>Macro-metastasis as demonstrated using H&E. Number of patients with macro-metastasis-positive (LN+) and macro-metastasis-negative (LN−) nodes in different groups.</p>
</caption>
<table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="2" colspan="1"> </th>
<th align="center" rowspan="2" colspan="1">Preoperative evaluation</th>
<th colspan="2" align="center" rowspan="1">Lower LN group</th>
<th align="center" rowspan="2" colspan="1">Upper LN group</th>
<th align="center" rowspan="2" colspan="1">Postoperative evaluation</th>
</tr>
<tr><th align="center" rowspan="1" colspan="1">SLN</th>
<th align="center" rowspan="1" colspan="1">Non-SLN</th>
</tr>
</thead>
<tbody><tr><td align="left" rowspan="1" colspan="1">LN (−)</td>
<td align="center" rowspan="1" colspan="1">43</td>
<td align="center" rowspan="1" colspan="1">57</td>
<td align="center" rowspan="1" colspan="1">53</td>
<td align="center" rowspan="1" colspan="1">69</td>
<td align="center" rowspan="1" colspan="1">53</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">LN (+)</td>
<td align="center" rowspan="1" colspan="1">29</td>
<td align="center" rowspan="1" colspan="1">15</td>
<td align="center" rowspan="1" colspan="1">19</td>
<td align="center" rowspan="1" colspan="1">3</td>
<td align="center" rowspan="1" colspan="1">19</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Number of samples</td>
<td align="center" rowspan="1" colspan="1">72</td>
<td align="center" rowspan="1" colspan="1">72</td>
<td align="center" rowspan="1" colspan="1">72</td>
<td align="center" rowspan="1" colspan="1">72</td>
<td align="center" rowspan="1" colspan="1">72</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn><p>SLN: sentinel lymph nodes group; non-SLN: non-sentinel lymph nodes group.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="tab4" orientation="portrait" position="float"><label>Table 4</label>
<caption><p>Macro-metastasis location in individual patients.</p>
</caption>
<table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="2" colspan="1"></th>
<th rowspan="2" colspan="1">Patient ID</th>
<th align="center" colspan="2" rowspan="1">Lower LN group</th>
<th align="center" rowspan="1" colspan="1">Upper LN</th>
</tr>
<tr><th align="center" rowspan="1" colspan="1">SLN group</th>
<th align="center" rowspan="1" colspan="1">Non-SLN</th>
</tr>
</thead>
<tbody><tr><td align="left" rowspan="1" colspan="1">1*</td>
<td align="center" rowspan="1" colspan="1">512961*</td>
<td align="center" rowspan="1" colspan="1">−*</td>
<td align="center" rowspan="1" colspan="1">+*</td>
<td align="center" rowspan="1" colspan="1">−*</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">2*</td>
<td align="center" rowspan="1" colspan="1">534504*</td>
<td align="center" rowspan="1" colspan="1">−*</td>
<td align="center" rowspan="1" colspan="1">+*</td>
<td align="center" rowspan="1" colspan="1">−*</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">3<sup>#</sup>
</td>
<td align="center" rowspan="1" colspan="1">540157<sup>#</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>#</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>#</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>#</sup>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">4*</td>
<td align="center" rowspan="1" colspan="1">595554*</td>
<td align="center" rowspan="1" colspan="1">−*</td>
<td align="center" rowspan="1" colspan="1">+*</td>
<td align="center" rowspan="1" colspan="1">−*</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">5<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">515192<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>$</sup>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">6<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">514209<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>$</sup>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">7<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">609109<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>§</sup>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">8<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">587996<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>$</sup>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">9<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">544091<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>$</sup>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">10<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">546770<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>$</sup>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">11<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">533853<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>$</sup>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">12<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">517425<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>$</sup>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">13<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">589776<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>$</sup>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">14<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">533191<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>$</sup>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">15<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">567965<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>$</sup>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">16<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">555070<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>$</sup>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">17<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">584967<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>§</sup>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">18<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">617172<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>$</sup>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">19<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">480261<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>$</sup>
</td>
</tr>
<tr><td align="left" colspan="5" rowspan="1"><hr></hr>
</td>
</tr>
<tr><td align="left" colspan="2" rowspan="1">Sum (+)</td>
<td align="center" rowspan="1" colspan="1">15</td>
<td align="center" rowspan="1" colspan="1">19</td>
<td align="center" rowspan="1" colspan="1">3</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn><p>SLN: sentinel lymph nodes group; non-SLN: non-sentinel lymph nodes group. </p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="tab5" orientation="portrait" position="float"><label>Table 5</label>
<caption><p>Number of patients with micro-metastasis (macro-metastasis-negative nodes stained with CK-22) in different node groups. </p>
</caption>
<table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="2" colspan="1"> </th>
<th align="center" rowspan="2" colspan="1">Pre-operative evaluation</th>
<th colspan="2" align="center" rowspan="1">Lower LN Group</th>
<th align="center" rowspan="2" colspan="1">Upper LN group</th>
<th align="center" rowspan="2" colspan="1">Post-operative evaluation</th>
</tr>
<tr><th align="center" rowspan="1" colspan="1">SLN</th>
<th align="center" rowspan="1" colspan="1">Non-SLN</th>
</tr>
</thead>
<tbody><tr><td align="left" rowspan="1" colspan="1">LNMM (−)</td>
<td align="center" rowspan="1" colspan="1">34</td>
<td align="center" rowspan="1" colspan="1">41</td>
<td align="center" rowspan="1" colspan="1">29</td>
<td align="center" rowspan="1" colspan="1">50</td>
<td align="center" rowspan="1" colspan="1">28</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">LNMM (+)</td>
<td align="center" rowspan="1" colspan="1">19</td>
<td align="center" rowspan="1" colspan="1">12</td>
<td align="center" rowspan="1" colspan="1">24</td>
<td align="center" rowspan="1" colspan="1">3</td>
<td align="center" rowspan="1" colspan="1">25</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Number of samples</td>
<td align="center" rowspan="1" colspan="1">53</td>
<td align="center" rowspan="1" colspan="1">53</td>
<td align="center" rowspan="1" colspan="1">53</td>
<td align="center" rowspan="1" colspan="1">53</td>
<td align="center" rowspan="1" colspan="1">53</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn><p>LNMM (−): micro-metastasis negative; LNMM (+): micro-metastasis positive; SLN: sentinel lymph nodes group; non-SLN: non-sentinel lymph nodes group.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="tab6" orientation="portrait" position="float"><label>Table 6</label>
<caption><p>Micro-metastasis (macro-metastasis-negative nodes stained with CK-22) in different node groups for individual patients.</p>
</caption>
<table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="2" colspan="1"></th>
<th rowspan="2" colspan="1">Patient ID</th>
<th align="center" colspan="2" rowspan="1">Lower LN group</th>
<th align="center" rowspan="1" colspan="1">Upper LN</th>
</tr>
<tr><th align="center" rowspan="1" colspan="1">SLN group</th>
<th align="center" rowspan="1" colspan="1">Non-SLN group</th>
</tr>
</thead>
<tbody><tr><td align="left" rowspan="1" colspan="1">1<sup>#</sup>
</td>
<td align="center" rowspan="1" colspan="1">596794<sup>#</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>#</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>#</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>#</sup>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">2<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">524841<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>§</sup>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">3<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">534928<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>§</sup>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">4<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">490306<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>§</sup>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">5<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">580431<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>§</sup>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">6<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">575327<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>§</sup>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">7<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">572801<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>§</sup>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">8<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">511855<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>§</sup>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">9<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">552392<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>§</sup>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">10<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">600862<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>§</sup>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">11<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">606324<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>§</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>§</sup>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">12<sup>¥</sup>
</td>
<td align="center" rowspan="1" colspan="1">566900<sup>¥</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>¥</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>¥</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>¥</sup>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">13*</td>
<td align="center" rowspan="1" colspan="1">533935*</td>
<td align="center" rowspan="1" colspan="1">−*</td>
<td align="center" rowspan="1" colspan="1">+*</td>
<td align="center" rowspan="1" colspan="1">+*</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">14*</td>
<td align="center" rowspan="1" colspan="1">603455*</td>
<td align="center" rowspan="1" colspan="1">−*</td>
<td align="center" rowspan="1" colspan="1">+*</td>
<td align="center" rowspan="1" colspan="1">+*</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">15<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">565404<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>$</sup>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">16<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">602786<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>$</sup>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">17<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">481275<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>$</sup>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">18<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">610052<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>$</sup>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">19<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">586968<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>$</sup>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">20<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">581075<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>$</sup>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">21<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">584976<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>$</sup>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">22<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">575268<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>$</sup>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">23<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">473538<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>$</sup>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">24<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">527037<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>$</sup>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">25<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">614530<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">+<sup>$</sup>
</td>
<td align="center" rowspan="1" colspan="1">−<sup>$</sup>
</td>
</tr>
<tr><td align="left" colspan="5" rowspan="1"><hr></hr>
</td>
</tr>
<tr><td align="left" colspan="2" rowspan="1">Sum (+)</td>
<td align="center" rowspan="1" colspan="1">12</td>
<td align="center" rowspan="1" colspan="1">24</td>
<td align="center" rowspan="1" colspan="1">3</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn><p>SLN: sentinel lymph nodes group; non-SLN: non-sentinel lymph nodes group; Sum (+): sum of positive staining nodes.</p>
</fn>
</table-wrap-foot>
</table-wrap>
</floats-group>
</pmc>
</record>
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