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Inicio Revista Española de Medicina Nuclear e Imagen Molecular (English Edition) Usefulness of histological superstudy of sentinel lymph nodes detected with radi...
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Original Article
Usefulness of histological superstudy of sentinel lymph nodes detected with radioisotopes in colon cancer
Utilidad del superestudio anatomopatológico de ganglio centinela detectado con radioisótopos en el cáncer de colon
Á. Serrano del Morala,
Corresponding author
aserranom@salud.madrid.org

Corresponding author.
, E. Pérez Viejoa, Á. Castaño Pascualc, E. Llorente Herrerod, G. Rodríguez Caravacab, M. Duran Povedae, F. Pereira Péreza
a Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitario de Fuenlabrada, Fuenlabrada, Madrid, Spain
b Unidad de Medicina Preventiva, Hospital Universitario Fundación de Alcorcón, Madrid, Spain
c Servicio de Anatomía Patológica, Hospital Universitario de Fuenlabrada, Madrid, Spain
d Unidad de Medicina Nuclear, Hospital Universitario de Fuenlabrada, Madrid, Spain
e Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitario Rey Juan Carlos de Móstoles, Madrid, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">At present&#44; the National Comprehensive Cancer Network&#44; the American Joint Committee on Cancer and the Union for International Cancer Control recommend a minimum of 12 lymph nodes &#40;LN&#41; in lymph node dissection for adequate staging of colon cancer &#40;CC&#41;&#46; Involvement of the LNs is the main predictor of survival and recurrence in CC cand the decision to apply adjuvant therapy fundamentally depends on this&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Unexpectedly&#44; however&#44; up to 30&#37; of the patients with CC and negative LNs in the conventional histological study &#40;CHS&#41; present recurrence after potentially curative surgery&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> This may reflect an inadequate histological evaluation&#44; overlooking the presence of occult tumoral cells &#40;not detected by the CHS&#41; and leading to understaging and the decision to not administer adjuvant treatment&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">In CHS of the LN&#44; hematoxyllin-eosin &#40;H&#38;E&#41; is used in only one or two slices of each LN&#46; Tschmelitsch estimated that the study of single sections of a 1&#8239;cm LN represents the evaluation of only 0&#46;4&#37; of the surface of the LN&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> With the use of more exhaustive histopathological and&#47;or molecular methods for the study of LNs&#44; 10&#37;&#8211;20&#37;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> of N0 cases present this involvement which had been occult in the CHS&#46; It is widely accepted that the presence of celluar clusters of 0&#46;2&#8211;2&#8239;mm called micrometastasis &#40;MM&#41; increase the probability of recurrence&#44; thereby reducing survival&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> This is considered in the 6th edition of the tumor&#44; node&#44; metastasis &#40;TNM&#41; system &#40;2003&#41;&#44; and thus&#44; patients with MM are suprastaged &#40;the stage changes from pN&#8239;&#61;&#8239;to pN1mic&#41; and are candidates for adjuvant chemotherapy treatment&#46; The same does not occur in the case of detecting isolated tumoral cells &#40;ITC&#41; &#40;clusters&#8239;&#60;&#8239;0&#46;2&#8239;mm&#41;&#44; which continue to be considered pN0&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">This exhaustive study &#40;or superstudy &#91;SS&#93;&#41; may be done with several techniques&#46; Serial section of the LN with a separation of 0&#46;2&#8239;mm &#40;minimum thickness of the MM&#41; to explore all the LN increases the detection of tumoral cells in sentinel lymph node &#40;SLN&#41; studies in breast cancer&#44; achieving superstaging of up to 30&#37; of the cases with respect to CHS&#46; Immunohistochemistry &#40;IHC&#41; which involves a reaction between a cellular&#47;tissular antigen &#40;Ag&#41; and an antibody &#40;Ac&#41;&#44; surpasses the diagnostic capacity of H&#38;E staining&#46; Normally Ac directed against the carcinoembryonary Ag&#44; the Ag of the epithelial membrane and cytokeratins is used&#46; The importance of the detection of MM by IHC staining of the SLN is controversial due to the low global sensitivity and the little standardization of IHC&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Lastly&#44; molecular biology techniques have been developed for the detection of MM by polymerase chain reaction &#40;PCR&#41; with the advantage that all the LN material is used&#46; A metaanalysis by Iddings described the prognostic significance of the determination of MM by reverse transcription PCR &#40;RT-PCR&#41; in patients with colorectal cancer with a lower survival than patients without MM &#40;<span class="elsevierStyleItalic">P</span>&#8239;&#60;&#8239;&#46;01&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> The one step nucleic acid amplification &#40;OSNA&#174;&#41; method is based on reverse transcription-loop mediated isothermal amplification &#40;RT-LAMP&#41; and consists in reverse transcription of mRNA of cytokeratin 19 &#40;CK19&#41;&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">However&#44; the application of SS is not possible in all the SLNs collected due to the time of processing&#44; resources and the prohibitive cost&#44; although it could be applied in a small group of SLNs which would be the most representative of the global N status from which the SLN concept emerged&#46; Selective SLN biopsy &#40;SLNB&#41; is already performed in the staging and therapeutic planning of breast cancer and cutaneous melanoma&#44;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> in which the representativeness of the SLN &#40;high sensitivity&#41; is of maximum importance since it is applied to avoid often unnecessary lymph node dissection with relevant sequelae &#40;definitive pN0&#41;&#46; However&#44; SLNB is done in another sense in CC&#44; since lymph node dissection in CC does not increase the morbidity of colon resection and is exclusively applied to identify patients who would most benefit from adjuvant chemotherapy&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The standard procedures for the identification of the SLN are the Morton<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> method which uses blue dyes or the injection of radioactive molecules initiated by Alex in 1993&#44;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> used individually or combined and <span class="elsevierStyleItalic">in vivo</span> or <span class="elsevierStyleItalic">ex vivo</span>&#46; On occasions&#44; aberrant lymphatic drainage is observed beyond the usual resection margin in the SLNB&#44; finding LN involvement in more distant territories than those considered as the first drainage station&#44; and allowing extension of the resection to include these LNs&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> This aberrant drainage was observed in 4&#37; of the patients with CC undergoing SLNB in a study from the Netherlands&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> However&#44; the possible role of the SLN in CC remains to be clarified&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">The aim of this study was to determine the representativeness of the SLN and the number of patients who are suprastaged following SS of the SLN&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Study design</span><p id="par0035" class="elsevierStylePara elsevierViewall">This was a prospective study of patients undergoing elective CC surgery by laparoscopic or open colectomy and standard oncologic lymph node dissection in whom the diagnostic validity of SLN involvement was studied&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The sample size was calculated to be of 60 patients&#44; with a confidence level of 90&#37;&#44; diagnostic validity &#237;ndices greater than 70&#37;&#44; a precisi&#243;n of 10&#37; and 5&#37; of losses&#46;</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Inclusion and exclusion criteria</span><p id="par0045" class="elsevierStylePara elsevierViewall">Inclusion criteria&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0050" class="elsevierStylePara elsevierViewall">Patients over 18 years of age diagnosed with colon neoplasia&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0055" class="elsevierStylePara elsevierViewall">Clinical stage 0&#44; I&#44; II&#44; III and IV&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0060" class="elsevierStylePara elsevierViewall">Patients undergoing elective surgery with intention to cure&#46;</p></li></ul></p><p id="par0065" class="elsevierStylePara elsevierViewall">Exclusion criteria&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">-</span><p id="par0070" class="elsevierStylePara elsevierViewall">Tumors of the rectum&#44; apendicular and other than adenocarcinoma&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">-</span><p id="par0075" class="elsevierStylePara elsevierViewall">Refusal to provide informed consent&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">-</span><p id="par0080" class="elsevierStylePara elsevierViewall">Palliative and&#47;or emergency surgery&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">-</span><p id="par0085" class="elsevierStylePara elsevierViewall">Interventions performed by surgeons not participating in the study&#46;</p></li></ul></p><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Surgical procedure&#46; Lymphatic mapping and sentinel lymph node</span><p id="par0090" class="elsevierStylePara elsevierViewall">All the patients underwent standard oncological study after receiving a single intraoperative <span class="elsevierStyleItalic">in vivo</span> injection of the isotope &#40;<span class="elsevierStyleSup">99m</span>Tc-albumin nanocolloid&#59; particle size&#8239;&#177;&#8239;80&#8239;nm&#59; dose 185&#8239;MBq&#41; in the peritumoral subserosa&#44; with a subcutaneous needle &#40;if open surgery&#41; or 22F lumbar puncture needle &#40;if laparoscopic surgery&#41;&#46; A surgical piece was obtained consisting of the main tumor with the conventional regional lymph node dissection&#46; Immediately afterwards&#44; images of the surgical bed were obtained with the gamma camera to ensure that no radiotracer remained &#40;considered as areas &#62;10&#37; of the SLN of greatest activity&#41; which would translate into aberrant lymphatic drainage outside the usual oncological resection area&#46; Then <span class="elsevierStyleItalic">ex vivo</span> detection and identification of the SLN is performed using a portable gamma camera &#40;Sentinella 102&#41;&#44; acquiring images &#40;60&#8239;s&#41; of the surgical piece with the mini gamma to localize colloid deposits in any regional SLN and identifying the lymphatic tissue with the highest count per second with the probe &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; This zone is resected &#40;first lymphatic drainage station of the tumor&#41; consisting in a mesocolon fragment of around 2&#8239;cm<span class="elsevierStyleSup">2</span> identified as the SLN &#40;which may include more than 1&#8239;LN&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Processing of the surgical simple</span><p id="par0095" class="elsevierStylePara elsevierViewall">The SLN and the remainder of the surgical piece &#40;the neoplasia with the standard lymph node dissection&#41; are sent separately to the Department of Anatomy Pathology&#46; The latter is processed according to the usual CC protocol by H&#38;E staining with conventional sections of the LNs isolated &#40;CHS&#41;&#46; The SLN also undergoes CHS and a SS using H&#38;E in serial slices&#44; IHC &#40;CK AE1&#47;AE3&#41; if the serial H&#38;E were negative and quantitative mRNA analysis of tumoral cells &#40;CK19&#41; by OSNA&#174; &#40;only SLNs weighing&#8239;&#62;&#8239;80&#8239;mg&#44; in which half are used for OSNA&#174; and the other half is prepared in formol&#47;paraffin for histological&#47;IHC study&#41;&#46; If the SLN weighs&#8239;&#60;&#8239;80&#8239;mg OSNA&#174; cannot be performed due a lack of sufficient material &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">According to the criteria of the Union for International Cancer Control 2010&#44; positive findings of malignancy for both the SLN and the remaining LNs are classified as follows&#58;<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">-</span><p id="par0105" class="elsevierStylePara elsevierViewall">ITC&#58; tumor cell clusters&#8239;&#60;&#8239;0&#46;2&#8239;mm&#44; with clusters of 10&#8211;20 cells called ITC or clusters of more than 20 cells called tumor colonies&#46; This does not lead to a change in staging and continues to be considered pN0&#44; although it is specified as pN0i&#43; &#40;isolated&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">-</span><p id="par0110" class="elsevierStylePara elsevierViewall">MM&#58; deposits of tumor cell clusters of between 0&#46;2 and 2&#8239;mm&#46; Staging is modified and is considered pN1 &#40;pN1mic&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">-</span><p id="par0115" class="elsevierStylePara elsevierViewall">Metastasis&#58; metastastic involvement of more than 2&#8239;mm &#40;pN1&#41;&#46;</p></li></ul></p><p id="par0120" class="elsevierStylePara elsevierViewall">A false negative &#40;FN&#41; is defined as the presence of a negative SLN in the presence of other affected LNs&#44; which would lead to understaging of the tumoral process if only the SLN were analyzed&#46; The sensitivity of the test is the percentage of patients with SLN&#43; over the total SLN&#43; &#40;percentage of true positives&#41;&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results</span><p id="par0125" class="elsevierStylePara elsevierViewall">From October 2010 to March 2014 lymphatic mapping was performed in 83 patients&#44; but was not completed in 5 due to technical problems or discoordination with Nuclear Medicine &#40;6&#37; of losses&#41;&#46; Finally&#44; another 7 patients were also excluded for non invasive disease in the definitive histopathological study&#44; and thus&#44; 71 patients were analyzed&#46; Of these&#44; 31 &#40;43&#37;&#41; tumor were localized in the right colon and 40 &#40;56&#46;3&#37;&#41; were detected in the left colon&#46; Of all the series&#44; 14 patients were pT1-2 &#40;19&#46;7&#37;&#41; and 57 pT3-4 &#40;80&#46;3&#37;&#41;&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Our SLN detection rate was 87&#46;3&#37; &#40;62 of the 71 patients studied&#41;&#44; confirming the presence of the lymph node in the sample sent of these 62 patients&#46; Among the 9 patients in whom the SLN was not found&#44; in 4&#44; the pathologist did not find the LN in the SLN sample&#44; and in 5 the search for the SLN in the operating room was not successful &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; All the failures to identify the SLN were produced in the first 17 cases&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0135" class="elsevierStylePara elsevierViewall">In regard to the factors that could influence SLN detection failure&#44; we analyzed several which may have been relevant without achieving statistical significance in any&#58; overweight&#47;obesity&#44; laparoscopic surgery&#44; tumor of right localization&#44; pT3-4 tumor&#44; tumor with circumferential growth &#62;75&#37;&#44; presence of lymphovascular infiltraton and tumor &#62;5&#8239;cm&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Based on the localization of the tumor &#40;right&#47;left colon&#41;&#44; the detection rate was 93&#46;54&#37; in the cases in which the tumor was in the right colon &#40;SLN found in 29 of the 31 cases&#41; and 82&#46;5&#37; for those with a tumor in the left colon &#40;SLN found in 33 of the 40 cases&#41;&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">The SS of the SLN consisted of serial H&#38;E in the 62 cases and IHC in 46 patients in whom the serial H&#38;E was negative &#40;not necessary to perform if the H&#38;E is positive&#41;&#46; On the other hand&#44; an OSNA&#174; study was performed independently of the serial H&#38;E results in 46 patients with a SLN of sufficient weight &#40;&#62;80&#8239;mg&#41;&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">A total of 1164&#8239;LN were studied in the 62 patients &#40;18&#46;8&#8239;LN&#47;patient&#41;&#44; of which 145 were SLNs &#40;2&#46;34 SLN&#47;patient&#41;&#46; One hundred three LNs were positive with the CHS&#44; and 112 were positive with the SS of the SLN&#46; By concept&#44; the SLN should be a cluster of LNs with a greater percentage of positivity&#44; as was found in our series&#58; positivity in the SLN group was 17&#46;24&#37; &#40;25&#47;145&#41;&#44; being 8&#46;53&#37; &#40;87&#47;1&#46;019&#41; in the remaining LN group&#8239;&#60;&#8239;0&#44;001&#41;&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">In the CHS&#44; 50&#37; of the patients &#40;31&#47;62&#41; were N&#43; &#40;4 were positive exclusively in the SLN&#41;&#44; and after SS of the SLN only 1 of the 31 N0 patients in the CHS &#40;3&#46;2&#37;&#41; became N&#43; with 51&#46;6&#37; of definitive N&#43; &#40;32&#47;62&#41; &#40;5 were only SLN&#43;&#41;&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Exclusively with the CHS of the SLN&#44; the FN rate &#40;&#171;SLN-&#44; other LNs &#43;&#187;&#41; was 54&#46;8&#37; &#40;17 of the 31 N&#43;&#41;&#46; With the SS of the SLN&#44; in addition to the patient who became N&#43; &#40;who was N0 in the CHS&#41;&#44; increasing the total number of N&#43; to 32 patients&#44; 5 of the 17&#8239;FN in the CHS became positive &#40;that is&#58; 5 patients who were N&#43; in the CHS but were SLN- became SLN&#43; in the SS&#44; but N status did not change because they were N&#43;&#41;&#44; reducing the FN to 37&#46;5&#37; &#40;12&#47;32 cases&#41;&#46; The sensitivity of our diagnostic test with CHS of the SLN was 45&#46;2&#37; &#40;14 SLN&#43; of the 31 N&#43; patients&#41;&#44; which notably improved to 62&#46;5&#37; with the SS &#40;20 SLN&#43; of the 32 patients who were now N&#43;&#41;&#46; There were no false positive&#44; and thus&#44; the specificity could not be calculated since if the SLN is positive&#44; the lymph node dissection is already considered N&#43;&#46; The global accuracy of the test with CHS &#40;the percentage of patients correctly diagnosed with CHS&#41; was 72&#46;58&#37; &#40;45 of the 62 patients the 31 N0 were SLN- plus 14 of the N1 were SLN&#43; with the CHS&#41;&#44; rising to 80&#46;64&#37; with the SS &#40;in 50 of the 62 patients the SLN was diagnosed the same as the N status&#58; the 30 N- patients after SS were SLN- plus 20 N&#43; patients were SLN&#43; &#91;the 14 in the CHS plus 1 patient who went from N0 to N&#43; after the SS plus 5 patients who did not change N status but were SLN- with N&#43; in the CHS and after SS were SLN&#43;&#93;&#41;&#46; The problem with the test is that the sensitivity was low due to the important number of FNs &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0165" class="elsevierStylePara elsevierViewall">The SS of the SLN increased the total number of affected SLN over the CHS in 8 of the 62 patients &#40;12&#46;9&#37;&#41; in whom 9 new positive LN were detected&#58; 2 by serial H&#38;E &#40;both with macrometastasis&#41;&#44; 3 by IHC &#40;all MM&#41; and 4 by OSNA&#174; &#40;3 macrometastasis and 1&#8239;MM&#41;&#46; In 6 of these 8 patients&#44; the SLN became positive &#40;reducing the FN of CHS&#41;&#44; finding both MM and macrometastases&#46; In the other 2 patients&#44; the SLN was already positive in the CHS&#46; One of these 6 went from N0 to N1a due to MM in OSNA&#174; &#40;superstaging from IIA to IIIB&#41;&#44; and the other 5&#44; who were already N&#43; in the CHS&#44; were no longer considered FN &#40;&#171;SLN-&#44; other LNs &#43;&#187; in CHS&#44; became &#171;SLN &#43;&#44; others &#43;&#187;&#41;&#44; modifying the pN subindex in 2 of these cases &#40;both from N1b to N2a&#44; although only one was superstaged from IIIB to IIIC for being T4&#41;&#46; In addition&#44; there were the other 2 SLN&#43; patients in the CHS in whom more positive LNs were identified in the SS of the SLN&#58; both changed the pN subindex &#40;pN1a to pN1b and pN1b to pN2a&#44; and the latter was superstaged from IIIB to IIIC for being T4&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; Therefore&#44; 3 patients went from being N1b to N2a &#40;2 were superstaged for being T4&#41;&#44; 1 patient went from N1a to N1b &#40;with no change in stage&#41; and another went from N0 to N1 &#40;superstaged from IIA to IIIB&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0170" class="elsevierStylePara elsevierViewall">In the end&#44; with the SS of the SLN&#44; of the 8 patients with more SLN&#43;&#44; in 3 the N subindex was not modified &#40;although the total LN affected increased&#41;&#44; and in 5 it was modified &#40;8&#46;06&#37;&#41; and 3 of these latter patients were superstaged &#40;superstaging rate&#8239;&#61;&#8239;4&#46;8&#37;&#44; 3&#47;62&#41;&#46; Among these 3 patients was the only patient who went from pN negative to pN positive leading to a change in the decision to implement adjuvant chemotherapy treatment according to the current standards &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0175" class="elsevierStylePara elsevierViewall">The rate of skip metastasis &#40;which did not fulfill ordered dissemination with initial SLN involvement and afterwards the most distal LNs&#44; and thus&#44; patients with any positive LNs but with a negative SLN&#44; referred to as the &#8220;SLN-&#44; others&#43;&#8221; group&#41; in the 62 patients was 27&#46;41&#37; &#40;17 of the 62 patients&#41; in the CHS&#44; decreasing to 19&#46;35&#37; &#40;12&#47;62 patients&#41; with SS &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#44; in which 5 patients who were SLN- in CHS were found to be SLN&#43;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Discussion</span><p id="par0180" class="elsevierStylePara elsevierViewall">According to the presence of the learning curve&#44;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> our SLN indentification success rate was 87&#46;3&#37;&#44; similar to the systematic review by van der Zaag&#44;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> in which the SLN was identified in 92&#37; of the cases&#46; Successful SLN identification is greater in series of more than 100 cases &#40;94&#46;6&#37;&#41; than in smaller series &#40;89&#46;55&#37;&#44; <span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239;&#46;02&#41;&#46; In our study this translates into identification failure in the first patients&#44; with a posterior detection rate of 100&#37;&#46; The results improve with volume&#44; standardization and training&#44; as mentioned by Wong when commenting on the work of Bertagnolli&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">With respect to the <span class="elsevierStyleItalic">in vivo</span> or <span class="elsevierStyleItalic">ex vivo</span> technique&#44; in the studies of Medina-Franco et al&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> and Roseano et al&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> there were no significant differences between the two in the detection of the SLN&#46; However&#44; in the review by van der Zaag<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> the detection rate was lower in studies using the <span class="elsevierStyleItalic">in vivo</span> technique &#40;89&#46;2&#37; <span class="elsevierStyleItalic">vs</span>&#46; 93&#46;7&#37; respectively&#44; <span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239;&#46;04&#41;&#46; One of the reasons for performing <span class="elsevierStyleItalic">in vivo</span> puncture &#40;as in our case&#41; is the detection of aberrant lymphatic drainage pathways&#44; estimated at 6&#37;&#8211;10&#37;&#44;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#44;17</span></a> which may lead to changes in the extension of lymph node dissection in up to 22&#37; of the patients&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> As in the series of Bertagnolli&#44;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> we did not find any case with aberrant pathways&#44; and therefore&#44; the extensi&#243;n of the lymph node dissection was not modified in any case &#40;<a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0190" class="elsevierStylePara elsevierViewall">For SLN identification both the techniques based on staining and the use of radiotracers have been widely used with satisfactory results&#46; We used the radiotracer because of its wide previous experience in breast cancer and melanoma&#46; To our knowledge this is the first series of SLNB performed with only a radiotracer in CC&#46; Only 2 studies in rectal cancer in the van der Zaag review only used a radiotracer&#44; reporting detection rates of 91&#37;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> and 96&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">The study by van der Zaag<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> published in 2010 described 4 times more occult tumor cells in the SLN &#40;12&#37; MM and 21&#37; ITC&#41; than in the remaining LNs&#44; confirming our results with 17&#46;24&#37; &#40;25&#47;145&#41; of positive LNs in the SS of the SLN &#40;both MM and macrometastasis&#41; compared with 8&#46;53&#37; &#40;87&#47;1&#44;019&#41; in the CHS of the remaining LN &#40;<span class="elsevierStyleItalic">P</span>&#8239;&#60;&#8239;&#46;001&#41;&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">The real reason for SLNB in CC is the superstaging of some patients classified as pN0 in the CHS in which LN involvement was not identified but was actually present&#46; Nonetheless&#44; the problems with respect to its sensitivity of the SLN in CC &#40;which is the inverse value of the FN rate&#41; is known&#46; In the review by van der Zaag&#44;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> the sensitivity was 69&#46;6&#37; &#40;FN 30&#46;4&#37;&#41;&#44; although it reached 80&#46;2&#37; by adding the SS of the SLN to IHC&#46; In our study&#44; despite the SS&#44; the sensitivity was lower &#40;45&#46;2&#37; with CHS and 62&#46;5&#37; with SS&#41;&#44; albeit similar to other studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;19&#44;21&#44;22</span></a> This low sensitivity weakens the predictive capacity of the SLN with respect to the global LN situation&#44; but this only reduces the number of patients who could benefit from superstaging &#40;already being pN&#43; in the remaining LN&#41; that is not possible in those in whom the SLN is falsely negative&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">Nevertheless&#44; this is not transcendental in colorectal cancer&#44; since the objective of SLNB is not to avoid lymph node dissection &#40;the opposite to breast cancer or melanoma in which standard lymph node dissection is not performed in patients with a negative SLN&#41;&#44; which continues to be obligatory in CC&#44; but rather to salvage cases that could benefit from adjuvant chemotherapy<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> in addition to classifying more patients in the correct pN subgroup with prognostic purposes&#46; The FN maintain their pN status &#40;with the CHS of the remaining LN&#41; and the remaining LNs benefit &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0210" class="elsevierStylePara elsevierViewall">Although SLNB provides increased LN restaging&#44; especially with IHC or molecular RT-PCR techniques&#44;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> and some authors conclude that SS of the SLN should be taken into account for adequately staging colorectal cancer &#40;considering the CHS of LNs inadequate for the detection of MM and ITC<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> since&#44; on one hand&#44; it is already considered in the TNM classification&#41;&#44; the rate of superstaging varies greatly&#46; In some studies both MM as ITC &#40;not relevant&#41; are included as restaging&#44; while others refer to the number of restaged LNs &#40;9&#37; in the series of Zheng&#44;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> 1&#46;82&#37; in that of Palma&#44;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> and 2&#46;6&#37; in the series of Messerini<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a>&#41; and in others the number of patients &#40;32&#37; in CC in the series by Saha&#44;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> 15&#46;78&#37; in that of Palma<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> and 38&#46;2&#37; in the series of Messerini<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a>&#41;&#46; Even when referring to patients&#44; the concept of superstaging is variable&#46; Some authors refer to cases in which SLN involvement is detected with histological techniques other than CHS in the absence of other positive LNs in the CHS &#40;with the consequent therapeutic implications&#41;&#44; while superstaging could also be considered when the number of positive LNs increases with SS of the SLN&#44; although there are already positive LNs in the CHS &#40;which could represent a change of the pN subindex or stage&#41;&#44; in which case the implications are only prognostic &#40;change in stage but not treatment&#41;&#46; In the review of van der Zaag<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> the &#8220;relevant&#8221; rate of superstaging &#40;defined as patients with MM&#47;patients classified as pN0 with CHS&#44; that is&#44; excluding the finding of ITC produced in 11&#46;2&#37; but considered as pN0&#41; is 7&#46;7&#37;&#46; In our study this only occurred in 1 of the 31 cases classified as pN0 in the CHS &#40;3&#46;2&#37;&#41;&#44; and thus&#44; the therapeutic impact of SLNB would be less than expected &#40;although it could be relevant if extrapolated to a large number of patients&#41;&#44; while in 8 of the 62 patients &#40;12&#46;9&#37;&#41;&#44; the number of affected LNs increased&#44; raising the pN subindex in 5 &#40;8&#46;06&#37;&#41;&#44; 3 of which were superstaged &#40;4&#46;8&#37;&#41; with the consequent prognostic implication&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">In the studies of SLNB in colorectal cancer&#44; the phenomenon of skip metastasis has been observed in 1 and 5&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">28&#44;29</span></a> Even with multisectcion and IHC staining&#44; 2 studies<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;30</span></a> reported 3&#46;6&#37; and 12&#46;5&#37; respectively&#46; We found a much higher and completely discordant percentage of skip metastasis &#40;27&#46;41&#37; with CHS and 19&#46;35&#37; with SS&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conclusions</span><p id="par0220" class="elsevierStylePara elsevierViewall">It can be concluded that the SS is a valid and reproducible technique with a high rate of SLN detection&#44; albeit with a clear learning curve in the operating room&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">While the number of affected SLN increases globally following SS&#44; the prognostic implications are scarce&#44; with a small percentage of pN0 patients in the CHS becoming pN&#43; after SS of the SLN&#46; Nonetheless&#44; this can have therapeutic consequences since without the SS these patients would be undertreated&#44; a finding which would be relevant if extrapolated to a large number of patients&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">On the other hand&#44; the high rate of FNs does not allow assuming the representativeness of the SLN as an index of global pN status&#46; Nonetheless&#44; the objective is not to avoid lymph node dissection but rather to salvage cases which could benefit from adjuvant chemotherapy&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Authors&#47;collaborators</span><p id="par0235" class="elsevierStylePara elsevierViewall">&#193;ngel Serrano del Moral&#58; study design&#44; data analysis and interpretation and redaction&#46; Critical revision&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall">Est&#237;balitz P&#233;rez Viejo&#58; data collection&#44; study design&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">&#193;ngel Casta&#241;o Pascual&#58; data analysis and study design&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">Esther Llorente Herrero&#58; data analysis and interpretation&#46;</p><p id="par0255" class="elsevierStylePara elsevierViewall">Manuel Duran Poveda&#58; critical revision&#46;</p><p id="par0260" class="elsevierStylePara elsevierViewall">Gil Rodr&#237;guez Caravaca&#58; interpretation of results&#44; critical revision&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall">Fernando Pereira P&#233;rez&#58; interpretation of results&#44; critical revisi&#243;n&#44; approval of final versi&#243;n&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conflict of interests</span><p id="par0270" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interests&#46;</p></span></span>"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Adjuvant chemotherapy &#40;CT&#41; significally reduces the rate of relapse in &#43;pN &#40;stage III&#41; colon cancer &#40;CC&#41; and in some pN0 &#40;stage II&#41; with risk factors such as pT4&#44; vascular invasion V1&#44; perineural invasion Pn1&#44; and complicated tumors&#46; However&#44; unexpectedly&#44; 20&#37;&#8211;30&#37; of pN0 present a relapse in the follow-up&#44; which may suggest that the lymph node involvement was not discovered in the conventional histological study &#40;CS&#41;&#44; and its finding with a superstudy &#40;SS&#41; could increase the number of patients who would benefit from neoadjuvant CT&#46; It is not possible to perform this SS in every lymph node &#40;LN&#41; from the specimen&#44; but it is possible in a small group of LN which are representative of the N status &#40;definition of sentinel node SN&#41;&#46; The aim of our work is to state the representativeness of the SN and to analyze de number of patients who are suprastaged after the SS of the SN&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and Methods</span><p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Prospective study of a series of patients who have undergone curative surgery for CC&#44; to whom we perform selective biopsy of sentinel node &#40;SBDN&#41;&#46; Identification of SN was carried out with <span class="elsevierStyleItalic">in vivo</span> injection of the radiotracer&#44; with ex vivo isolation of SN&#46; Once the specimen is out&#44; we take pictures of the surgical bed to rule out the presence of aberrant drainage routes&#44; out of the routine oncological resection area&#46; We performed the histological CS &#40;Hematoxilin-Eosin stain &#40;H-E&#41; in conventional sections&#41; in the rest of the LN from the mesocolon&#46; In the SN we performed the CS and a SS with H-E in serial sections&#44; immunohistochemistry &#40;IHC&#41; and molecular study with OSNA&#174; &#40;One Step Nucleic Acid Amplification&#41;&#46; Diagnostic validity study od SBSN was carried out&#44; defining the false negative &#40;FN&#41; as the negativity of the SN while other LN are positive &#40;N&#43;&#41;&#44; as well as a valuation of the suprastaging due to the SS of the SN&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">We performed lymphatic map in 72 patients&#44; finding the SN in 62 of them &#40;87&#46;3&#37;&#41;&#46; The 9 identification failures happened in the first 17 cases&#46; We have not found aberrant drainage routes&#46; A total of 1&#46;164&#8239;LN were studied in the 62 patients &#40;18&#46;8&#8239;LN&#47;patient&#41;&#44; from which 145 are SN &#40;2&#44;34&#8239;SN&#47;patient&#41;&#44; having found 103 positive LN with the CS and 112 positive with the SS of SN &#40;9&#43; LN more in 8 patients than detected with the CS&#41;&#46; Positivity after CS in the SN group is 17&#46;24&#37; &#40;25&#47;145&#41;&#44; while it is 8&#46;53&#37; in the rest &#40;87&#47;1&#46;019&#41; &#40;<span class="elsevierStyleItalic">P</span>&#8239;&#60;&#8239;&#46;001&#41;&#46; With the CS&#44; 50&#37; of the patients &#40;31&#47;62&#41; were pN&#43; &#40;4 are N&#43; exclusively in the SN&#41;&#44; and after the SS of the SN&#44; only 1 of the 31 pN0 patients &#40;3&#46;2&#37;&#41; becomes pN1a&#44; with a definitive 51&#46;6&#37; of N&#43; in the whole series &#40;32 N&#43; in the 62 patients&#41; &#40;5 are N&#43; exclusively in the SN&#41;&#46;</p><p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Exclusively with the SS of the SN&#44; FN rate &#40;&#8220;-SN&#44; &#43;others&#8221;&#44; meaning patients who are N&#43; having -SN&#41; is 54&#46;8&#37; &#40;17&#47;31&#41;&#46; With the SS of the SN&#44; 8 of the 62 patients &#40;12&#46;9&#37;&#41; increase their total number of &#43;LN&#58; apart from the patient who turns from pN0 to pN1a&#44; suprastaging from IIA to IIIB &#40;and therefore increasing the total number of pN&#43; to 32&#41;&#44; 5 of the 17&#8239;FN in the CS turns into positive &#40;2 change the pN subindex and one is suprastaged from IIIB to IIIC&#41;&#44; decreasing FN to 37&#46;5&#37; &#40;12&#47;32 cases&#41;&#46; Besides&#44; 2 patients whose SN is already positive in the CS increase the number of &#43;SN after the SS of the SN&#44; therefore both changing their pN subindex and one of them suprastaging from IIIB to IIIC&#46; In summary&#44; 8 patients increase the total number of positive SN after the SS &#40;8&#47;62&#44; 12&#46;9&#37;&#41;&#44; 5 of them changing the pN subindex &#40;5&#47;62&#44; 12&#46;9&#37;&#41;&#44; even if only 3 of them get suprastaged &#40;3&#47;62&#44; 4&#46;8&#37;&#41;&#44; among them the one who turns from pN0 to pN1a&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">Technique is valid and reproducible&#44; with a high detection rate even with a high learning curve&#46; It globally increases the number of affected LN in 12&#46;9&#37; of patients&#44; having prognostic implications in 4&#46;8&#37; &#40;suprastaging rate&#41;&#46; Only 3&#46;2&#37; of pN0 patients in the CS turn to be &#43;pN after the SS of the SN&#44; with its therapeutic implications &#40;prescription of adjuvant CT&#41;&#44; which could be relevant when extrapolated to a big number of patients&#46; The high FN rate &#40;37&#46;5&#37;&#41; prevents us from accepting the representativeness of SN as the global N status&#44; but it is not clinically relevant in CC&#44; as its aim is not to avoid lymphadenectomy&#44; which remains mandatory &#40;opposite to breast cancer or melanoma in which SN detection decides upon whether to perform or not the lymphadenectomy&#41;&#44; but to decide which patients would benefit from adjuvant CT&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">La quimioterapia &#40;QT&#41; adyuvante reduce significativamente las recidivas en el c&#225;ncer de colon &#40;CC&#41; pN&#43; &#40;estadio III&#41; y en algunos pN0 &#40;estadio II&#41; con factores de riesgo &#40;pT4&#44; infiltraci&#243;n vascular V1&#44; infiltraci&#243;n perineural Pn1&#44; tumores complicados&#41;&#46; Sin embargo&#44; de manera no esperada&#44; un 20&#37;&#8211;30&#37; de los pN0 presentan recidivas en el seguimiento&#44; lo que hace pensar que es posible que haya afectaci&#243;n ganglionar que haya quedado oculta tras el estudio convencional histol&#243;gico &#40;EC&#41;&#44; y su identificaci&#243;n mediante un superestudio &#40;SE&#41; podr&#237;a aumentar el n&#250;mero de pacientes que se beneficiar&#237;an de QT adyuvante&#46; No es posible hacer este superestudio de todos los ganglios linf&#225;ticos &#40;GL&#41; aislados en la linfadenectom&#237;a&#44; pero s&#237; ser&#237;a factible en un peque&#241;o grupo de GL que fueran representativos del estatus N global &#40;concepto de ganglio centinela &#40;GC&#41;&#41;&#46; El objetivo de nuestro trabajo es determinar esa representatividad del GC y analizar el n&#250;mero de pacientes que se supraestadifican tras el SE del GC&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y M&#233;todos</span><p id="spar0110" class="elsevierStyleSimplePara elsevierViewall">Estudio prospectivo en una serie de pacientes operados por CC con intenci&#243;n curativa&#44; a los que se les realiza biopsia selectiva de GC &#40;BSGC&#41;&#46; La identificaci&#243;n del GC se realiz&#243; mediante la inyecci&#243;n <span class="elsevierStyleItalic">in vivo</span> del radiotrazador&#44; con aislamiento posterior ex vivo del GC&#46; Tras la extracci&#243;n de la pieza se toman im&#225;genes del lecho quir&#250;rgico para descartar v&#237;as aberrantes de drenaje linf&#225;tico fuera del &#225;rea de resecci&#243;n oncol&#243;gica habitual&#46; Se realiz&#243; el EC histol&#243;gico &#40;tinci&#243;n con Hematoxilina-Eosina &#40;H-E&#41; con secciones convencionales&#41; del resto de GL aislados del mesocolon&#46; En el GC se realiz&#243; el EC y adem&#225;s un SE mediante H-E en cortes seriados&#44; inmunohistoqu&#237;mica &#40;IHQ&#41; y estudio molecular con la t&#233;cnica OSNA&#174; &#40;One Step Nucleic Acid Amplification&#41;&#46; Se efectu&#243; un estudio de validez diagn&#243;stica de la BSGC definiendo como falso negativo &#40;FN&#41; a la existencia de un GC negativo en presencia de otros GL afectados &#40;N&#43;&#41;&#44; as&#237; como una valoraci&#243;n de la supraestadificaci&#243;n conseguida gracias al SE del GC&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0115" class="elsevierStyleSimplePara elsevierViewall">Se realiz&#243; mapeo linf&#225;tico en 71 pacientes&#44; detect&#225;ndose el GC en 62 de los 71 pacientes &#40;87&#44;3&#37;&#41;&#46; Los 9 fallos de identificaci&#243;n se concentran en los primeros 17 casos&#46; No hemos encontrado pacientes con drenaje linf&#225;tico aberrante&#46;</p><p id="spar0120" class="elsevierStyleSimplePara elsevierViewall">Se estudian un total 1&#46;164&#8239;GL en los 62 pacientes &#40;18&#44;8&#8239;GL&#47;paciente&#41;&#44; de los que 145 son GC &#40;2&#44;34 GC&#47;paciente&#41;&#44; encontr&#225;ndose 103&#8239;GL positivos con el EC y 112 positivos con el SE del GC &#40;9 GL&#43; m&#225;s en 8 pacientes que los detectados en el EC&#41;&#46; La positividad tras el SE en el grupo GC es del 17&#44;24&#37; &#40;25&#47;145&#41; mientras en el resto es del 8&#44;53&#37; &#40;87&#47;1&#46;019&#41; &#40;<span class="elsevierStyleItalic">P</span>&#8239;&#60;&#8239;&#44;001&#41;&#46; Con el EC&#44; el 50&#37; de los pacientes &#40;31&#47;62&#41; fueron pN&#43; &#40;4 son N&#43; exclusivamente en el GC&#41;&#44; y tras el SE del GC&#44; s&#243;lo 1 de los 31 pacientes pN0 &#40;3&#44;2&#37;&#41; se hace pN1a&#44; con un 51&#44;6&#37; definitivo de N&#43; en el total de pacientes &#40;32 N&#43; de los 62 pacientes&#41; &#40;5 son N&#43; exclusivamente en el GC&#41;&#46; Exclusivamente con el EC del GC&#44; la tasa de FN &#40;&#8220;GC-&#44; otros &#43;&#8221;&#44; es decir&#44; pacientes que son N&#43; teniendo GC negativo&#41; es del 54&#44;8&#37; &#40;17&#47;31&#41;&#46; Con el SE del GC&#44; 8 de los 62 pacientes &#40;12&#44;9&#37;&#41; aumentan el n&#250;mero total de GL afectados&#58; adem&#225;s del paciente que pasa de pN0 a pN1a supraestadific&#225;ndose de IIA a IIIB &#40;y aumentando el n&#250;mero total de pN&#43; a 32&#41;&#44; 5 de los 17&#8239;FN del EC se hacen positivos &#40;dos cambian de sub&#237;ndice pN y uno se supraestadifica de IIIB a IIIC&#41;&#44; reduci&#233;ndose los FN al 37&#44;5&#37; &#40;12&#47;32 casos&#41;&#46; Adem&#225;s hay otros dos pacientes en los que el GC ya es positivo en el EC&#44; que aumentan el n&#250;mero de GL&#43; tras el SE del GC&#44; cambiando ambos su sub&#237;ndice pN y supraestadific&#225;ndose uno de ellos de IIIB a IIIC&#46; En resumen&#44; 8 pacientes aumentan el n&#250;mero total de GL afectados gracias al SE &#40;8&#47;62&#44; 12&#44;9&#37;&#41;&#44; cambiando el sub&#237;ndice pN en cinco de ellos &#40;5&#47;62&#44; 8&#37;&#41;&#44; aunque s&#243;lo tres de estos se supraestadifican &#40;3&#47;62&#44; 4&#44;8&#37;&#41;&#44; entre los que se encuentra el que pasa de pN0 a pN1a&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0125" class="elsevierStyleSimplePara elsevierViewall">La t&#233;cnica es v&#225;lida y reproducible&#44; con alta tasa de detecci&#243;n aunque con una clara curva de aprendizaje&#46; Globalmente aumenta el n&#250;mero de GL afectados en un 12&#44;9&#37; de los pacientes&#44; con implicaciones pron&#243;sticas en un 4&#44;8&#37; &#40;tasa de supraestaadificaci&#243;n&#41;&#46; S&#243;lo un 3&#44;2&#37; de los pacientes pN0 en el EC pasan a ser pN&#43; tras el SE del GC&#44; con la correspondiente consecuencia terap&#233;utica &#40;indicaci&#243;n de QT adyuvante&#41;&#44; hallazgo que ser&#237;a relevante si se extrapola a un gran n&#250;mero de pacientes&#46; La alta tasa de FN &#40;37&#44;5&#37;&#41; impide asumir la representatividad de GC como &#237;ndice del estatus pN global&#44; pero esto no es trascendente en el CCR ya que su finalidad no es evitar la linfadenectom&#237;a&#44; que sigue siendo obligatoria&#44; &#40;al rev&#233;s que en c&#225;ncer de mama o melanoma en los que la detecci&#243;n del GC s&#237; se usa para decidir sobre si se realiza o no la linfadenectom&#237;a&#41;&#44; sino rescatar casos que pueden beneficiarse de quimioterapia adyuvante&#46;</p></span>"
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                  <table border="0" frame="\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">SLN&#58; sentinel lymph node&#59; CHS&#58; conventional histological study&#59; SS&#58; superstudy&#46;</p>"
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            0 => array:2 [
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                0 => """
                  <table border="0" frame="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#46;&#176; case&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">pTN CHS &#40;n&#176; SLN&#43;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">CHS stage&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">SLN in CHS&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">pTN Ss&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">T3N0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">T3N1a &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">39&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">T4N1b &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IIIB&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NEG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">T4N2a &#40;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IIIC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">T3N1b &#40;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">IIIB&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NEG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">T3N2a &#40;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IIIB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">T3N1b &#40;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IIIB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NEG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">T3N1b &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IIIB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">T3N1b &#40;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IIIB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NEG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">T3N1b &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IIIB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">T3N2b &#40;13&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IIIC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NEG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">T3N2b &#40;14&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">IIIC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">77<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">T3N1a &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IIIB&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">POS&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">T3N1b &#40;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">IIIB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t">IIIB&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">POS&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">T3N2a &#40;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IIIC&nbsp;\t\t\t\t\t\t\n
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                  """
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Changes in the pN subindex and stage after superstudy&#8239;&#43;&#8239;of the sentinel lymph node&#46;</p>"
        ]
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        "etiqueta" => "Table 4"
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          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">SLN&#58; sentinel lymph node&#59; CHS&#58; conventional histological study&#59; SS&#58; superstudy&#46;</p>"
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">CHS&#44; n&#8239;&#61;&#8239;62&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">SS&#44; n&#8239;&#61;&#8239;62&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">SLN&#43;&#44; others -&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">4 &#40;6&#46;45&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22&#46;6&#37; SLN&#43; in CHS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;8&#46;06&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&#46;3&#37; SLN&#43; in SS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SLN&#43;&#44; others &#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 &#40;16&#46;12&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15 &#40;24&#46;19&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SLN-&#44; others -&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31 &#40;50&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">77&#46;4&#37; SLN- in CHS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30 &#40;48&#46;38&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">67&#46;7&#37; SLN- in SS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SLN-&#44; others &#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17 &#40;27&#46;41&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12 &#40;19&#46;35&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Total N&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#8239;&#43;&#8239;10&#8239;&#43;&#8239;17&#8239;&#61;&#8239;31 &#40;50&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#8239;&#43;&#8239;15&#8239;&#43;&#8239;12&#8239;&#61;&#8239;32 &#40;51&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Others&#58; remaining lymph nodes of the lymph node dissection&#46;</p>"
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">SLN&#47;other ratio<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a> in conventional histological study and superstudy &#40;reduction in the rate of skip metastasis &#40;SLN-&#44; other&#43;&#41; and increase of N positive after the superstudy&#46;</p>"
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          0 => array:3 [
            "identificador" => "at0045"
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          "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">References in parenthesis&#46;</p><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">CHS&#58; conventional histological study&#59; FN&#58; false negatives&#59; SS&#58; superstudy&#46; ND&#58; not determined&#46;</p>"
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            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Aberrant pathway&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">FN in CHS&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">FN in SS&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">Present series&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#47;62 &#40;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&#47;32 &#40;53&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#47;33 &#40;36&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Bertagnolli 2004<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">a</span></a> &#40;13&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#47;66 &#40;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#47;24 &#40;54&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Saha 2004 &#40;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#47;17 &#40;18&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#47;17 &#40;18&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Bilchik 2003 &#40;23&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#47;42 &#40;12&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#47;65 &#40;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Saha 2001<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">a</span></a> &#40;17&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#47;198 &#40;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#47;54 &#40;15&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#47;81 &#40;10&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Bilchik 2001<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">a</span></a> &#40;11&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#47;40 &#40;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#47;10 &#40;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#47;14 &#40;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab2732352.png"
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            0 => array:3 [
              "identificador" => "tblfn0015"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Multicenter study&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Comparison with other studies&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:30 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Colon cancer survival is associated with increasing number of lymph nodes analyzed&#58; a secondary survey of intergroup trial INT-0089"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "T&#46;E&#46; Le Voyer"
                            1 => "E&#46;R&#46; Sigurdson"
                            2 => "A&#46;L&#46; Hanlon"
                            3 => "R&#46;J&#46; Mayer"
                            4 => "J&#46;S&#46; Macdonald"
                            5 => "P&#46;J&#46; Catalano"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1200/JCO.2003.05.062"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Oncol&#46;"
                        "fecha" => "2003"
                        "volumen" => "21"
                        "paginaInicial" => "2912"
                        "paginaFinal" => "2919"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12885809"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prognosis of node-positive colon cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "A&#46;M&#46; Cohen"
                            1 => "S&#46; Tremiterra"
                            2 => "F&#46; Candela"
                            3 => "H&#46;T&#46; Thaler"
                            4 => "E&#46;R&#46; Sigurdson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/1097-0142(19910401)67:73.0.co;2-a"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cancer&#46;"
                        "fecha" => "1991"
                        "volumen" => "67"
                        "paginaInicial" => "1859"
                        "paginaFinal" => "1861"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2004298"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lymph node micrometastases do not predict relapse in stage II colon cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "J&#46; Tschmelitsch"
                            1 => "D&#46;S&#46; Klimstra"
                            2 => "A&#46;M&#46; Cohen"
                          ]
                        ]
                      ]
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Article information
ISSN: 22538089
Original language: English
DOI:10.1016/j.remnie.2021.03.019
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