Surgery for colorectal cancer: improving staging by the sentinel lymph node procedure van der Zaag, E.S.

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1 UvA-DARE (Digital Academic Repository) Surgery for colorectal cancer: improving staging by the sentinel lymph node procedure van der Zaag, E.S. Link to publication Citation for published version (APA): van der Zaag, E. S. (20). Surgery for colorectal cancer: improving staging by the sentinel lymph node procedure. General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 02 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. UvA-DARE is a service provided by the library of the University of Amsterdam ( Download date: 0 Apr 209

2 Systematic review of sentinel lymph node mapping in colorectal cancer We determined the accuracy of this procedure from published data and identified factors that contribute to the conflicting reports.

3 Introduction Although improvements in screening and treatment have contributed to reduced disease-specific incidence and mortality, colorectal cancer (CRC) remains the third leading cause of cancer-related deaths. The primary treatment for nonmetastatic CRC is surgical resection of the primary tumour with en-bloc resection of the regional node bearing mesentery. The role for regional lymphadenectomy in CRC is well established: local-regional control, cancer staging, adjuvant treatment planning, and overall survival. Nodal involvement is the most important prognostic parameter, and is the pillar in consensus-driven treatment decision-making for adjuvant chemotherapy. 2 The American Joint Committee on Cancer (AJCC) recommends at least 2 harvested lymph nodes per resection specimen for accurate nodal staging, but in daily clinical practice the nodal yield varies with over 50% of resection specimens containing fewer than 2 lymph nodes. 3 This relates to a clinically significant understaging in CRC. Up to 30% of early, presumably node-negative, patients will develop recurrences or distant metastases following potentially curative resection. 4 Apart from incomplete surgical resection, inadequate staging of CRC may result from insufficient pathologic regional nodal retrieval, sampling error or overlooked small volume nodal disease. Serial sectioning and additional immunohistochemistry or reverse transcriptase(rt)-polymerase chain reaction (PCR) could diagnose lymphatic spread more accurately. 5 Ideally, all regional lymph nodes should be examined with these techniques, but this would be too expensive and time consuming and therefore not feasible in everyday practice. The sentinel lymph node concept (SN) could offer a solution. 6 This procedure allows the pathologist to study the few SNs removed in greater detail for tumour burden compared to the conventional H&E staining currently used in routine daily practice. Therefore, SN procedure could refine staging, possibly identifying a patient group benefitting from adjuvant chemotherapy. In contrast to breast cancer and melanoma treatment SN procedure is not routinely used for surgery in colorectal cancert 7, 8. Regional lymphadenectomy is an integral part of the resection in CRC. Therefore, SN biopsy is an adjunct potentially improving staging without defined prognostic impact at this point in time. Numerous, generally small and singleinstitution studies assessed the feasibility of SN with varying conclusions. The SN procedure for CRC has not been standardized, and the methods, materials, and patient selection vary by institution and surgeon. In this report, we present a systematic review of all published studies of SN in CRC to analyze the diagnostic accuracy of this procedure. Our study provides a thorough assessment of the test performance characteristics of the SN procedure reported in the literature and explores the reasons for the observed heterogeneity in study results. 2

4 chapter Material and methods Literature search A systematic review of all published literature was undertaken independently by two investigators (ESZ and CJB) to identify reports regarding lymphatic mapping in CRC patients. The PubMed and Embase databases and the Cochrane Library were search until July 20. The following expanded Medical Subject Headings terms were used: sentinel node, lymphatic mapping, colon cancer, rectal cancer, colorectal cancer/tumo(u)r. References from included studies, review articles and editorials were cross-checked for additional relevant publications. Data from meeting abstract were not studied as these were judged unlikely to present sufficient detail for data extraction required by our study protocol. Inclusion and exclusion criteria for identified literature Only English language publications analysing lymphatic mapping in human patients with CRC were included. Duplicate articles based on the same group of patients were excluded. For follow-up studies that included a subset of previously reported patients, only the most recent article was included. Studies describing the use of indocyanine green were judged to be experimental and were therefore excluded. Finally, if quantitative results were not presented or SN performance parameters could not be extracted from the presented data, studies were also excluded. Data extraction All data extraction was performed by two authors (ESZ and CJB) with crosschecking to ensure validation. When there was a discrepancy between the results, the original article was reanalysed. The fields for data capture were pre-specified before analysis and included extensive information on publication details, patient demographics, methodology, and SN efficacy by binary classification (i.e. detection, accuracy, sensitivity and false negative rates as well as negative predictive values). The quantitative results were used to build 2x2 contingency tables comprising true positive, true negative, and false negative. The term false positive (and hence the calculation of specificity) is not appropriate because the presence of metastases in the SN confers node positivity. The term upstaging is used to describe the immunohistochemical or PCR findings in SNs in the absence of tumour-positive non-sns. The American Joint Committee on Cancer (AJCC) definition for occult tumour cells was used, classifying micrometatases (lesions between 0.2mm and 2.0mm) as true upstaging to pn whereas patients with isolated tumour cells (ITC)(tumour cell deposits smaller than 0.2mm) are still considered pn0 (pn0itc+). 9 SN accuracy parameters were recalculated from the quantitative data presented in the original manuscript without taking immunohistochemical or PCR results into account. Standard definitions were used to facilitate comparison across studies. Outcome parameters may, therefore, differ from the original manuscript. The following definitions were used to describe the performance rates of SN biopsy: Detection rate refers to the number of times a SN was actually identifiable = (number of successful attempts to retrieve a SN / number of attempts to retrieve a SN) x 00%. Accuracy rate refers to the ability of the SN to reflect the overall status of the lymphatic basin = (number of correct predictions of the nodal status by SN biopsy / number of patients with successful SN biopsy) x 00%. Sensitivity refers to the number of times the sentinel reflects the fact that nodal disease is present = (number of patients with tumour involved SNs / number of patients with any lymph node containing tumour) x 00% The false negative rate reflects the proportion of patients in whom no cancer was identified in the SN but who had nodal deposits found in their non-sns compared to the total number of patients with nodal metastases = (number of false negative patients / number of true positive cases + number of false negative cases) x 00%. Upstaging rate refers to the number of cases in which additional serial sectioning and immunohistochemistry or PCR reveals tumour deposits in lymph nodes that would have been classified as pn0 with conventional staging techniques = (number of patients with micrometastases or isolated tumour cells / number of patients classified as pn0 with routine histopathological examination) x00%. Assessment of methodological quality Each of the studies identified was assessed for validity criteria laid down by QUADRAS (an evidence base tool for the assessment of the quality of diagnostic studies). 0 The criteria for validity were adjusted for this review and the following items were scored. ; prospective study, 2; consecutive patients, 3; specifications of inclusion and exclusion criteria 4; SN criteria and detection procedures (i.e. whether the procedure was described in sufficient detail to permit replication), 5; valid reference test (histology), 6; at least 20 procedures every year in each participating centre, 7; outcome parameters reduced to stage of disease or location of disease, 8; use of additional immunohistochemistry or PCR-techniques with classification of upstaging. Statistical analysis A random effects model with an exact likelihood approach was used to calculate pooled SN accuracy parameters and 95% confidence intervals (CIs). The variation in sensitivity in the individual studies was displayed graphically as a forest plot using review manager version 5.0. Bivariate correlations between continuous measures 22 23

5 chapter were based on the Pearson coefficient. To correlate sensitivity results to various study parameters, a linear regression model was used. For sensitivity analysis of individual patient data, a logistic-regression analysis was applied. When appropriate, cut-off points for continuous variables were selected a priori based on clinically relevant criteria or reporting convention. All data were processed with SPSS version 6.0, and a p-value of 0.05 or less was used as the level of statistical significance. Results Included studies The literature search yielded 98 publications on SN biopsy in humans with CRC between January 999 (the year of the earliest series) and July 20. Of these, two studies did not assess the SN procedure, two articles were not in English, 34 articles were either duplicate studies or had more recent data updating the principal studies, and from three articles the quantitative data could not be retrieved. The remainder of this analysis is based on the 57 included studies that were available for data extraction (Figure ). -68 Study characteristics Selected study characteristics from the 57 articles are presented in Table. In total, 3934 patients were enrolled across all studies with 3944 SN procedures performed. There were ten multicenter studies. 23, 27-29, 3, 39, 4, 49, 54, 56 Most studies analysed a limited number of patients, with only ten studies including more than 00 patients. There were 2 studies that solely included patients with colon cancer and three studies that examined rectal cancer only. However, the majority of studies (33) included both patient with colon and rectal cancer. In 32 studies the in technique was used, in 8 studies the ex technique and in seven studies both methods were used to identify SNs. The two methods employed to identify SNs were blue dyes or radiolabeled tracers. Three blue dyes were used: patent blue dye V (25 studies), isosulfan blue (lymphazurin) % (5 studies) and % methylene blue (four studies). Two studies used sulfur colloid for SN identification and studies used a combination of blue dye and radioactive colloid. The mean number of harvested lymph nodes reported was 6.7, and ranged from 7.5 to 30.0 across studies. The overall average number of SNs identified was 2.8 (range between studies from.0 to 7.). All studies had a prospective design and used a valid reference test (histology) with clear SN criteria and detection protocols. However, only 20 of the 57 eligible studies met at least three out of the five other validity criteria (consecutive patients, inclusion and exclusion criteria clearly described, >20 SN procedures per year, separate presentation of outcome parameters for colon versus rectum or early versus advanced carcinomas, use of, 8-2, 24, 25, 28, 29, 32, 39, 4, 43-45, 56, 57, 59, 64, 67 additional upstaging techniques with classification of upstaging). Figure Flow chart showing the selection and exclusion of publications. Medline and Embase search SN studies colorectal cancer (n=453) Publications retrieved for detailed assessment (n=98) Publications analysed for SN performance parameters (n=60) Publications analysed (n=57) Reports excluded based on title or abstract. review articles (n=94) 2. irrelevant or non-comparative (n=25) 3. indocyanine green tracer (n=0) Not in English (n=2) Duplicate/updates available (n=34) SN procedure not used (n=2) No quantitative data available (n=3) SN identification rate In 3643 specimens (92.4%) one or more SN could be identified. The proportion of successful lymphatic mapping across studies ranged from 58% to 00%, with the majority of studies (4/57) demonstrating an identification rate over 90%. The detection rate in studies analysing colon carcinomas was significantly higher than studies including only rectal cancers (93.% versus 83.% resp., p=0.03). Identification rate was significantly higher in studies including more than 00 patients (mean 94.6%) compared to smaller studies (89.5%, p=0.02). In the 32 studies employing the in method, the SN was significantly less often successfully identified than in the 8 studies with ex procedures (89.2% and 93.7% resp., p=0.04). In identification did not improve in the studies were colloid was added to blue dye. Eighteen in 3, 24, 25, 27, studies commented on aberrant lymphatic drainage with a mean rate of 3.9%. 28, 30, 3, 34-36, 42, 44, 47, 49, 6-63, 67 No SNs were found outside the planned resection area in studies. When analysing other parameters, no predictive factors for identification rate could be identified (i.e. multicentre studies, tracer used)

6 chapter Table Results of lymphatic mapping in patients with colorectal cancer Study No patients Colon Rectum No ln Tracer Method No SN True pos True neg False neg Analysis SN Upstaging Vilcea NR Methylene blue In / Ex, HE, IHC of SN 9.4% Ceranic 2 45 NR NR 22,9 Methylene blue Ex, HE, IHC of SN 22,0 Retter ,5 Patent blue In, HE, IHC of SN 20,8% Finan , Isosulfan blue Ex 2, HE, IHC of SN 0 Sommariva ,4 Patent blue Ex 5, HE, IHC of SN 2,0 Dragan NR Isosulfan blue Ex 4, HE, IHC of SN 26,9 Ivanov NR Patent blue In NR HE, IHC of SN 20,0 Nordgärd ,8 Patent blue Ex 4, HE, RT-PCR of SN Van der Zaag ,4 Patent blue Ex 2, HE, IHC of SN 28,8 2,4 Park ,5 Methylene bue In / Ex 2, HE, IHC of SN 8,5 Chan ,5 Methylene blue In,3 3 HE, IHC of SN 0 Quadros ,0 Patent blue/ In 3, HE, IHC of SN 37,5 Faerden ,0 Patent blue In 4, HE, IHC of all ln Lim ,0 Isosulfan blue/ In 4, HE, IHC of SN,3 29,8 Sandrucci ,7 Patent blue/ In 2,2 2 3 HE, IHC of SN 36,4 Köksal ,0 Isosulfan blue In / Ex, HE, IHC of SN 8,7 Kelder ,0 Patent blue In 2, HE, IHC of SN 8,4 Bembenek ,0 Patent blue In 2, HE, IHC of SN 2,3 Stojadinovic ,2 Isosulfan blue Ex 2, HE, IHC of SN 26,8 Matter ,0 Patent blue In 2, HE, IHC of all ln Tiffet ,0 Patent blue/ In 2, HE, IHC of SN 5,7 9,4 Van schaik ,5 Patent blue Ex 5, HE, IHC of SN 30,3 Murawa NR Patent blue In NR 2 22 HE, IHC of SN 9, Liberale ,0 Patent blue In / Ex 2, HE, IHC of SN 9,5 Covarelli , Patent blue/ In,3 6 2 HE, IHC of SN 7,7 Bianchi ,3 Patent blue In 2,3 5 6 HE, IHC of SN 2,5 Yagci ,6 Patent blue Ex 5, HE, IHC of SN 4,8 Thomas ,8 Isosulfan blue In 2, HE, IHC of SN 5,3 Terwisscha ,0 Patent blue/ In 2, HE, IHC of all ln Smith ,0 Isosulfan blue Ex, HE, IHC of SN 0 4,8 Saha ,0 Isosulfan blue In 2, HE, IHC of SN 26, Tuech ,0 Patent blue In / Ex, HE, IHC of SN 2,0 Khafagy NR Patent blue In NR HE, IHC of all ln 46,

7 chapter Table Continued Codignola ,0 Patent blue In 2, HE, IHC of SN 37,5 Braat ,7 Patent blue Ex, HE, IHC of SN 0,5 Smith ,9 Isosulfan blue Ex 4, HE, IHC of SN 24,0 Dahl ,4 Patent blue/ In 2, HE only Bell ,9 Patent blue Ex 2, HE, IHC of SN and equal no of other ln Bertagnolli ,3 Isosulfan blue In 2, HE, serial sections of all ln Demirbas ,6 Patent blue Ex 3, HE, IHC of SN,8 6, Wong ,0 Isosulfan blue Ex 3, HE, IHC of all ln Patten ,4 Isosulfan blue/ In 3,5 4 3 HE, IHC of SN 4,3 27,3 Bembenek ,0 Ex 3, HE, IHC of SN 0 Bertoglio ,4 Patent blue In 2, HE, serial section of SN only Roseano ,6 Patent blue In / Ex 2, HE, IHC of SN 0 Viehl ,6 Isosulfan blue In 2, HE, IHC of SN NR Bilchik ,0 Isosulfan blue/ In, HE, IHC of SN 29,5 Broderick-Villa NR Isosulfan blue In / Ex, HE, IHC of SN NR Kitagawa ,9 In 3, HE only Nastro NR Patent blue/ In NR HE, IHC of SN 50% Paramo , Isosulfan blue In, HE, IHC of SN 20,0% Cox ,5 Isosulfan blue In / Ex 5, HE, IHC of SN 24,0 Gandy ,0 Patent blue Ex 7, 5 6 HE only Esser ,0 Isosulfan blue In,7 2 5 HE only Merrie ,5 Patent blue/ In 3, HE, RT-PCR of all ln Cserni NR NR 5,5 Patent blue In 4,0 8 5 HE only 25,0 Joosten ,0 Patent blue In 3, HE, IHC of SN 3,3 SN = sentinel lymph node, HE = haematoxylin and eosin staining, IHC = immunohistochemistry, RT-PCR = real-time polymerase chain reaction, NR = not reported 28 29

8 chapter Test performance measures The pooled sensitivity of the recalculated outcome parameters was 69.6% ( ), with an accompanying false negative rate of 30.4 ( ). The overall pooled accuracy of the SN procedure was 88.2% ( ). The sensitivity ranged from 33.3% to 00% across studies (Figure 2). There was a strong correlation between the sensitivity and the number of identified SNs (Pearson correlation 0.37, p=0.007, Figure 3), with a good predictive accuracy for lymph node involvement when four or more SNs were identified (mean sensitivity <4 SNs = 66.3% versus 4 SNs = 85.2%, p=0.003). There was no relation between the sensitivity and the method of SN detection (ex versus in ) or tracer used (blue versus radioactive colloid). Apart from the 24 studies only analysing colon or rectal malignancies, another, 5, 9-2, 32, studies presented the separate sensitivity results for the two types of cancer. 37, 4, 45, 64 Combing the outcome parameters a significantly higher sensitivity of SN procedures in colon cancer was found (77,6% versus 65.7% for rectal carcinomas, p=0.04). In 6 studies, sensitivity results could be calculated separately for early (T/ T2) and advanced (T3/ T4) carcinomas. 5, 2, 3, 4, 53, 59 Statistically, a significantly higher sensitivity was seen in the early group compared to advanced carcinomas (93.4% versus 58.8%, p=0.0), but the number of patients with positive lymph nodes in early carcinomas in these studies was small. Unfortunately, the reported parameters associated with heterogeneity in the sensitivity results could not be analysed in a prediction model since different studies commented on different variables. Overall the sensitivity of 20 high quality studies was higher than the other studies, although not statistically significant (57.6% versus 66.4% resp., p=0.07). (Table 2) Figure 2 Weighted sensitivity for the 57 sentinel lymph node studies included in the meta-analysis. Upstaging In 46 studies, immunohistochemistry staining was performed on specimens histologically classified as pn0. -7, 9-46, 48, 50-53, 55, 57, 60-62, 67 Most studies only analyzed the SN when the haematoxylin and eosin staining results were negative. In two studies RT-PCR on the SN was used after a negative haematoxylin and eosin staining result. 8, 65 Sectioning and staining of the lymph nodes was not uniformly undertaken. Serial sectioning was used in most of the studies with intervals ranging from μm with a large variety of monoclonal and polyclonal antibodies used (e.g. cytokeratin markers, cell surface glycoproteins, tumour specific proteins). Mean upstaging was 8.9% (0-50%). However, only ten studies classified these 3, 9, 22, 27, 28, finding into micrometastases or isolated tumour cells according to the AJCC. 3, 34, 36, 38, 59 In these studies the true upstaging rate was significantly lower with 7.7% (0-5.4%). If the immunohistochemical findings of the SN were included in the 5, 8, 9, accuracy parameters, an increased mean sensitivity of 80.2% was found (20 studies -5, 30, 33, 35, 39, 43-46, 48, 49, 52, 57, 60 ). TP= true positive, FP= false positive FN= false negative TN= true negative 30 3

9 chapter Figure 3 Scatter plot illustrating the correlation between the sensitivity of the sentinel lymph node (SN) procedure across studies and the number of identified SNs (Pearson correlation 0.37, p=0.004). A fitted linear-regression equation is shown with 95% confidence intervals. Table 2 Overall results Sensitivity results of sentinel lymph node mapping in patients with colorectal cancer. Sensitivity (%) 95% CI Sensitivity (%) 95% CI p-value HE analysis (57 studies, n=3934) HE + IHC analysis (20 studies, n=477) Subgroup analysis Ex 8 studies, n=69 Blue dye 44 studies, n=3246 Number of SN 4 (0 studies, n=434) Colon cancer (3 studies, n=2224) Early carcinoma 6 studies, n=56 High validity study (20 studies, n=2009) In 32 studies, n= Colloid 3 studies, n= Number of SN < 4 (45 studies, n=3320) Rectal cancer (4 studies, n=468) Advanced carcinoma (6 studies, n= Low validity study (37 studies, n=925) Discussion Our meta-analysis of 57 studies analyzing the SN procedure for CRC shows an overall acceptable identification rate (92%). The higher detection rate in studies including over 00 patients indicates the existing of a learning curve. Furthermore, technical issues may influence successful SN detection given the superiority of the ex technique over the in method. Usually, the in technique is propagated since this procedure has the advantage of identifying aberrant lymphatic drainage with the possibility to adjust the planned resection. However, in the 8 studies analyzing aberrant drainage, a SN outside the planned resection margins was only found in 4% of the patients. With a minority of these nodes being tumour-positive, it will have limited impact on staging. The addition of radio- colloid to blue dye did not improve the in results. Also considering the complexity of the procedure, these observations make ex mapping the method of choice

10 chapter A low pooled sensitivity of 69.6% for predicting lymph node metastases was found with an accompanying false negative rate of 30.4%. Therefore pathological examination of only the SN cannot replace routine examination of the complete mesentery. However, subgroups could be identified with higher sensitivity rates. Sensitivity improved when the number of identified SNs was higher. The latter has been previously established as independent predictive factors of false negative mapping in a prediction model created with Bayesian Network Analysis. 69 Another factor predictive of sensitivity in our study was depth of invasion. Early (T and T2) carcinomas had higher accuracy parameters when compared to advanced carcinomas. Our results are in line with a review of two prospectively maintained databases describing a sensitivity of 89% in for T/ T2 carcinomas. A recent review with comparable overall sensitivity rates did not find a relation with T-stage, but the authors stratified for individual T-stages in colon and rectal cancer separately which might yield different results. 70,7 The lower sensitivity in advanced cancers is probably due to obstruction of afferent lymph vessels or nodes by tumour growth, changing the lymphatic drainage. Since the aim of SN mapping is to refine staging, high accuracy is less important in advanced stage CRC that already meet criteria for adjuvant chemotherapy. Because of progress in diagnostic technology and screening programmes, diagnosis of CRC will occur at earlier stages. 72, 73 It is especially important in these early cancers to identify the small subgroup of high risk patients who may benefit from adjuvant systemic treatment. The additional value of SN mapping is most debatable in rectal cancer. Both identification rate and sensitivity were lower in comparison to colon cancer. Neo-adjuvant treatment in rectal cancer may change tumour status of the SN and hampers lymph node retrieval in general. Furthermore, the clinical consequences of node-positivity in rectal cancer, especially after neo-adjuvant chemo radiotherapy, are less clear than in colon cancer with respect to adjuvant systemic treatment. Previously, we demonstrated that occult tumour cells are predominantly found in the SN. 74 The mean upstaging rate of 9% found in this meta-analysis with most studies only analyzing the SN is therefore probably an accurate estimate of the percentage of patients with occult tumour cells. However, only ten studies classified these cells in isolated tumour cells or micrometastases (2,3% pn0itc+ versus 7,7% pnmi+) as recommended by the AJCC staging manual, which makes the upstaging results difficult to interpret. 9 The prognostic value of isolated tumour cells is still unclear. A reduced survival is described associated with the presence of occult tumour cells in a consecutive series of patients with stage II colon cancer, suggesting also clinical significance of isolated tumour cells. 75 This would be in line with the prognostic role of isolated tumour cells established in breast, colon, and prostate cancer patients However, it is conceivable that isolated tumour cells in patients with distant metastasis have different prognostic value when compared to the pn0 patients. Another report demonstrated that pn0 patients with or without isolated tumour cells in lymph nodes show similar survival rates, whereas patients with micrometastases had lower survival rates. 79 As long as the prognostic significance is not sorted, the AJCC recommends additional treatment only in patients with micrometastases and the 9% upstaging found in this study should be regarded as overestimation. Apart from improving staging by additional staining, SN mapping has also been described to increase the yield of harvested lymph nodes with corresponding upstaging. The number of lymph nodes analysed has been recognized as a prognostic factor for a long time. 80 It has been demonstrated that SN mapping results in an increased proportion of N patients with a corresponding better prognosis of the pn0 patient group 8, 82 which would be an additional reason to recommend SN mapping in patients with early staged colorectal cancer. It should be borne in mind that, in contrast to breast cancer and melanomas, this procedure is not used for therapeutic purposes but mainly to refine staging. The SN procedure is quite safe (especially ex ) and the procedure is not a difficult technique, a learning curve of cases is described. 8 A major drawback of our study is the tremendous diversity across reports in patient selection, technical details of the SN procedures, and pathological analysis. The results should therefore be interpreted with caution. As with any meta-analysis, the possibility of publication bias should be taken into account. Conclusion In conclusion, our meta-analysis demonstrates an overall disappointing sensitivity of SN mapping in colorectal patients. However, in early staged colon cancer the SN procedure has acceptable accuracy rates and refines staging. We recommend that SN mapping should always be considered in addition to conventional resection in colon cancer

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