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Chilaka S, Samuel EMK, Mude NN, G B, Badhe B, Nagarajan RK. Comparison of conventional unstained lymph nodal harvesting vs methylene blue-stained lymph nodal harvesting in colorectal specimen in staging left-sided colorectal carcinoma: a randomized controlled trial. J Gastrointest Surg 2024; 28:199-204. [PMID: 38445909 DOI: 10.1016/j.gassur.2023.11.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Revised: 08/19/2023] [Accepted: 11/04/2023] [Indexed: 03/07/2024]
Abstract
BACKGROUND The management and prognosis of colorectal carcinomas (CRCs) are related to the stage of the disease, which, in turn, relies on the lymph node harvest from the surgical specimen. The guidelines recommend that at least 12 lymph nodes are required, which is not achieved in most resections. In this study, we propose a method to improve the lymph node yield in such cases. This study aimed to determine whether ex vivo injection of methylene blue into the inferior mesenteric artery or its branches improves lymph node retrieval in left-sided CRCs. METHODS This study was conducted as a single-center, double-blinded, superiority randomized controlled trial. Patients who underwent elective surgery for left-sided CRCs with curative intent were randomized into 2 groups: stained and unstained. The sample size was calculated as 66. In all patients, details of disease stage, history of neoadjuvant therapy, and number of isolated lymph nodes were recorded. RESULTS The mean number of lymph nodes extracted from the stained group was significantly higher than that from the unstained group (15.9 ± 5.2 vs 9.1 ± 5.7, respectively; P < .001). Among the patients who had received neoadjuvant therapy, the yield was higher in the stained group (P < .001). The yield was found to be greater in patients who had undergone upfront surgery than in those who had undergone neoadjuvant therapy, even in the stained group (100% vs 66.7%, respectively). CONCLUSION The use of methylene blue injection into resected specimens of left-sided CRCs significantly improved the lymph node yield.
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Affiliation(s)
- Suresh Chilaka
- Department of Surgery, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | | | - Naveen Naik Mude
- Department of Surgery, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Balasubramanian G
- Department of Surgery, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Bhawana Badhe
- Department of Pathology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Raj Kumar Nagarajan
- Department of Surgery, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.
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Lucas K, Melling N, Giannou AD, Reeh M, Mann O, Hackert T, Izbicki JR, Perez D, Grass JK. Lymphatic Mapping in Colon Cancer Depending on Injection Time and Tracing Agent: A Systematic Review and Meta-Analysis of Prospective Designed Studies. Cancers (Basel) 2023; 15:3196. [PMID: 37370806 PMCID: PMC10296374 DOI: 10.3390/cancers15123196] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2023] [Revised: 06/08/2023] [Accepted: 06/13/2023] [Indexed: 06/29/2023] Open
Abstract
An optimized lymph node yield leads to better survival in colon cancer, but extended lymphadenectomy is not associated with survival benefits. Lymphatic mapping shows several colon cancers feature aberrant drainage pathways inducing local recurrence when not resected. Currently, different protocols exist for lymphatic mapping procedures. This meta-analysis assessed which protocol has the best capacity to detect tumor-draining and possibly metastatic lymph nodes. A systematic review was conducted according to PRISMA guidelines, including prospective trials with in vivo tracer application. The risk of bias was evaluated using the QUADAS-2 tool. Traced lymph nodes, total resected lymph nodes, and aberrant drainage detection rate were analyzed. Fifty-eight studies met the inclusion criteria, of which 42 searched for aberrant drainage. While a preoperative tracer injection significantly increased the traced lymph node rates compared to intraoperative tracing (30.1% (15.4, 47.3) vs. 14.1% (11.9, 16.5), p = 0.03), no effect was shown for the tracer used (p = 0.740) or the application sites comparing submucosal and subserosal injection (22.9% (14.1, 33.1) vs. 14.3% (12.1, 16.8), p = 0.07). Preoperative tracer injection resulted in a significantly higher rate of detected aberrant lymph nodes compared to intraoperative injection (26.3% [95% CI 11.5, 44.0] vs. 2.5% [95% CI 0.8, 4.7], p < 0.001). Analyzing 112 individual patient datasets from eight studies revealed a significant impact on aberrant drainage detection for injection timing, favoring preoperative over intraoperative injection (OR 0.050 [95% CI 0.010-0.176], p < 0.001) while indocyanine green presented itself as the superior tracer (OR 0.127 [95% CI 0.018-0.528], p = 0.012). Optimized lymphatic mapping techniques result in significantly higher detection of aberrant lymphatic drainage patterns and thus enable a personalized approach to reducing local recurrence.
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Affiliation(s)
- Katharina Lucas
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany; (K.L.); (N.M.); (A.D.G.); (M.R.); (O.M.); (T.H.); (J.R.I.); (D.P.)
- Department of Visceral, Thoracic, Vascular Surgery and Angiology, City Hospital Triemli, Birmensdorferstrasse 497, 8063 Zürich, Switzerland
| | - Nathaniel Melling
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany; (K.L.); (N.M.); (A.D.G.); (M.R.); (O.M.); (T.H.); (J.R.I.); (D.P.)
| | - Anastasios D. Giannou
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany; (K.L.); (N.M.); (A.D.G.); (M.R.); (O.M.); (T.H.); (J.R.I.); (D.P.)
| | - Matthias Reeh
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany; (K.L.); (N.M.); (A.D.G.); (M.R.); (O.M.); (T.H.); (J.R.I.); (D.P.)
| | - Oliver Mann
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany; (K.L.); (N.M.); (A.D.G.); (M.R.); (O.M.); (T.H.); (J.R.I.); (D.P.)
| | - Thilo Hackert
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany; (K.L.); (N.M.); (A.D.G.); (M.R.); (O.M.); (T.H.); (J.R.I.); (D.P.)
| | - Jakob R. Izbicki
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany; (K.L.); (N.M.); (A.D.G.); (M.R.); (O.M.); (T.H.); (J.R.I.); (D.P.)
| | - Daniel Perez
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany; (K.L.); (N.M.); (A.D.G.); (M.R.); (O.M.); (T.H.); (J.R.I.); (D.P.)
- Department of General and Visceral Surgery, Asklepios Hospital Altona, Paul-Ehrlich-Straße 1, 22763 Hamburg, Germany
| | - Julia K. Grass
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany; (K.L.); (N.M.); (A.D.G.); (M.R.); (O.M.); (T.H.); (J.R.I.); (D.P.)
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Rawat S, Selvasekar C, Bansal S. Laparoscopic Lymphadenectomy for Colorectal Cancers: Concepts and Current Results. RECENT CONCEPTS IN MINIMAL ACCESS SURGERY 2022:155-192. [DOI: 10.1007/978-981-16-5473-2_7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Weixler B, Rickenbacher A, Raptis DA, Viehl CT, Guller U, Rueff J, Zettl A, Zuber M. Sentinel Lymph Node Mapping with Isosulfan Blue or Indocyanine Green in Colon Cancer Shows Comparable Results and Identifies Patients with Decreased Survival: A Prospective Single-Center Trial. World J Surg 2018; 41:2378-2386. [PMID: 28508233 DOI: 10.1007/s00268-017-4051-2] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND Sentinel lymph node (SLN) mapping was reported to improve lymph node staging in colon cancer. This study compares isosulfan blue (IB) with indocyanine green (ICG)-based SLN-mapping and assesses the prognostic value of isolated tumor cells (ITC) and micro-metastases in upstaged patients. METHODS A total of 220 stage I-III colon cancer patients were included in this prospective single-center study. In 170 patients, SLN-mapping was performed in vivo with IB and in 50 patients ex vivo with ICG. Three levels of each SLN were stained with H&E. If negative for tumor infiltration, immunostaining for cytokeratin (AE1/3; cytokeratin-19) was performed. RESULTS SLN detection rate for IB and ICG was 100 and 98%, respectively. Accuracy and sensitivity was 88 and 75% for IB, 82 and 64% for ICG, respectively (p = 0.244). Overall, 149 (68%) patients were node negative. In these patients, ITC and micro-metastases were detected in 26% (31/129) with IB and 17% (5/29) with ICG (p = 0.469). Patients with ITC and micro-metastases did show decreased overall survival (hazard ratio = 1.96, p = 0.09) compared to node negative disease. CONCLUSIONS This study demonstrates a high diagnostic accuracy for both the IB and the ICG SLN-mapping. SLN-mapping upstaged a quarter of patients with node negative colon cancer, and the detected ITC and micro-metastases were an independent negative prognostic marker in multivariate analysis.
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Affiliation(s)
- Benjamin Weixler
- Department of Surgery, University Hospital Basel, Basel, Switzerland.,Department of Surgery, Kantonsspital Olten, 4600, Olten, Switzerland
| | - Andreas Rickenbacher
- Department of Surgery, Kantonsspital Olten, 4600, Olten, Switzerland.,Department of Visceral Surgery, University Hospital Zürich, Zurich, Switzerland
| | - Dimitri Aristotle Raptis
- Department of Surgery, Kantonsspital Olten, 4600, Olten, Switzerland.,Department of Visceral Surgery, University Hospital Zürich, Zurich, Switzerland
| | - Carsten T Viehl
- Department of Surgery, Hospital Center Biel, Biel/Bienne, Switzerland
| | - Ulrich Guller
- Division of Oncology/Hematology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.,University Clinic for Visceral Surgery and Medicine, Inselspital Berne, University of Berne, Berne, Switzerland
| | - Jessica Rueff
- Department of Surgery, Kantonsspital Olten, 4600, Olten, Switzerland
| | - Andreas Zettl
- Viollier AG, Histopathology/Cytology, Basel, Switzerland
| | - Markus Zuber
- Department of Surgery, Kantonsspital Olten, 4600, Olten, Switzerland.
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In vivo and ex vivo sentinel node mapping does not identify the same lymph nodes in colon cancer. Int J Colorectal Dis 2017; 32:983-990. [PMID: 28210851 DOI: 10.1007/s00384-017-2777-9] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/03/2017] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Identification of lymph nodes and pathological analysis is crucial for the correct staging of colon cancer. Lymph nodes that drain directly from the tumor area are called "sentinel nodes" and are believed to be the first place for metastasis. The purpose of this study was to perform sentinel node mapping in vivo with indocyanine green and ex vivo with methylene blue in order to evaluate if the sentinel lymph nodes can be identified by both techniques. METHODS Patients with colon cancer UICC stage I-III were included from two institutions in Denmark from February 2015 to January 2016. In vivo sentinel node mapping with indocyanine green during laparoscopy and ex vivo sentinel node mapping with methylene blue were performed in all patients. RESULTS Twenty-nine patients were included. The in vivo sentinel node mapping was successful in 19 cases, and ex vivo sentinel node mapping was successful in 13 cases. In seven cases, no sentinel nodes were identified. A total of 51 sentinel nodes were identified, only one of these where identified by both techniques (2.0%). In vivo sentinel node mapping identified 32 sentinel nodes, while 20 sentinel nodes were identified by ex vivo sentinel node mapping. Lymph node metastases were found in 10 patients, and only two had metastases in a sentinel node. CONCLUSION Placing a deposit in relation to the tumor by indocyanine green in vivo or of methylene blue ex vivo could only identify sentinel lymph nodes in a small group of patients.
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Pouw JJ, Grootendorst MR, Klaase JM, van Baarlen J, Ten Haken B. Ex vivo sentinel lymph node mapping in colorectal cancer using a magnetic nanoparticle tracer to improve staging accuracy: a pilot study. Colorectal Dis 2016; 18:1147-1153. [PMID: 27218666 DOI: 10.1111/codi.13395] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2015] [Revised: 02/24/2016] [Accepted: 02/29/2016] [Indexed: 02/08/2023]
Abstract
AIM Nodal status is the most important prognostic factor in colorectal cancer (CRC). Small occult metastases may remain undetected on conventional histopathological examination, potentially resulting in undertreatment. Ex vivo sentinel lymph node mapping (SLNM) can be used to improve the accuracy of nodal staging, but the currently used tracers suffer from drawbacks, which hamper implementation of the technique in routine clinical practice. Magnetic tracers are the optimal size for sentinel lymph node (SLN) retention and allow objective quantitative selection of SLNs; they therefore have great potential for SLNM in CRC. The study evaluates the feasibility of ex vivo magnetic SLNM and compares the performance of this technique with blue dye SLNM. METHOD Twenty-eight ex vivo SLNM procedures were performed in 27 histological node-negative patients with CRC using a magnetic tracer and blue dye. A magnetometer was used to select magnetic SLNs after formalin fixation of the CRC specimen. Both magnetic and blue SLNs were subjected to serial sectioning and immunohistochemical staining to reveal occult metastases. RESULTS At least one SLN was successfully identified in 27/28 (96%) and 25/28 (89%) of the cases with the magnetic technique and blue dye. Isolated tumour cells were detected in 10 patients. This was predicted with 100% sensitivity and accuracy using the magnetic technique, and with 91% sensitivity and 96% accuracy using the blue dye technique. CONCLUSION This study demonstrates that ex vivo magnetic SLNM is a feasible technique for use in routine clinical practice, improving nodal staging accuracy of CRC patients.
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Affiliation(s)
- J J Pouw
- MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands
| | - M R Grootendorst
- MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands.,Department of Surgery, Medisch Spectrum Twente, Enschede, The Netherlands
| | - J M Klaase
- Department of Surgery, Medisch Spectrum Twente, Enschede, The Netherlands
| | - J van Baarlen
- Laboratorium Pathologie Oost Nederland, Hengelo, The Netherlands
| | - B Ten Haken
- MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands
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Oh SY, Kim DY, Kim YB, Suh KW. Clinical application of sentinel lymph node mapping in colon cancer: in vivo vs. ex vivo techniques. Ann Surg Treat Res 2014; 87:118-22. [PMID: 25247164 PMCID: PMC4170583 DOI: 10.4174/astr.2014.87.3.118] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2013] [Revised: 03/12/2014] [Accepted: 03/25/2014] [Indexed: 12/17/2022] Open
Abstract
Purpose Clinical usefulness of sentinel lymph node (SLN) mapping in colorectal cancer remains controversial. The aim of this study is to evaluate the accuracy of the SLN mapping technique using serial sectioning, and to compare the results between ex vivo and in vivo techniques. Methods From February 2011 to October 2012, 34 colon cancer patients underwent SLN mapping during surgical resection. Eleven patients were analyzed with the in vivo method, and 23 patients with the ex vivo method. Patient characteristics and results of SLN mapping were evaluated. Results The SLN mapping was performed in 34 patients. Mean age was 67.3 years (range, 44-81 years). Primary tumors were located in the following sites: 13 in the right colon (38.2%) and 21 in the left colon (61.8%). SLN mapping was performed successfully in 88.2% of the patients. There was no significant difference in the identification rate between the two methods (90.9% vs. 87.0%, P = 1.000). Both the mapping methods showed a low sensitivity and high rate of skip metastasis. Conclusion This study showed that SLN evaluation using serial sectioning could not predict the nodal status with clinically acceptable accuracy despite the high detection rate.
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Affiliation(s)
- Seung Yeop Oh
- Department of Surgery, Ajou University School of Medicine, Suwon, Korea
| | - Do Yoon Kim
- Department of Surgery, Ajou University School of Medicine, Suwon, Korea
| | - Young Bae Kim
- Department of Pathology, Ajou University School of Medicine, Suwon, Korea
| | - Kwang Wook Suh
- Department of Surgery, Ajou University School of Medicine, Suwon, Korea
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Viehl CT, Guller U, Langer I, Laffer U, Oertli D, Zuber M. Factors influencing the success of in vivo sentinel lymph node procedure in colon cancer patients: Swiss prospective, multicenter study sentinel lymph node procedure in colon cancer. World J Surg 2013; 37:873-7. [PMID: 23354923 DOI: 10.1007/s00268-013-1910-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
BACKGROUND The sentinel lymph node (SLN) procedure has the potential to provide relevant improvement in nodal staging in colon cancer patients. However, there remains room for improvement for SLN identification and sensitivity. Therefore, the objective of the present investigation was to analyze factors influencing the success of the SLN procedure in colon cancer patients. METHODS One hundred seventy-four consecutive colon cancer patients were prospectively enrolled in this multicenter study and underwent in vivo SLN procedure with isosulfan blue 1 % followed by open standard oncologic colon resection. Several patient-, tumor-, and procedure-related factors possibly influencing the SLN identification and sensitivity were analyzed. RESULTS Sentinel lymph node identification rate and accuracy were 89.1 and 83.9 %, respectively. Successful identification of SLN was significantly associated with the intraoperative visualization of blue lymphatic vessels (p < 0.001) and with female gender (p = 0.024). True positive SLN results were significantly associated with higher numbers of SLN (p = 0.026) and with pN2 stage (p = 0.004). There was a trend toward better sensitivity in patients with lower body mass index (BMI) (p = 0.050). CONCLUSIONS The success of the SLN procedure in colon cancer patients depends on both procedure-related factors (intraoperative visualization of blue lymphatic vessels, high number of SLN identified) and patient factors (gender, BMI). While patient factors can not be influenced, intraoperative visualization of blue lymphatics and identification of high numbers of SLN are key for a successful SLN procedure.
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Affiliation(s)
- Carsten T Viehl
- Department of Surgery, University Hospital Basel, 4031, Basel, Switzerland.
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van der Zaag ES, Bouma WH, Tanis PJ, Ubbink DT, Bemelman WA, Buskens CJ. Systematic review of sentinel lymph node mapping procedure in colorectal cancer. Ann Surg Oncol 2012; 19:3449-59. [PMID: 22644513 DOI: 10.1245/s10434-012-2417-0] [Citation(s) in RCA: 73] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2011] [Indexed: 12/21/2022]
Abstract
BACKGROUND The clinical impact of sentinel lymph node (SN) biopsy in colorectal cancer is still controversial. The aim of our study was to determine the accuracy of this procedure from published data and to identify factors that contribute to the conflicting reports. METHODS A systematic search of the Medline, Embase, and Cochrane databases up to July 2011 revealed 98 potentially eligible studies, of which 57 were analyzed including 3,934 patients (3,944 specimens). RESULTS The pooled SN identification rate was 90.7% (95% CI 88.2-93.3), with a significant higher identification rate in studies including more than 100 patients or studies using the ex vivo SN technique. The pooled sensitivity of the SN procedure was 69.6% (95% CI 64.7-74.6). Including the immunohistochemical findings increased the pooled sensitivity of SN procedure to 80.2% (95% CI 4.7-10.7). Subgroups with significantly higher sensitivity could be identified: ≥4 SNs versus <4 SNs (85.2 vs. 66.3%, p = 0.003), colon versus rectal cancer (77.6 vs. 65.7%, p = 0.04), early T1 or T2 versus advanced T3 or T4 carcinomas (93.4 vs. 58.8%, p = 0.01). Serial sectioning and immunohistochemistry resulted in a mean upstaging of 18.9% (range 0-50%). True upstaging defined as micrometastases (pN1mi+) rather than isolated tumor cells (pN0itc+) was 7.7%. CONCLUSIONS The SN procedure in colorectal cancer has an overall sensitivity of 70%, with increased sensitivity and refined staging in early-stage colon cancer. Because the ex vivo SN mapping is an easy technique it should be considered in addition to conventional resection in colon cancer.
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Märkl B, Arnholdt HM, Jähnig H, Spatz H, Anthuber M, Oruzio DV, Kerwel TG. A new concept for the role of ex vivo sentinel lymph nodes in node-negative colorectal cancer. Ann Surg Oncol 2010; 17:2647-55. [PMID: 20333553 DOI: 10.1245/s10434-010-1030-3] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2009] [Indexed: 12/13/2022]
Abstract
BACKGROUND We recently introduced ex vivo, intra-arterial methylene blue injection as a simple method to improve the lymph node (LN) harvest in gastrointestinal cancer. We now combined it with a novel ex vivo sentinel lymph node (evSLN) mapping technique. METHODS evSLN mapping was performed by subserosal (n = 20) or submucosal (n = 30) India ink injection. Subsequently, methylene blue was injected intra-arterially to enhance visibility of all LNs to improve the overall LN harvest. Manual LN dissection was carried out after fixing overnight. evSLNs nodes were identified by detecting carbon particles during histological examination. In primary node-negative cases, all detected LNs were step sectioned and immunohistochemically stained for pan-cytokeratin. RESULTS India ink injection was easy to perform. Methylene blue injection failed in 1 case. The mean lymph node harvest was 42 ± 18 LNs, and the SLN detection rate was 78%. The sensitivity for detecting metastases was 75%. The mean SLN number was 3 ± 1. LN metastases were found in 20 of 47 malignant cases (43%). Skip metastases occurred in 4 cases. Of these cases, 3 showed involvement of at least 1 entire LN. True upstaging (N0 → N1mi) was found in 1 of 23 cases (4%) within a SLN after advanced evaluation. CONCLUSIONS Combination of methylene blue technique and ex vivo sentinel mapping is feasible, easy to perform, and cost effective. It guarantees an optimal LN harvest and has the potential to heighten the sensitivity of metastasis detection.
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Affiliation(s)
- Bruno Märkl
- Institute of Pathology, Klinikum Augsburg, Augsburg, Germany.
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Abstract
BACKGROUND Improvement in staging accuracy is the principal aim of targeted nodal assessment in colorectal carcinoma. Technical factors independently predictive of false negative (FN) sentinel lymph node (SLN) mapping should be identified to facilitate operative decision making. PURPOSE To define independent predictors of FN SLN mapping and to develop a predictive model that could support surgical decisions. PATIENTS AND METHODS Data was analyzed from 2 completed prospective clinical trials involving 278 patients with colorectal carcinoma undergoing SLN mapping. Clinical outcome of interest was FN SLN(s), defined as one(s) with no apparent tumor cells in the presence of non-SLN metastases. To assess the independent predictive effect of a covariate for a nominal response (FN SLN), a logistic regression model was constructed and parameters estimated using maximum likelihood. A probabilistic Bayesian model was also trained and cross validated using 10-fold train-and-test sets to predict FN SLN mapping. Area under the curve (AUC) from receiver operating characteristics curves of these predictions was calculated to determine the predictive value of the model. RESULTS Number of SLNs (<3; P = 0.03) and tumor-replaced nodes (P < 0.01) independently predicted FN SLN. Cross validation of the model created with Bayesian Network Analysis effectively predicted FN SLN (area under the curve = 0.84-0.86). The positive and negative predictive values of the model are 83% and 97%, respectively. CONCLUSION This study supports a minimum threshold of 3 nodes for targeted nodal assessment in colorectal cancer, and establishes sufficient basis to conclude that SLN mapping and biopsy cannot be justified in the presence of clinically apparent tumor-replaced nodes.
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van der Zaag ES, Kooij N, van de Vijver MJ, Bemelman WA, Peters HM, Buskens CJ. Diagnosing occult tumour cells and their predictive value in sentinel nodes of histologically negative patients with colorectal cancer. Eur J Surg Oncol 2010; 36:350-7. [PMID: 20163930 DOI: 10.1016/j.ejso.2009.11.008] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2009] [Revised: 11/11/2009] [Accepted: 11/16/2009] [Indexed: 12/13/2022] Open
Abstract
PURPOSE Most studies on the sentinel node (SN) procedure in patients with colorectal cancer include immunohistochemical analysis of the SN only. To evaluate the real diagnostic accuracy of the SN procedure with immunohistochemical analysis, the presence of occult tumour cells in all histologically negative lymph nodes was compared to the presence of these cells in SNs. Also the reproducibility of diagnosing occult tumour cells (OTC) and the sensitivity of three different antibodies was assessed. METHODS Between November 2006 en July 2007, an ex vivo SN procedure was performed in 58 histologically N0 patients with colorectal cancer. All lymph nodes (n = 908, mean 15.7) were step-sectioned and immunohistochemistry was performed using two antibodies against cytokeratins (Cam5.2, and CK 20) and one antibody against BerEp-4. RESULTS OTC were identified in 19 of 58 patients, with micrometastases (0.2-2 mm) in 7 and isolated tumour cells (ITC)(<0.2 mm) in 12 patients. The overall agreement in diagnosing OTC between two independent pathologists was 86%. An SN was identified in 53 of 58 patients. All micrometastases were found in SNs. In two patients with negative SNs, ITC's were demonstrated in non-SNs (sensitivity 88%, and overall accuracy 96%). CONCLUSION Additional immunohistochemical analysis of histologically negative lymph nodes demonstrates occult tumour cells in 33% of the patients resulting in an upstaging rate of 12%. Occult tumour cells are predominantly found in the SN, therefore SN mapping has the potential to refine the staging system for patients with colorectal cancer.
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Affiliation(s)
- E S van der Zaag
- Department of Surgery, Gelre Ziekenhuizen, Albert Schweitzerlaan 31, 7334 DZ Apeldoorn, The Netherlands.
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Park JS, Chang IT, Park SJ, Kim BG, Choi YS, Cha SJ, Park ES, Kwon GY. Comparison of ex vivo and in vivo injection of blue dye in sentinel lymph node mapping for colorectal cancer. World J Surg 2010; 33:539-46. [PMID: 19132443 DOI: 10.1007/s00268-008-9872-6] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND The technique of sentinel lymph node (SLN) mapping in patients with colorectal cancer varies between reports, and the optimal method has not been established. The purpose of this study was to determine the optimal injection technique for SLN mapping. METHODS Sixty-nine consecutive patients who underwent curative surgery for colorectal cancer were enrolled. The SLNs was identified intraoperatively by subserosal blue dye injection (in vivo) or by submucosal injection after standard colectomy (ex vivo). If negative by conventional hematoxylin and eosin staining analysis, all lymph nodes, SLNs and non-SLNs, were subjected to further analysis by multi-level section and immunohistochemical examination. RESULTS The in vivo and ex vivo injected groups were similar in demographic character, tumor size, and histological grade. The mean number of SLNs identified was 2.3 in the in vivo group and 2.6 in the ex vivo group (p = 0.192). The detection rate of SLNs by blue dye injection was somewhat higher in the ex vivo group than in the in vivo group: 90.6 vs. 81.1% (p = 0.219). The false-negative rate was 23.5% for the in vivo group and 13.3% for the ex vivo group (p = 0.392). The upstaging rate, which was 18.5% overall, was similar in both groups (p = 0.538). CONCLUSIONS These findings suggest that ex vivo blue dye injection is an effective alternative to in vivo injection for identifying SLNs in patients with colorectal cancer. Because of its simplicity and applicability in routine clinical settings, further investigation of the ex vivo mapping technique is warranted.
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Affiliation(s)
- Jun Seok Park
- Department of Surgery, Chung-Ang University, College of Medicine, 224-1 Heukseok_Dong, Dongjak-Gu, Seoul 156-755, South Korea
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15
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van der Zaag E, Buskens C, Kooij N, Akol H, Peters H, Bouma W, Bemelman W. Improving staging accuracy in colon and rectal cancer by sentinel lymph node mapping: A comparative study. Eur J Surg Oncol 2009; 35:1065-70. [DOI: 10.1016/j.ejso.2009.02.001] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2008] [Revised: 11/22/2008] [Accepted: 02/02/2009] [Indexed: 10/21/2022] Open
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Märkl B, Wünsch K, Hebick KU, Anthuber M, Probst A, Arnholdt HM, Spatz H. Methylene blue-assisted lymph node dissection in combination with ex vivo sentinel lymph node mapping in gastric cancer. Histopathology 2009; 54:433-41. [PMID: 19309395 DOI: 10.1111/j.1365-2559.2009.03243.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
AIMS Lymph node (LN) stage is still the strongest prognostic marker in potentially curable gastric cancer. Accuracy of histopathological lymph node assessment depends on the number of investigated LNs and detection rate of metastases and micrometastases. The aim was to perform a feasibility study employing intra-arterial methylene blue injection - a novel method to improve LN harvest - and ex vivo sentinel LN mapping. METHODS AND RESULTS A total of 33 cases were enrolled, including 14 retrospective cases that served as a control group. The methylene group showed a highly significant improved mean LN harvest compared with unstained cases, with 38 +/- 14 versus 21 +/- 10 LNs (P < 0.001), respectively. The detection rate of ex vivo sentinel mapping was 88%. No skip metastases occurred. CONCLUSION Both techniques have the potential to improve the accuracy of histopathological LN staging and can be combined successfully.
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Affiliation(s)
- Bruno Märkl
- Department of Visceral Surgery, Klinikum Augsburg, Augsburg, Germany.
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Chan SH, Ng C, Looi LM. Intraoperative methylene blue sentinel lymph node mapping in colorectal cancer. ANZ J Surg 2008; 78:775-9. [PMID: 18844907 DOI: 10.1111/j.1445-2197.2008.04648.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND Isosulfan blue is not available for clinical use in Malaysia. This study describes the use of methylene blue as an alternative to isosulfan blue in colorectal sentinel node mapping. METHODS Methylene blue dye was injected around colonic and rectal tumours and the first blue-stained nodes were suture tagged and harvested after standard colorectal resection. Standard histopathological examination was then carried out to detect nodal metastasis. All negative sentinel lymph nodes (SLN) were subjected to 10 further step sectioning and immunoperoxidase staining for cytokeratin 20 to detect tumour deposits. RESULTS Thirty-one patients were enrolled from August 2005 to July 2006. Twenty-five attempts at identifying the SLN were successful (80.7%). Of the 18 (58.1%) who had nodal metastases (stage III), 3 had negative SLN but positive other lymph nodes (false-negative rate of 21.4%). In one (4%), the SLN was the exclusive site of metastasis. CONCLUSION Methylene blue can be used as an alternative sentinel node marker for rectal cancer (above the peritoneal reflection) and colonic cancer.
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Affiliation(s)
- Siew H Chan
- Department of Surgery, University of Malaya Medical Centre, Kuala Lumpur, Malaysia.
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Quadros CA, Lopes A, Araujo I, Fregnani JH, Fahel F. Upstaging benefits and accuracy of sentinel lymph node mapping in colorectal adenocarcinoma nodal staging. J Surg Oncol 2008; 98:324-30. [PMID: 18618578 DOI: 10.1002/jso.21112] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND OBJECTIVES Sentinel lymph node (SLN) mapping is an additional method for improving colorectal cancer nodal staging. The purpose of the study was to define the method's accuracy in nodal staging, its upstaging benefits and to identify the predictive factors for its failure. METHODS Lymphatic mapping was performed using technetium-99m-phytate and patent blue in 52 consecutive colorectal adenocarcinoma patients. Enhanced pathological examination was carried out on SLNs with hematoxylin-eosin step-sectioning and immunochemistry. RESULTS The patients studied had an average tumor size of 6.5 cm; 85% had T3/T4 tumors; and rectal tumors represented 57.7% of the group. Overall SLN mapping accuracy was 79.5%, with sensitivity of 65.2% and 34.8% false negatives. Upstaging with SLN mapping was 23.1%. Colon tumors had an SLN identification rate of 90.9% and rectal tumors had 63.3% (P = 0.023). Multivariate statistical analysis identified lower rectal tumor (P = 0.009), neoadjuvant treatment (P = 0.029) and tumor size (P = 0.036) as independent risk factors for the inability to detect SLNs. CONCLUSIONS Upstaging benefits of SLN mapping should be considered in colon and mid- and upper rectal tumors. The method should be avoided in patients with lower rectal tumors, large tumors and having had neoadjuvant therapy.
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Deelstra N, de Haas RJ, Wicherts DA, van Diest PJ, Borel Rinkes IHM, van Hillegersberg R. The current status of sentinel lymph node staging in rectal cancer. CURRENT COLORECTAL CANCER REPORTS 2008. [DOI: 10.1007/s11888-008-0034-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
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Cahill RA, Leroy J, Marescaux J. Could lymphatic mapping and sentinel node biopsy provide oncological providence for local resectional techniques for colon cancer? A review of the literature. BMC Surg 2008; 8:17. [PMID: 18816403 PMCID: PMC2565653 DOI: 10.1186/1471-2482-8-17] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2008] [Accepted: 09/24/2008] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Endoscopic resectional techniques for colon cancer are undermined by their inability to determine lymph node status. This limits their application to only those lesions at the most minimal risk of lymphatic dissemination whereas their technical capacity could allow intraluminal or even transluminal address of larger lesions. Sentinel node biopsy may theoretically address this breach although the variability of its reported results for this disease is worrisome. METHODS Medline, EMBASE and Cochrane databases were interrogated back to 1999 to identify all publications concerning lymphatic mapping for colon cancer with reference cross-checking for completeness. All reports were examined from the perspective of in vivo technique accuracy selectively in early stage disease (i.e. lesions potentially within the technical capacity of endoscopic resection). RESULTS Fifty-two studies detailing the experiences of 3390 patients were identified. Considerable variation in patient characteristics as well as in surgical and histological quality assurances were however evident among the studies identified. In addition, considerable contamination of the studies by inclusion of rectal cancer without subgroup separation was frequent. Indeed such is the heterogeneity of the publications to date, formal meta-analysis to pool patient cohorts in order to definitively ascertain technique accuracy in those with T1 and/or T2 cancer is not possible. Although lymphatic mapping in early stage neoplasia alone has rarely been specifically studied, those studies that included examination of false negative rates identified high T3/4 patient proportions and larger tumor size as being important confounders. Under selected circumstances however the technique seems to perform sufficiently reliably to allow it prompt consideration of its use to tailor operative extent. CONCLUSION The specific question of whether sentinel node biopsy can augment the oncological propriety for endoscopic resective techniques (including Natural Orifice Transluminal Endoscopic Surgery [NOTES]) cannot be definitively answered at present. Study heterogeneity may account for the variability evident in the results from different centers. Enhanced capacity (perhaps to the level necessary to consider selective avoidance of en bloc mesenteric resection) by its confinement to only early stage disease is plausible although not proven. Specific study of the technique in early stage tumors is clearly essential before proffering this approach.
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Affiliation(s)
| | - Joel Leroy
- Department of Surgery, IRCAD/EITS, Strasbourg, France
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Abstract
Despite near-universal embrace of the concept and clinical relevance of lymphatic mapping for sentinel node identification and analysis for cancers of the breast and integument, the same technique has struggled to a find a role in gastrointestinal cancers in general and, perhaps, in colon cancer in particular. Despite many studies demonstrating its feasibility in malignancies of the large bowel, concern is continually aroused by the variable and often unacceptably low sensitivity rates. Additionally, many confess uncertainty as to what benefit it could ever confer to patients even if it were proven sufficiently accurate given that standard surgical resection incorporates mesenteric resection anyway. However, the huge impact sentinel node mapping has had on clinical practice in certain cancers means that each of these aspects merit careful reconsideration, from very first principles.
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Des Guetz G, Uzzan B, Nicolas P, Cucherat M, de Mestier P, Morere JF, Breau JL, Perret G. Is sentinel lymph node mapping in colorectal cancer a future prognostic factor? A meta-analysis. World J Surg 2007; 31:1304-12. [PMID: 17460811 DOI: 10.1007/s00268-007-9012-8] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
The diagnostic value of sentinel lymph node mapping (SLNM) in patients with colorectal cancer (CRC) is controversial. Prognostic factors for CRC must be detected to improve its treatment. A PubMed query (key words: colorectal cancer, sentinel node) provided 182 studies on the sentinel lymph node (SLN) for CRC, the abstracts of which were reviewed. Altogether, 48 studies dealing with the diagnostic value of SLNM were selected from PubMed, and 6 other studies were retrieved from reviews. We compared the diagnostic value of SLNM with that of conventional histopathologic examination. We used the diagnostic accuracy odds ratio (DAOR) method. Because of significant heterogeneity, we chose the random effect model (Der Simonian and Laird). Statistics were performed on 33 studies, including 1794 patients (1201 colon and 332 rectum cancers). The mean SLNM failure rate was 10%. The global sensitivity and specificity of the SLNM were, respectively, 70% and 81%. The pooled DAOR was 10.7 (95% confidence interval 7.0-16.5). That means that a patient whose SLN is invaded has 10.7 times more risk to be node-positive than an SLN-negative patient. Lymphatic mapping appears to be readily applicable to CRC. One of the main reasons for the heterogeneity is the performance of the SLNM by Saha et al., whose data had better sensitivity (90%) than those in other studies. The SLNM technique should be better standardized in future studies. Understanding the cause of false-negative SLNs (9%) is a major issue to resolve before routinely using this technique in CRC management. The prognostic implication of micrometastases found in SLNs requires further evaluation.
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Affiliation(s)
- Gaëtan Des Guetz
- Department of Oncology, Hôpital Avicenne AP-HP, 125 Route de Stalingrad, Bobigny, France.
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Tuech JJ, Le Pessot F, Michel P. [Sentinel node biopsy in colorectal cancer. A multifunctional tool or a missing link?]. ACTA ACUST UNITED AC 2007; 31:279-80. [PMID: 17396085 DOI: 10.1016/s0399-8320(07)89373-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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