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Huang Y, Pan M, Chen B. A Systematic Review and Meta-Analysis of Sentinel Lymph Node Biopsy in Gastric Cancer, an Optimization of Imaging Protocol for Tracer Mapping. World J Surg 2021; 45:1126-1134. [PMID: 33389000 DOI: 10.1007/s00268-020-05900-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/27/2020] [Indexed: 12/24/2022]
Abstract
BACKGROUND Sentinel lymph node biopsy (SLNB) plays an essential role in the evaluation of lymph node (LN) metastasis status and the extent of LN dissection in gastric cancer. The aim of our study was to perform a systematic review and meta-analysis for corresponding identification rate and sensitivity of different SLNB techniques. METHODS Systematic search using PubMed, Embase, and Cochrane library databases was conducted for studies on SLNB in patients with gastric cancer. Studies were stratified according to the sentinel lymph node (SLN) biopsy technique: blue dye (BD), radiocolloid tracer (RI), indocyanine green (ICG), a combination of radiocolloid with blue dye (RI + BD), and a combination of radiocolloid with ICG (RI + ICG). A random-effect model was used to pool the identification rate, sensitivity, and accuracy. RESULTS A total of 54 eligible studies (3767 patients) was included. The pooled identification rates of SLNB using BD, RI, ICG, RI + BD, RI + ICG were 95% (95%CI: 92-97%), 95% (95%CI: 93-97%), 99% (95%CI: 97-99%), 97% (95%CI: 96-98%), and 95% (95%CI: 87-99%), respectively. The pooled sensitivities were 82% (95%CI: 77-86%), 87% (95%CI: 81-92%), 90% (95%CI: 82-95%), 89% (95%CI: 84-93%), and 88% (95%CI: 79-94%), respectively. The pooled accuracies were 94% (95%CI: 91-96%), 95% (95%CI: 92-97%), 98% (95%CI: 95-99%), 97% (95%CI: 95-99%), and 98% (95%CI: 95-99%), respectively. CONCLUSIONS The current meta-analysis provides reliable evidence that favors the use of ICG and dual tracer method (RI + BD/ICG) for the identification of the SLN. Considering the high costs and potential biohazard of using radioactive substances in dual tracer method, performing SLNB with ICG is the technique of choice for experienced surgeons.
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Affiliation(s)
- Yuqiang Huang
- Department of Clinical Medicine, Fujian Medical University, Fuzhou, 350122, China.,Department of Gastrointestinal Surgery, Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Road, Xiamen, 361003, China
| | - Mengting Pan
- Department of Gastrointestinal Surgery, Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Road, Xiamen, 361003, China
| | - Bo Chen
- Department of Clinical Medicine, Fujian Medical University, Fuzhou, 350122, China. .,Department of Gastrointestinal Surgery, Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Road, Xiamen, 361003, China.
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Feasibility and diagnostic performance of dual-tracer-guided sentinel lymph node biopsy in cT1-2N0M0 gastric cancer: a systematic review and meta-analysis of diagnostic studies. World J Surg Oncol 2017; 15:103. [PMID: 28511723 PMCID: PMC5434631 DOI: 10.1186/s12957-017-1159-7] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2016] [Accepted: 04/23/2017] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Dual-tracer-guided sentinel lymph node (SLN) biopsy may provide a promising diagnostic tool to assess accurately the status of lymph node metastasis in the surgical operation and assure the oncologic safety of the function or stomach preserving surgery. The diagnostic performance of this technology in recent studies varied. Thus, we conducted this meta-analysis. METHODS This systematic review and meta-analysis was registered at the PROSPERO. Eligible studies were searched in the PubMed, EMBASE, Web of Knowledge, and Cochrane Library databases. A random-effect model was used to pool the data. Summary receiver operator characteristic curves, analysis for publication bias, meta-regression, and subgroup analysis were also performed. RESULTS The pooled SLN identification rate and sensitivity were 0.97 and 0.89. 99mTc-human serum albumin with indocyanine green (ICG), 99mTc-antimony sulfur colloid with ICG, performing SLN biopsy ≥15 min after dye injection, an SLN ≥5, the basin dissection, laparoscopic surgery, in studies conducted in Japan and studies published after 2012, were associated with higher sensitivity. CT1 stage, performing SLN biopsy ≥15 min after dye injection, in studies conducted in Japan and studies published after 2012, were related with a higher identification rate. CONCLUSIONS Dual tracer is promising in SLN biopsy in gastric cancer, and the clinical application of SLN biopsy should be limited to the patients of cT1N0M0 gastric cancer. The combination of 99mTc-human serum albumin and ICG as well as the combination of 99mTc-antimony sulfur colloid and ICG may be the optimal tracer combination. However, it seems not justified to put this technique into routine clinical application recently. Some factors that might enhance diagnostic value are identified.
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Mitsumori N, Nimura H, Takahashi N, Kawamura M, Aoki H, Shida A, Omura N, Yanaga K. Sentinel lymph node navigation surgery for early stage gastric cancer. World J Gastroenterol 2015. [PMID: 24914329 DOI: 10.3748/wjg.v20.i19] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
We attempted to evaluate the history of sentinel node navigation surgery (SNNS), technical aspects, tracers, and clinical applications of SNNS using Infrared Ray Electronic Endoscopes (IREE) combined with Indocyanine Green (ICG). The sentinel lymph node (SLN) is defined as a first lymph node (LN) which receives cancer cells from a primary tumor. Reports on clinical application of SNNS for gastric cancers started to appear since early 2000s. Two prospective multicenter trials of SNNS for gastric cancer have also been accomplished in Japan. Kitagawa et al reported that the endoscopic dual (dye and radioisotope) tracer method for SN biopsy was confirmed acceptable and effective when applied to the early-stage gastric cancer (EGC). We have previously reported the usefulness of SNNS in gastrointestinal cancer using ICG as a tracer, combined with IREE (Olympus Optical, Tokyo, Japan) to detect SLN. LN metastasis rate of EGC is low. Hence, clinical application of SNNS for EGC might lead us to avoid unnecessary LN dissection, which could preserve the patient's quality of life after operation. The most ideal method of SNNS should allow secure and accurate detection of SLN, and real time observation of lymphatic flow during operation.
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Affiliation(s)
- Norio Mitsumori
- Norio Mitsumori, Hiroshi Nimura, Naoto Takahashi, Masahiko Kawamura, Hiroaki Aoki, Atsuo Shida, Nobuo Omura, Katsuhiko Yanaga, Department of surgery, the Jikei University School of Medicine, Nisi-shinbashi, Minato-ku, Tokyo 105-8461, Japan
| | - Hiroshi Nimura
- Norio Mitsumori, Hiroshi Nimura, Naoto Takahashi, Masahiko Kawamura, Hiroaki Aoki, Atsuo Shida, Nobuo Omura, Katsuhiko Yanaga, Department of surgery, the Jikei University School of Medicine, Nisi-shinbashi, Minato-ku, Tokyo 105-8461, Japan
| | - Naoto Takahashi
- Norio Mitsumori, Hiroshi Nimura, Naoto Takahashi, Masahiko Kawamura, Hiroaki Aoki, Atsuo Shida, Nobuo Omura, Katsuhiko Yanaga, Department of surgery, the Jikei University School of Medicine, Nisi-shinbashi, Minato-ku, Tokyo 105-8461, Japan
| | - Masahiko Kawamura
- Norio Mitsumori, Hiroshi Nimura, Naoto Takahashi, Masahiko Kawamura, Hiroaki Aoki, Atsuo Shida, Nobuo Omura, Katsuhiko Yanaga, Department of surgery, the Jikei University School of Medicine, Nisi-shinbashi, Minato-ku, Tokyo 105-8461, Japan
| | - Hiroaki Aoki
- Norio Mitsumori, Hiroshi Nimura, Naoto Takahashi, Masahiko Kawamura, Hiroaki Aoki, Atsuo Shida, Nobuo Omura, Katsuhiko Yanaga, Department of surgery, the Jikei University School of Medicine, Nisi-shinbashi, Minato-ku, Tokyo 105-8461, Japan
| | - Atsuo Shida
- Norio Mitsumori, Hiroshi Nimura, Naoto Takahashi, Masahiko Kawamura, Hiroaki Aoki, Atsuo Shida, Nobuo Omura, Katsuhiko Yanaga, Department of surgery, the Jikei University School of Medicine, Nisi-shinbashi, Minato-ku, Tokyo 105-8461, Japan
| | - Nobuo Omura
- Norio Mitsumori, Hiroshi Nimura, Naoto Takahashi, Masahiko Kawamura, Hiroaki Aoki, Atsuo Shida, Nobuo Omura, Katsuhiko Yanaga, Department of surgery, the Jikei University School of Medicine, Nisi-shinbashi, Minato-ku, Tokyo 105-8461, Japan
| | - Katsuhiko Yanaga
- Norio Mitsumori, Hiroshi Nimura, Naoto Takahashi, Masahiko Kawamura, Hiroaki Aoki, Atsuo Shida, Nobuo Omura, Katsuhiko Yanaga, Department of surgery, the Jikei University School of Medicine, Nisi-shinbashi, Minato-ku, Tokyo 105-8461, Japan
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Mitsumori N, Nimura H, Takahashi N, Kawamura M, Aoki H, Shida A, Omura N, Yanaga K. Sentinel lymph node navigation surgery for early stage gastric cancer. World J Gastroenterol 2014; 20:5685-93. [PMID: 24914329 PMCID: PMC4024778 DOI: 10.3748/wjg.v20.i19.5685] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2013] [Revised: 12/28/2013] [Accepted: 01/20/2014] [Indexed: 02/06/2023] Open
Abstract
We attempted to evaluate the history of sentinel node navigation surgery (SNNS), technical aspects, tracers, and clinical applications of SNNS using Infrared Ray Electronic Endoscopes (IREE) combined with Indocyanine Green (ICG). The sentinel lymph node (SLN) is defined as a first lymph node (LN) which receives cancer cells from a primary tumor. Reports on clinical application of SNNS for gastric cancers started to appear since early 2000s. Two prospective multicenter trials of SNNS for gastric cancer have also been accomplished in Japan. Kitagawa et al reported that the endoscopic dual (dye and radioisotope) tracer method for SN biopsy was confirmed acceptable and effective when applied to the early-stage gastric cancer (EGC). We have previously reported the usefulness of SNNS in gastrointestinal cancer using ICG as a tracer, combined with IREE (Olympus Optical, Tokyo, Japan) to detect SLN. LN metastasis rate of EGC is low. Hence, clinical application of SNNS for EGC might lead us to avoid unnecessary LN dissection, which could preserve the patient's quality of life after operation. The most ideal method of SNNS should allow secure and accurate detection of SLN, and real time observation of lymphatic flow during operation.
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O'Connor V, Kitagawa Y, Stojadinovic A, Bilchik AJ. Targeted lymph node assessment in gastrointestinal neoplasms. Curr Probl Surg 2013; 51:9-37. [PMID: 24331086 DOI: 10.1067/j.cpsurg.2013.09.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Affiliation(s)
- Victoria O'Connor
- Gastrointestinal Research Program, John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, CA
| | | | - Alexander Stojadinovic
- Bon Secours Cancer Institute, Richmond, Virginia, and the Uniformed Services University of the Health Sciences, Bethesda, Maryland
| | - Anton J Bilchik
- Gastrointestinal Research Program, John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, CA; California Oncology Research Institute, Los Angeles, CA.
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Cardoso R, Bocicariu A, Dixon M, Yohanathan L, Seevaratnam R, Helyer L, Law C, Coburn NG. What is the accuracy of sentinel lymph node biopsy for gastric cancer? A systematic review. Gastric Cancer 2012; 15 Suppl 1:S48-59. [PMID: 22262403 DOI: 10.1007/s10120-011-0103-8] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2011] [Accepted: 09/23/2011] [Indexed: 02/07/2023]
Abstract
BACKGROUND In gastric cancer, the utility of sentinel lymph node (SLN) biopsy has not been established. SLN may be a good predictor of the pathological status of other lymph nodes and thus the necessity for more extensive surgery or lymph node dissection. We aimed to identify and synthesize findings on the performance of SLN biopsies in gastric cancer. METHODS Electronic literature searches were conducted using Medline, EMBASE, and the Cochrane Central Register of Controlled Trials from 1998 to 2009. Titles and abstracts were independently rated for relevance by a minimum of two reviewers. Techniques, detection rates, accuracy, sensitivity, specificity, and false-negative rates (FNRs) were analyzed. Analysis was performed based on the FNR. RESULTS Twenty-six articles met our inclusion criteria. SLN detection using the dye method (DM) was reviewed in 18 studies, the radiocolloid method (RM) was used in 12 studies, and both dye and radiocolloid methods (DUAL) were used in 5 studies. The DM had an overall calculated FNR of 34.7% (95% confidence interval [CI] 21.2, 48.1). The RM had an overall calculated FNR of 18.5% (95% CI 9.1, 28.0). DUAL had an overall calculated FNR of 13.1% (95% CI -0.9, 27.2). CONCLUSION Application of the SLN technique may be practical for early gastric cancer. The use of DUAL for identifying SLN may yield a lower FNR than either method alone, although statistical significance was not met.
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Affiliation(s)
- Roberta Cardoso
- Division of Surgical Oncology, Sunnybrook Research Institute, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Suite T2-60, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada
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Ru Y, Zhang L, Chen Q, Gao SG, Wang GP, Qu ZF, Shan TY, Qian N, Feng XS. Detection and clinical significance of lymph node micrometastasis in gastric cardia adenocarcinoma. J Int Med Res 2012; 40:293-9. [PMID: 22429368 DOI: 10.1177/147323001204000129] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
OBJECTIVES Lymph node micro metastasis was investigated in gastric cardia adenocarcinoma (GCA) patients without lymph node metastasis on routine pathological examination. The relationship between micrometastasis and clinicopathological features was also evaluated. METHODS A total of 349 lymph nodes were obtained from 45 patients with GCA. Micrometastases were detected by immunohistochemical staining for the markers cytokeratin 19 (CK19) and CD44 variant 6 (CD44v6). RESULTS A total of 33 lymph nodes (9.5%) from 15 patients (33.3%) were positive for CK19. Of these, 27 lymph nodes (7.7%) from 12 patients (26.7%) were also positive for CD44v6. Micrometastasis was significantly related to depth of tumour invasion and Lauren classification (intestinal or diffuse). The recurrence rate was significantly higher and 2-year survival rate significantly lower in patients with than in those without lymph node micrometastasis, showing the necessity of detecting micrometastasis in GCA patients who test negative for lymph node metastasis on routine examination. CONCLUSION CK19 and CD44v6 were shown to be good markers for micrometastasis detection.
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Affiliation(s)
- Y Ru
- Department of Oncology, Cancer Institute, First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China
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Wang Z, Dong ZY, Chen JQ, Liu JL. Diagnostic value of sentinel lymph node biopsy in gastric cancer: a meta-analysis. Ann Surg Oncol 2011; 19:1541-50. [PMID: 22048632 DOI: 10.1245/s10434-011-2124-2] [Citation(s) in RCA: 80] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2011] [Indexed: 02/06/2023]
Abstract
BACKGROUND The possible application and validity of the sentinel lymph node (SLN) concept in gastric cancer (GC) is still debated. A systematic review to evaluate the diagnostic value of SLN biopsy (SLNB) in GC is urgently needed. METHODS A systematic review of relevant literatures was performed in PubMed, Embase, and The Cochrane Library. A random-effect model was used to pool the data, and subgroup analysis was used to explain the heterogeneities. RESULTS A total of 38 included studies (2,128 patients) were included. The pooled SLN identification rate, sensitivity, negative predictive value, and accuracy were 93.7% (95% confidence interval [95% CI]: 91.1-95.6%), 76.9% (95% CI: 71.6-81.4%), 90.3% (95% CI: 86.9-92.9%), and 92.0% (95% CI: 89.9-93.7%), respectively. Subgroup analysis showed that early T stage, combined tracers, submucosal injection method, conventional open surgery, and usage of immunohistochemistry were associated with higher SLN identification rate and sensitivity. CONCLUSIONS SLNB in GC is technically feasible with an acceptable sensitivity. However, further studies are needed to confirm the best procedure and standard criteria.
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Affiliation(s)
- Zhen Wang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
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Ryu KW, Eom BW, Nam BH, Lee JH, Kook MC, Choi IJ, Kim YW. Is the sentinel node biopsy clinically applicable for limited lymphadenectomy and modified gastric resection in gastric cancer? A meta-analysis of feasibility studies. J Surg Oncol 2011; 104:578-84. [PMID: 21695700 DOI: 10.1002/jso.21995] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2010] [Accepted: 05/23/2011] [Indexed: 12/14/2022]
Abstract
BACKGROUND Sentinel node biopsies (SNBs) have been clinically applied in melanoma and breast cancer for limited lymphadenectomy. However, the use of SNB remains controversial in gastric cancer due to unsatisfactory sensitivity and variability. This meta-analysis was performed to determine the sensitivity of SNB in gastric cancer and to identify factors that improve its sensitivity. METHODS Feasibility studies on SNB in gastric cancer were searched for from 2001 to 2009 in Pubmed, Cochrane, and Embase. Forty-six reports, which included 2,684 patients, were found. Estimated sensitivities, detection rates, and negative (NPV), and positive predictive values (PPV) were calculated using a random effects model. Inter-study heterogeneity, meta-regression, and subgroup analysis for sensitivity was performed. RESULTS The estimated sensitivity, detection rate, NPV, and PPV were 87.8%, 97.5%, 91.8%, and 38.0%, respectively, with significant inter-study heterogeneity (P < 0.0001). However, no significant contributor to heterogeneity was identified. By subgroup analysis, sensitivity was found to depend significantly on the number of SNs harvested. CONCLUSIONS SNB in gastric cancer is probably not clinically applicable for limited lymphadenectomy due its unsatisfactory sensitivity and heterogeneity between practicing surgeons. To improve sensitivity, more than four SNs should be harvested, and a tumor specific SNB method should be developed.
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Affiliation(s)
- Keun Won Ryu
- Gastric Cancer Branch, Research Institute & Hospital, National Cancer Center, Gyeonggi-do, Republic of Korea
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Leong SPL, Zuber M, Ferris RL, Kitagawa Y, Cabanas R, Levenback C, Faries M, Saha S. Impact of nodal status and tumor burden in sentinel lymph nodes on the clinical outcomes of cancer patients. J Surg Oncol 2011; 103:518-30. [PMID: 21480244 DOI: 10.1002/jso.21815] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
The validation of sentinel lymph node (SLN) concept in melanoma and breast cancer has established a new paradigm in cancer metastasis that, in general, cancer cells spread in a orderly fashion from the primary site to the SLNs in the regional nodal basin and then to the distant sites. In this review article, we examine the development of SLN concept in penile carcinoma, melanoma and breast carcinoma and its application to other solid cancers with emphasis of the relationship between micrometastasis in SLNs and clinical outcomes.
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Affiliation(s)
- Stanley P L Leong
- Center for Melanoma Research and Treatment, Department of Surgery, California Pacific Medical and Research Institute, San Francisco, California 94115, USA.
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Abstract
Recent epidemiological studies in Serbia revealed that gastric carcinoma is the third and the fifth main cause of cancer morbidity in men and women, respectively. Despite the declining incidence of gastric cancer, it remains the second most common cause of cancer-related deaths as it is worldwide. A well-defined carcinogenic inflammation-metaplasia-dysplasia-cancer sequence typically precedes the development of most gastric adenocarcinomas. Alterations such as gastric mucosal atrophy and intestinal metaplasia are merely markers of increased risk, while gastric epithelial dysplasia (GED) represent a direct precursor of cancer. DNA damage and increased mucosal proliferation secondary to H pylori infection, combined with a suitable host susceptibility phenotype (eg, genetic polymorphisms in interleukin IL-1B, IL-1RN, and tumor necrosis factor a TNF-alpha genes), are important factors in this progression pathway. However, only a small minority of patients infected with H. pylori eventually develops gastric cancer, and eradication of H pylori in these patients does not seem to eliminate the risk of cancer completely. It has been shown that atrophy may be a better indicator of risk of cancer than intestinal metaplasia, and remains to be validated in routine clinical practice according to recent proposal for new quantitative methods. It is often associated with pseudopyloric gland metaplasia in the gastric corpus mucosa, which expresses a type of trefoil peptide, the spasmolytic polypeptide (termed spasmolytic polypeptide-expressing metaplasia or SPEM) and has been shown to be linked more closely to gastric cancer than intestinal metaplasia. Better histological characterization of adenomatous (or type I), hyperplastic (foveolar or type II) and tubule-neck (mucocellular or type III) GED, two-tiered grading system (low and high grade dysplasia) as well as the introduction of Padova and Vienna international classifications of dysplasia seem to be more helpful in GED surveillance and comparative studies. A combination of histopathological features, serum markers such as pepsinogen I, and molecular tests that analyze host susceptibility polymorphisms and bacterial virulence factors, may allow development of strategies for early detection of cancer in the future. At present, pathobiology of gastric cancerogenesis is far from known, despite the progressive knowledge on predisposing environmental conditions and genetic and epigenetic abnormalities, including tumour suppressor genes, oncogenes, microsatellite instability and hypermethylation or the significance of E-cadherin mutational status association with hereditary diffuse gastric cancer syndrome. Recent evidence regarding the importance of several histopathologically derived prognostic factors, such as resection margin status and lymph node metastases and their implications have also been discussed. We aim to review these aspects, with special relevance to gastric cancer specimen reporting.
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Bhat MA, Naikoo ZA, Dass TA, Lone RA, Dar AM. Role of intraoperative sentinel lymph node mapping in the management of carcinoma of the esophagus. Saudi J Gastroenterol 2010; 16:168-73. [PMID: 20616411 PMCID: PMC3003219 DOI: 10.4103/1319-3767.65186] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND/AIM Precise evaluation of lymph node status is one of the most important factors in determining clinical outcome in treating gastro-intestinal (GI) cancer. Sentinel lymph node (SLN) mapping clearly has become highly feasible and accurate in staging GI cancer. This study aims to investigate the feasibility and accuracy of detection of SLN using methylene blue dye in patients with carcinoma of the esophagus and assess its potential role in determining the rational extent of lymphadenectomy in esophageal cancer surgery. MATERIALS AND METHODS Thirty-two patients of esophageal cancer diagnosed on endoscopic biopsy were enrolled in this prospective study. After laparotomy, patent methylene blue was injected into the subserosal layer adjacent to the tumor. SLNs were defined as blue stained nodes within a period of 5 min. Standard radical esophagogastrectomy with lymphadenectomy was performed in all the patients. All the resected nodes were examined postoperatively by routine hematoxylin and eosin stain for elucidating the presence of metastasis, and the negative SLNs were examined further with cytokeratin immunohistochemical staining. RESULTS SLNs were detected in 26 (81.25%) patients out of 32 patients who were studied. The number of SLNs ranged from 1 to 4 with a mean value of 1.7 per case. The SLNs of esophageal cancer were only found in N1 area in 21 (80.77%) cases, and in N2 or N3 area in only 19.33%. The overall accuracy of the procedure was 75% in predicting nodal metastasis. SLN had a sensitivity of 85.71% in mid esophageal tumors and 93.33% in lower esophageal tumors. The SLN biopsy had sensitivity of 87.5% in the case of squamous cell carcinoma and 92.86% in the cases of adenocarcinoma of the esophagus. The accuracy of the procedure for squamous cell carcinoma and adenocarcinoma was 60% and 76.47%, respectively. CONCLUSION SLN mapping is an accurate diagnostic procedure for detecting lymph node metastasis in patients with esophageal cancer and may indicate rational extent of lymphadenectomy in these patients. SLN mapping provides "right nodes" to the pathologists for detailed analysis and appropriate staging, thereby helping in individualizing the multi-modal treatment for esophageal cancer.
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Affiliation(s)
- Mohammad A. Bhat
- Department of Cardiovascular and Thoracic Surgery, Sheri-Kashmir Institute of Medical Sciences, Srinagar -190 011, Kashmir, India,Address for correspondence: DR. Mohammad Bhat, P.B No. 1061, GPO, Srinagar - 190 001, Jammu & Kashmir, India. E-mail:
| | - Zahoor A. Naikoo
- Department of Cardiovascular and Thoracic Surgery, Sheri-Kashmir Institute of Medical Sciences, Srinagar -190 011, Kashmir, India
| | - Tufail A. Dass
- Department of Cardiovascular and Thoracic Surgery, Sheri-Kashmir Institute of Medical Sciences, Srinagar -190 011, Kashmir, India
| | - Riyaz A. Lone
- Department of Cardiovascular and Thoracic Surgery, Sheri-Kashmir Institute of Medical Sciences, Srinagar -190 011, Kashmir, India
| | - Abdul M. Dar
- Department of Cardiovascular and Thoracic Surgery, Sheri-Kashmir Institute of Medical Sciences, Srinagar -190 011, Kashmir, India
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Yanagita S, Natsugoe S, Uenosono Y, Arima H, Kozono T, Ehi K, Arigami T, Higashi H, Aikou T. Morphological distribution of metastatic foci in sentinel lymph nodes with gastric cancer. Ann Surg Oncol 2007; 15:770-6. [PMID: 18157577 DOI: 10.1245/s10434-007-9713-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2006] [Revised: 11/01/2007] [Accepted: 11/01/2007] [Indexed: 12/16/2022]
Abstract
BACKGROUND The TNM classification defines micrometastasis (MM) and isolated tumor cells (ITC) in lymph nodes (LN). Sentinel node (SN) navigation surgery has been introduced in gastrointestinal cancer. Few reports have examined the morphological distribution of MM and ITC of SN in gastric cancer. The purpose of this study was to clarify the clinical significance of the morphological distribution of cancer cells in SNs according to metastasis (MA), MM, and ITC. METHODS All dissected LNs obtained from 160 consecutive patients with mapped SNs arising from cT1-2 N0 tumors were examined. Metastasis in these LNs was examined by histology and cytokeratin staining. The distribution of MA, MM, and ITC was classified as marginal sinus (MS), intermediate sinus (IS), parenchymal (PA), and diffuse types (DF). RESULTS Nodal metastases were detected in 65 SNs from 30 patients and MA, MM, and ITC accounted for 53.9%, 21.5%, and 24.6%, respectively. MS, IS, PA, and DF accounted for 57%, 6%, 17%, and 20.0%, respectively. Patients with metastasis of non-MS had more nodal metastasis in non-SNs (P = .025) and had nodal metastasis in second tier (P = .009), compared with the patients with metastasis of MS. The incidence of metastasis in non-MS was higher in tumors larger than 40 mm than those smaller than 40 mm (P = .011). CONCLUSION When performing SN navigation surgery in gastric cancer, we should keep in mind that the patients with tumor larger than 40 mm in size and nodal metastasis of non-MS may have non-SN metastasis and nodal metastasis in second tier.
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Affiliation(s)
- Shigehiro Yanagita
- Department of Surgical Oncology and Digestive Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
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Boff MF, Schirmer CC, Edelweiss MIA, Meurer L. Pesquisa do linfonodo sentinela em câncer gástrico com o corante azul patente. Rev Col Bras Cir 2007. [DOI: 10.1590/s0100-69912007000600003] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
OBJETIVO: Avaliar a factibilidade e os resultados de uma técnica pouco invasiva para a pesquisa do linfonodo sentinela (LFNsn) com o uso do corante vital azul patente. MÉTODO: A pesquisa do LFNsn foi realizada em 12 pacientes portadores de adenocarcinoma gástrico que não apresentavam linfonodos suspeitos de metastases durante o estadiamento clínico pré-operatório. Injetou-se nos quatro quadrantes do tumor, 0,5 ml de corante vital azul patente. Os linfonodos que se coraram de azul foram classificados como LFNsn e foram obtidos após a gastrectomia com linfadenectomia D2. Utilizou-se a coloração HE para avaliação anatomopatológica dos LFNsn, e nos casos com LFNsn negativo para HE, foi realizada imuno-histoquímica com pan-citoqueratinas AE1/AE3. RESULTADOS: Dos 12 pacientes, oito eram mulheres, com média de idade de 64,5 (48-87) anos. Identificaram-se em média 3,25 (2-6) LFNsn por paciente. A factibilidade da técnica foi de 100%. A acurácia do método foi de 91,6% . Em 11 de 12 casos foi possível predizer as características linfonodais regionais pela concordância da análise anatomopatológica entre os LFNsn e não sentinelas(LFNñsn). CONCLUSÃO: A pesquisa do linfonodo sentinela em câncer gástrico é factível com o uso da técnica do corante azul patente. O método mostrou ser promissor como técnica minimamente invasiva para estadiar tumores gástricos, nesta casuística inicial.
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Bembenek A, Gretschel S, Schlag PM. Sentinel lymph node biopsy for gastrointestinal cancers. J Surg Oncol 2007; 96:342-52. [PMID: 17726666 DOI: 10.1002/jso.20863] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
Sentinel lymph node biopsy (SLNB) in gastrointestinal-(GI)-tract cancer is not yet of clinical relevance. Nevertheless, the results in the upper GI-tract promise to be helpful to individualize the indication for surgical therapy. SLNB in colon cancer still fails to show high validity to predict the nodal status, but may be helpful to clarify the prognostic role of micrometastases/isolated tumor cells. In anal cancer SLNB is able to guide the indication for groin irradiation.
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Affiliation(s)
- A Bembenek
- Department of Surgery and Surgical Oncology, Robert-Rössle-Klinik, Charité Universitätsmedizin Berlin, Campus Buch, Lindenberger, Berlin, Germany
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Koyama T, Tsubota A, Nariai K, Mitsunaga M, Yanaga K, Takahashi H. Novel biomedical imaging approach for detection of sentinel nodes in an experimental model of gastric cancer. Br J Surg 2007; 94:996-1001. [PMID: 17380563 DOI: 10.1002/bjs.5650] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND The aim of this study was to validate a novel imaging system that uses ATX-S10Na(II) to detect sentinel nodes (SNs) in gastric cancer. The new technique was compared with the enhanced visualization method using indocyanine green (ICG). METHODS Human gastric carcinoma cells were implanted orthotopically into 50 nude rats, which were divided into two groups. In the first group (n = 25), ATX-S10Na(II) was injected subserosally into the implanted site and visualized by a fluorescence spectrolaparoscope. In the second group (n = 25), ICG was similarly injected and observed through a near-infrared laparoscope. The presence of metastatic tumour cells was determined by reverse transcriptase-polymerase chain reaction specific for human beta-actin. RESULTS ATX-S10Na(II) was clearly identified as a bright red colour, and was rapidly incorporated into the lymphatic system. Detection rates of SNs were 100 (95 per cent confidence interval (c.i.) 52 to 100) per cent (25 of 25) for ATX-S10Na(II) and 95 (95 per cent c.i. 40 to 100) per cent (21 of 22) for ICG. Sensitivity was 96 (95 per cent c.i. 45 to 100) and 81 (95 per cent c.i. 58 to 95) per cent respectively. CONCLUSION These results support the validity of the ATX-S10Na(II)-guided approach in the detection of SNs in gastric cancer in vivo.
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Affiliation(s)
- T Koyama
- Institute of Clinical Medicine and Research, Jikei University School of Medicine, Chiba, Japan
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17
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Abstract
AIM: To evaluate the relationship between lymph node micrometastases and prognosis of patients with gastric carcinoma and to evaluate the significance of the new assessment of nodal status in determining the pN categories in the 5th edition of the UICC TNM classification.
METHODS: A total of 850 lymph nodes from 30 patients with gastric carcinoma who underwent gastrectomy with lymphadenectomy were assessed by reverse transcription polymerase chain reaction assay in addition to histologic examination. Cytokeratin-20 gene marker was used in this assay.
RESULTS: Routine examination by HE staining confirmed metastasis in 233 lymph nodes from 20 patients. All these 233 lymph nodes were cytokeratin-20 positive. Moreover, lymph node micrometastases were detected in an additional 67 lymph nodes in 12 of these 20 patients. Lymph node micrometastases were also detected in 10 lymph nodes from 2 of 10 patients who had no obvious metastases identified by HE staining. Totally, lymph node micrometastases were identified by the reverse transcription polymerase chain reaction assay in 77 (12.5%) lymph nodes from 14 (46.7%) patients with gastric carcinoma. Of 27 patients who underwent curative resection, 7 (25.9%) were up-staged (fromIB stage to II stage in 1 patient, from IB stage to IIIA stage in 1 patient, from II stage to IIIA stage in 1 patient, from IIIA stage to IIIB stage in 1 patient, from IIIA stage to IV stage in 1 patient, from IIIB stage to IV stage in 2 patients). In a median follow-up of 32 (range 8-36) mo, Kaplan-Meier survival analysis showed significant improvements in median survival (22.86 ± 3.17 mo, 95% CI: 16.64-29.08 mo vs 18.00 ± 7.4 mo, 95% CI: 3.33-32.67 mo) of patients with negative lymph node micrometastases over patients with positive lymph node micrometastases (log-rank, P < 0.05).
CONCLUSION: Lymph node micrometastases have a significant impact on the current staging system of gastric carcinoma, and are significant risk factors for prognosis of patients with gastric carcinoma.
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Affiliation(s)
- Ze-Yu Wu
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangzhou 510080, Guangdong Province, China.
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Gretschel S, Bembenek A, Hünerbein M, Dresel S, Schneider W, Schlag PM. Efficacy of different technical procedures for sentinel lymph node biopsy in gastric cancer staging. Ann Surg Oncol 2007; 14:2028-35. [PMID: 17453300 DOI: 10.1245/s10434-007-9367-y] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2006] [Accepted: 01/12/2007] [Indexed: 12/20/2022]
Abstract
BACKGROUND The clinical impact of sentinel lymph node biopsy (SLNB) in gastric cancer is controversial. We performed a prospective trial to compare different methods: radiocolloid method (RM), dye method (DM), and both methods simultaneously (dual method, or DUM) for reliability and therapeutic consequences. METHODS RM and DM were applied in 35 gastric cancer patients. After endoscopic peritumoral injection of (99m)Tc-colloid and Patent Blue V, the positions of all blue sentinel lymph nodes (SLNs) were recorded, and the SLNs microscopically examined by hematoxylin and eosin, step sections, and immunohistochemistry. RESULTS RM, DM, and DUM identified the SLNs in 34 (97%) of 35 patients. The sensitivity for the prediction of positive lymph node status for RM was 22 (92%) of 24, for DM 16 (66%) of 24, and for DUM 22 (92%) of 24. In 7 of 17 (RM), 5 of 15 (DM), and 7 of 17 (DUM) patients classified as N0 by routine hematoxylin and eosin staining, micrometastases or isolated tumor cells were found in the SLN (upstaging) after focused examination. If only a limited lymph node dissection of the SLN basins would have been performed in patients, residual lymph node metastases were left in 9 of 24 (RM), in 7 of 34 (DM), and in 5 of 24 (DUM) of patients with node-positive disease. CONCLUSIONS Use of RM was superior. DUM did not further increase the sensitivity. A limited lymph node dissection-i.e., lymphatic basin in patients with SLN-positive disease-is associated with a high risk of residual metastases. Patients with negative SLNs may be selected for a limited surgical procedure if they meet certain criteria.
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Affiliation(s)
- Stephan Gretschel
- Department of Surgery and Surgical Oncology, Charité, University Medicine Berlin, Campus Buch, Robert-Rössle-Cancer Hospital, HELIOS Klinikum, Lindenberger Weg 80, Berlin, 13125, Germany
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Saikawa Y, Otani Y, Kitagawa Y, Yoshida M, Wada N, Kubota T, Kumai K, Sugino Y, Mukai M, Kameyama K, Kubo A, Kitajima M. Interim results of sentinel node biopsy during laparoscopic gastrectomy: possible role in function-preserving surgery for early cancer. World J Surg 2007; 30:1962-8. [PMID: 17043938 DOI: 10.1007/s00268-006-0142-1] [Citation(s) in RCA: 62] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
INTRODUCTION Intraoperative detection of sentinel nodes (SNs) has been used clinically to predict regional lymph node (LN) metastasis in patients with breast cancer and malignant melanoma. Intraoperative lymphatic mapping and SN biopsy can potentially be combined with minimally invasive surgery. However, few reports have demonstrated the validity of SN biopsy during laparoscopic gastrectomy. The aim of this study was to investigate the feasibility and accuracy of laparoscopic lymphatic mapping in predicting LN status in patients with gastric cancer. METHODS A total of 35 patients with gastric cancer diagnosed preoperatively as T1, N0 were enrolled. Endoscopic injection of technetium-99m-radiolabeled tin colloid was completed 16 hours before surgery, and radioactive SNs were identified with a gamma probe intraoperatively. Isosulfan blue dye was injected endoscopically during the operation. Laparoscopy-assisted gastrectomy with LN dissection was performed. All resected LNs were evaluated by routine pathology examination. RESULTS SNs were detected in 33 (94.3%) of 35 patients. The mean number of SNs was 3.9, and the diagnostic accuracy according to SN status was 97.0% (32/33), as one patient with a false-negative result was observed. The patient with the false-negative specimen was finally diagnosed as having advanced gastric cancer with invasion into the proper muscular layer and severe lymphatic vessel invasion, causing destruction of normal lymphatic flow by the tumor. CONCLUSIONS Radio-guided SN mapping during laparoscopic gastrectomy is an accurate diagnostic tool for detecting lymph node metastasis in patients with early-stage gastric cancer. Validation of this method requires further studies on technical issues, including indications, tracers, methods of lymph node retrieval, and diagnostic modalities of metastasis.
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Affiliation(s)
- Yoshiro Saikawa
- Department of Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
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Horibe D, Ochiai T, Shimada H, Tomonaga T, Nomura F, Gun M, Tanizawa T, Hayashi H. Rapid detection of metastasis of gastric cancer using reverse transcription loop-mediated isothermal amplification. Int J Cancer 2007; 120:1063-9. [PMID: 17139607 DOI: 10.1002/ijc.22397] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Tailor-made surgeries for patients with solid malignancies have been under consideration on the basis of the development of new approaches for minor metastatic foci of malignant tumors. Accurate and reliable methods to detect metastases in biopsy specimens with certain rapidity are essential for the performance of these surgeries. The aim of this study was to develop a rapid and practical method to detect metastasis in specimens from patients with gastric carcinoma with the use of reverse transcription loop-mediated isothermal amplification (RT-LAMP) reaction, a novel technique for detecting mRNA expressions of targeted sequences with high sensitivity, specificity and rapidity under isothermal conditions. RT-LAMP primers to detect cytokeratin19 (CK19) mRNA were generated and 92 lymph nodes (LNs) obtained from 9 patients with gastric cancer were tested for tumor metastases with this technique. Among 92 LNs, 15 were metastasis-positive by routine histopathological examination. RT-LAMP reaction detected CK19 expression in all of the pathologically positive LNs and in 16 of 77 negative LNs. Nested RT-PCR assay for CK19 expression was also performed on 2 of the 9 cases including 32 LNs. The agreement rate of CK19 expression detection by RT-LAMP and RT-PCR analysis was 31/32 (97%). The RT-LAMP technique showed similar sensitivity to detect metastases as nested RT-PCR assay, with a rapidity comparable to that of intraoperative histopathological examination with frozen sectioning and hematoxylin and eosin staining. This method is expected to play an essential role in the performance of tailor-made surgeries in the near future.
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Affiliation(s)
- Daisuke Horibe
- Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
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Abstract
During the twentieth century, surgical management of gastroesophageal carcinoma was developed by an establishment of standard procedures with lymph node dissection according to the metastatic distribution. The "fear" of invisible micrometastasis caused surgeons to perform more aggressive resection with lymphadenectomy to control the disease locally. Although several promising results of extensive lymph node dissection have been reported, the prognostic benefits of extensive surgery have not been proven by prospective randomized trials. A novel technology to detect micrometastasis without extensive surgical resection is required to gastroesophageal carcinoma. The lymphatic mapping technique is one of the attractive candidates for a novel tool to approach this issue.
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Affiliation(s)
- Yuko Kitagawa
- Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
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Wu ZY, Li JH, Zhan WH, He YL. Lymph node micrometastasis and its correlation with MMP-2 expression in gastric carcinoma. World J Gastroenterol 2006; 12:2941-4. [PMID: 16718824 PMCID: PMC4087816 DOI: 10.3748/wjg.v12.i18.2941] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To examine matrix metalloproteinase-2 (MMP-2) expression in gastric cancer tissues and to evaluate its relationship with lymph node micrometastasis.
METHODS: The authors studied 850 lymph nodes resected from 30 patients with gastric carcinoma who underwent gastrectomy with lymphadenectomy using reverse transcription polymerase chain reaction (RT-PCR) assay in addition to H-E staining. MMP-2 expression of the tumor tissues was detected by immunohistochemical technique (EliVisionTM plus).
RESULTS: MMP-2 expression was positive in 21 (70%) cases and negative in 9 (30%) cases. No significant correlations were found between MMP-2 expression and other variables such as age, gender, tumor location, tumor diameter, Lauren classification and lymphatic invasion. In contrast, MMP-2 expression correlated significantly with depth of tumor infiltration (P = 0.022), lymph node metastasis (P = 0.030) and tumor differentiation (P = 0.043). Lymph node micrometastases were detected in 77 (12.5%) lymph nodes of 14 (46.7%) gastric carcinoma patients. MMP-2 expression was positive in 12 (85.7%) of the 14 patients with lymph node micrometastasis, and in 9 (56.3%) of the 16 patients without lymph node micrometastasis (P = 0.118).
CONCOUSION: Our results demonstrate that MMP-2 expression has significant correlation with tumor invasion, tumor differentiation and lymph node metastases. MMP-2 expression may be an important biological characteristics and significant prognostic parameter of gastric carcinoma. We also conclude that MMP-2 may participate in the development of lymph node micrometastasis of gastric carcinoma. Further investigations are needed to draw a conclusion.
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Affiliation(s)
- Ze-Yu Wu
- Department of Gastrointestinal and Pancreatic Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
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