Application value of indocyanine green fluorescence imaging in guiding sentinel lymph node biopsy diagnosis of gastric cancer: Meta-analysis

BACKGROUND Gastric cancer is a common malignant tumor of the digestive system worldwide,and its early diagnosis is crucial to improve the survival rate of patients.Indocyanine green fluorescence imaging(ICG-FI),as a new imaging technology,has shown potential application prospects in oncology surgery.The meta-analysis to study the application value of ICG-FI in the diagnosis of gastric cancer sentinel lymph node biopsy is helpful to comprehensively evaluate the clinical effect of this technology and provide more reliable guidance for clinical practice.AIM To assess the diagnostic efficacy of optical imaging in conjunction with indocya-nine green(ICG)-guided sentinel lymph node(SLN)biopsy for gastric cancer.METHODS Electronic databases such as PubMed,Embase,Medline,Web of Science,and the Cochrane Library were searched for prospective diagnostic tests of optical imaging combined with ICG-guided SLN biopsy.Stata 12.0 software was used for analysis by combining the"bivariable mixed effect model"with the"midas"command.The true positive value,false positive value,false negative value,true negative value,and other information from the included literature were extracted.A literature quality assessment map was drawn to describe the overall quality of the included literature.A forest plot was used for heterogeneity analysis,and P<0.01 was considered to indicate statistical significance.A funnel plot was used to assess publication bias,and P<0.1 was considered to indicate statistical significance.The summary receiver operating characteristic(SROC)curve was used to calculate the area under the curve(AUC)to determine the diagnostic accuracy.If there was interstudy heterogeneity(I2>50%),meta-regression analysis and subgroup analysis were performed.analysis were performed.RESULTS Optical imaging involves two methods:Near-infrared(NIR)imaging and fluorescence imaging.A combination of optical imaging and ICG-guided SLN biopsy was useful for diagnosis.The positive likelihood ratio was 30.39(95%CI:0.92-1.00),the sensitivity was 0.95(95%CI:0.82-0.99),and the specificity was 1.00(95%CI:0.92-1.00).The negative likelihood ratio was 0.05(95%CI:0.01-0.20),the diagnostic odds ratio was 225.54(95%CI:88.81-572.77),and the SROC AUC was 1.00(95%CI:The crucial values were sensitivity=0.95(95%CI:0.82-0.99)and specificity=1.00(95%CI:0.92-1.00).The Deeks method revealed that the"diagnostic odds ratio"funnel plot of SLN biopsy for gastric cancer was significantly asymmetrical(P=0.01),suggesting significant publication bias.Further meta-subgroup analysis revealed that,compared with fluorescence imaging,NIR imaging had greater sensitivity(0.98 vs 0.73).Compared with optical imaging immediately after ICG injection,optical imaging after 20 minutes obtained greater sensitivity(0.98 vs 0.70).Compared with that of patients with an average SLN detection number<4,the sensitivity of patients with a SLN detection number≥4 was greater(0.96 vs 0.68).Compared with hematoxylin-eosin(HE)staining,immunohistochemical(+HE)staining showed greater sensitivity(0.99 vs 0.84).Compared with subserous injection of ICG,submucosal injection achieved greater sensitivity(0.98 vs 0.40).Compared with 5 g/L ICG,0.5 and 0.05 g/L ICG had greater sensitivity(0.98 vs 0.83),and cT1 stage had greater sensitivity(0.96 vs 0.72)than cT2 to cT3 clinical stage.Compared with that of patients≤26,the sensitivity of patients>26 was greater(0.96 vs 0.65).Compared with the literature published before 2010,the sensitivity of the literature published after 2010 was greater(0.97 vs 0.81),and the differences were statistically significant(all P<0.05).CONCLUSION For the diagnosis of stomach cancer,optical imaging in conjunction with ICG-guided SLN biopsy is a therapeut-ically viable approach,especially for early gastric cancer.The concentration of ICG used in the SLN biopsy of gastric cancer may be too high.Moreover,NIR imaging is better than fluorescence imaging and may obtain higher sensitivity.

Combining lymph node ratio to develop prognostic models for postoperative gastric neuroendocrine neoplasm patients

BACKGROUND Lymph node ratio(LNR)was demonstrated to play a crucial role in the prognosis of many tumors.However,research concerning the prognostic value of LNR in postoperative gastric neuroendocrine neoplasm(NEN)patients was limited.AIM To explore the prognostic value of LNR in postoperative gastric NEN patients and to combine LNR to develop prognostic models.METHODS A total of 286 patients from the Surveillance,Epidemiology,and End Results database were divided into the training set and validation set at a ratio of 8:2.92 patients from the First Affiliated Hospital of Soochow University in China were designated as a test set.Cox regression analysis was used to explore the relationship between LNR and disease-specific survival(DSS)of gastric NEN patients.Random survival forest(RSF)algorithm and Cox proportional hazards(CoxPH)analysis were applied to develop models to predict DSS respectively,and compared with the 8th edition American Joint Committee on Cancer(AJCC)tumornode-metastasis(TNM)staging.RESULTS Multivariate analyses indicated that LNR was an independent prognostic factor for postoperative gastric NEN patients and a higher LNR was accompanied by a higher risk of death.The RSF model exhibited the best performance in predicting DSS,with the C-index in the test set being 0.769[95%confidence interval(CI):0.691-0.846]outperforming the CoxPH model(0.744,95%CI:0.665-0.822)and the 8th edition AJCC TNM staging(0.723,95%CI:0.613-0.833).The calibration curves and decision curve analysis(DCA)demonstrated the RSF model had good calibration and clinical benefits.Furthermore,the RSF model could perform risk stratification and individual prognosis prediction effectively.CONCLUSION A higher LNR indicated a lower DSS in postoperative gastric NEN patients.The RSF model outperformed the CoxPH model and the 8th edition AJCC TNM staging in the test set,showing potential in clinical practice.

Assessment of programmed death-ligand 1 expression in primary tumors and paired lymph node metastases of gastric adenocarcinoma

BACKGROUND Anti-programmed death-1/programmed death-ligand 1(PD-1/PD-L1)immuno-therapy has demonstrated promising results on gastric cancer(GC).However,PD-L1 can express differently between metastatic sites and primary tumors(PT).AIM To compare PD-L1 status in PT and matched lymph node metastases(LNM)of GC patients and to determine the correlation between the PD-L1 status and clinicopathological characteristics.METHODS We retrospectively reviewed 284 GC patients who underwent D2-gastrectomy.PD-L1 was evaluated by immunohistochemistry(clone SP142)using the com-bined positive score.All PD-L1+PT staged as pN+were also tested for PD-L1 expression in their LNM.PD-L1(-)GC with pN+served as the comparison group.RESULTS Among 284 GC patients included,45 had PD-L1+PT and 24 of them had pN+.For comparison,44 PD-L1(-)cases with pN+were included(sample loss of 4 cases).Of the PD-L1+PT,54.2%(13/24 cases)were also PD-L1+in the LNM.Regarding PD-L1(-)PT,9.1%(4/44)had PD-L1+in the LNM.The agreement between PT and LNM had a kappa value of 0.483.Larger tumor size and moderate/severe peritumoral inflammatory response were associated with PD-L1 positivity in both sites.There was no statistical difference in overall survival for PT and LNM according to the PD-L1 status(P=0.166 and P=0.837,respectively).CONCLUSION Intra-patient heterogeneity in PD-L1 expression was observed between the PT and matched LNM.This disagreement in PD-L1 status may emphasize the importance of considering different tumor sites for analyses to select patients for immunotherapy.

Analysis of lymph node metastasis and survival prognosis in early gastric cancer patients: A retrospective study

BACKGROUND Early gastric cancer(EGC)is a common malignant tumor of the digestive system,and its lymph node metastasis and survival prognosis have been concerning.By retrospectively analyzing the clinical data of EGC patients,we can better under-stand the status of lymph node metastasis and its impact on survival and prog-nosis.AIM To evaluate the prognosis of EGC patients and the factors that affect lymph node METHODS The clinicopathological data of 1011 patients with EGC admitted to our hospital between January 2015 and December 2023 were collected in a retrospective cohort study.There were 561 males and 450 females.The mean age was 58±11 years.The patient underwent radical gastrectomy.The status of lymph node metastasis in each group was determined according to the pathological examination results of surgical specimens.The outcomes were as follows:(1)Lymph node metastasis in EGC patients;(2)Analysis of influencing factors of lymph node metastasis in EGC;and(3)Analysis of prognostic factors in patients with EGC.Normally distributed measurement data are expressed as mean±SD,and a t test was used for comparisons between groups.The data are expressed as absolute numbers or percentages,and the chi-square test was used for comparisons between groups.Rank data were compared using a nonparametric rank sum test.A log-rank test and a logistic regression model were used for univariate analysis.A logistic stepwise regression model and a Cox stepwise regression model were used for multivariate analysis.The Kaplan-Meier method was used to calculate the survival rate and construct survival curves.A log-rank test was used for survival analysis.RESULTS Analysis of influencing factors of lymph node metastasis in EGC.The results of the multifactor analysis showed that tumor length and diameter,tumor site,tumor invasion depth,vascular thrombus,and tumor differentiation degree were independent influencing factors for lymph node metastasis in patients with EGC(odds ratios=1.80,1.49,2.65,5.76,and 0.60;95%CI:1.29–2.50,1.11–2.00,1.81–3.88,3.87-8.59,and 0.48-0.76,respectively;P<0.05).Analysis of prognostic factors in patients with EGC.All 1011 patients with EGC were followed up for 43(0–13)months.The 3-year overall survival rate was 97.32%.Multivariate analysis revealed that age>60 years and lymph node metastasis were independent risk factors for prognosis in patients with EGC(hazard ratio=9.50,2.20;95%CI:3.31-27.29,1.00-4.87;P<0.05).Further analysis revealed that the 3-year overall survival rates of gastric cancer patients aged>60 years and≤60 years were 99.37%and 94.66%,respectively,and the difference was statistically significant(P<0.05).The 3-year overall survival rates of patients with and without lymph node metastasis were 95.42%and 97.92%,respectively,and the difference was statistically significant(P<0.05).CONCLUSION The lymph node metastasis rate of EGC patients was 23.64%.Tumor length,tumor site,tumor infiltration depth,vascular cancer thrombin,and tumor differentiation degree were found to be independent factors affecting lymph node metastasis in EGC patients.Age>60 years and lymph node metastasis are independent risk factors for EGC prognosis.

Prediction of lymph node metastasis and sentinel node navigation surgery for patients with early-stage gastric cancer

Accurate prediction of lymph node(LN) status is crucially important for appropriate treatment planning in patients with early gastric cancer(EGC). However,consensus on patient and tumor characteristics associated with LN metastasis are yet to be reached. Through systematic search,we identified several independent variables associated with LN metastasis in EGC,which should be included in future research to assess which of these variables remain as significant predictors of LN metastasis. On the other hand,even if we use these promising parameters,we should realize the limitation and the difficulty of predicting LN metastasis accurately. The sentinel LN(SLN) is defined as first possible site to receive cancer cells along the route of lymphatic drainage from the primary tumor. The absence of metastasis in SLN is believed to correlate with the absence of metastasis in downstream LNs. In this review,we have attempted to focus on several independent parameters which have close relationship between tumor and LN metastasis in EGC. In addition,we evaluated the history of sentinel node navigation surgery and the usefulness for EGC.

Single skip metastasis in sentinel lymph node: In an early gastric cancer

Lymph node status is considered a key prognostic and predictive factor in patients with gastric cancer(GC).Although there is a practical approach to the intraoperative detection of sentinel lymph nodes(SLNs),such a procedure is not included in the European surgical protocol.In this report,we present a practical approach to SLN mapping in a representative case with early gastric cancer(EGC).A 74-year-old female was hospitalized with an endoscopically observed,superficially ulcerated tumor located in the antral region.Subtotal gastrectomy with D2 lymphadenectomy and SLN mapping was performed by injecting methylene blue dye into the peritumoral submucosal layer.An incidentally detected blue-stained lymph node located along the middle colic artery was also removed.This was detected 40 min after injection of the methylene blue.Histopathologic examination showed a p T1b-staged well-differentiated HER-2-negative adenocarcinoma.All of the 41 LNs located at the first,third,and fifth station of the regional LN compartments were found to be free of tumor cells.The only lymph node with metastasis was located along the middle colicartery and was considered a non-regional lymph node.This incidentally identified skip metastasis indicated stage Ⅳ GC.A classic chemotherapy regimen was given,and no recurrences were observed six months after surgery.In this representative case,low-cost SLN mapping,with a longer intraoperative waiting time,totally changed the stage of the tumor in a patient with EGC.

Near-infrared fluorescence sentinel lymph node detection in gastric cancer: A pilot study

AIM: To investigate feasibility and accuracy of near-infrared fluorescence imaging using indocyanine green: nanocolloid for sentinel lymph node (SLN) detection in gastric cancer.METHODS: A prospective, single-institution, phase I feasibility trial was conducted. Patients suffering from gastric cancer and planned for gastrectomy were included. During surgery, a subserosal injection of 1.6 mL ICG:Nanocoll was administered around the tumor. NIR fluorescence imaging of the abdominal cavity was performed using the Mini-FLARE&#x02122; NIR fluorescence imaging system. Lymphatic pathways and SLNs were visualized. Of every detected SLN, the corresponding lymph node station, signal-to-background ratio and histopathological diagnosis was determined. Patients underwent standard-of-care gastrectomy. Detected SLNs outside the standard dissection planes were also resected and evaluated.RESULTS: Twenty-six patients were enrolled. Four patients were excluded because distant metastases were found during surgery or due to technical failure of the injection. In 21 of the remaining 22 patients, at least 1 SLN was detected by NIR Fluorescence imaging (mean 3.1 SLNs; range 1-6). In 8 of the 21 patients, tumor-positive LNs were found. Overall accuracy of the technique was 90% (70%-99%; 95%CI), which decreased by higher pT-stage (100%, 100%, 100%, 90%, 0% for respectively Tx, T1, T2, T3, T4 tumors). All NIR-negative SLNs were completely effaced by tumor. Mean fluorescence signal-to-background ratio of SLNs was 4.4 (range 1.4-19.8). In 8 of the 21 patients, SLNs outside the standard resection plane were identified, that contained malignant cells in 2 patients.CONCLUSION: This study shows successful use of ICG:Nanocoll as lymphatic tracer for SLN detection in gastric cancer. Moreover, tumor-containing LNs outside the standard dissection planes were identified.

Sentinel lymph node navigation surgery for gastric cancer: Does it really benefit the patient?

Sentinel lymph node (SLN) navigation surgery is accepted as a standard treatment procedure for malignant melanoma and breast cancer. However, the benefit of reduced lymphadenectomy based on SLN examination remains unclear in cases of gastric cancer. Here, we review previous studies to determine whether SLN navigation surgery is beneficial for gastric cancer patients. Recently, a large-scale prospective study from the Japanese Society of Sentinel Node Navigation Surgery reported that the endoscopic dual tracer method, using a dye and radioisotope for SLN biopsy, was safe and effective when applied to cases of superficial and relatively small gastric cancers. SLN mapping with SLN basin dissection was preferred for early gastric cancer since it is minimally invasive. However, previous studies reported that limited gastrectomy and lymphadenectomy may not improve the patient&#x02019;s postoperative quality of life (QOL). As a result, the benefit of SLN navigation surgery for gastric cancer patients, in terms of their QOL, is limited. Thus, endoscopic and laparoscopic limited gastrectomy combined with SLN navigation surgery has the potential to become the standard minimally invasive surgery in early gastric cancer.

Sentinel lymph node biopsy for gastric cancer:Where do we stand?

Development of sentinel node navigation surgery (SNNS) and advances in minimally invasive surgical techniques have greatly shaped the modern day approach to gastric cancer surgery.An extensive body of knowledge now exists on this type of clinical application but is principally composed of single institute studies.Certain dye tracers,such as isosulfan blue or patent blue violet,have been widely utilized with a notable amount of success;however,indocyanine green is gaining popularity.The double tracer method,a synchronized use of dye and radio-isotope tracers,appears to be superior to any of the dyes alone.In the meantime,the concepts of infrared ray electronic endoscopy,florescence imaging,nanoparticles and near-infrared technology are emerging as particularly promising alternative techniques.Hematoxylin and eosin staining remains the main method for the detection of sentinel lymph node (SLN) metastases.Several specialized centers have begun to employ immunohistochemical staining for this type of clinical analysis but the equipment costs involving the associated ultra-rapid processing systems is limiting its widespread application.Laparoscopic function-preserving resection of primary tumor from the stomach in conjunction with lymphatic basin dissection navigated by SLN identification represents the current paramount of SNNS for early gastric cancer.Patients with cT3 stage or higher still require standard D 2 dissection.

Life prognosis of sentinel node navigation surgery for early-stage gastric cancer:Outcome of lymphatic basin dissection

BACKGROUND Lymphatic basin dissection is a sentinel node biopsy method that is specific for gastric cancer.In this method,the dyed lymphatic system is dissected en bloc,and sentinel nodes are identified at the back table(ex vivo).Even with lymphatic basin dissection,blood flow to the residual stomach can be preserved,and functionpreserving curative gastrectomy can be performed.The oncological safety of function-preserving curative gastrectomy combined with lymphatic basin dissection has not yet been fully investigated.We hypothesized that the oncological safety of sentinel node navigation surgery(SNNS)is not inferior to that of the guidelines.AIM To investigate the life prognosis of SNNS for gastric cancer in comparison with guidelines surgery.METHODS This was a retrospective cohort study.Patients were selected from gastric cancer patients who underwent sentinel node biopsy from April 1999 to March 2016.Patients from April 1999 to August 2008 were from the Department of Surgery II,Kanazawa University Hospital,and patients from August 2009 to March 2016 were from the Department of Surgical Oncology,Kanazawa Medical University Hospital.Patients who were diagnosed with gastric cancer,which was preoperatively diagnosed as superficial type(type 0),5 cm or less in length,clinical T1-2 and node negative,and underwent various gastrectomies guided by sentinel node navigation were retrospectively collected.The overall survival(OS)and relapsefree survival(RFS)of these patients(SNNS group)were investigated.Patients with gastric cancer of the same stage and who underwent guidelines gastrectomy with standard nodal dissection were also selected as the control group.RESULTS A total of 239 patients in the SNNS group and 423 patients in the control group were included.Pathological nodal metastasis was observed in 10.5%and 10.4%of the SNNS and control groups,respectively.The diagnostic abilities of sentinel node biopsy were 84%and 98.6%for sensitivity and accuracy,respectively.In the SNNS group,81.6%of patients underwent modified gastrectomy or functionpreserving curative gastrectomy with lymphatic basin dissection,in which the extent of nodal dissection was further reduced compared to the guidelines.The OS rate in the SNNS group was 96.8%at 5 years and was significantly better than 91.3%in the control group(P=0.0014).The RFS rates were equal in both groups.After propensity score matching,there were 231 patients in both groups,and the cumulative recurrence rate was 0.43%at 5 years in the SNNS group and 1.30%in the control group,which was not statistically different.CONCLUSION The oncological safety of patients who undergo gastrectomy guided by sentinel node navigation is not inferior to that of the guidelines surgery.

Combination of endoscopic submucosal dissection and laparoscopic sentinel lymph node dissection in early mucinous gastric cancer:Role of lymph node metastasis

BACKGROUND Recent evidence showed that combining endoscopic submucosal dissection(ESD)and laparoscopic sentinel lymph node dissection may avoid unnecessary gastrectomy in treating early mucinous gastric cancer(EMGC)patients with risks of positive lymph node metastasis(pLNM).AIM To explore the predictive factors for pLNM in EMGC,and to optimize the clinical application of combing ESD and sentinel lymph node dissection in a proper subgroup of patients with EMGC.METHODS Thirty-one patients with EMGC who had undergone gastrectomy with lymph node dissection were consecutively enrolled from January 1988 to December 2016.Univariate and multivariate logistic regression analyses were used to estimate the association between the rates of pLNM and clinicopathological factors,providing odds ratio(OR)with 95%confidence interval.And the association between the number of predictors and the pLNM rate was also investigated.RESULTS Depth of invasion(OR=7.342,1.127-33.256,P=0.039),tumor diameter(OR=9.158,1.348-29.133,P=0.044),and lymphatic vessel involvement(OR=27.749,1.821-33.143,P=0.019)turned out to be significant and might be the independent risk factors for predicating pLNM in the multivariate analysis.For patients with 1,2,and 3 risk factors,the pLNM rates were 9.1%,33.3%,and 75.0%,respectively.pLNM was not detected in seven patients without any of these risk factors.CONCLUSION ESD might serve as a safe and sufficient treatment for intramucosal EMGC if tumor size≤2 cm,and when lymphatic vessel involvement is absent by postoperative histological examination.Combining ESD and sentinel lymph node dissection could be recommended as a safe and effective treatment for EMGC patients with a potential risk of pLNM.

Effects of extended lymphadenectomy and postoperative chemotherapy on node-negative gastric cancer

AIM:To investigate the effects of extended lymphadenectomy and postoperative chemotherapy on gastric cancer without lymph node metastasis.METHODS:Clinical data of 311 node-negative gastric cancer patients who underwent potentially curative gastrectomy with more than 15 lymph nodes resected,from January 2002 to December 2006,were analyzed retrospectively.Patients with pT4 stage or distant metastasis were excluded.We analyzed the relationship between the D2 lymphadenectomy and the 5-year survival rate among different subgroups stratified by clinical features,such as age,tumor size,tumor location and depth of invasion.At the same time,the relationship between postoperative chemotherapy and the5-year survival rate among different subgroups were also analyzed.RESULTS:The overall 5-year survival rate of the entire cohort was 63.7%.The 5-year survival rate was poor in those patients who were:(1)more than 65 years old;(2)with tumor size larger than 4 cm;(3)with tumor located in the upper portion of the stomach;and(4)with pT3 tumor.The survival rate was improved significantly by extended lymphadenectomy only in patients with pT3 tumor(P=0.019),but not in other subgroups.Moreover,there was no significant difference in survival rate between patients with and without postoperative chemotherapy among all of the subgroups(P>0.05).CONCLUSION:For gastric cancer patients without lymph node metastasis,extended lymphadenectomy could improve the survival rate of those who have pT3-stage tumor.However,there was no evidence of a survival benefit from postoperative chemotherapy alone.

Tumor differentiation as related to sentinel lymph node status in gastric cancer

AIM:To investigate the influence of tumor grade on sentinel lymph node(SLN)status in patients with gastric cancer(GC).METHODS:We retrospectively studied 71 patients with GC who underwent SLN mapping during gastric surgery to evaluate the relationship between SLN status and tumor grade.RESULTS:Poorly differentiated tumors were detected in 50/71 patients,while the other 21 patients had moderately differentiated tumors.SLNs were identified in 58/71 patients(82%).In 41 of the 58 patients that were found to have stained nodes(70.7%),the tumor was of the poorly differentiated type(groupⅠ),while in the remaining patients with stained nodes 17/58(29.3%),the tumor was of the moderately differentiated type(groupⅡ).Positive SLNs were found in22/41 patients in group I(53.7%)and in 7/17 patients in groupⅡ(41.2%)(P=0.325).The rate of positivity for the SLNs in the two groups(53.7%vs 41.2%)was not statistically significant(P=0.514).CONCLUSION:Most of our patients were found to have poorly differentiated adenocarcinoma of the stomach and there was no correlation between tumor grade and SLN involvement.

Location of Sentinel Lymph Node in Gastric Cancer:A Modified,Painless And Noninvasive Approach

Objective： The presence of lymph node metastases is an important factor in the prognosis of gastric cancer patient. Therefore, the precise identification of sentinel lymph nodes （SLN） in these patients is critical. In this work, we investigated the feasibility and preciseness by injection of 99mTc-sulfur colloid （SC） 2 hours before operation after general anesthesia, instead of one day before surgery. Methods： Thirty-one patients of gastric cancer diagnosed as T1-T3 were enrolled in this study. During operation, a SLN was defined as those containing 10 times more radioactivity than surrounding tissue with a hand-held gamma probe and removed. All the patients underwent radical gastrectomy with extended lymphadenectomy. All resected nodes were examined postoperatively by routine H＆E stain and those negative SLNs were examined with further cytokeratin immunohistochemistical staining. Results： The incidence of metastasis was significantly higher in SLNs than in non-SLNs （x2=67.48, P〈0.001）. The overall sensitivity, specificity and accuracy of the SLN status in the diagnosis of the lymph node status of the patient were 86.36%, 100% and 96.77%, respectively. The positive predictive value and negative predictive value of SLN biopsy were 100%, and 75.0%, respectively. SLNs were used to diagnose the lymph node status with 100% accuracy in the T1 group. In the T2 and T3 groups, the sensitivity, specificity, and diagnostic accuracy were 92.3%, 100%, and 94.44%, 60.0%, 100%, and 66.66%, respectively. Most of the SLNs were located in the #1, #2, #3, #4, #5, and #6, except in 3 patients （9.68%）.With cytokeratin immunohistochemical staining, lymphatic pathologic staging in 1 patient was upstaged. Conclusion： SLN biopsy with the above approach is a feasible and accurate diagnostic procedure for detecting lymph node metastasis in patients with gastric cancer, which is painless, noninvasive, easily accepted by patients and suitable for extensive clinical applications.

Endoscopic fluorescent lymphography for gastric cancer

Lymphography by radioisotope or dye is a well-known technique for visualizing the lymphatic drainage pattern in a neoplastic lesion and it is in use in gastric cancer.Indocyanine green(ICG)more recently has been validated in fluorescent lymphography studies and is under evaluation as a novel tracer agent in gastric cancer.The amount and dilution of ICG injected as well as the site and the time of the injection are not standardized.In our unit,endoscopic submucosal injections of ICG are made as 0.5 mg in 0.5 mL at four peritumoral sites the day before surgery(for a total of 2.0 mg in 2.0 mL).Detection instruments for ICG fluorescence are evolving.Near-infrared systems integrated into laparoscopic or robotic instruments(near-infrared fluorescence imaging)have shown the most promising results.ICG fluorescence recognizes the node that receives lymphatic flow directly from a primary tumor.This is defined as the sentinel lymph node,and it has a high predictive negative value at the cT1 stage,able to reduce the extent of gastrectomy and lymph node dissection.ICG also enhances the number of lymph nodes detected during extended lymphadenectomy for advanced gastric cancer.Nevertheless,the practical effects of ICG use in a single patient are not yet clear.Standardization of the technique and further studies are needed before fluorescent lymphography can be used extensively worldwide.Until then,current guidelines recommend an extensive lymphadenectomy as the standard approach for gastric cancer with suspected metastasis.

Prediction of risk factors for lymph node metastasis in early gastric cancer

AIM:To explore risk factors for lymph node metastases in early gastric cancer(EGC) and to confirm the appropriate range of lymph node dissection.METHODS:A total of 202 patients with EGC who underwent curative gastrectomy with lymphadenectomy in the Department of Surgery,Xinhua Hospital and Ruijin Hospital of Shanghai Jiaotong University Medical School between November 2003 and July 2009,were retrospectively reviewed.Both the surgical procedure and the extent of lymph node dissection were based on the recommendations of the Japanese gastric cancer treatment guidelines.The macroscopic type was classified as elevated(type Ⅰ or Ⅱa),flat(Ⅱb),or depressed(Ⅱc or Ⅲ).Histopathologically,papillary and tubular adenocarcinomas were grouped together as differentiated adenocarcinomas,and poorly differentiated and signet-ring cell adenocarcinomas were regarded as undifferentiated adenocarcinomas.Univariate and multivariate analyses of lymph node metastases and patient and tumor characteristics were undertaken.RESULTS:The lymph node metastases rate in patients with EGC was 14.4%.Among these,the rate for mucosal cancer was 5.4%,and 8.9% for submucosal cancer.Univariate analysis showed an obvious correlation between lymph node metastases and tumor location,depth of invasion,morphological classification and venous invasion(χ 2 = 122.901,P = 0.001;χ 2 = 7.14,P = 0.008;χ 2 = 79.523,P = 0.001;χ 2 = 8.687,P = 0.003,respectively).In patients with submucosal cancers,the lymph node metastases rate in patients with venous invasion(60%,3/5) was higher than in those without invasion(20%,15/75)(χ 2 = 4.301,P = 0.038).Multivariate logistic regression analysis revealed that the depth of invasion was the only independent risk factor for lymph node metastases in EGC [P = 0.018,Exp(B) = 2.744].Among the patients with lymph node metastases,29 cases(14.4%) were at N1,seven cases were at N2(3.5%),and two cases were at N3(1.0%).Univariate analysis of variance revealed a close relationship between the depth of invasion and lymph node metastases at pN 1(P = 0.008).CONCLUSION:The depth of invasion was the only independent risk factor for lymph node metastases.Risk factors for metastases should be considered when choosing surgery for EGC.

Precision surgical approach with lymph-node dissection in early gastric cancer

The gravest prognostic factor in early gastric cancer is lymph-node metastasis,with an incidence of about 10% overall. About two-thirds of early gastric cancer patients can be diagnosed as node-negative prior to treatment based on clinicpathological data. Thus, the tumor can be resected by endoscopic submucosal dissection. In the remaining third, surgical resection is necessary because of the possibility of nodal metastasis. Nevertheless, almost all patients can be cured by gastrectomy with D1+ lymph-node dissection. Laparoscopic or robotic gastrectomy has become widespread in East Asia because perioperative and oncological safety are similar to open surgery. However, after D1+ gastrectomy,functional symptoms may still result. Physicians must strive to minimize postgastrectomy symptoms and optimize long-term quality of life after this operation.Depending on the location and size of the primary lesion, preservation of the pylorus or cardia should be considered. In addition, the extent of lymph-node dissection can be individualized, and significant gastric-volume preservation can be achieved if sentinel node biopsy is used to distinguish node-negative patients.Though the surgical treatment for early gastric cancer may be less radical than in the past, the operative method itself seems to be still in transition.

Gastric cancer: Current status of lymph node dissection

D2 procedure has been accepted in Far East as the standard treatment for both early(EGC) and advanced gastric cancer(AGC) for many decades. Recently EGC has been successfully treated with endoscopy by endoscopic mucosal resection or endoscopic submucosal dissection, when restricted or extended Gotoda's criteria can be applied and D1+ surgery is offered only to patients not fitted for less invasive treatment. Furthermore, two randomised controlled trials(RCTs) have been demonstrating the non inferiority of minimally invasive technique as compared to standard open surgery for the treatment of early cases and recently the feasibility of adequate D1+ dissection has been demonstrated also for the robot assisted technique. In case of AGC the debate on the extent of nodal dissection has been open for many decades. While D2 gastrectomy was performed as the standard procedure in eastern countries, mostly based on observational and retrospective studies, in the west the Medical Research Council(MRC), Dutch and Italian RCTs have been conducted to show a survival benefit of D2 over D1 with evidence based medicine. Unfortunately both the MRC and the Dutch trials failed to show a survival benefit after the D2 procedure, mostly due to the significant increase of postoperative morbidity and mortality, which was referred to splenopancreatectomy. Only 15 years after the conclusion of its accrual, the Dutch trial could report a significant decrease of recur-rence after D2 procedure. Recently the long term survival analysis of the Italian RCT could demonstrate a benefit for patients with positive nodes treated with D2 gastrectomy without splenopancreatectomy. As nowadays also in western countries D2 procedure can be done safely with pancreas preserving technique and without preventive splenectomy, it has been suggested in several national guidelines as the recommended procedure for patients with AGC.

Prognostic impact of metastatic lymph node ratio on gastric cancer after curative distal gastrectomy

AIM:To investigate the prognostic impact of metastatic lymph node ratio(rN) on gastric cancer after curative distal gastrectomy.METHODS:A total of 634 gastric cancer patients who underwent curative resection(R0) of lymph nodes at distal gastrectomy in 1995-2004.Correlations between positive nodes and retrieved nodes,between rN and retrieved nodes,and between rN and negative lymph node(LN) count were analyzed respectively.Prognostic factors were identif ied by univariate and multivariate analyses.Staging accuracy of the pN category(5th UICC/TNM system) and the rN category was compared according to the survival rates of patients.A linear regression model was used to identify the relation between rN and 5-year survival rate of the patients.RESULTS:The number of dissected LNs was related with metastatic LNs but not related with rN.Cox regression analysis showed that depth of invasion,pN and rN category were the independent predictors of survival(P < 0.05).There was a signif icant difference in survival between LN stages classif ied by the rN category or by the pN category(P < 0.05).However,no signif icant difference was found in survival rate between LN stages classif ied by the pN category or by the rN category(P > 0.05).Linear regression model showed a signif icant linear correlation between rN and the 5-year survival rate of gastric cancer patients(β = 0.862,P < 0.001).Pearson's correlation test revealed that negative LN count was negatively correlated with rN(P < 0.001).CONCLUSION:rN category is a better prognostic tool than the 5th UICC pN category for gastric cancer patients after curative distal gastrectomy.Increased negative LN count can reduce rN and improve the survival rate of gastric cancer patients.

Prognosis of metastatic splenic hilum lymph node in patients with gastric cancer after total gastrectomy and splenectomy

AIM:To clarify the significance of combined resection of the spleen to dissect the No.10 lymph node(LN). METHODS:We studied 191 patients who had undergone total gastrectomy with splenectomy,excluding non-curative cases,resection of multiple gastric cancer, and those with remnant stomach cancer.Various clinico-pathological factors were evaluated for any independent contributions to No.10 LN metastasis,usingχ 2 test. Significant factors were extracted for further analysis, carried out using a logistic regression method.Furthermore,lymph node metastasis was evaluated for any independent contribution to No.10 LN metastasis,using the same methods.The cumulative survival rate was calculated using the Kaplan-Meier method.The significance of any difference between the survival curves was determined using the Cox-Mantel test,and any difference was considered significant at the 5%level. RESULTS:From the variables considered to be potentially associated with No.10 LN metastasis,age, depth,invasion of lymph vessel,N factor,the numberof lymph node metastasis,Stage,the number of sites, and location were found to differ significantly between those with metastasis(the Positive Group)and those without(the Negative Group).A logistic regression analysis showed that the localization and Stage were significant parameters for No.10 LN metastasis.There was no case located on the lesser curvature in the Posi-tive Group.The numbers of No.2,No.3,No.4sa,No. 4sb,No.4d,No.7,and No.11 LN metastasis were each found to differ significantly between the Positive Group and the Negative Group.A logistic regression analysis showed that No.4sa,No.4sb,and No.11 LN metastasis were each a significant parameter for No.10 LN metastasis.There was no significant difference in survival curves between the Positive Group and the Negative Group. CONCLUSION:Splenectomy should be performed to dissect No.10 LN for cases which have No.4sa,No. 4sb or No.11 LN metastasis.However,in cases where the tumor is located on the lesser curvature,splenectomy can be omitted.