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.

Predictive value of positive lymph node ratio in patients with locally advanced gastric remnant cancer

BACKGROUND Traditional lymph node stage(N stage)has limitations in advanced gastric remnant cancer(GRC)patients;therefore,establishing a new predictive stage is necessary.AIM To explore the predictive value of positive lymph node ratio(LNR)according to clinicopathological characteristics and prognosis of locally advanced GRC.METHODS Seventy-four patients who underwent radical gastrectomy and lymphadenectomy for locally advanced GRC were retrospectively reviewed.The relationship between LNR and clinicopathological characteristics was analyzed.The survival analysis was performed using Kaplan-Meier survival curves and Cox regression model.RESULTS Number of metastatic LNs,tumor diameter,depth of tumor invasion,Borrmann type,serum tumor biomarkers,and tumor-node-metastasis(TNM)stage were correlated with LNR stage and N stage.Univariate analysis revealed that the factors affecting survival included tumor diameter,anemia,serum tumor biomarkers,vascular or neural invasion,combined resection,LNR stage,N stage,and TNM stage(all P<0.05).The median survival time for those with LNR0,LNR1,LNR2 and LNR3 stage were 61,31,23 and 17 mo,respectively,and the differences were significant(P=0.000).Anemia,tumor biomarkers and LNR stage were independent prognostic factors for survival in multivariable analysis(all P<0.05).CONCLUSION The new LNR stage is uniquely based on number of metastatic LNs,with significant prognostic value for locally advanced GRC,and could better differentiate overall survival,compared with N stage.

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.

Superiority of metastatic lymph node ratio to the 7th edition UICC N staging in gastric cancer

AIM:To compare and evaluate the appropriate prog-nostic indicators of lymph node basic staging in gastric cancer patients who underwent radical resection.METHODS:A total of 1042 gastric cancer patients who underwent radical resection and D2 lymphadenectomy were staged using the 6th and 7th edition International Union Against Cancer(UICC)N staging methods and the metastatic lymph node ratio(MLNR)staging.Ho-mogeneity,discriminatory ability,and gradient mono-tonicity of the various staging methods were compared using linear trend χ2,likelihood ratio χ2 statistics,and Akaike information criterion(AIC)calculations.The area under the curve(AUC)was calculated to compare the predictive ability of the aforementioned three stag-ing methods.RESULTS:Optimal cut-points of the MLNR were cal-culated as MLNR0(0),MLNR1(0.01-0.30),MLNR2(0.31-0.50),and MLNR3(0.51-1.00).In univariate,multivariate,and stratified analyses,MLNR staging was superior to the 6th and 7th edition UICC N stag-ing methods.MLNR staging had a higher AUC,higher linear trend and likelihood ratio χ2 scores and lower AIC values than the other two staging methods.CONCLUSION:MLNR staging predicts survival after gastric cancer more precisely than the 6th and 7th edi-tion UICC N classif ications and should be considered as an alternative to current pathological N staging.

Prognostic impact of metastatic lymph node ratio in advanced gastric cancer from cardia and fundus

AIM: To investigate the prognostic impact of the metastatic lymph node ratio (MLR) in advanced gastric cancer from the cardia and fundus. METHODS: Two hundred and thirty-six patients with gastric cancer from the cardia and fundus who underwent D2 curative resection were analyzed ret- rospectively. The correlations between MLR and the total lymph nodes, positive nodes and the total lymph nodes were analyzed respectively. The influence of MLR on the survival time of patients was determined with univariate Kaplan-Meier survival analysis and mul- tivariate Cox proportional hazard model analysis. And the multiple linear regression was used to identify the relation between MLR and the 5-year survival rate of the patients. RESULTS: The MLR did not correlate with the total lymph nodes resected (r = -0.093, P = 0.057). The 5-year overall survival rate of the whole cohort was 37.5%. Kaplan-Meier survival analysis identified that the following eight factors influenced the survival time of the patients postoperatively: gender (χ2 = 4.26, P = 0.0389), tumor size (χ2 = 18.48, P < 0.001), Borrmann type (χ2 = 7.41, P = 0.0065), histological grade (χ2 = 5.07, P = 0.0243), pT category (χ2 = 49.42, P < 0.001), pN category (χ2 = 87.7, P < 0.001), total number of re- trieved lymph nodes (χ2 = 8.22, P = 0.0042) and MLR (χ2 = 34.3, P < 0.001). Cox proportional hazard model showed that tumor size (χ2 = 7.985, P = 0.018), pTcategory (χ2 = 30.82, P < 0.001) and MLR (χ2 = 69.39, P < 0.001) independently influenced the prognosis. A linear correlation between MLR and the 5-year survival was statistically significant based on the multiple lin- ear regression (β = -0.63, P < 0.001). Hypothetically, the 5-year survival would surpass 50% when MLR was lower than 10%. CONCLUSION: The MLR is an independent prognostic factor for patients with advanced gastric cancer from the cardia and fundus. The decrease of MLR due to adequate number of total resected lymph nodes can improve the survival.

Effect of the number of positive lymph nodes and lymph node ratio on prognosis of patients after resection of pancreatic adenocarcinoma

BACKGROUND： The prognostic factors related to lymph node involvement [lymph node status, the number of positive lymph nodes, lymph node ratio （LNR）] and the number of nodes evaluated in patients with pancreatic adenocarcinoma after pancreatectomy are poorly defined. METHODS： A total of 167 patients who had undergone resection of pancreatic adenocarcinoma from February 2010 to August 2011 were included in this study. Histological examination was performed to evaluate the tumor differentiation and lymph node involvement. Univariate and multivariate analyses were made to determine the relationship between the variables related to nodal involvement and the number of nodes and survival. RESULTS： The median number of total nodes examined was 10 （range 0-44） for the entire cohort. The median number of total nodes examined in node-negative （pN0） patients was similar to that in node-positive （pN1） patients. Patients with pN1 diseases had significantly worse survival than those with pN0 ones （P=0.000）. Patients with three or more positive nodes had a poorer prognosis compared with those with the negative nodes （P=0.000）. The prognosis of the patients with negative nodes was similar to that of those with one to two positive nodes （P=0.114）. The median survival of patients with an LNR ≥0.4 was shorter than that of patients with an LNR 〈0.4 in the pN1 cohort （P=0.014）. No significance was found between the number of total nodes examined and the prognosis, regardless of the cutoff of 10 or 12 and in the entire cohort or the pN0 and pN1 groups. Based on the multivariate analysis of the entire cohort and the pN1 group, the nodal status, the number of positive nodes and the LNR were all associated with survival. CONCLUSIONS： In addition to the nodal status, the number of positive nodes and the LNR can serve as comprehensive factors for the evaluation of nodal involvement. This approach may be more effective for predicting the survival of patients with pancreatic adenocarcinoma after pancreatectomy.

Neoadjuvant chemoradiation is associated with decreased lymph node ratio in borderline resectable pancreatic cancer:A propensity score matched analysis

Background:Lymph node ratio(LNR)and margin status have prognostic significance in pancreatic cancer.Herein we examined the pathologic and clinical outcomes in patients with borderline resectable pancreatic cancer(BRPC)following neoadjuvant therapy(NAT)and pancreaticoduodenectomy.Methods:Patients who underwent treatment between January 1,2012 and June 30,2017 were included.Sequential patients in the BRPC group were compared to a propensity score matched cohort of patients with radiographically resectable pancreatic cancer who underwent upfront surgical resection.The BRPC group was also compared to sequential patients with radiographically resectable pancreatic cancer who required vein resection(VR)during upfront surgery.Results:There were 50 patients in the BRPC group,50 patients in the matched control group,and 38 patients in the VR group.Negative margins(R0)were seen in 72%,64%,and 34%of the BRPC,control,and VR groups,respectively(P=0.521 for BRPC vs.control;P=0.002 for BRPC vs.VR),with 24%of the BRPC group requiring a vascular resection.Nodal stage was N0 in 64%,20%,and 18%of the BRPC,control,and VR groups,respectively(P<0.001 for BRPC vs.control or VR).When nodal status was stratified into four groups(N0,or LNR≤0.2,0.2–0.4,≥0.4),the BRPC group had a more favorable distribution(P<0.001).The median overall survival were 28.8,38.6,and 19.0 months for the BRPC,control,and VR groups,respectively(log-rank P=0.096).Conclusions:NAT in BRPC was associated with more R0 and N0 resections and lower LNR compared to patients undergoing upfront resection for resectable disease.

Impact of metastatic lymph node ratio in node-positive colorectal cancer

Colorectal cancer(CRC) is one of the most common malignant diseases in the world.Presently,the most widely used staging system for CRC is the tumor nodes metastasis classification system,which classifies patients into prognostic groups according to the depth of the primary tumor,presence of regional lymph node(LN) metastases,and evidence of distant metastatic spread.The number of LNs with confirmed metastasis is related to the severity of the disease,but this number depends on the number of LNs retrieved,which varies depending on patient age,tumor grade,surgical extent,and tumor site.Numerous studies and a recent structured review have demonstrated associated improvements in the survival of CRC patients with increasing numbers of LNs retrieved for examination.Hence,the impact of lymph node ratio(LNR),defined as the number of metastatic LNs divided by the number of LNs retrieved,has been investigated in various malignancies,including CRC.In this editorial,we review the literature demonstrating the clinicopathological significance of LNR in CRC pati-ents.Some reports have indicated the advantage of considering the LNR compared to the number of LNs retrieved and/or LN status.When the LNR is taken into consideration for survival analysis,the number of LNs retrieved and/or the LN status is not always found to be a prognostic factor.The cut-off points for LNRs were proposed in numerous studies.However,optimal thresholds for LNRs have not yet received consensus.It is still unclear whether the LNR has more prognostic validity than N stage.For all these reasons,the potential advantages of LNRs in the staging system should be investigated in large prospective data sets.

Prognostic value of the lymph node ratio in stage Ⅲ colorectal cancer

The nodal stage of colorectal cancer is based on the number of positive nodes.It is inevitably affected by the number of removed lymph nodes,but lymph node ratio can be unaffected.We investigated the value of lymph node ratio in stage Ⅲ colorectal cancer in this study.The clinicopathologic factors and follow-up data of 145 cases of stage Ⅲ colorectal cancer between January 1998 and December 2008 were analyzed retrospectively.The Pearson and Spearman correlation analyses were used to determine the correlation coefficient,the Kaplan-Meier method was used to analyze survival,and the Cox proportional hazard regression model was used for multivariate analysis in forward stepwise regression.We found that lymph node ratio was not correlated with the number of removed lymph nodes(r =-0.154,P = 0.065),but it was positively correlated with the number of positive lymph nodes(r = 0.739,P < 0.001) and N stage(r = 0.695,P < 0.001).Kaplan-Meier survival analysis revealed that tumor configuration,intestinal obstruction,serum carcinoembryonic antigen(CEA) concentration,T stage,N stage,and lymph node ratio were associated with disease-free survival of patients with stage Ⅲ colorectal cancer(P < 0.05).Multivariate analysis showed that serum CEA concentration,T stage,and lymph node ratio were prognostic factors for disease-free survival(P < 0.05),whereas N stage failed to achieve significance(P = 0.664).We confirmed that lymph node ratio was a prognostic factor in stage Ⅲ colorectal cancer and had a better prognostic value than did N stage.

Lymph node ratio and preoperative CA 19-9 levels predict overall survival and recurrence-free survival in patients with resected pancreatic adenocarcinoma

AIM:Clinicopathologic factors predicting overall survival (OS) would help identify a subset to benefit from adjuvant therapy. METHODS: One hundred and sixty-nine patients patients from 1984 to 2009 with curative resections for pancreatic adenocarcinoma were included. Tumors were staged by American Joint Committee on Cancer 7th edition criteria. Univariate and multivariable analyses were performed using Kaplan-Meier methodology or Cox proportional hazard models. Log-rank tests were performed. Statistical inferences were assessed by two-sided 5% significance level. RESULTS: Median age was 67.1 (57.2-73.0) years with equal gender distribution. Tumors were in the head (89.3%) or body/tail (10.7%). On univariate analysis, adjuvant therapy, lymph node (LN) ratio, histologic grade, negative margin status, absence of peripancreatic extension, and T stage were associated with improved OS. Adjuvant therapy, LN ratio, histologic grade, number of nodes examined, negative LN status, and absence of peripancreatic extension were associated with improved recurrence-free survival (RFS). On multivariable analysis, LN ratio and carbohydrate antigen (CA) 19-9 levels were associated with OS. LN ratio was associated with RFS. CONCLUSION: The LN ratio and CA 19-9 levels are independent prognostic factors following curative resections of pancreatic cancer.

Lymph node ratio-based staging system for esophageal squamous cell carcinoma

AIM: To analyze a modified staging system utilizing lymph node ratio(LNR) in patients with esophageal squamous cell carcinoma(ESCC).METHODS: Clinical data of 2011 patients with ESCC who underwent surgical resection alone between January 1995 and June 2010 at the Cancer Hospital of Shantou University Medical College were reviewed. The LNR, or node ratio(Nr) was defined as the ratio of metastatic LNs ompared to the total number of resected LNs. Overall survival between groups was compared with the log-rank test. The cutoff point of LNR was established by grouping patients with 10% increment in Nr, and then combining the neighborhood survival curves using the log-rank test. A new TNr M staging system, was constructed by replacing the American Joint Committee on Cancer(AJCC) N categories with the Nr categories in the new TNM staging system. The time-dependent receiver operating characteristic curves were used to evaluate the predictive performance of the seventh edition AJCC staging system and the TNr M staging system.RESULTS: The median number of resected LNs was 12(range: 4-44), and 25% and 75% interquartilerangeswere8 and 16. Patients were classified into four Nr categories with distinctive survival differences(Nr0: LNR = 0; Nr1: 0% < LNR ≤ 10%; Nr2: 10% < LNR ≤ 20%; and Nr3: LNR > 20%). From N categories to Nr categories, 557 patients changed their LN stage. The median survival time(MST) for the four Nr categories(Nr0-Nr3) was 155.0 mo, 39.0 mo, 28.0 mo, and 19.0 mo, respectively, and the 5-year overall survival was 61.1%, 41.1%, 33.0%, and 22.9%, respectively(P < 0.001). Overall survival was significantly different for the AJCC N categories when patients were subgrouped into 15 or more vs fewer than 15 examined nodes, except for the N3 category(P = 0.292). However, overall survival was similar when the patients in all four Nr categories were subgrouped into 15 or more vs fewer than 15 nodes. Using the time-dependent receiver operating characteristic, we found that the Nr category and TNr M stage had higher accuracy in predicting survival than the AJCC N category and TNM stage. CONCLUSION: A staging system based on LNR may have better prognostic stratification of patients with ESCC than the current TNM system, especially for those undergoing limited lymphadenectomy.

Lymph node ratio in resected pancreatic head cancers: time for a broader clinical implementation?

Lymph node ratio(LNR)has emerged as a promising predictor for survival outcome after surgery in different tumor types(1,2).The concept of evaluating LNR as a prognostic factor also after pancreatic surgery has been described in several publications(3,4).Most of the previous reports on LNR in this setting are single-center studies with rather small cohorts and/or mixed histological tumor types,possibly limiting the generalizability of the results.Even if the role of LNR in pancreatic cancer has been acknowledged,it is still regarded as having mostly academical implications when comparing results from different studies and is probably rarely being used as a tool in clinical decision-making world-wide.

Different lymph node staging systems for predicting the prognosis of colorectal neuroendocrine neoplasms

BACKGROUND Colorectal neuroendocrine neoplasms(NENs)are a rare malignancy that primarily arises from the diffuse distribution of neuroendocrine cells in the colon and rectum.Previous studies have pointed out that the status of lymph node may be used to predict the prognosis.AIM To investigate the predictive values of lymph node ratio(LNR),positive lymph node(PLN),and log odds of PLNs(LODDS)staging systems on the prognosis of colorectal NENs treated surgically,and compare their predictive values.METHODS This cohort study included 895 patients with colorectal NENs treated surgically from the Surveillance,Epidemiology,and End Results database.The endpoint was mortality of patients with colorectal NENs treated surgically.X-tile software was utilized to identify most suitable thresholds for categorizing the LNR,PLN,and LODDS.Participants were selected in a random manner to form training and testing sets.The prognosis of surgically treating colorectal NENs was examined using multivariate cox analysis to assess the associations of LNR,PLN,and LODDS with the prognosis of colorectal NENs.C-index was used for assessing the predictive effectiveness.We conducted a subgroup analysis to explore the different lymph node staging systems’predictive values.RESULTS After adjusting all confounding factors,PLN,LNR and LODDS staging systems were linked with mortality in patients with colorectal NENs treated surgically(P<0.05).We found that LODDS staging had a higher prognostic value for patients with colorectal NENs treated surgically than PLN and LNR staging systems.Similar results were obtained in the different G staging subgroup analyses.Furthermore,the area under the receiver operating characteristic curve values for LODDS staging system remained consistently higher than those of PLN or LNR,even at the 1-,2-,3-,4-,5-and 6-year follow-up periods.CONCLUSION LNR,PLN,and LODDS were found to significantly predict the prognosis of patients with colorectal NENs treated surgically.

Prognostic value of lymph node ratio in hypopharyngeal squamous cell carcinoma after chemoradiotherapy

Background Lymph node ratio （LNR） has recently been reported as a potential prognostic marker in many malignant diseases. We aimed to analyze the potential prognostic effect of LNR on hypopharyngeal squamous cell carcinoma （HPSCC） after neoadjuvant therapy in our institution.

The value of the lymph node ratio and total number of lymph nodes examined for resected pancreatic signet ring cell carcinoma:a retrospective cohort study

Background:Pancreatic signet ring cell carcinoma(SRCC)is an exceedingly rare histological subtype of pancreatic cancer.Previous studies have focused on the trends of incidence and independent predictors of pancreatic SRCC.Our objectives of the study were to analyze the prognostic value of the lymph node ratio(LNR)and to explore the minimal number of lymph nodes examined to accurately evaluate the N stage in resected pancreatic SRCC.Method:We analyzed 120 patients diagnosed from January 1,1990,to December 31,2016,constituted the study cohort from the Surveillance,Epidemiology,and End Results(SEER)registry.We calculated the overall survival(OS)of these patients by using a Kaplan–Meier analysis.The Kaplan–Meier analysis was used to analyze the influence of various factors on the prognosis of patients in the univariate analysis.The multivariate Cox analysis were applied to find independent prognostic factors of patients with pancreatic SRCC.Receiver-operating characteristic curve(ROC)analysis to investigate the discriminatory ability of the total number of lymph nodes examined(TNLE)relative to whether lymph node metastasis was present.Results:The median number of lymph nodes examined among 120 patients with resected pancreatic SRCC was 14(interquartile range:6.25–20.0).According to the univariate analysis of OS,age,grade,chemotherapy,LNR,and TNLE were significantly different(P<.05).We demonstrated the prognostic benefit of chemotherapy in resected pancreatic SRCC,whereas radiotherapy was not associated with improved survival.The multivariate survival analysis showed that LNR and grade were independent prognostic indicators after pancreatic SRCC resection for OS.TNLE≥8 showed the highest discriminatory power for evaluating lymph node metastasis(Area under curve(AUC):0.656,95%confidence interval:0.564–0.741,Youden index:0.2533,sensitivity:78.67%,specificity:46.67%,P=.003).Conclusion:Our study indicated that the LNR was a valuable independent prognostic factor for resected pancreatic SRCC.Regional lymphadenectomy of at least 8 lymph nodes was necessary to accurately stage patients.An adequate number of lymph nodes examined are necessary for clinicians to accurately predict the significance of the LNR in resected pancreatic SRCC.

Colorectal cancer and lymph nodes:The obsession with the number 12

Lymphadenectomy of colorectal cancer is a decisive factor for the prognostic and therapeutic staging of the patient. For over 15 years, we have asked ourselves if the minimum number of 12 examined lymph nodes (LNs) was sufficient for the prevention of understaging. The debate is certainly still open if we consider that a limit of 12 LNs is still not the gold standard mainly because the research methodology of the first studies has been criticized. Moreover many authors report that to date both in the United States and Europe the number &#x0201c;12&#x0201d; target is uncommon, not adequate, or accessible only in highly specialised centres. It should however be noted that both the pressing nature of the debate and the dissemination of guidelines have been responsible for a trend that has allowed for a general increase in the number of LNs examined. There are different variables that can affect the retrieval of LNs. Some, like the surgeon, the surgery, and the pathology exam, are without question modifiable; however, other both patient and disease-related variables are non-modifiable and pose the question of whether the minimum number of examined LNs must be individually assigned. The lymph nodal ratio, the sentinel LNs and the study of the biological aspects of the tumor could find valid application in this field in the near future.

Prognostic impact of number of examined lymph nodes on survival of patients with appendiceal neuroendocrine tumors

BACKGROUND The prognosis of patients with appendiceal neuroendocrine tumors(ANETs) is related to lymph node(LN) metastasis and other factors.However,it is unclear how the number of examined LNs(ELNs) impact on survival.AIM To determine the factors affecting the cancer-specific survival(CSS) of patients with ANET and to evaluate the impact of the number of ELNs on survival.METHODS A total of 4583 ANET patients were analyzed in the Surveillance,Epidemiology,and End Results database.Univariate survival analysis was used to identify factors related to survival and the optimal number of ELNs and lymph node ratio(LNR) were determined by the Kaplan–Meier method.The survival difference was determined by CSS.RESULTS Except for sex,the other factors,such as age,year,race,grade,histological type,stage,tumor size,ELNs,LNR,and surgery type,were associated with prognosis.The 3-,5-,and 10-year CSS rates of ANET patients were 91.2%,87.5,and 81.7%,respectively(median follow-up period of 31 mo and range of 0-499 mo).There was no survival difference between the two surgery types,namely,local resection and colectomy or greater,in both stratifications of tumor size ≥ 2 cm(P = 0.523)and < 2 cm(P = 0.068).In contrast to patients with a tumor size < 2 cm,those with a tumor size ≥ 2 cm were more likely to have LN metastasis(χ~2 = 378.16,P < 0.001).The optimal number of ELNs was more than 11,7,and 18 for all patients,nodenegative patients,and node-positive patients,respectively.CSS rates of patients with a larger number of ELNs were significantly improved(≤ 10 vs ≥ 11,χ~2 =20.303,P < 0.001;≤ 6 vs ≥ 7,χ~2 = 11.569,P < 0.001;≤ 17 vs ≥ 18,χ~2 = 21.990,P < 0.001;respectively).ANET patients with an LNR value ≤ 0.16 were more likely to have better survival than those with values of 0.17-0.48(χ~2 = 48.243,P < 0.001) and 0.49-1(χ~2 = 168.485,P < 0.001).CONCLUSION ANET ≥ 2 cm are more likely to develop LN metastasis.At least 11 ELNs are required to better evaluate the prognosis.For patients with positive LN metastasis,18 or more LNs need to be detected and lower LNR values(LNR ≤ 0.16) indicate a better survival prognosis.

Radical lymph node dissection and assessment:Impact on gallbladder cancer prognosis

AIM: To investigate the lymph node metastasis patterns of gallbladder cancer(GBC) and evaluate the optimal categorization of nodal status as a critical prognostic factor.METHODS: From May 1995 to December 2010,a total of 78 consecutive patients with GBC underwent a radical resection at Liaocheng People's Hospital.A radical resection was defined as removing both the primary tumor and the regional lymph nodes of the gallbladder.Demographic,operative and pathologic data were recorded.The lymph nodes retrieved were examined histologically for metastases routinely from each node.The positive lymph node count(PLNC) as well as the total lymph node count(TLNC) was recorded for each patient.Then the metastatic to examined lymph nodes ratio(LNR) was calculated.Disease-specific survival(DSS) and predictors of outcome were analyzed.RESULTS: With a median follow-up time of 26.50 mo(range,2-132 mo),median DSS was 29.00 ± 3.92 mo(5-year survival rate,20.51%).Nodal disease was found in 37 patients(47.44%).DSS of node-negative patients was significantly better than that of nodepositive patients(median DSS,40 mo vs 17 mo,χ2= 14.814,P < 0.001),while there was no significant difference between N1 patients and N2 patients(median DSS,18 mo vs 13 mo,χ2= 0.741,P = 0.389).Optimal TLNC was determined to be four.When node-negative patients were divided according to TLNC,there was no difference in DSS between TLNC < 4 subgroup and TLNC ≥ 4 subgroup(median DSS,37 mo vs 54 mo,χ2 = 0.715,P = 0.398).For node-positive patients,DSS of TLNC < 4 subgroup was worse than that of TLNC ≥ 4 subgroup(median DSS,13 mo vs 21 mo,χ2= 11.035,P < 0.001).Moreover,for node-positive patients,a new cut-off value of six nodes was identified for the number of TLNC that clearly stratified them into 2 separate survival groups(< 6 or ≥ 6,respectively;median DSS,15 mo vs 33 mo,χ2= 11.820,P < 0.001).DSS progressively worsened with increasing PLNC and LNR,but no definite cut-off value could be identified.Multivariate analysis revealed histological grade,tumor node metastasis staging,TNLC and LNR to be independent predictors of DSS.Neither location of positive lymph nodes nor PNLC were identified as an independent variable by multivariate analysis.CONCLUSION: Both TLNC and LNR are strong predictors of outcome after curative resection for GBC.The retrieval and examination of at least 6 nodes can influence staging quality and DSS,especially in nodepositive patients.

Lymph node staging in colorectal cancer:Old controversies and recent advances

Outcome prediction based on tumor stage reflected by the American Joint Committee on Cancer(AJCC)/Union for International Cancer Control(UICC)tumor node metastasis(TNM)system is currently regarded as the strongest prognostic parameter for patients with colorectal cancer.For affected patients,the indication for adjuvant therapy is mainly guided by the presence of regional lymph node metastasis.In addition to the extent of surgical lymph node removal and the thoroughness of the pathologist in dissecting the resection specimen,several parameters that are related to the pathological work-up of the dissected nodes may affect the clinical significance of lymph node staging.These include changing definitions of lymph nodes,involved lymph nodes,and tumor deposits in different editions of the AJCC/UICC TNM system as well as the minimum number of nodes to be dissected.Methods to increase the lymph node yield in the fatty tissue include methylene blue injection and acetone compression.Outcome prediction based on the lymph node ratio,defined as the number of positive lymph nodes divided by the total number of retrieved nodes,may be superior to the absolute numbers of involved nodes.Extracapsular invasion has been identified as additional prognostic factor.Adding step sectioning and immunohistochemistry to the pathological work-up may result in higher accuracy of histological diagnosis.The clinical value of more recent technical advances,such as sentinel lymph node biopsy and molecular analysis of lymph nodes tissue still remains to be defined.

Prognostic assessment of different metastatic lymph node staging methods for gastric cancer after D2 resection

AIM: To compare the prognostic assessment of lymph node ratio and absolute number based staging system for gastric cancer after D2 resection. METHODS: The clinical, pathologic, and long-term follow-up data of 427 patients with gastric cancer that underwent D2 curative gastrectomy were retrospectively analyzed. The relationships between the metastatic lymph node ratio (MLR), log odds of positive lymph nodes (LODDS), and positive lymph nodes (pN) staging methods and the long-term prognoses of the patients were compared. In addition, the survival curves, accuracy, and homogeneity were compared with stratification to evaluate the prognostic assessment of the 3 methods when the number of tested lymph nodes was insufficient (< 10 and 10-15). RESULTS: MLR [hazard ratio (HR) = 1.401, P = 0.012], LODDS (HR = 1.012,P = 0.034), and pN (HR = 1.376, P = 0.005) were independent risk factors for gastric cancer patients. The receiver operating characteristic (ROC) curves showed that the prognostic accuracy of the 3 methods was comparable (P > 0.05). Spearman correlation analysis confirmed that MLR, LODDS, and pN were all positively correlated with the total number of tested lymph nodes. When the number of tested lymph node was < 10, the value of survival curves staged by MLR and LODDS was superior to those of pN staging. However, the difference in survival curves between adjacent stages was not significant. In addition, the survival rate of stage 4 patients using the MLR and LODDS staging methods was 26.7% and 27.3% with < 10 lymph node, respectively which were significantly higher than the survival rate of patients with > 15 tested lymph nodes (< 4%). The ROC curve showed that the accuracy of the prognostic assessment of MLR, LODDS, and pN staging methods was comparable (P > 0.05), and the area under the ROC curve of all 3 methods were increased progressively with the enhanced levels of examined lymph nodes. In addition, the homogeneity of the 3 methods in patients with ≤ 15 tested lymph nodes also showed no significant difference. CONCLUSION: Neither MLR or LODDS could reduce the staging bias. A sufficient number of tested lymph nodes is key to ensure an accurate prognosis for patients underwent D2 radical gastrectomy.