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.

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.

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 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.

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.

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.

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.

Optimal treatment for Siewert type Ⅱ and Ⅲ adenocarcinoma of the esophagogastric junction: A retrospective cohort study with long-term follow-up

AIM To determine the optimal treatment strategy for Siewert type Ⅱ and?Ⅲ?adenocarcinoma of the esophagogastric junction.METHODS We retrospectively reviewed the medical records of 83 patients with Siewert type?Ⅱ?and?Ⅲ?adenocarcinoma of the esophagogastric junction and calculated both an index of estimated benefit from lymph node dissection for each lymph node(LN) station and a lymph node ratio(LNR: ratio of number of positive lymph nodes to the total number of dissected lymph nodes). We used Cox proportional hazard models to clarify independent poor prognostic factors. The median duration of observation was 73 mo.RESULTS Indices of estimated benefit from LN dissection were as follows, in descending order: lymph nodes(LN) along the lesser curvature, 26.5; right paracardial LN, 22.8; left paracardial LN, 11.6; LN along the left gastric artery, 10.6. The 5-year overall survival(OS) rate was 58%. Cox regression analysis revealed that vigorous venous invasion(v2, v3)(HR = 5.99; 95%CI: 1.71-24.90) and LNR of > 0.16(HR = 4.29, 95%CI: 1.79-10.89) were independent poor prognostic factors for OS.CONCLUSION LN along the lesser curvature, right and left paracardial LN, and LN along the left gastric artery should be dissected in patients with Siewert type?Ⅱ?or?Ⅲ?adenoca rcinoma of the esophagogastric junction. Patients with vigorous venous invasion and LNR of > 0.16 should be treated with aggressive adjuvant chemotherapy to improve survival outcomes.

A homogenized approach to classify advanced gastric cancer patients with limited and adequate number of pathologically examined lymph nodes

Background:The prognosis of gastric cancer patients with a limited number of pathologically examined lymph nodes(eLN,<16)is dismal compared to those with adequately eLN(≥16),yet they are still classified within the same subgroups using the American Joint Committee on Cancer(AJCC)staging system.We aimed at formulating an easy-to-adopt and clinically reliable stratification approach to homogenize the classification for these two categories of patients.Methods:Patients staged according to the 8th AJCC pathological nodal(N)and tumor-node-metastasis(TNM)clas-sification were stratified into a Limited and Adequate eLN cohort based on their number of pathologically examined LNs.The statistical differences between the 5-year overall survival(OS)rates of both cohorts were determined and based on which,patients from the Limited eLN cohort were re-classified to a proposed modified nodal(N′)and TNM(TN′M)classification,by matching their survival rates with those of the Adequate eLN cohort.The prognostic perfor-mance of the N′and TN′M classification was then compared to a formulated lymph-node-ratio-based nodal classifica-tion,in addition to the 8th AJCC N and TNM classification.Results:Significant heterogeneous differences in 5-year OS between patients from the Limited and Adequate eLN cohort of the same nodal subgroups were identified(all P<0.001).However,no significant differences in 5-year OS were observed between the subgroups N0,N1,N2,and N3a of the Limited eLN cohort when compared with N1,N2,N3a,and N3b from the Adequate eLN cohort,respectively(P=0.853,0.476,0.114,and 0.230,respectively).A novel approach was formulated in which only patients from the Limited eLN cohort were re-classified to one higher nodal subgroup,denoted as the N′classification.This re-classification demonstrated superior stratifying and prognostic ability as compared to the 8th AJCC N and lymph-node-ratio classification(Akaike information criterion values[AIC]:12,276 vs.12,358 vs.12,283,respectively).The TN′M classification also demonstrated superior prognostic ability as compared to the 8th AJCC TNM classification(AIC value:12,252 vs.12,312).Conclusion:The proposed lymph node classification approach provides a clinically practical and reliable technique to homogeneously classify cohorts of gastric cancer patients with limited and adequate number of pathologically examined lymph nodes.

Retrieved lymph nodes from different anatomic groups in gastric cancer:a proposed optimal number,comparison with other nodal classification strategies and its impact on prognosis

Background:The optimal number of retrieved lymph nodes(LNs)in gastric cancer(GC)is still debatable and previ-ous studies proposing new classification alternatives mostly focused on the number of retrieved LNs without proper consideration on the anatomic nodal groups’location.Here,we assessed the impact of retrieved LNs from different nodal location groups on the survival of GC patients.Methods:Stage I-III gastric cancer patients who had radical gastrectomy were investigated.LN grouping was deter-mined according to the 13th edition of the JCGC.The optimal cut-off values of retrieved LNs in different LN groups(Group 1 and 2)were calculated,based on which a proposed nodal classification(rN)simultaneously accounting the optimal number and location of retrieved LNs was proposed.The performance of rN was then compared to that of LN ratio,log-odds of metastatic LNs(LODDs)and the 8th edition of the Union for International Cancer Control/American Joint Committee on Cancer(UICC/AJCC)N classification.Results:The optimal cut-off values for Group 1 and 2 were 13 and 9,respectively.The 5-year overall survival(OS)was higher for patients in retrieved Group 1 LNs>13(vs.Group 1 LNs≤13,63.2%vs.57.9%,P=0.005)and retrieved Group 2 LNs>9(vs.Group 2 LNs≤9,72.5%vs.60.7%,P=0.009).Patients staged as pN0-3b were sub classified using this Group 1 and 2 nodal analogy.The OS of pN0-N2 patients in retrieved Group 1 LNs>13 or Group 2 LNs>9 were superior to those in retrieved Group 1 LNs≤13 and Group 2 LNs≤9(All P<0.05);except for pN3 patients.The rN clas-sification was formulated and demonstrated better 5-year OS prognostication performance as compared to the LNR,LODDs,and the 8th UICC/AJCC N staging system.Conclusions:The retrieval of>13 and>9 LNs for Group 1 and Group 2,respectively,could represent an alternative lymph node retrieval approach in radical gastrectomy for more precise survival prognostication and minimizing staging migration,especially if>16 LNs is found to be difficult.

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.

Analysis on Survival and Prognostic Factors in Patients with Resectable Pancreatic Adenocarcinoma

Survival after pancreatic cancer surgery is extremely unfavorable even after curative resection. Prognostic factors have been explored but remain largely undefined. The present study was to identify the role of clinical and laboratory variables in the prognostic significance of resectable pancreatic adenocarcinoma. A total of 96 patients who underwent curative resection for pancreatic cancer were included. Survival was evaluated based on complete follow-up visits and was associated with potential prognostic factors using the Kaplan-Meier method and Cox proportional hazard model survival analyses. The results showed that prognostic variables significantly reduced survival, including old age, poorly differentiated tumors, elevated tumor markers and positive lymph node metastasis（LNM）. Age of older than 60 years（HR=1.83, P=0.04）, LNM（HR=2.22, P=0.01）, lymph node ratio（00.2, HR=1.92, P=0.017）, initial CA199（HR=4.80, P=0.004）, and CEA level（HR=2.59, P=0.019） were identified as independent prognostic factors by multivariate analysis. It was concluded that LNR may be potent predictor of survival and suggests that surgeons and the pathologists should thoroughly assess lymph nodes prior to surgery.