Number Of Examined Nodes Research Articles

Prognostic impact of log odds of positive lymph nodes (LODDS) in the stratification of patients with rectal cancer

IntroductionThe use of the N category of the TNM staging system, lymph node ratio (LNR) and log odds of positive lymph nodes (LODDS) in predicting overall survival (OS) and disease-free survival (DFS) in patients with rectal cancer is still controversial. Material and methodsA retrospective study of 445 patients with rectal cancer who underwent surgery between 2008 and 2017 in the University Complex Hospital was performed. Patients were stratified according to number of lymph nodes examined (NLNE), N staging, LNR and LODDS. The analysis was performed using the log-rank test, Kaplan-Meier functions, Cox regression and ROC curves. ResultsFive-year OS and DFS were 73.7% and 62.5%, respectively. No statistically significant differences were observed depending on NLNE. Increased LNR and LODDS were associated with shorter OS and DFS, independently of NLNE.Multivariate analysis showed that N stage, LNR and LODDS were independently associated with OS and DFS; however, the LODDS system obtained the best area under the curve, with greater predictive capacity for OS (AUC: 0.679) and DFS (AUC: 0.711). ConclusionLODDS and LNR give prognostic information that is not related to NLNE. LODDS provides better prognostic accuracy in patients with negative nodes than LNR and N stage.

Prognostic and predictive value of examined lymph node count in stage III colorectal cancer: a population based study

BackgroundThe role of tumor-draining lymph nodes in the progression of malignant tumors, including stage III colorectal cancer (CRC), is critical. However, the prognostic and predictive value of the number of examined lymph nodes (ELNs) are not fully understood.MethodsThis population-based study retrospectively analyzed data from 106,843 patients with stage III CRC who underwent surgical treatment and registered in three databases from 2004 to 2021. The Surveillance, Epidemiology, and End Results (SEER) cohort was divided using into training and test cohorts at a ratio of 3:2. We employed restricted cubic spline (RCS) curves to explore nonlinear relationships between overall survival (OS) and ELNs counts and performed Cox regression to evaluate hazard ratios across different ELNs count subtypes. Additional validation cohorts were utilized from the First Affiliated Hospital, Sun Yat-sen University and The Cancer Genome Atlas (TCGA) under the same criteria. Outcomes measured included OS, cancer-specific survival (CSS), and progression-free survival (PFS). Molecular analyses involved differential gene expression using the “limma” package and immune profiling through CIBERSORT. Tissue microarray slides and multiplex immunofluorescence (MIF) were used to assess protein expression and immune cell infiltration.ResultsPatients with higher ELNs counts (≥ 17) demonstrated significantly better long-term survival outcomes across all cohorts. Enhanced OS, CSS, and PFS were notably evident in the LN-ELN group compared to those with fewer ELNs. Cox regression models underscored the prognostic value of higher ELNs counts across different patient subgroups by age, sex, tumor differentiation, and TNM stages. Subtype analysis based on ELNs count revealed a marked survival benefit in patients treated with adjuvant chemotherapy in the medium and large ELNs counts (≥ 12), whereas those with fewer ELNs showed negligible benefits. RNA sequencing and MIF indicated elevated immune activation in the LN-ELN group, characterized by increased CD3+, CD4+, and CD8 + T cells within the tumor microenvironment.ConclusionsThe number of ELNs independently predicts survival and the immunological landscape at the tumor site in stage III CRC, underscoring its dual prognostic and predictive value.

Surgical outcomes and predictors of overall survival of stage I-III appendiceal adenocarcinoma: Retrospective cohort analysis of the national cancer database

BackgroundThis study aimed to determine predictors of overall survival (OS) after surgical treatment of stage I-III appendiceal adenocarcinoma and compare the outcomes of partial colectomy and hemicolectomy. MethodsA retrospective analysis of the U.S. National Cancer Database (NCDB) including patients who underwent surgery for stage I-III appendiceal adenocarcinoma between 2005 and 2019 was conducted. A propensity-score matched analysis was undertaken to compare the outcomes of partial and hemicolectomy and multivariate analysis was performed to determine predictive factors of OS. The main outcome was OS and its independent predictors. Results2607 patients (51.6 % male) with a mean age of 61.6 ± 13.9 years were included. 61.7 % of patients underwent hemicolectomy while 31.7 % underwent partial colectomy. After matching, partial colectomy, and hemicolectomy had similar OS (117.3 vs 117.2 months; p = 0.08), positive resection margins, short-term mortality, and 30-day readmission. The hemicolectomy group was associated with more examined lymph nodes and longer hospital stays. Older age (HR: 1.047, p < 0.0001), rural residence area (HR: 3.6, p = 0.025), higher Charlson score (HR: 1.6, p = 0.016), signet-ring cell carcinoma (HR: 2.37, p = 0.009), adjuvant systemic treatment (HR: 1.55, p = 0.015), positive surgical margins (HR: 1.83, p = 0.017), positive lymph nodes number (HR: 1.09, p < 0.0001), and examined lymph nodes number (HR: 0.962, p = 0.001) were independent predictors of OS. ConclusionsPartial colectomy and hemicolectomy had similar OS and clinical outcomes. Older age, rural residence, higher Charlson score, signet-ring pathology, adjuvant systemic treatment, positive surgical margins, positive lymph node number, and examined lymph node number were independent predictors of OS.

Lymph node examination and survival in resected pancreatic ductal adenocarcinoma: retrospective study.

The minimum number of examined lymph nodes (ELN) required for adequate staging and best prediction of survival has not been established in pancreatic ductal adenocarcinoma (PDAC). The aim of the study was to investigate the influence of ELN on staging and survival in PDAC. Patients undergoing partial or total pancreatectomy for PDAC at two European university hospitals between 2007 and 2018 were retrospectively reviewed. Multivariate Cox regression model and survival analyses were performed to verify adequate staging. Overall 341 (73 per cent) patients showed lymph node metastasis (N1/N2), whereas 125 (27 per cent) patients had no lymph node involvement (N0). With increasing number of ELN, the proportion of positive lymph nodes increased. The minimum number of ELN needed to detect lymph node involvement was 21. In multivariate analysis, examination of <21 lymph nodes was a significant negative predictor for survival. Examination of ≥21 ELN reversed this effect and ruled out possible misclassification. The number of ELN affects survival in PDAC. Possible misclassification was identified when <21 lymph nodes were examined. Therefore, at least 21 lymph nodes must be examined to avoid false lymph node classification in all types of resection.

Impact of Removal of Lymph Nodes on Survival in Stage I-III Gastric Signet-Ring Cell Cancer: The More, the Better?

There is an ongoing debate over the prognostic value of the number of examined lymph nodes (ELNs) in cases of gastric signet-ring cell cancer (GSRCC). In this study, we sought to evaluate the correlation between the number of ELNs and the prognosis of GSRCC and identify the optimal number of ELNs. A total of 1020 patients diagnosed with GSRCC between 2011 and 2018 in the National Cancer Center database were identified. Clinicopathological characteristics were retrospectively collected, and optimal cutoff values of ELNs were calculated by using X-tile. The impact of different ELNs on overall survival (OS) was compared by using Kaplan-Meier curves. We used univariate and multivariate Cox and subgroup analyses to explore the relationship between ELNs and OS. Furthermore, nonlinear correlations were investigated by using restricted cubic splines (RCSs). X-tile showed that the optimal cutoff value of ELNs was 22. The 5-year OS was higher for patients with ELNs > 22 (vs. ELNs ≤ 22, 66.9% vs. 74.9%, P = 0.026). Multivariate Cox analyses showed that high ELNs were associated with superior OS (hazard ratio = 0.56, 95% confidence interval 0.43-0.74, P < 0.001). In subgroup analyses, the significant association between tumor size > 4cm, and TNM III stage was still observed. The RCS regression model showed a U-shaped dose-response nonlinear relationship between ELNs and OS; the inflection point, as well as the lowest risk points, corresponded to 44-52 ELNs. A U-shaped, nonlinear correlation with inflection points of 44-52 ELNs between ELNs and prognosis in GSRCC was identified.

Speculation on optimal numbers of examined lymph node for early-stage epithelial ovarian cancer from the perspective of stage migration.

In early-stage epithelial ovarian cancer (EOC), how to perform lymphadenectomy to avoid stage migration and achieve reliable targeted excision has not been explored in depth. This study comprehensively considered the stage migration and survival to determine appropriate numbers of examined lymph node (ELN) for early-stage EOC and high-grade serous ovarian cancer (HGSOC). From the Surveillance, Epidemiology, and End Results database, we obtained 10372 EOC cases with stage T1M0 and ELN ≥ 2, including 2849 HGSOC cases. Generalized linear models with multivariable adjustment were used to analyze associations between ELN numbers and lymph node stage migration, survival and positive lymph node (PLN). LOESS regression characterized dynamic trends of above associations followed by Chow test to determine structural breakpoints of ELN numbers. Survival curves were plotted using Kaplan-Meier method. More ELNs were associated with more node-positive diseases, more PLNs and better prognosis. ELN structural breakpoints were different in subgroups of early-stage EOC, which for node stage migration or PLN were more than those for improving outcomes. The meaning of ELN structural breakpoint varied with its location and the morphology of LOESS curve. To avoid stage migration, the optimal ELN for early-stage EOC was 29 and the minimal ELN for HGSOC was 24. For better survival, appropriate ELN number were 13 and 8 respectively. More ELNs explained better prognosis only at a certain range. Neither too many nor too few numbers of ELN were ideal for early-stage EOC and HGSOC. Excision with appropriate numbers of lymph node draining the affected ovary may be more reasonable than traditional sentinel lymph node resection and systematic lymphadenectomy.

The minimum number of examined lymph nodes was 24 for optimal survival of pathological T2-4 gastric cancer: a multi-center, hospital-based study covering 20 years of data

IntroductionThe current National Comprehensive Cancer Network (NCCN) guidelines recommend that at least 16 lymph nodes should be examined for gastric cancer patients to reduce staging migration. However, there is still debate regarding the optimal management of examined lymph nodes (ELNs) for gastric cancer patients. In this study, we aimed to develop and test the minimum number of ELNs that should be retrieved during gastrectomy for optimal survival in patients with gastric cancer.MethodsWe used the restricted cubic spline (RCS) to identify the optimal threshold of ELNs that should be retrieved during gastrectomy based on the China National Cancer Center Gastric Cancer (NCCGC) database. Northwest cohort, which sourced from the highest gastric cancer incidence areas in China, was used to verify the optimal cutoff value. Survival analysis was performed via Kaplan-Meier estimates and Cox proportional hazards models.ResultsIn this study, 12,670 gastrectomy patients were included in the NCCGC cohort and 4941 patients in the Northwest cohort. During 1999–2019, the average number of ELNs increased from 17.88 to 34.45 nodes in the NCCGC cohort, while the number of positive lymph nodes remained stable (5–6 nodes). The RCS model showed a U-curved association between ELNs and the risk of all-cause mortality, and the optimal threshold of ELNs was 24 [Hazard ratio (HR) = 1.00]. The ELN ≥ 24 group had a better overall survival (OS) than the ELN < 24 group clearly (P = 0.003), however, with respect to the threshold of 16 ELNs, there was no significantly difference between the two groups (P = 0.101). In the multivariate analysis, ELN ≥ 24 group was associated with improved survival outcomes in total gastrectomy patients [HR = 0.787, 95% confidence interval (CI): 0.711–0.870, P < 0.001], as well as the subgroup analysis of T2 patients (HR = 0.621, 95%CI: 0.399–0.966, P = 0.035), T3 patients (HR = 0.787, 95%CI: 0.659–0.940, P = 0.008) and T4 patients (HR = 0.775, 95%CI: 0.675–0.888, P < 0.001).ConclusionIn conclusion, the minimum number of ELNs for optimal survival of gastric cancer with pathological T2-4 was 24.

The minimal number of examined lymph nodes for accurate nodal staging and favorable prognosis in T1-2 supraglottic laryngeal squamous cell carcinoma

ObjectiveThe study aimed to investigate the minimal number of examined lymph nodes (ELNs) for accurate assessment of lymph node status and favorable prognosis in patients with stage T1-2 supraglottic laryngeal squamous cell carcinoma (LSCC) who received radical resection. MethodsPatients with stage T1-2 supraglottic LSCC from the Surveillance, Epidemiology, and End Results (SEER) database and the Chinese Academy of Medical Sciences, Cancer Hospital/National Cancer Center (NCC) were reviewed. The association of the ELN count with the identification of nodal metastasis and overall survival (OS) was analyzed using a multivariate regression model. Locally weighted scatterplot smoothing fitting curve and the ‘changepoint’ package were adopted to identify the optimal cut points using R. ResultsA total of 429 patients from the SEER database and 53 patients from NCC were enrolled. The probability of identifying nodal metastasis was positively related to the ELN count. For patients diagnosed with pathological stage N0 (pN0) disease, the mortality risks rapidly decreased when the amount of ELNs exceeded ten, and those with ELNs >10 had better OS. ConclusionAn adequate amount of ELNs benefits precise nodal staging in patients with stage T1-2 supraglottic LSCC. Ten lymph nodes are the minimum number of ELNs. For pN0 patients, an ELN count ≤10 is an unfavorable prognostic factor.

Optimal examined lymph node number for accurate staging and long-term survival in rectal cancer: a population-based study.

Although the recommended minimal examined lymph node (ELN) number in rectal cancer (RC) is 12, this standard remains controversial because of insufficient evidence. We aimed to refine this definition by quantifying the relationship between ELN number, stage migration and long-term survival in RC. Data from a Chinese multi-institutional registry (2009-2018) and the Surveillance, Epidemiology, and End Results (SEER) database (2008-2017) on stages I-III resected RC were analysed to determine the relationship between ELN count, stage migration, and overall survival (OS) using multivariable models. The series of odds ratios (ORs) for negative-to-positive node stage migration and hazard ratios (HRs) for survival with more ELNs were fitted using a Locally Weighted Scatterplot Smoothing (LOWESS) smoother, and structural breakpoints were determined using the Chow test. The relationship between ELN and survival was evaluated on a continuous scale using restricted cubic splines (RCS). The distribution of ELN count between the Chinese registry ( n =7694) and SEER database ( n =21332) was similar. With increasing ELN count, both cohorts exhibited significant proportional increases from node-negative to node-positive disease (SEER, OR, 1.012, P <0.001; Chinese registry, OR, 1.016, P =0.014) and serial improvements in OS (SEER: HR, 0.982; Chinese registry: HR, 0.975; both P <0.001) after controlling for confounders. Cut-point analysis showed an optimal threshold ELN count of 15, which was validated in the two cohorts, with the ability to properly discriminate probabilities of survival. A higher ELN count is associated with more precise nodal staging and better survival. Our results robustly conclude that 15 ELNs are the optimal cut-off point for evaluating the quality of lymph node examination and stratification of prognosis.

The optimal number of examined lymph nodes for accurate staging of intrahepatic cholangiocarcinoma: A multi-institutional analysis using the nodal staging score model

BackgroundThis study aims to develop a nodal staging score (NSS) to determine the optimal number of lymph nodes (LNs) examined in intrahepatic cholangiocarcinoma (iCCA) patients. MethodsClinicopathologic data were collected from the SEER database (development cohort, n = 2782) and seven Chinese tertiary hospitals (validation cohort, n = 363). NSS was constructed based on a binomial distribution to indicate the probability of nodal disease absence. In addition, its prognostic value was examined by survival analysis and multivariable modeling on pN0 patients. ResultsA model fit was performed in node-positive patients and a subgroup analysis was performed according to clinical characteristics. Statistically significant differences were only found in the subgroups when divided by the tumor size of 3 cm. As the number of examined lymph nodes (ELNs) increased, the likelihood of missing a metastatic LN decreased. NSS escalated as ELNs increased in groups with different tumor sizes, with plateaus at 7 and 11 LNs ensuring an NSS of 90.0% for ≤3 cm and >3 cm tumors, respectively. For pN0 patients, multivariate analysis revealed that NSS was an independent prognostic factor for overall survival (OS) and recurrence-free survival (RFS). ConclusionsFor accurate staging of iCCA, the optimal number of ELNs was related to tumor size. We recommend that at least 7 and 11 LNs should be examined for tumor size ≤3 cm and >3 cm, respectively. Therefore, the NSS model could be helpful to make clinical decisions for pN0 iCCA.

Survival Outcome of Gastric Signet Ring Cell Carcinoma Based on the Optimal Number of Examined Lymph Nodes: A Nomogram- and Machine-Learning-Based Approach.

The optimal number of examined lymph nodes (ELNs) for gastric signet ring cell carcinoma recommended by National Comprehensive Cancer Network guidelines remains unclear. This study aimed to determine the optimal number of ELNs and investigate its prognostic significance. In this study, we included 1723 patients diagnosed with gastric signet ring cell carcinoma in the Surveillance, Epidemiology, and End Results database. X-tile software was used to calculate the cutoff value of ELNs, and the optimal number of ELNs was found to be 32 for adequate nodal staging. In addition, we performed propensity score matching (PSM) analysis to compare the 1-, 3-, and 5-year survival rates; 1-, 3-, and 5-year survival rates for total examined lymph nodes (ELNs < 32 vs. ELNs ≥ 32) were 71.7% vs. 80.1% (p = 0.008), 41.8% vs. 51.2% (p = 0.009), and 27% vs. 30.2% (p = 0.032), respectively. Furthermore, a predictive model based on 32 ELNs was developed and displayed as a nomogram. The model showed good predictive ability performance, and machine learning validated the importance of the optimal number of ELNs in predicting prognosis.

A nomogram model based on the number of examined lymph nodes-related signature to predict prognosis and guide clinical therapy in gastric cancer.

Increasing evidence suggests that the number of examined lymph nodes (ELNs) is strongly linked to the survivorship of gastric cancer (GC). The goal of this study was to assess the prognostic implications of the ELNs number and to construct an ELNs-based risk signature and nomogram model to predict overall survival (OS) characteristics in GC patients. This inception cohort study included 19,317 GC patients from the U.S. Surveillance, Epidemiology, and End Results (SEER) database, who were separated into a training group and an internal validation group. The nomogram was built with the training set, then internally verified with SEER data, and externally validated with two different data sets. Based on the RNA-seq data, ELNs-related DERNAs (DElncRNAs, DEmiRNAs, andDEmRNAs) and immune cells were identified. The LASSO-Cox regression analysis was utilized to construct ELNs-related DERNAs and immune cell prognostic signature in The Cancer Genome Atlas (TCGA) cohort. The OS of subgroups with high- and low-ELN signature was compared using the Kaplan-Meier (K-M) analysis. A nomogram was successfully constructed based on the ELNs signature and other clinical characteristics. The concordance index (C-index), calibration plot, receiver operating characteristic curve, and decision curve analysis (DCA) were all used to evaluate the nomogram model. The meta-analysis, the Gene Expression Profiling Interactive Analysis database, and reverse transcription-quantitative PCR (RT-qPCR) were utilized to validate the RNA expression or abundance of prognostic genes and immune cells between GC tissues and normal gastric tissues, respectively. Finally, we analyzed the correlations between immune checkpoints, chemotherapy drug sensitivity, and risk score. The multivariate analysis revealed that the high ELNs improved OS compared with low ELNs (hazard ratio [HR] = 0.659, 95% confidence interval [CI]: 0.626-0.694, p < 0.0001). Using the training set, a nomogram incorporating ELNs was built and proven to have good calibration and discrimination (C-index [95% CI], 0.714 [0.710-0.718]), which was validated in the internal validation set (C-index [95% CI], 0.720 [0.714-0.726]), the TCGA set (C-index [95% CI], 0.693 [0.662-0.724]), and the Chinese set (C-index [95% CI], 0.750 [0.720-0.782]). An ELNs-related signature model based on ELNs group, regulatory T cells (Tregs), neutrophils, CDKN2B-AS1, H19, HOTTIP, LINC00643, MIR663AHG, TMEM236, ZNF705A, and hsa-miR-135a-5p was constructed by the LASSO-Cox regression analysis. The result showed that OS was remarkably lower in patients with high-ELNs signature compared with those with low-ELN signature (HR = 2.418, 95% CI: 1.804-3.241, p < 0.001). This signature performed well in predicting 1-, 3-, and 5-year survival (AUC [95% CI] = 0.688 [0.612-0.763], 0.744 [0.659-0.830], and 0.778 [0.647-0.909], respectively). The multivariate Cox analysis illustrated that the risk score was an independent predictor of survival for patients with GC. Moreover, the expression of prognostic genes (LINC00643, TMEM236, and hsa-miR-135a-5p) displayed differences between GC tissues and adjacent non-tumor tissues. The C-index of the nomogram that can be used to predict the OS of GC patients was 0.710 (95% CI: 0.663-0.753). Both the calibration plots and DCA showed that the nomogram has good predictive performance. Moreover, the signature was significantly correlated with the N stage and T stage. According to our analysis, GC patients in the low-ELN signature group may have a better immunotherapy response and OS outcome. We explored the prognostic role of ELNs in GC and successfully constructed an ELNs signature linked to the GC prognosis in TCGA. The findings manifested that the signature is a powerful predictive indicator for patients with GC. The signature might contain potential biomarkers for treatment response prediction for GC patients. Additionally, we identified a novel and robust nomogram combining the characteristics of ELNs and clinical factors for predicting 1-, 3-, and 5-year OS in GC patients, which will facilitate personalized survival prediction and aid clinical decision-making in GC patients.

Impact of examined lymph node number on accurate nodal staging and long-term survival of resected Siewert type II-III adenocarcinoma of the esophagogastric junction: A large population-based study.

We aimed to investigate the association between the number of examined lymph nodes (ELNs) and accurate nodal staging and long-term survival in Siewert type II-III Adenocarcinoma of the Esophagogastric Junction (AEG) by using large population-based databases and determined the optimal ELN number threshold. Data on Stage I-III Siewert type II-III AEG patients from 2010 to 2014 respectively from the United States (US) SEER database and a Chinese large medical center institutional registry were analyzed for correlation between the ELN number and stage migration (node negative-to-positive) and overall survival (OS) by using multivariable-adjusted logistic and Cox regression models, respectively. The series of odds ratios (ORs), and hazard ratios (HRs) were fitted with a LOWESS smoother, and the structural breakpoints were determined by Chow test. The selected optimal cut point was then validated with the 2015 to 2016 SEER database. Both the US cohort(n=1387) and China cohort(n=981) showed significantly increases from node-negative to node-positive disease (ORtheUS1.032,95%CI 1.017-1.046;ORChina1.034,95%CI 1.002-1.065) and enhancements in overall survival (HRtheUS0.970,95%CI 0.961-0.979;HRChina0.960,95%CI 0.940-0.980) with the increasing ELN number after controlling for confounders. Associations for both stage migration and overall survival were still significant in most subgroups' stratification. Cut point analysis showed a threshold ELN number of 18, which was validated both in the cohorts where it originated and in an independent SEER data cohort(n=379). More ELNs are associated with accurate nodal staging(negative-to-positive) as well as higher overall survival in resected Siewert types II-III AEG, We recommend 18 ELNs as the optimal cut point for the quality assessment of postoperative lymph node examination or prognostic stratification in clinical practice.

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

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. 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. 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. 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, node-negative 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). 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.

Impact of examined lymph node number on lymph node status and prognosis in FIGO stage IB-IIA cervical squamous cell carcinoma: A population-based study.

ObjectiveWe aimed to investigate the association of examined lymph node (ELN) number with lymph node status and long-term survival in FIGO stage IB-IIA cervical squamous cell carcinoma(CSCC) and to determine the minimum number of ELN associated with survival improvement.MethodData from the Surveillance, Epidemiology, and End Results Program (SEER) database of FIGO stage IB-IIA CSCC patients undergoing hysterectomy and pelvic lymphadenectomy in 2004-2016 were analyzed to explore the relationship between ELN number and lymph node status and overall survival (OS) by using the multivariable approach. The estimated probability of falsely identifying a patient as node-negative and the hazard ratios (HRs) for each ELN was fitted with a LOWESS smoother, and the structural breakpoints were determined. X-tile software was used to determine the optimal cutoff value for ELNs.ResultsA total of 2627 patients were analyzed. The optimal cutoff value of the ELN number was identified as 7 based on the results of X-tile software. The structural breakpoints according to the associations between the number of ELNs and the estimated risk of false-negative lymph node dissection and HRs for overall survival were 9 and 8, respectively. The multivariate analysis indicated that ELN number was an independent prognostic factor for OS, both as a continuous or categorical variable. To further explore the effect of more ELNs on survival, another cutoff value of 17 was chosen to compare the survival curves of patients. The multivariate-adjusted COX model showed that patients with ELN<8 had a significantly higher risk of death than those with ELN8-17 (HR=1.447, 95% CI =1.075-1.947, p=0.015), but there was no significant difference in overall survival between patients with ELN>17 and patients with ELN8-17 (HR=0.822, 95%CI =0.665-1.016, p=0.070).ConclusionA sufficient number of ELNs was associated with better long-term survival in FIGO stage IB-IIA CSCC. At least 8 ELNs need to be examined for prognostic stratification. Excessive lymph node dissection (ELN>17) may not confer additional survival benefits.

Analysis of the risk factor of insufficient examined lymph nodes in stage II colon cancer from the perspective of stage migration: A retrospective study combined with external validation

BackgroundAn insufficient examined lymph node (ELN) count is a high risk factor for recurrence in patients with stage II colon cancer (CC). This study aimed to explore this risk factor in relation to stage migration. MethodsWe screened 18,544 patients with stage II (pT3/4N0M0) and IIIB (pT3/4N1M0) CC diagnosed after radical resection from 2010 to 2015, using the National Cancer Institute Surveillance, Epidemiology, and End Results database. Propensity score matching was used to balance confounding factors for short-term and long-term survival, and survival analysis was carried out using the Kaplan–Meier method and log-rank test. The optimal cutoff for the number of ELNs in patients with stage II CC was determined using X-tile software. Independent prognostic factors were screened using Cox proportional hazards regression analysis. Finally, the results were externally validated in 318 patients with stage Ⅱ and ⅢB CC in our hospital from 2013 to 2015. ResultsThe best cutoff value for the number of ELNs in patients with stage II CC was 14. Multivariate analysis identified age, grade, histology, tumor size, T stage, N stage, ELN count, and chemotherapy as independent prognostic factors, and the Akaike and Bayesian information criteria values for the prognostic value of ELN count were relatively small. Patients with stage II CC with <15 ELNs had similar prognoses to patients with stage ⅢB CC (P = 0.939). Subgroup analysis and external validation yielded similar results. ConclusionPatients with stage II CC should be considered as stage ⅢB if the ELN count is insufficient.

The Least Nodal Disease Burden Defines the Minimum Number of Nodes Retrieved for Esophageal Squamous Cell Carcinoma.

BackgroundClinically, a single positive lymph node (SPLN) should indicate the least nodal disease burden in node-positive patients with esophageal squamous cell carcinoma (ESCC) and may also be used to define the minimum number of examined lymph nodes (NELNs) in ESCC patients.MethodsData from three Chinese cohorts of 2448 ESCC patients who underwent esophagectomy between 2008 and 2012 were retrospectively analyzed. Based on lymph node status, patients were divided into two groups: N0 ESCC and SPLN ESCC. A Cox proportional hazards regression model was used to determine the minimum NELNs retrieved to maximize survival for ESCC patients with localized lymph node involvement. The results were then validated externally in the SEER database.ResultsA total of 1866 patients were pathologically diagnosed with N0 ESCC, and 582 patients were diagnosed with SPLN ESCC. The overall survival rate of patients with N0 ESCC was significantly better than that of patients with SPLN ESCC (HR 1.88, 95% CI 1.64-2.13, P<0.001), but no significant difference was found between SPLN ESCC patients with ≥ 20 lymph nodes harvested and N0 ESCC patients (HR 1.20, 95% CI 0.95-1.52, P=0.13). Analysis of patients selected from the SEER database showed the same trend, and no significant difference was observed between N0 ESCC patients and SPLN ESCC patients with ≥ 20 lymph nodes retrieved (HR: 1.02, 95% CI 0.72-1.43, P=0.92).ConclusionsA minimum of 20 lymph nodes retrieved should be introduced as a quality indicator for ESCC patients with localized lymph node involvement.

Accurate Nodal Staging in Pancreatic Cancer in the Era of Neoadjuvant Therapy.

Nodal disease is prognostic in pancreatic ductal adenocarcinoma (PDAC); however, optimal number of examined lymph nodes (ELNs) required to accurately stage nodal disease in the current era of neoadjuvant therapy remains unknown. The aim of the study was to evaluate the optimal number of ELNs in patients with neoadjuvantly treated PDAC. A retrospective study was performed on patients with PDAC undergoing resection following neoadjuvant treatment between 2011 and 2018. Clinicopathological data were extracted and analyzed. Of 546 patients included, 232 (42.5%) had lymph node metastases. The median recurrence free survival (RFS) was 10.6months (95% confidence interval: 9.7-11.7) and nodal disease was independently associated with shorter RFS (9.1 vs 11.9months; p < 0.001). A cutoff of 22 ELNs was identified that stratified patients by RFS. Patients with N1 and N2 disease had similar median RFS (9.1 vs 8.9months; p = 0.410). On multivariable analysis, ELN of ≥ 22 was found to be significantly associated with longer RFS among patients with N0 disease (14.2 vs. 10.9months, p = 0.046). However, ELN has no impact on RFS for patients with N1/N2 disease (9.5 vs. 8.4months, p = 0.190). Adjuvant therapy was associated with RFS only in patients with residual nodal disease. Lymph node metastases remain prognostic in PDAC patients after neoadjuvant treatment. Among N0 patients, a cutoff of 22 ELN was associated with improved RFS and resulted in optimal nodal staging.

The Independent Prognostic Effect of Lymph Node Dissection on Patients With Stage IA NSCLC With Different T Stages.

Background: Currently, the extent of lymph node evaluation necessary for patients with early-stage non-small-cell lung cancer (NSCLC) remains controversial according to the latest ESMO and NCCN guidelines. In this study, we aimed to evaluate the survival effect of different numbers of lymph nodes examined (LNE) and regions of lymph nodes removed (LNR) in patients with stage IA NSCLC.Method: All patients with stage IA NSCLC undergoing lobectomy or bilobectomy were selected from the surveillance, epidemiology, and end results (SEER) database. The number of LNE and LNR were stratified into 4 groups (0, 1–2, 3–8, and ≥9 lymph nodes) and 3 groups (0, 1–3, and ≥4 regions) respectively. Additionally, the survival curves of overall survival (OS) and cancer-specific survival (CSS) were plotted and compared with the Kaplan-Meier method and log-rank test. Independent prognostic clinicopathological factors were evaluated via Cox proportional hazard regression and subgroup analysis.Results: Totally, 12,490 patients with stage IA NSCLC were enrolled in our study. Patients with ≥9 LNE and ≥4 LNR in both the T1b and T1c stages consistently demonstrated the significantly best OS and CSS outcomes. In the multivariate analysis, patients with ≥9 LNE consistently had a significantly better CSS [hazards ration (HR) (95% CI):0.539 (0.438–0.663)], and those with ≥4 LNR consistently had a significantly better OS [HR (95% CI):0.678 (0.476–0.966)]. Furthermore, ≥9 LNE and ≥4 LNR were associated with better survival in most subgroups.Conclusion: This study demonstrated that ≥9 LNE and ≥4 LNR are highly recommended for stage IA2 and stage IA3 patients but optional for stage IA1 patients.

Comparison of Four Lymph Node Stage Methods for Predicting the Prognosis of Distal Cholangiocarcinoma Patients After Surgery

BackgroundThe metastatic status of regional lymph nodes is an effective risk factor for the prognosis of distal cholangiocarcinoma (dCCA). But existing lymph node staging is not accurate enough and is susceptible to interference. This study aims to explore the predictive ability of the log odds of positive lymph nodes (LODDS) staging system of dCCA compared with existing lymph node staging systems.MethodsA total of 928 dCCA patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database as the training cohort, and 207 dCCA patients from West China Hospital who underwent surgery were reviewed as the validation cohort. The least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression were conducted to identify the most meaningful factors relevant to prognosis. The performance of four lymph node stage systems was compared by a model-based approach.ResultAge at diagnosis, pathological grade, American Joint Committee on Cancer (AJCC) tumor 7th T stage, tumor size, radiotherapy, chemotherapy, and lymph node stage system were independent prognostic factors. The model with the LODDS system had a better model fit with the highest C-index (0.679) and 1-/3-/5- area under the receiver operating characteristic curve (AUC) (0.739/0.671/0.658) as well as the lowest Akaike information criterion (AIC) (5,020.52). External validation results from 207 dCCA patients showed a C-index of 0.647 and 1-/3-/5-AUC of 0.740/0.683/0.589. Compared with the lymph node ratio (LNR), AJCC 8th N system, and 7th N system, the 5-year net reclassification improvement (NRI) of the LODDS system was 0.030 (95% CI: −0.079 to 0.147), 0.042 (95% CI: −0.062 to 0.139), and 0.040 (95% CI: −0.057 to 0.146), respectively. The integrated discrimination improvement (IDI) of LODDS improved compared with the LNR model (0.016; 95% CI: −0.001 to 0.036), AJCC 8th N system (0.020; 95% CI: 0.003–0.037), and AJCC 7th N system (0.019; 95% CI: 0.002–0.036). Decision curve analysis (DCA) also shows a greater net benefit of LODDS. In lymph node-negative patients, LODDS reveals a positive linear relationship with the hazard ratio (HR). The stage capacity of LODDS in a subgroup analysis stratified by examined lymph node number (ELNN) was consistent.ConclusionsThe LODDS lymph node stage system has superior predictive performance as compared with the LNR, AJCC 7th, and 8th lymph node stage systems. Meanwhile, LODDS has a more detailed staging ability and good stability.