Predictive value of number of metastatic lymph nodes and lymph node ratio for prognosis of patients with FIGO 2018 stage IIICp cervical cancer: a multi-center retrospective study.

BACKGROUND: To identify the cut-off values for the number of metastatic lymph nodes (nMLN) and lymph node ratio (LNR) that can predict outcomes in patients with FIGO 2018 IIICp cervical cancer (CC). METHODS: Patients with CC who underwent radical hysterectomy with pelvic lymphadenectomy were identified for a propensity score-matched (PSM) cohort study. A receiver operating characteristic (ROC) curve analysis was performed to determine the critical nMLN and LNR values. Five-year overall survival (OS) and disease-free survival (DFS) rates were compared using Kaplan-Meier and Cox proportional hazard regression analyses. RESULTS: This study included 3,135 CC patients with stage FIGO 2018 IIICp from 47 Chinese hospitals between 2004 and 2018. Based on ROC curve analysis, the cut-off values for nMLN and LNR were 3.5 and 0.11, respectively. The final cohort consisted of nMLN ≤ 3 (n = 2,378) and nMLN > 3 (n = 757) groups and LNR ≤ 0.11 (n = 1,748) and LNR > 0.11 (n = 1,387) groups. Significant differences were found in survival between the nMLN ≤ 3 vs the nMLN > 3 (post-PSM, OS: 76.8% vs 67.9%, P = 0.003; hazard ratio [HR]: 1.411, 95% confidence interval [CI]: 1.108-1.798, P = 0.005; DFS: 65.5% vs 55.3%, P < 0.001; HR: 1.428, 95% CI: 1.175-1.735, P < 0.001), and the LNR ≤ 0.11 and LNR > 0.11 (post-PSM, OS: 82.5% vs 76.9%, P = 0.010; HR: 1.407, 95% CI: 1.103-1.794, P = 0.006; DFS: 72.8% vs 65.1%, P = 0.002; HR: 1.347, 95% CI: 1.110-1.633, P = 0.002) groups. CONCLUSIONS: This study found that nMLN > 3 and LNR > 0.11 were associated with poor prognosis in CC patients.

Development and external validation of a nomogram predicting overall survival for Gastric adenocarcinoma patients with radical gastrectomy.

PURPOSE: The aim of this study was to develop and externally validate a nomogram to accurately predict the overall survival (OS) of patients with gastric adenocarcinoma who underwent radical gastrectomy. MATERIALS AND METHODS: A total of 3492 patients with gastric adenocarcinoma who underwent radical gastrectomy from 2012 to 2017 were included as the training cohort. Survival analysis was performed via Kaplan Meier method and log-rank test. Independent postoperative prognostic factors in patients with gastric adenocarcinoma were analyzed using univariate and multifactorial COX analysis methods. The prognosis nomogram was established in the training cohort and verified externally in the Surveillance, Epidemiology and End Results (SEER) database. RESULTS: According to the univariate and multifactorial COX analyses, metastatic lymph node ratio (MLNR) and five other independent prognostic factors (age at surgery, type of gastrectomy, tumor size, T stage, and pathological grade) were included in the prognostic nomogram. The nomogram had better prognostic predictive ability than the American Joint Committee on Cancer (AJCC) TNM staging in both the training (C-index: 0.736 VS. 0.668) and external validation cohort (C-index: 0.712 VS. 0.627). The calibration plots showed that the predicted survival rate was in good agreement with the actual survival rate. And the decision curve analysis (DCA) curves revealed that nomogram showed stronger ability in predicting 1-year, 3-year, and 5-year OS. CONCLUSION: This study estimated the excellent prognostic predictive power and clinical application potential of the MLNR-based nomogram, which may be used to facilitate postoperative clinical treatment decisions and potentially improve patient survival outcomes.

Lymph Node Ratio as a Predictive Factor of Persistent/Recurrent Disease in Patients With Medullary Thyroid Cancer: A Single-Center Retrospective Study.

OBJECTIVE: Thyroidectomy with neck lymph node dissection is curative for most patients with medullary thyroid cancer (MTC). Lymph node ratio (LNR, ie, the ratio between the metastatic and the removed lymph nodes) is a reliable parameter with which to estimate both disease extent and quality of neck dissection. The aim of this study was to investigate the prognostic role of LNR to predict persistent/recurrent disease in patients with MTC. METHODS: A single-center, retrospective study of a consecutive cohort of 95 patients with MTC treated with total thyroidectomy and neck dissection. Receiver operating characteristics curve analysis was performed to identify the LNR cut-off. RESULTS: LNR was positively associated with tumor size, preoperative and postoperative calcitonin values, postsurgery carcinoembryonic antigen values, persistent/recurrent disease, and the occurrence of distant metastases during follow-up. At multivariate analysis, persistent/recurrent disease was independently associated with the LNR value and was accurately predicted by a cut-off value of 0.12 (area under the curve = 0.85). Indeed, patients with LNR ≥0.12 had a higher probability of developing persistent/recurrent disease (79.3% vs 10.6%, odds ratio = 32.3, 95% CI = 9.8-106.4; P < .001) and distant metastasis (34.5% vs 3.0%, odds ratio = 16.8, 95% CI = 3.4-83.6; P < .001) than patients with LNR <0.12. The median time to progression was 15 months in patients with LNR ≥0.12 whereas it was not reached in patients with LNR <0.12 (hazard ratio: 7.18, 95% CI = 3.01-17.11, P < .001). CONCLUSIONS: LNR is a reliable prognostic factor to predict the risk of recurrence, persistence, and distant metastases in patients with MTC.

Prognostic significance of negative lymph node count in microsatellite instability-high colorectal cancer.

BACKGROUND: Microsatellite instability-high (MSI-H) tumors, with elevated tumor mutational burden and expression of neoantigens, represent a distinct immune-activated subpopulation in colorectal cancer (CRC), characterized by strong lymph node reaction, locally advanced tumor and higher total lymph nodes harvested (TLN), but less metastatic lymph nodes and fewer incidence of III-IV stage. Host immune response to tumor and lymph nodes may be an important prognostic factor. However, N stage and LNR (Lymph-Node Ratio) have limitations in predicting the prognosis of MSI-H patients. Negative lymph node count (NLC) provided a more precise representation of immune activation status and extent of tumor metastasis. The study aims to detect prognostic significance of NLC in MSI-H CRC patients, and compare it with N stage, TLN and LNR. METHODS: Retrospective data of 190 consecutive MSI-H CRC patients who received curative resection were collected. Survival analyses were performed using the Kaplan-Meier method. Clinicopathological variables including NLC, N stage, TLN and LNR were studied in univariate and multivariate COX regression analyses. ROC (receiver operating characteristic curve) and concordance index were employed to compare the differences in predictive efficacy between NLC, N stage, TLN and LNR. RESULTS: Patients with increased NLC experienced a significantly improved 5-years DFS and OS in Kaplan-Meier analysis, univariate analysis, and multivariate analysis, independent of potential confounders examined. Increased NLC corresponded to elevated 5-years DFS rate and 5-years OS rate. AUC (area under curve) and concordance index of NLC in DFS and OS predicting were both significantly higher than N stage, TLN and LNR. CONCLUSIONS: Negative lymph node is an important independent prognostic factor for MSI-H patients. Reduced NLC is associated with tumor recurrence and poor survival, which is a stronger prognostic factor than N stage, TLN and LNR.

Number of positive lymph nodes and lymph node ratio predict recurrence and survival in hypopharyngeal cancer based on SEER database and validation of real-world data.

PURPOSE: This study investigated the impacts of the number of positive lymph nodes (NPLN) and lymph node ratio (LN ratio) for patients with hypopharyngeal squamous cell carcinoma (HPSCC) based on SEER database, which were validated in the real-world data of China. METHODS: A total of 520 patients from SEER database were analyzed. Then 195 patients with pathologically stage III or IV HPSCC in our center were retrospectively studied. RESULTS: In the SEER database, NPLN ≥ 3 was found in 36.9% of patients. Multivariate analysis revealed that LN ratio ≥ 0.138 was significant with poorer overall survival (OS) (hazard ratio [HR] = 1.525, p = 0.001) and cancer-specific survival (CSS) (HR = 1.697, p < 0.001), so was the NPLN ≥ 3 (HR = 1.388, p = 0.013; HR = 1.479, p = 0.008). Patients with NPLN ≥ 3 were found in 103 (52.8%) in our center. Multivariate analysis confirmed a significant association regarding OS (p = 0.005) or CSS (p = 0.003) between patients with LN ratio ≥ 0.138 or not. In addition, disease recurrence rate differed significantly between the patients with NPLN ≥ 3 (27.2%) and NPLN < 3 (14.1%, p = 0.026). Moreover, postoperative chemoradiotherapy (CCRT) was significantly associated with better prognosis in patients with NPLN ≥ 3. CONCLUSION: In the SEER database, NPLN ≥ 3 and LN ratio ≥ 0.138 were independent poor prognostic factors for patients with HPSCC. Whereas identifying worldwide cut-off values for LN ratio is difficult and surgeon-dependent. In our cohort, adjuvant CCRT was beneficial for OS in patients with NPLN ≥ 3.

Lymph node ratio prognosticates overall survival in patients with stage IV colorectal cancer.

BACKGROUND: Lymph node ratio (LNR) is suggested to address the shortcomings of using only lymph node yield (LNY) or status in colorectal cancer (CRC) prognosis. This study explores how LNR affects survival in patients with metastatic colorectal cancer (mCRC), seeking to provide clearer insights into its application. METHODS: This observational cohort study investigated stage IV patients with CRC (1995-2021) who underwent an upfront resection of their primary tumour at Concord Hospital, Sydney. Clinicopathological data were extracted from a prospective database, and LNR was calculated both continuously and dichotomously (LNR of 0 and LNR > 0). The primary endpoint was overall survival (OS). The associations between LNR and various clinicopathological variables were tested using regression analyses. Kaplan-Meier and Cox regression analyses estimated OS in univariate and multivariate survival models. RESULTS: A total of 464 patients who underwent a primary CRC resection with clear margins (mean age 68.1 years [SD 13.4]; 58.0% M; colon cancer [n = 339,73.1%]) had AJCC stage IV disease. The median LNR was 0.18 (IQR 0.05-0.42) for colon cancer (CC) resections and 0.21 (IQR 0.09-0.47) for rectal cancer (RC) resections. A total of 84 patients had an LNR = 0 (CC = 66 patients; RC = 18 patients). The 5-year OS for the CC cohort was 10.5% (95% CI 8.7-12.3) and 11.5% (95% CI 8.4-14.6) for RC. Increasing LNR demonstrated a decline in OS in both CC (P < 0.001) and RC (P < 0.001). In patients with non-lymphatic dissemination only (LNR = 0 or N0 status), there was better survival compared with those with lymphatic spread (CC aHR1.50 [1.08-2.07;P = 0.02], RC aHR 2.21 [1.16-4.24;P = 0.02]). CONCLUSIONS: LNR is worthy of consideration in patients with mCRC. An LNR of 0 indicates patients have a better prognosis, underscoring the need for adequate lymphadenectomy to facilitate precise mCRC staging.

Evaluating prognostic value and stage migration effects using a positive lymph node ratio in adenocarcinoma of the esophagogastric junction.

BACKGROUND: Adenocarcinoma of the esophagogastric junction (AEG) is increasing worldwide. Lymph node metastasis is an important clinical issue in AEG patients. This study investigated the usefulness of a positive lymph node ratio (PLNR) to stratify prognosis and evaluate stage migration. METHODS: We retrospectively analysed 117 consecutive AEG patients (Siewert type I or II) who received a lymphadenectomy between 2000 and 2016. RESULTS: A PLNR cut-off value of 0.1 most effectively stratified patient prognosis into two groups (P < 0.001). Also, prognosis could be clearly stratified into four groups: PLNR = 0, 0 < PLNR < 0.1, 0.1 ≤ PLNR < 0.2, and 0.2 ≤ PLNR (P < 0.001, 5-year survival rates (88.6%, 61.1%, 34.3%, 10.7%)). A PLNR ≥ 0.1 significantly correlated with tumour diameter ≥ 4 cm (P < 0.001), tumour depth (P < 0.001), greater pathological N-status (P < 0.001), greater pathological Stage (P < 0.001), and oesophageal invasion length ≥ 2 cm (P = 0.002). A PLNR ≥ 0.1 was a poor independent prognostic factor (hazard ratio 6.47, P < 0.001). The PLNR could stratify prognosis if at least 11 lymph nodes were retrieved. A 0.2 PLNR cut-off value discriminated a stage migration effect in pN3 and pStage IV (P = 0.041, P = 0.015) patients; PLNR ≥ 0.2 might potentially diagnose a worse prognosis and need meticulous follow-up post-surgery. CONCLUSION: Using PLNR, we can evaluate the prognosis and detect higher malignant cases who need meticulous treatments and follow-up in the same pStage.

The Prognostic Significance of Lymph Node Ratio for Esophageal Cancer: A Meta-Analysis.

INTRODUCTION: This meta-analysis aimed to investigate the prognostic significance of positive lymph node ratio (LNR) in patients with esophageal cancer. MATERIALS AND METHODS: The meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We conducted a systematic search of relevant literature published until April 2022 in PubMed, EMBASE, and the Cochrane Library. The primary and secondary outcomes were overall survival (OS) and disease-free survival (DFS), with corresponding hazard ratios (HR) and 95% confidence intervals (CI). The included studies were subgrouped based on age, study area, adjuvant therapy, sensitivity analysis, and assessment of publication bias. We analyzed and discussed the results. RESULTS: We included 21 studies with 29 cohorts and 11,849 patients. The Newcastle-Ottawa Scale scores of the included studies were no less than six, indicating high research quality. The combined results of HR and 95% CI showed that patients with esophageal cancer with a lower LNR had better OS (HR, 2.58; 95% CI, 2.15-3.11; P < 0.001) and DFS (HR, 3.07; 95% CI, 1.85-5.10; P < 0.001). The subgroup analysis suggested that geographic region, age, and adjuvant therapy affected OS. When any cohort was excluded, no significant changes were observed in the pooled HR of the OS group, indicating reliable and robust results. Egger's and Begg's tests showed no potential publication bias in the studies that used OS as an outcome measurement index, indicating reliable results. Sensitivity analyses and assessments of publication bias (<10) were not performed because of an insufficient number of DFS studies. CONCLUSION: Patients with a lower positive LNR had a higher survival rate, suggesting that positive LNR may be a promising predictor of EC prognosis in esophageal cancer. After radical resection of esophageal cancer, the ratio of the number of dissected lymph nodes to the number of positive lymph nodes in patients with esophageal cancer should be considered to accurately evaluate the prognosis.

Conditional survival in patients treated for gastric cancer with a curative intent.

BACKGROUND AND OBJECTIVES: Conditional survival (CS) provides the probability that a patient who has already survived a certain number of years after treatment will survive an additional number of years. We aim to study the CS of patients with gastric cancer. METHODS: Patients who underwent curative intent treatment for gastric cancer in a single institution between 2007 and 2018 were included in the analysis. The probability (CS) that a patient who has already survived x years will survive an additional y year, was calculated as CS (y/x) = S(x + y)/S(x). RESULTS: The probability of surviving an additional 3 years if a patient had already survived 1, 2, 3, 4, and 5 years after treatment were 64.2%, 74.5%, 81.6%, 83.2%, and 88.2%, respectively whereas the 4-, 5-, 6-, 7-, and 8-year actuarial OS were only 47.2%, 43.2%, 41%, 39.4%, and 38.2%, respectively. The independent prognostic factors associated with poor survival were age >60 years, T stage ≥T3, N stage ≥N2, proximal tumor location, and lymph node ratio > 0.18. Patients with these high-risk features showed the greatest increase in CS3 over time. CONCLUSION: CS estimates provided a more dynamic prognostic information over time for patients treated for gastric cancer with curative intent.

Use of lymph node ratio to guide clinical decision-making concerning adjuvant radiotherapy in pT1-2N1 rectal cancer.

PURPOSE: Lymph node metastases are uncommon in pT1-2 rectal cancer. pT1-2N1 are often characterized with low tumor burden and intermediate prognosis. Therefore, adjuvant radiotherapy (ART) is controversial in these patients. This study aimed to investigate the value of ART in pT1-2 rectal cancer and evaluate the guiding role of lymph node ratio (LNR) for utilization of ART. METHODS: pT1-2N1 rectal cancer patients who received surgery without neoadjuvant radiotherapy between 2000 and 2018 with at least 12 lymph node harvest were extracted from the Surveillance, Epidemiology and End Results (SEER) database. We used time-dependent receiver operating characteristic (ROC) analysis to determine the optimal cutoff of LNR. Kaplan-Meier methods and Cox proportional hazards regression models were performed to determine the prognostic value of ART in pT1-2N1 rectal cancer patients and subgroups stratified by LNR. RESULTS: A total of 674 and 1321 patients with pT1N1 and pT2N1 rectal cancer were eligible for analysis. There was no statistical cancer-specific survival (CSS) difference in pT1N1 rectal cancer patients between receiving and not receiving ART (P = 0.464). The 5-year CSS was 89.6% and 83.2% in pT2N1 rectal cancer patients between receiving and not receiving ART, respectively (P = 0.003). A total of 7.0% was identified as the optimal cutoff value of LNR. Survival improvement offered by ART was only found in LNR ≥ 7.0% subgroup (5-year CSS: 89.5% versus 79.6%, P = 0.003) instead of LNR < 7.0% subgroup (5-year CSS: 89.9% versus 86.3%, P = 0.208). CONCLUSION: ART show substantial survival benefit in pT2N1 rectal cancer patients with LNR ≥ 7.0%, warranting the conventional adoption of ART in this subgroup.

Metastatic lymph node ratio as an important prognostic factor in advanced gallbladder carcinoma with at least 6 lymph nodes retrieved.

BACKGROUND: The metastatic lymph node (LN) ratio (LNR) has shown to be an important prognostic factor in various gastrointestinal malignancies. Nevertheless, the prognostic significance of LNR in gallbladder carcinoma (GBC) remains to be determined. METHODS: From January 2007 to January 2018, 144 advanced GBC patients (T2-4 stages) who underwent curative surgery with at least 6 LNs retrieved were enrolled. Receiver operating characteristic (ROC) curve was performed to identify the optimal cut-off value for LNR. The clinicopathological features stratified by LNR level were analyzed. Meanwhile, univariate and multivariate Cox regression proportional hazard models were performed to identify risk factors for overall survival (OS). RESULTS: The optimal cut-off point for LNR was 0.28 according to the ROC curve. LNR>0.28 was associated with higher rate of D2 LN dissection (P=0.004) and higher tumor stages (P<0.001). Extent of liver resection, extrahepatic bile duct resection, tumor stage, LNR, margin status, tumor differentiation, and perineural invasion were associated with OS in univariate analysis (all P<0.05). GBC patients with LNR≤0.28 had a significantly longer median OS compared to those with LNR>0.28 (27.5 vs 18 months, P=0.004). Multivariate analysis indicated that tumor stage (T2 vs T3/T4; hazard ratio (HR) 1.596; 95% confidence interval (CI) 1.195-2.132), LNR (≤0.28 vs >0.28; HR 0.666; 95% CI 0.463-0.958), margin status (R0 vs R1; HR 1.828; 95% CI 1.148-2.910), and tumor differentiation (poorly vs well/moderately; HR 0.670; 95% CI 0.589-0.892) were independent prognostic factors for GBC (all P<0.05). CONCLUSIONS: LNR is correlated to advanced GBC prognosis and is a potential prognostic factor for advanced GBC with at least 6 LNs retrieved.

Lymph node ratio as a tool to stratify patients with N1b papillary thyroid cancer.

BACKGROUND: The prognostic significance of lymph node ratio (LNR) in N1b papillary thyroid cancer is unclear. Therefore, the impact of LNR on disease-specific mortality (DSM) and overall survival (OS) in patients with N1b papillary thyroid cancer (PTC) needs to be defined. METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) database of patients who had undergone thyroidectomy and lymph node dissection. Factors associated with DSM and OS were analyzed and identified using univariate and multivariate Cox proportional risk models. X-tile software was used to find the best cutoff value of LNR. Kaplan-Meier estimates for DSM were plotted for LNR and were compared with the log-rank test. The ROC curve evaluated the validity of the model. RESULTS: A total of 3223 patients with N1b PTC were identified in the SEER database between 1975 and 2019. The best cutoff value for LNR was 0.6. The multivariate Cox proportional risk model showed that age, race, T3/T4 classification, distant metastasis, extent of surgery, number of metastatic lymph nodes, and LNR > 0.6 were independent risk factors for DSM (all p < 0.05). Age, sex, T4 classification, distant metastasis, extent of surgery, and LNR > 0.6 were independent risk factors for OS (all p < 0.05). The Kaplan-Meier method plotted a cumulative risk curve and showed that patients with LNR > 0.6 had a significantly higher risk of DSM than patients with LNR ≤ 0.6 (p = 0.002). CONCLUSION: LNR was a powerful predictor of DSM and OS in N1b PTC patients. LNR could be a useful tool for the stratification of PTC patients with lateral neck metastases.

Prognostic significance of metastatic lymph node ratio in gastric cancer: a Western-center analysis.

BACKGROUND: Tumor-node-metastasis (TNM) staging is the central gastric cancer (GC) staging system, but it has some disadvantages. However, the lymph node ratio (LNR) can be used regardless of the type of lymphadenectomy and is considered an important prognostic factor. This study aimed to evaluate the relationship between LNR and survival in patients who underwent curative GC surgery. METHODS: All patients who underwent radical gastric surgery between January 2014 and June 2022 were retrospectively evaluated. Clinicopathological features of tumors, TNM stage, and survival rates were analyzed. LNR was defined as the ratio between metastatic lymph nodes and total lymph nodes removed. The LNR groups were classified as follows: LNR0 = 0, 0.01 < LNR1 ≤ 0.1, 0.1 < LNR2 ≤ 0.25 and LNR3 > 0.25. Tumor characteristics and overall survival (OS) of the patients were compared between LNR groups. RESULTS: After exclusion, 333 patients were analyzed. The mean age was 62 ± 14 years. According to the LNR classification, no difference was found between groups regarding age and sex. However, TNM stage III disease was significantly more common in LNR3 patients. Most patients (43.2%, n = 144) were in the LNR3 group. In terms of tumor characteristics (lymphatic, vascular, and perineural invasion), the LNR3 group had significantly poorer prognostic factors. The Cox regression model defined LNR3, TNM stage II-III disease, and advanced age as independent risk factors for survival. Patients with LNR3 demonstrated the lowest 5-year OS rate (35.7%) (estimated mean survival was 30 ± 1.9 months) compared to LNR 0-1-2. CONCLUSION: Our study showed that a high LNR was significantly associated with poor OS in patients who underwent curative gastrectomy. LNR can be used as an independent prognostic predictor in GC patients.

The effect of lymph node ratio on survival in non-small-cell lung cancer.

BACKGROUND: The aim of this study was to evaluate the effect of prognostic factors and lymph node ratio (LNR) on survival in patients with resected non-small-cell lung cancer (NSCLC). METHODS: Data from 421 patients with NSCLC who underwent complete resection between 2009 and 2015 were evaluated retrospectively. LNR was defined as the ratio of positive lymph nodes to the total number of lymph nodes removed. Associations between overall survival (OS) and LNR, node (N) status, and histopathologic status were evaluated. RESULTS: The 5-year survival rate was 42.5% among all patients and 26.6% for patients aged 65 years or older. In the multivariate analysis, age ≥65 years, advanced-stage disease, non-squamous cell carcinomas, pN status, and having multiple-station pN2 and multiple-station pN1 disease were found to be poor prognostic factors (p < 0.05). There was no statistical difference in survival between patients with LNR (hazard ratio: 1.04, p = 0.45). CONCLUSION: The results of our study indicate that pN stage, histopathologic type, pT stage, and geriatric age were the most important poor prognostic factors associated with survival after NSCLC resection. Although LNR is a factor associated with survival in gastrointestinal cancers, it did not impact survival in our study.

The Prognostic Utility of the Metastatic Lymph Node Ratio and the Number of Regional Lymph Nodes Removed from Patients with Small Bowel Adenocarcinomas.

Background and Objectives: Small bowel adenocarcinomas (SBAs) are rare tumors of the gastrointestinal system. Lymph node metastasis in patients with curatively resected SBAs is associated with poor prognosis. In this study, we determined the prognostic utility of the number of removed lymph nodes and the metastatic lymph node ratio (the N ratio). Materials and Methods: The data of 97 patients who underwent curative SBA resection in nine hospitals of Turkey were retrospectively evaluated. Univariate and multivariate analyses of potentially prognostic factors including the N ratio and the numbers of regional lymph nodes removed were evaluated. Results: Univariate analysis showed that perineural and vascular invasion, metastatic lymph nodes, advanced TNM stage, and a high N ratio were significant predictors of poor survival. Multivariate analysis revealed that the N ratio was a significant independent predictor of disease-specific survival (DSS). The group with the lowest N ratio exhibited the longest disease-free survival (DFS) and DSS; these decreased significantly as the N ratio increased (both, p < 0.001). There was no significant difference in either DFS or DSS between groups with low and high numbers of dissected lymph nodes (i.e., <13 and ≥13) (both, p = 0.075). Conclusions: We found that the N ratio was independently prognostic of DSS in patients with radically resected SBAs. The N ratio is a convenient and accurate measure of the severity of lymph node metastasis.

CHRNB2 represses pancreatic cancer migration and invasion via inhibiting ß-catenin pathway.

BACKGROUND: Pancreatic cancer is one of the most lethal disease with highly fatal and aggressive properties. Lymph node ratio (LNR), the ratio of the number of metastatic lymph nodes to the total number of examined lymph nodes, is an important index to assess lymphatic metastasis and predict prognosis, but the molecular mechanism underlying high LNR was unclear. METHODS: Gene expression and clinical information data of pancreatic cancer were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Patients in TCGA were averagely divided into low and high LNR groups. Then, Weighted Gene Co-expression Network Analysis (WGCNA) was utilized to build co-expression network to explore LNR-related modules and hub genes. GO and KEGG analysis was performed to find key pathways related to lymph node metastasis. Next, GSE101448 and the overall survival data in TCGA was employed to further select significant genes from hub genes. Considering the key role of CHRNB2 in LNR and survival, gene set enrichment analysis (GSEA) was applied to find pathways related to CHRNB2 expression in pancreatic cancer. The contribution of CHRNB2 to migrative and invasive ability of pancreatic cancer cells was confirmed by Transwell assays. We finally explored the role of CHRNB2 in EMT and ß-catenin pathway via Western Blot. RESULTS: High LNR was significantly related to high T stages and poor prognosis. In WGCNA, 14 hub genes (COL5A1, FN1, THBS2, etc.) were positively related to high LNR, 104 hub genes (FFAR1, SCG5, TMEM63C, etc.) were negatively related to high LNR. After taking the intersection with GSE101448, 13 genes (CDK5R2, SYT7, CACNA2D2, etc.) which might prevent lymph node metastasis were further selected. Among them, CHRNB2 showed the strongest relationship with long survival. Moreover, CHRNB2 also negatively related to the T stages and LNR. Next, knockdown of CHRNB2 expression could acetylcholine (ACh)-independently increase the migration and invasion of pancreatic cancer cells, while CHRNB2 overexpression ACh-independently decrease the migration and invasion of pancreatic cancer cells. For exploring the underlying mechanism, CHRNB2 downregulated ß-catenin pathway might through controlling its upstream regulators such as SOX6, SRY, SOX17, and TCF7L2. CONCLUSIONS: CHRNB2 negatively relates to lymph node metastasis in pancreatic cancer patients. CHRNB2 could inhibit ß-catenin pathway, EMT, migration and invasion of pancreatic cancer cells via ACh-independent mechanism.

Prognostic significance of metastatic lymph node ratio in patients with gastric cancer after curative gastrectomy: a single-center retrospective study.

BACKGROUND: The objective of this study was to evaluate the prognostic value of Metastatic lymph node ratio (MLNR) after curative gastrectomy in patients with gastric cancer (GC) and the potential for new indicators to strengthen the current guidelines. METHODS: We retrospectively researched 3864 GC patients with curative gastrectomy between February 2011 and February 2016. The following clinical data were collected from the included patients: gender, type of gastrectomy, tumor location, T stage, N stage, ELN, tumor size, age at surgery, perineural invasion, vascular invasion, TNM stage, survival time and survival status. Patients were divided into low-MLNR (L-MLNR), and high-MLNR (H-MLNR) groups based on adjusted the X-tile cutoff-value of 0.25 for MLNR, the survival rates and clinicopathological characteristics of each group were compared. For the assessment of significant associations between clinicopathological characteristics and patients' survival, univariate and multivariate analyses were performed using the Kaplan-Meier method and Cox proportional hazards analysis. The log-rank test was used to examine the statistical significance of differences among different survival curves. Clinicopathological features significantly associated with MLNR were assessed by the Chi-square test and multinomial logistic regression. The discriminative ability was measured by calculating the Bayesian Information Criterion (BIC) values for each category. Assessment of the effect of clinicopathological features on MLNR for predicting prognosis of GC patients used stratum analysis through Kaplan-Meier analysis and Cox proportional risk Analysis. RESULTS: Survival analysis indicated that MLNR was negatively associated with overall survival (OS) (p < .001) and was an independent prognostic predictor in 3864 GC patients (p < .001). MLNR had significant prognostic significance in various subgroups with clinicopathological characteristics (gender, type of gastrectomy, tumor location, T stage, N stage, ELN, tumor size, age at surgery, perineural invasion, vascular invasion, and TNM stage) (p < .001). CONCLUSIONS: The MLNR may become a new indicator to assess the prognosis of GC patients who underwent curative gastrectomy. The results may have potential clinical implications that should be considered when developing clinical practice guidelines or the design of the future investigation.

The prognostic value of the number of positive lymph nodes and the lymph node ratio in early-stage cervical cancer.

INTRODUCTION: To establish the impact of the number of lymph node metastases (nLNM) and the lymph node ratio (LNR) on survival in patients with early-stage cervical cancer after surgery. MATERIAL AND METHODS: In this nationwide historical cohort study, all women diagnosed between 1995 and 2020 with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IA2-IIA1 cervical cancer and nodal metastases after radical hysterectomy and pelvic lymphadenectomy from the Netherlands Cancer Registry were selected. Optimal cut-offs for prognostic stratification by nLNM and LNR were calculated to categorize patients into low-risk or high-risk groups. Kaplan-Meier overall survival analysis and flexible parametric relative survival analysis were used to determine the impact of nLNM and LNR on survival. Missing data were imputed. RESULTS: The optimal cut-off point was ≥4 for nLNM and ≥0.177 for LNR. Of the 593 women included, 500 and 501 (both 84%) were categorized into the low-risk and 93 and 92 (both 16%) into the high-risk groups for nLNM and LNR, respectively. Both high-risk groups had a worse 5-year overall survival (p < 0.001) compared with the low-risk groups. Being classified into the high-risk groups is an independent risk factor for relative survival, with excess hazard ratios of 2.4 (95% confidence interval 1.6-3.5) for nLNM and 2.5 (95% confidence interval 1.7-3.8) for LNR. CONCLUSIONS: Presenting a patient's nodal status postoperatively by the number of positive nodes, or by the nodal ratio, can support further risk stratification regarding survival in the case of node-positive early-stage cervical cancer.

Prognostic value of lymph node ratio in resectable rectal cancer after preoperative short-course radiotherapy-results from randomized clinical trial.

PURPOSE: The value of the lymph node ratio (LNR) in patients with rectal cancer has not yet been unequivocally established. This study aims to assess the effect of the lymph node ratio on the prognosis of rectal cancer in patients operated after short-course preoperative 25 Gy radiotherapy, at 10-year follow-up. METHODS: This is a substudy based on data from a prospective randomized clinical trial. A total of 141 patients with resectable rectal cancer were included. Lymph node yield was compared in patients with short and long time intervals between radiotherapy and surgery. Survival curves were compared between patients with different ypN and LNR categories. Univariate and multivariate analyses were performed to identify independent prognostic factors for overall survival and disease-free survival. RESULTS: Survival and recurrence data were available for a median follow-up of 11.6 years. The lymph node yield did not differ significantly between the patients in the short- and long-interval groups. A greater difference in 10-year survival was observed in patients with LNR ≤ 0.41 and > 0.41 when compared to the ypN categories. Separate prognostic factor analyses were performed for the entire population and for subgroups that had < 12 and 12 lymph nodes resected. LNR was identified as an independent prognostic factor for overall survival, in multivariate analyses, for all patients and those with less than 12 retrieved lymph nodes. CONCLUSION: The lymph node yield is comparable in patients with different time intervals between radiation therapy and surgery. LNR better discriminates patients in terms of overall survival than ypN categories. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT01444495, date of registration: September 30, 2011.

Development and external validation of a novel nomogram for predicting cancer-specific survival in patients with ascending colon adenocarcinoma after surgery: a population-based study.

BACKGROUND: This study aimed to develop and validate a novel nomogram to predict the cancer-specific survival (CSS) of patients with ascending colon adenocarcinoma after surgery. METHODS: Patients with ascending colon adenocarcinoma were enrolled from the Surveillance, Epidemiology, and End Results (SEER) database from 1973 to 2015 and randomly divided into a training set (5930) and a validation set (2540). The cut-off values for age, tumour size and lymph node ratio (LNR) were calculated via X-tile software. In the training set, independent prognostic factors were identified using univariate and multivariate Cox analyses, and a nomogram incorporating these factors was subsequently built. Data from the validation set were used to assess the reliability and accuracy of the nomogram and then compared with the 8th edition of the American Joint Committee on Cancer (AJCC) tumour-node-metastasis (TNM) staging system. Furthermore, external validation was performed from a single institution in China. RESULTS: A total of 8470 patients were enrolled from the SEER database, 5930 patients were allocated to the training set, 2540 were allocated to the internal validation set and a separate set of 473 patients was allocated to the external validation set. The optimal cut-off values of age, tumour size and lymph node ratio were 73 and 85, 33 and 75 and 4.9 and 32.8, respectively. Univariate and multivariate Cox multivariate regression revealed that age, AJCC 8th edition T, N and M stage, carcinoembryonic antigen (CEA), tumour differentiation, chemotherapy, perineural invasion and LNR were independent risk factors for patient CSS. The nomogram showed good predictive ability, as indicated by discriminative ability and calibration, with C statistics of 0.835 (95% CI, 0.823-0.847) and 0.848 (95% CI, 0.830-0.866) in the training and validation sets and 0.732 (95% CI, 0.664-0.799) in the external validation set. The nomogram showed favourable discrimination and calibration abilities and performed better than the AJCC TNM staging system. CONCLUSIONS: A novel validated nomogram could effectively predict patients with ascending colon adenocarcinoma after surgery, and this predictive power may guide clinicians in accurate prognostic judgement.