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Background: The site of lymph node metastasis (LNM) may affect the prognosis of patients with esophageal squamous cell carcinoma (ESCC). To investigate the prognoses of pararespiratory and paradigestive LNM and to propose a novel N (nN) staging system that integrates both the LNM site and count., Methods: This study was a multicenter, large-sample, retrospective cohort study that included ESCC patients with LNM between January 2014 and December 2019 from three Chinese institutes. Patients were set into training (two institutes) and external validation (one institute) cohorts. The primary outcomes were survival differences in LNM site and the development of novel nodal staging system. The overall survival (OS) of patients with pararespiratory LNM only (Group A), paradigestive LNM only (Group B), and both sites (Group C) was evaluated by Kaplan-Meier. Cox proportional hazards models were used to identify the independent prognostic factors. An nN staging system considering both the LNM site and count was developed and evaluated by the area under the receiver operating characteristic curve (AUC)., Results: In total, 1313 patients were included and split into training (n = 1033) and external validation (n = 280) cohorts. There were 342 (26.0%), 568 (43.3%) and 403 (30.7%) patients in groups A, B and C, respectively. The OS of patients with pararespiratory and patients with paradigestive LNM presented significant differences in the training and validation cohorts (P < 0.050). In the training cohort, LNM site was an independent prognostic factor (hazard ratio: 1.58, 95% confidence intervals: 1.41-1.77, P < 0.001). The nN staging definition: nN1 (1-2 positive pararespiratory/paradigestive LNs), nN2 (3-6 pararespiratory LNs or 1 pararespiratory with 1paradigestive LN), nN3 (3-6 LNs with ≥ 1 paradigestive LN), nN4 (≥ 7 LNs). Subsets of patients with different nN stages showed significant differences in OS (P < 0.050). The prognostic model of the nN staging system presented higher performance in the training and validation cohorts at 3-year OS (AUC, 0.725 and 0.751, respectively) and 5-year OS (AUC, 0.740 and 0.793, respectively) than the current N staging systems., Conclusions: Compared to pararespiratory LNM, the presence of paradigestive LNM is associated with worse OS. The nN staging system revealed superior prognostic ability than current N staging systems., (© 2023. The Author(s).)

Background: The extent of lymphadenectomy during esophagectomy remains controversial for patients with T1-2 ESCC. The aim of this study was to identify the minimum number of examined lymph node (ELN) for accurate nodal staging and overall survival (OS) of patients with T1-2 esophageal squamous cell carcinoma (ESCC)., Materials and Methods: Patients with T1-2 ESCC from three institutes between January 2011 and December 2020 were retrospectively reviewed. The associations of ELN count with nodal migration and OS were evaluated using multivariable models, and visualized by using locally weighted scatterplot smoothing (LOWESS). Chow test was used to determine the structural breakpoints of ELN count. External validation in the SEER database was performed., Results: In total, 1537 patients were included. Increased ELNs was associated with an increased likelihood of having positive nodal disease and incremental OS. The minimum numbers of ELNs for accurate nodal staging and optimal survival were 14 and 18 with validation in the SEER database (n = 519), respectively. The prognostic prediction ability of N stage was improved in the group with ≥14 ELNs compared with those with fewer ELNs (iAUC, 0.70 (95%CI 0.66-0.74) versus 0.61(95%CI 0.57-0.65)). The higher prognostic value was found for patients with ≥18 ELNs than those with <18 ELNs (iAUC, 0.78 (95%CI 0.74-0.82) versus 0.73 (95%CI 0.7-0.77))., Conclusion: The minimum numbers of ELNs for accurate nodal staging and optimal survival of stage T1-2 ESCC patients were 14 and 18, respectively., (Copyright © 2022 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Lymph node metastasis (LNM) affects the application and outcomes of endoscopic resection in T1 esophageal squamous cell carcinoma (ESCC). However, reports of the risk factors for LNM have been controversial., Aim: To evaluate risk factors for LNM in T1 ESCC., Methods: We searched Embase, PubMed and Cochrane Library to select studies related to LNM in patients with T1 ESCC. Included studies were divided into LNM and non-LNM groups. We performed a meta-analysis to examine the relationship between LNM and clinicopathologic features. Odds ratio (OR), mean differences and 95% confidence interval (CI) were assessed using a fixed-effects or random-effects model., Results: Seventeen studies involving a total of 3775 patients with T1 ESCC met the inclusion criteria. After excluding studies with heterogeneity based on influence analysis, tumor size (OR = 1.93, 95%CI = 1.49-2.50, P < 0.001), tumor location (OR = 1.46, 95%CI = 1.17-1.82, P < 0.001), macroscopic type (OR = 3.17, 95%CI = 2.33-4.31, P < 0.001), T1 substage (OR = 6.28, 95%CI = 4.93-8.00, P < 0.001), differentiation (OR = 2.11, 95%CI = 1.64-2.72, P < 0.001) and lymphovascular invasion (OR = 5.86, 95%CI = 4.60-7.48, P < 0.001) were found to be significantly associated with LNM. Conversely, sex, age and infiltrative growth pattern were not identified as risk factors for LNM., Conclusion: A tumor size > 2 cm, lower location, nonflat macroscopic type, T1b stage, poor differentiation and lymphovascular invasion were associated with LNM in patients with T1 ESCC., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Patients with esophageal squamous cell carcinoma (ESCC) undergoing definitive chemoradiotherapy (CRT) seem to have a disparity in therapeutic response. The identification of CRT sensitivity-related clinicopathological factors would be helpful for selecting patients most likely to benefit from CRT. Cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) and carcinoembryonic antigen (CEA) have been reported as useful tumor markers for esophageal cancer. The aim of this study was to examine the predictive value of CYFRA21-1 in comparison with CEA and other clinicopathological factors in patients with ESCC treated with definitive CRT., Methods: Pretreatment serum CYFRA21-1 and CEA levels were measured by immunoradiometric assays. The relationships between pretreatment clinicopathological factors and the efficacy of CRT were analyzed. Overall survival (OS) was estimated by univariate and multivariate analysis., Results: The results from a univariate analysis indicated that the efficacy of CRT was significantly associated with the serum levels of CYFRA21-1 and CEA before treatment (P = 0.001 and P = 0.023, respectively). It also indicated that the efficacy of CRT was significantly associated with the pretreatment tumor location (P = 0.041). By Logistic regression analysis, the independent predictive factor associated with efficacy of CRT was CYFRA21-1 (P = 0.002). The OS of the patients with high CYFRA 21-1 levels was worse than that of those with low CYFRA21-1 levels (P = 0.001). In multivariate analysis, a low level of CYFRA21-1 was the most significant independent predictor of good OS (P = 0.007)., Conclusions: CEA and tumor location may be useful in predicting the sensitivity of ESCC to CRT. CYFRA21-1 may be an independent predictor for definitive CRT sensitivity in ESCC.

Purpose: To evaluate the prognostic value of serum CYFRA21-1, CEA and hemoglobin levels regarding long-term survival of patients with esophageal squamous cell carcinoma (ESCC) treated with concurrent chemoradiotherapy (CRT)., Methods: Age, gender, Karnofsky Performance Status (KPS), tumor location, tumor length, T stage, N stage and serum hemoglobin, and CYFRA21-1 and CEA levels before concurrent CRT were retrospectively investigated and related to outcome in 113 patients receiving 5-fluorouracil and cisplatin combined with radiotherapy for ESCC. The Kaplan-Meier method was used to analyze prognosis, the log-rank to compare groups, the Cox proportional hazards model for multivariate analysis, and ROC curve analysis for assessment of predictive performance of biologic markers., Results: The median survival time was 20.1 months and the 1-, 2-, 3-, 5- year overall survival rates were 66.4%, 43.4%, 31.9% and 15.0%, respectively. Univariate analysis showed that factors associated with prognosis were KPS, tumor length, T-stage, N-stage, hemoglobin, CYFRA21-1 and CEA level. Multivariate analysis showed T-stage, N-stage, hemoglobin, CYFRA21-1 and CEA level were independent predictors of prognosis. By ROC curve, CYFRA21-1 and hemoglobin showed better predictive performance for OS than CEA (AUC= 0.791, 0.704, 0.545; P=0.000, 0.000, 0.409)., Conclusions: Of all clinicopathological and molecular factors, T stage, N stage, hemoglobin, CYFRA21-1 and CEA level were independent predictors of prognosis for patients with ESCC treated with concurrent CRT. Among biomarkers, CYFRA21-1 and hemoglobin may have a better predictive potential than CEA for long-term outcomes.