To determine the prognostic and survival surrogate value of major pathologic response (MPR) in esophageal squamous cell carcinoma (ESCC) patients undergoing neoadjuvant chemotherapy/chemoimmunotherapy(nCT/nICT) and surgery. A retrospective multi-center study cohort study enrolled 305 ESCC patients who underwent neoadjuvant chemotherapy/chemoimmunotherapy followed by esophagectomy. Endpoints included recurrence-free survival (RFS), locoregional recurrence-free survival(L-RFS), distant metastasis-free survival(D-MFS), and recurrence patterns. The Cox regression analysis and Harrell's C-index were used to analyze survival differences and surrogate endpoints. The Kaplan-Meier method was used for the subgroup analysis in two subgroups(the patients receiving nICT and patients receiving nCT) and the prognostic value analysis of adjuvant therapy in non-MPR and MPR patients. Of the 305 patients, 105 achieved MPR, demonstrating a significantly improved RFS (P value < 0.001), L-RFS (P value < 0.001), and D-MFS (P value = 0.003). MPR was identified as an independent risk factor for RFS(HR:0.415, 95%CI:[0.227, 0.759], P value = 0.004) and demonstrated equal predictive capacity to be a surrogate of survival endpoints with T stage and N stage(Harrell's C-index: 0.613). In subgroup analysis, patients with MPR showed better survival outcomes in subgroups that received neoadjuvant chemoimmunotherapy (P value = 0.012) and neoadjuvant chemotherapy(P value < 0.001). Additionally, adjuvant therapy did not confer additional survival benefits to both MPR and non-MPR patients. Compared with patients who achieved MPR, non-MPR patients exhibited a higher recurrence rate, although the recurrence sites were similar between the two groups. MPR can serve as an independent prognostic factor and a surrogate of survival endpoints in ESCC patients undergoing nCT/nICT. Besides, as a potential indicator for postoperative management, MPR can provide reference basis and evidence support in clinical practice.

Background: Growing evidence suggested that B‐ and T‐lymphocyte attenuator (BTLA) polymorphisms raised the susceptibility to a wide range of cancers. This study aimed to evaluate whether BTLA variants were related to the risk of esophageal squamous cell carcinoma (ESCC).Methods: A total of 721 ESCC patients and 1208 matched non‐cancer controls were included in this research, and four tagging BTLA polymorphisms (rs2171513 G > A, rs3112270 A > G, rs1982809 G > A, and rs16859629 T > C) were selected and genotyped using SNPscan™ Assays.Results: In the present study, no significant relationship between BTLA polymorphisms and ESCC was observed. However, stratified analyses suggested that the variant of BTLA rs3112270 A > G reduced the risk of ESCC in the male subgroup (AG vs AA: adjusted OR = 0.78, 95% CI = 0.61‐0.99, P = .042), BMI < 24 kg/m² subgroup (AG vs AA: adjusted OR = 0.72, 95% CI = 0.55‐0.93, P = .012; AG/GG vs AA: adjusted OR = 0.77, 95% CI = 0.60‐0.98, P = .032), and ever drinking subgroup (AG vs AA: adjusted OR = 0.61, 95% CI = 0.38‐0.97, P = .037). But when stratified by BMI ≥ 24 kg/m², the rs3112270 A > G polymorphism increased the susceptibility to ESCC (GG vs AA: adjusted OR = 1.91, 95% CI = 1.02‐3.59, P = .045). Besides, we demonstrated that BTLA rs2171513 G > A polymorphism was protective of ESCC in the ever drinking subgroup (GA/AA vs GG: adjusted OR = 0.62, 95% CI = 0.39‐0.97, P = .037).Conclusion: Taken together, our initial investigation postulated that the rs3112270 A > G and rs2171513 G > A variants in the BTLA gene are candidates for the risk of ESCC, which might be helpful for the early diagnosis and treatment of ESCC.

Investigation of TCF7L2, LEP and LEPR polymorphisms with esophageal squamous cell carcinomas Investigation of TCF7L2, LEP and LEPR polymorphisms with esophageal squamous cell carcinomas

Purpose: Neoadjuvant chemoimmunotherapy (nICT) is a novel and promising therapy model for locally advanced esophageal squamous cell carcinoma.The objective of this study aimed to assessed the impact of additional neoadjuvant immunotherapy on patients’ short-term outcomes, particularly the incidence of anastomotic leakage (AL) and pathological response. Methods: Patients with locally advanced esophageal squamous cell carcinoma who received neoadjuvant chemotherapy (nCT)/ nICT combination with radical esophagectomy were enrolled from three medical centers in China. The authors used propensity score matching (PSM, ration:1:1, caliper=0.01) and inverse probability processing weighting (IPTW) to balance the baseline characteristics and compare the outcomes. Conditional logistic regression and weighted logistic regression analysis were used to further evaluate whether additional neoadjuvant immunotherapy would increase the risk of postoperative AL. Results: A total of 331 patients getting partially advanced ESCC receiving nCT or nICT were enrolled from three medical centers in China. After PSM/IPTW, the baseline characteristics reached an equilibrium between the two groups. After matching, there were no significant difference in the AL incidence between the two groups (P=0.68, after PSM; P=0.97 after IPTW), and the incidence of AL in the two groups was 15.85 versus 18.29%, and 14.79 versus 15.01%, respectively. After PSM/IPTW, both groups were similar in pleural effusion and pneumonia. After IPTW, the nICT group had a higher incidence of bleeding (3.36 vs. 0.30%, P=0.01), chylothorax (5.79 0.30%, P=0.001), and cardiac events (19.53 vs. 9.20%, P=0.04). recurrent laryngeal nerve palsy (7.85 vs. 0.54%, P=0.003). After PSM, both groups were similar in palsy of the recurrent laryngeal nerve (1.22 vs. 3.66%, P=0.31) and cardiac events (19.51 vs. 14.63%, P=0.41). Weighted logistic regression analysis showed that additional neoadjuvant immunotherapy was not responsible for AL (OR=0.56, 95% CI: [0.17, 1.71], after PSM; 0.74, 95% CI: [0.34,1.56], after IPTW). The nICT group had dramatically higher pCR in primary tumor than the nCT group (P=0.003, PSM; P=0.005, IPTW), 9.76 versus 28.05% and 7.72 versus 21.17%, respectively. Conclusions: Additional neoadjuvant immunotherapy could benefit pathological reactions without increasing the risk of AL and pulmonary complications. The authors require further randomized controlled research to validate whether additional neoadjuvant immunotherapy would make a difference in other complications, and determine whether pathologic benefits could translate into prognostic benefits, which would require longer follow-up.

Background: The textbook outcome (TO) emerges as a novel prognostic factor in surgical oncology. The present study aimed to evaluate the effect of TO on the risk of death and recurrence in patients with esophageal squamous cell carcinoma (ESCC) after minimally invasive esophagectomy (MIE). Methods: The study involved retrospective analysis of 528 patients with ESCC who were subjected to MIE from January 2011 to December 2017. TO included 8 parameters: complete resection; microscopically tumor-negative resection margins (R0); ≥15 lymph nodes removed and examined; no serious postoperative complications; no postoperative intervention; no re-admission to the intensive care unit (ICU); hospital stay ≤21 days; and no readmission ≤30 days. The Cox and logistic regression model were used to analyze the prognostic factors of survival and risk factors for TO. Results: Among the 528 patients with ESCC who were subjected to MIE, 53.2% reached TO. In the case of patients with locally advanced ESCC, 5-year overall survival (OS) was 51.1% (41.2–61.2%) for the TO group but 33.7% (23.7–43.7%) for the non-TO group (HR =0.644, 95% CI: 0.449–0.924, P=0.015). Similarly, 5-year disease-free survival (DFS) was 47.6% (38.0–57.2%) for the TO group but 29.1% (20.1–38.1%) for the non-TO group (HR =0.671, 95% CI: 0.479–0.940, P=0.018). In addition, 5-year recurrence-free survival (RFS) was 62.9% (53.7–72.1%) for the TO group but 39.8% (29.4–50.2%) for the non-TO group (HR =0.606, 95% CI: 0.407–0.902, P=0.012). Multivariate logistic regression analysis further showed that age, American Society of Anesthesiology (ASA) score, intraoperative blood loss, and smoking status acted as independent risk factors for TO. The results of the multivariate analysis assisted in the establishment of a nomogram for the prediction of TO occurrence. This nomogram exhibited satisfactory consistency and prediction ability [area under the receiving operator characteristic (AUROC) =0.717]. Conclusions: The present study showed that achieving of TO after MIE improves survival rate and reduce the recurrence rate in patients with locally advanced ESCC. The study further determined the independent factors associated with TO achievement and established a prediction model.

Objective: This study investigates the prognostic significance of inflammatory nutritional scores in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC) undergoing neoadjuvant chemoimmunotherapy.Methods: A total of 190 LA-ESCC patients were recruited from three medical centers across China. Pre-treatment laboratory tests were utilized to calculate inflammatory nutritional scores. LASSO regression and multivariate logistic regression analyses were conducted to pinpoint predictors of pathological response. Kaplan-Meier and Cox regression analyses were employed to assess disease-free survival (DFS) prognostic factors.Results: The cohort comprised 154 males (81.05%) and 36 females (18.95%), with a median age of 61.4 years. Pathological complete response (pCR) was achieved in 17.38% of patients, while 44.78% attained major pathological response (MPR). LASSO and multivariate logistic regression analyses identified that hemoglobin, albumin, lymphocyte, and platelet (HALP) (P=0.02) as an independent predictors of MPR in LA-ESCC patients receiving neoadjuvant chemoimmunotherapy. Kaplan-Meier and log-rank tests indicated that patients with low HALP, MPR, ypT1-2, ypN0 and, ypTNM I stages had prolonged DFS (P < 0.05). Furthermore, univariate and multivariate Cox regression analyses underscored HALP (P = 0.019) and ypT (P = 0.029) as independent predictive factors for DFS in ESCC.Conclusion: Our study suggests that LA-ESCC patients with lower pre-treatment HALP scores exhibit improved pathological response and reduced recurrence rate. As a comprehensive index of inflammatory nutritional status, pre-treatment HALP may be a reliable prognostic marker in ESCC patients undergoing neoadjuvant chemoimmunotherapy.