Esophageal Cancer: Molecular Biology/Pathology
To use bioinformatics methods to evaluate the prognostic value of Programmed Cell Death Related Genes (PCDRGs) in esophageal carcinoma (EC), and to explore the development and immune regulatory mechanisms of EC from multiple perspectives.
Using TCGA, GSE53622 data sets, and downloaded key regulatory genes of 18 PCD patterns, combined with 10 different machine learning methods to develop a prediction model, named this model ‘Characteristics of Cell Deaths’ (CDS). Seven prognosis-related genes were screened out by the model. The correlationbetween these seven genes and EC was analyzed.
The PCDRGs prognostic model developed using the StepCox[both] + RSF method performed the best. CDS showed significant and powerful performance in predicting EC clinical outcomes and was able to serve as an independent risk factor in TCGA and GEO datasets.
This study successfully developed a novel EC PCDRGs model, which could predict the prognosis and drug treatment sensitivity of EC patients in the future based on further validation.
Si-Han Lu, Yi Zhu, Yong-Tao Han et al.· Diseases of the esophagus· 0 citations
Esophageal Cancer: Surgical Treatment of Esophageal Cancer – technique
Robot-assisted minimally invasive esophagectomy (RAMIE) is increasingly adopted, yet comparative patient-reported outcome (PRO) data against conventional minimally invasive esophagectomy (MIE) remains scarce. We aimed to compare perioperative PROs, including quality of life, nutritional status, cough-related quality of life, and anxiety, between RAMIE and MIE for esophageal squamous cell carcinoma (ESCC).
We enrolled 214 patients with ESCC who underwent RAMIE (n = 47) or conventional MIE (n = 167) from an ongoing prospective cohort study. PROs were assessed using the EQ-5D-5L, PG-SGA, Leicester Cough Questionnaire (LCQ), and Self-rating Anxiety Scale (SAS). A 1:1 propensity score-matched (PSM) analysis was performed to balance baseline covariates. Nutritional trajectory was tracked from admission through discharge using serial PG-SGA assessments.
Before PSM, the RAMIE group had significantly higher preoperative PG-SGA scores at admission (5.18 ± 3.32 vs 4.09 ± 3.01, P = 0.015) and pre-surgery (5.44 ± 3.69 vs 3.78 ± 2.88, P = 0.006), indicating worse baseline nutritional status. However, PG-SGA scores at discharge were comparable (4.56 ± 2.74 vs 4.42 ± 2.28, P = 0.931), demonstrating nutritional convergence. No significant differences were observed in EQ-5D-5L utility index (0.92 vs 0.93, P = 0.934), LCQ total score (121.6 vs 122.6, P = 0.751), or SAS standard score (45.4 vs 45.4, P = 0.551). The RAMIE group had a higher anastomotic leak rate (14.9% vs 4.8%, P = 0.025) but no Clavien-Dindo grade ≥III complications.
RAMIE and conventional MIE achieved comparable perioperative PROs in ESCC patients. Despite worse baseline nutritional status in the RAMIE group, nutritional recovery by discharge was equivalent. These findings support RAMIE as a viable alternative with comparable patient-centered outcomes, though the higher anastomotic leak rate warrants further investigation.
Si-miao Lu, Yi Zhu, Yong-tao Han et al.· Diseases of the esophagus· 0 citations
Esophageal Cancer: Surgical Treatment of Esophageal Cancer
Esophagectomy for esophageal cancer carries substantial morbidity, yet the extent to which institutional surgical strategy—encompassing operative approach, lymphadenectomy extent, and neoadjuvant treatment protocol—determines postoperative complication profiles remains poorly characterized across different geographic practice environments.
We performed a retrospective analysis of a prospectively maintained international multicenter database (ISDE) comprising 2,490 patients who underwent curative-intent esophagectomy across four centers (Centers A–D; n=825, 499, 1,012, and 154 respectively). Primary outcomes were postoperative complication rates, in-hospital mortality, and length of stay. Given substantial heterogeneity in neoadjuvant therapy rates (Center A 81.1% versus Center D 11.0%), pathological stage distribution, and lymphadenectomy extent, all cross-institutional comparisons were performed descriptively with formal confounding adjustment deferred to propensity-matched subgroup analyses.
Marked inter-institutional variation in surgical strategy was observed. Center A was characterized by near-universal thoracoscopic-laparoscopic esophagectomy (93.7% thoracoscopy), three-field lymphadenectomy, and the highest neoadjuvant treatment rate (81.1%). Center B predominantly underwent open Ivor-Lewis esophagectomy (80.6%), with robotic assistance in 13.6% and concurrent chemoradiotherapy in 46.3%. Center C demonstrated approximately 70% minimally invasive adoption with two-field dissection, while Center D uniformly employed McKeown esophagectomy with selected cervical dissection. Center A exhibited the highest rate of recurrent laryngeal nerve palsy (28.6%) and chylothorax (7.8%), reflecting systematic radical dissection. Despite this, in-hospital mortality was 0.7%, ICU stay was a median of 3 days (IQR 2–3), and postoperative length of stay was 14 days (IQR 12–19). Anastomotic leakage rates were comparable across centers with available data (Center A 9.3%; Center C 10.7%; Center D 11.0%). Recurrent laryngeal nerve injury was lower in centers employing two-field dissection (Center C 8.3%; Center D 15.6%).
Operative strategy is the primary driver of postoperative complication phenotype in esophageal cancer surgery. Three-field lymphadenectomy uniquely confers high recurrent laryngeal nerve palsy and chylothorax rates despite low mortality. Valid cross-institutional outcome benchmarking requires rigorous adjustment for neoadjuvant treatment exposure, pathological stage composition, and dissection field extent.
Si-miao Lu, Yi Zhu, Yong-tao Han et al.· Diseases of the esophagus· 0 citations
Esophageal Cancer: Adjuvant and Neo-Adjuvant Therapies
The survival benefit of neoadjuvant therapy for esophageal squamous cell carcinoma (ESCC) remains controversial, as landmark trials were conducted predominantly in adenocarcinoma populations. This study evaluated the association between neoadjuvant therapy and long-term survival in a large international multicenter ESCC cohort using propensity score methods and multivariable Cox regression.
We retrospectively analyzed 2,449 patients with ESCC who underwent curative esophagectomy at five institutions across three countries (Japan, China, and South Korea) between 2008 and 2022. Patients receiving neoadjuvant therapy (n=941) were compared with a surgery-first cohort (n=880) after excluding 41 cases with inconsistent survival data. Propensity score matching (PSM) 1:1 was performed using nearest-neighbor matching (caliper=0.1 SD of logit propensity score) with exact matching on center, adjusting for sex, age, clinical T and N stage. Inverse probability of treatment weighting (IPTW) with trimming (1st–99th percentile) served as a sensitivity analysis. Center-stratified univariate and multivariable Cox proportional hazards regression were applied. Primary endpoints were overall survival (OS) and disease-free survival (DFS).
In analysis, neoadjuvant therapy appeared protective for OS (HR 0.60, 95% CI 0.48–0.75, p<0.001) while DFS was worse (HR 1.57, 95% CI 1.34–1.84, p<0.001). This discordant finding reversed after center-stratified Cox regression, revealing substantial confounding by center. Univariate analysis showed neoadjuvant therapy was associated with worse OS (HR 2.22, 95% CI 1.75–2.83, p<0.001) and DFS (HR 2.31, 95% CI 1.89–2.82, p<0.001). Multivariable analysis confirmed neoadjuvant therapy as an independent predictor of worse OS (HR 1.48, 95% CI 1.11–1.96, p=0.007) and DFS (HR 1.39, 95% CI 1.09–1.77, p=0.007). PSM yielded 255 pairs; after matching, neoadjuvant therapy was associated with worse OS (HR 1.56, 95% CI 1.05–2.30, p=0.027) and DFS (HR 1.60, 95% CI 1.18–2.19, p=0.003). IPTW sensitivity analysis yielded consistent results (OS: HR 2.21, 95% CI 1.74–2.82; DFS: HR 2.30, 95% CI 1.89–2.81; both p<0.001).
In this international multicenter analysis of 2,449 ESCC patients, neoadjuvant therapy was not associated with improved survival after esophagectomy and remained an independent predictor of worse OS and DFS across univariate, multivariable, PSM, and IPTW analyses. These findings underscore the critical importance of histology-specific evidence and support the urgent need for contemporary randomized controlled trials designed specifically for ESCC populations.
Si-miao Lu, Yi Zhu, Qiulin Shi et al.· Diseases of the esophagus· 0 citations
Symptom persistence does not adversely affect overall survival; its association with improved DFS likely reflects the tumor-control benefit of adjuvant therapy.
Si-miao Lu, Yi Zhu, Yong-tao Han et al.· Diseases of the esophagus· 0 citations
An end-to-end multimodal AI system can accurately automate PRO assessment from natural patient conversations and provide clinically meaningful early warning for postoperative complications, with external validation confirming generalisability across cohorts.
Si-miao Lu, Yi Zhu, Yong-tao Han et al.· Diseases of the esophagus· 0 citations
Surgical timing, particularly esophagectomy performed in February, is associated with inferior long-term survival in ESCC patients, and concurrent low burnout levels during this period suggest that reduced surgical volume and altered case selection during the holiday season, rather than staff fatigue, may underlie this disparity.
Si-miao Lu, Yi Zhu, Yong-tao Han et al.· Diseases of the esophagus· 0 citations
Standard preoperative variables are insufficient for individualized risk stratification of RLNP, anastomotic leak, or vocal cord palsy after esophagectomy, and improved prediction will require prospective integration of real-time intraoperative data.
Si-miao Lu, Yi Zhu, Yong-tao Han et al.· Diseases of the esophagus· 0 citations
A multimodal early warning system integrating PROs, laboratory trajectories, and large language model-extracted clinical text features to enable real-time, automated complication surveillance substantially outperforms single-modality approaches for detecting postoperative complications after esophagectomy.
Si-miao Lu, Yi Zhu, Yong-tao Han et al.· Diseases of the esophagus· 0 citations
Postoperative CRP trajectory patterns are significantly associated with complication severity after esophagectomy, and the High-Persistent trajectory identifies a high-risk subgroup, and the D3/D1 ratio enables early risk stratification by POD 3.
Si-miao Lu, Yi Zhu, Yong-tao Han et al.· Diseases of the esophagus· 0 citations
The natural product compounds CNP0456830 and CNP0467494 exhibited the lowest binding free energies for both EGFR and PIK3CA, identifying them as the most promising dual-target inhibitors.
Si-miao Lu, Yi Zhu, Yong-tao Han et al.· Diseases of the esophagus· 0 citations
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