Tongue pressure is a predictor of postoperative aspiration. This study aimed to examine changes in tongue pressure during neoadjuvant chemotherapy (NAC), identify associated factors, and investigate whether these changes are related to other functional outcomes, including exercise capacity and muscle function. This prospective, single-center, observational study enrolled 68 patients with esophageal cancer scheduled to undergo NAC. Patients were classified into marked reduction (n=17) and remaining (n=51) groups based on the rate of change in tongue pressure. Tongue pressure, muscle function, walking ability, and exercise capacity were evaluated before and after NAC. Multivariate logistic regression analysis was performed to identify the factors significantly associated with a marked reduction in tongue pressure. Spearman’s correlation analysis was used to evaluate the relationships between the rate of change in tongue pressure and the rates of change in each functional parameter. Multivariable logistic regression analysis identified age and the number of days during NAC when oral intake was not possible as significant independent factors associated with a marked reduction in tongue pressure. Spearman’s correlation analysis revealed no significant correlations between the rate of change in tongue pressure during NAC and the rates of change in handgrip strength, isometric knee extensor strength, 30-s chair stand test performance, quadriceps thickness, maximum inspiratory pressure, maximum expiratory pressure, 10-m walk test result, or 6-min walk distance. These findings underscore the importance of incorporating swallowing function, including tongue pressure, into prehabilitation programs.
Recently, the application of Intensity-Modulated Radiotherapy (IMRT) and changes in fractionation schedules have been increasingly introduced in radiotherapy practice for esophageal cancer. However, the extent of their adoption and prevalence in real-world clinical practice remains unclear. This study aimed to describe nationwide trends in radiotherapy for esophageal cancer using a large-scale health insurance claims database. Using the DeSC database, we identified patients newly diagnosed with esophageal cancer between April 2017 and March 2023. Patients treated with definitive radiotherapy (defined as 25–35 treatment days in patients without distant metastasis) were selected. We analyzed temporal trends in radiotherapy, regional differences, and the incidence of radiation pneumonitis. Among patients with an identified initial treatment, the proportion of radiotherapy declined from 28.6
The prevalence of gastroesophageal reflux disease (GERD) has increased worldwide, and metabolic syndrome (MS) was reported as a risk factor for its incidence. This study retrospectively evaluated the relationship between endoscopic GERD classification and MS-related parameters in a Japanese cohort. We reviewed the medical records of 3,635 adults who underwent upper gastrointestinal endoscopy as part of health checkups. Based on endoscopic findings, GERD was classified according to the Los Angeles (LA) system. Body mass index (BMI), waist circumference, blood pressure (BP), and laboratory parameters—including glucose, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides—were compared across the LA grade groups. The numbers of patients classified as LA grade N, M, A, B, C, and D were 2,557 (70.3
Phase III trials have established the efficacy of immune-based therapies for unresectable advanced or recurrent esophageal squamous cell carcinoma (ESCC). However, real-world evidence comparing regimens and clinically applicable prognostic biomarkers remains limited. We retrospectively evaluated 245 patients with unresectable advanced/recurrent ESCC treated with first-line 5-fluorouracil plus cisplatin combined with nivolumab or pembrolizumab (CF + ICI; n = 114), first-line ipilimumab plus nivolumab (Ipi + Nivo; n = 46), or nivolumab monotherapy as second-line or later treatment (Nivo; n = 85). Efficacy, safety, and survival outcomes were assessed, focusing on inflammation-based nutritional indices and multivariate prognostic modelling. The objective response rates were 56
Once an esophago–airway fistula develops during chemoradiotherapy for cT4b esophageal cancer, further curative treatment is often precluded. We describe a robotic technique for closure of a large esophago–left main bronchial fistula using a pedicled autologous pericardial patch reinforced with a latissimus dorsi muscle flap. A 66-year-old woman with squamous cell carcinoma of the middle to upper thoracic esophagus invading the left main bronchus developed a fistula after definitive chemoradiotherapy. After temporary airway stenting, salvage surgery was performed in the semi-prone position under single-lung ventilation and CO₂ pneumothorax. Following thoracic esophagectomy, a horseshoe-shaped pedicled pericardial patch was created robotically, flipped cranially, and sutured to the bronchial defect. A right latissimus dorsi muscle flap was then introduced into the right thoracic cavity through a second intercostal opening and robotically fixed over the repair. To our knowledge, this is the first report of this robotic technique.
Enteral nutrition after esophagectomy is commonly provided via jejunostomy; however, conventional jejunostomy carries the risk of small bowel obstruction (SBO). Feeding jejunostomy via the gastric tube (FJ‑GT), especially through the round ligament of the liver (RL), has been reported to reduce the risk of SBO or catheter site infection. However, previous reports have only described open procedures. We describe a novel laparoscopic technique for performing FJ‑GT through the RL during minimally invasive esophagectomy (MIE) with retrosternal reconstruction. Through an umbilical mini-laparotomy, the specimen was extracted, and a gastric tube was created. A jejunostomy catheter was inserted 30 cm into the duodenum from the gastric antrum, fixed to the gastric wall, and covered with the omentum. After retrosternal reconstruction, the catheter was laparoscopically exteriorized through the RL. Among the 75 consecutive patients, no catheter-related complications of Clavien–Dindo grade III or higher, including SBO, were observed. This technique is feasible and applicable in MIE.
Upper gastrointestinal endoscopy traverses the full upper aerodigestive tract, unlike radiography, potentially enabling incidental detection of non-gastric malignancies. However, its population-level incidental detection rate for non-gastric upper aerodigestive tract cancers has not been systematically quantified. The aim of this study was to compare endoscopic screening with radiography and quantify detection of non-gastric upper aerodigestive tract cancers in a population-based setting. This population-based cohort study was conducted by linking the Okayama City municipal gastric cancer screening registry with the Kokuho Database (KDB) for fiscal years 2016–2021. Among 36,326 participants contributing 64,822 screening examinations (40,832 radiography; 23,990 endoscopy), diagnoses of oral cavity, pharyngeal, laryngeal, and esophageal cancer occurring within 2 months of screening were ascertained from the KDB. Generalized estimating equations with modified Poisson regression were used to estimate adjusted risk ratios (aRRs) comparing endoscopy with radiography. Endoscopic screening was significantly associated with higher composite incidental detection rates for non-gastric upper aerodigestive tract cancers (95.9 vs. 34.3 per 100,000 examinations; aRR 2.94, 95
The association between electronic cigarette (e-cigarette) use and Barrett’s esophagus (BE) is still unclear. While traditional, combustible cigarette smoking is a known risk factor for BE, growing evidence on e-cigarette exposure has raised concerns about potential esophageal injury. Our aim is to evaluate the relationship between e-cigarette use and BE in a large and diverse population. We conducted a cross-sectional analysis using the All of Us Research Program to examine the association between e-cigarette use and BE. Adults aged 18 years or older with an ICD-10 diagnosis of BE (K22.7) were included. E-cigarette exposure was categorized as (1) ever vs. never use, (2) former vs. current vs. never use, and (3) dual use (concurrent e-cigarette and traditional cigarette smoking). Covariates including demographics, BMI, smoking status, alcohol use, GERD, hiatal hernia, diabetes, NSAID use, education, income, employment, and insurance status, were obtained. Multivariable logistic regression estimated adjusted odds ratios (AORs) with 95
Esophageal atresia (EA) is a congenital malformation intrinsically associated with esophageal dysmotility. Its etiology is poorly understood and it is unclear why motility is better preserved in some patients than in others. Esophageal motility is a three-dimensional (3D) process orchestrated by microscale structures, but conventional histology offers two-dimensional insight in the organization of the esophageal wall, hindering the identification of subtle, but potentially relevant, microarchitectural abnormalities that may contribute to understanding of the etiology of EA and variability in motility patterns. We aimed to evaluate the 3D microscale architecture of the esophagus in EA patients and identify potential anomalies using microfocus computed tomography (micro-CT). Full thickness esophageal samples from the proximal and distal pouch of eleven neonates undergoing EA repair and three fetal control esophagus samples (gestational age: 24 weeks) were collected, contrast-enhanced, and imaged with high-resolution micro-CT (2–5 μm voxel size). Muscle layers were segmented using the machine learning software RootPainter and EA samples were compared with the fetal controls. Findings were validated by histology. Micro-CT enabled clear visualization of epithelial, submucosal, vascular, and muscular structures in all samples. 3D reconstructions consistently revealed a previously unreported oblique muscle layer situated medial to the circular muscle layer in all EA specimens. This layer varied in prominence and was not recognizable on 2D histology alone. Fetal control samples displayed only the typical circular and longitudinal layers, with oblique muscle fibres confined to the stomach. Three-dimensional assessment of esophageal microarchitecture using micro-CT allows differentiation between epithelium, musculature and vascularization. Moreover, it facilitated the identification of an oblique muscle layer in proximal pouch and distal trachea-esophageal fistula specimens from EA patients. It remains to be studied whether these findings can explain the observed variation in motility patterns in EA patients.
Recurrence following curative esophagectomy remains a major clinical challenge and is associated with poor prognosis. Treatment strategies for postoperative recurrent esophageal squamous cell carcinoma must be individualized based on recurrence patterns, prior treatment history, and patient-related factors. Locoregional recurrence and oligo-recurrence in some non-regional lymph nodes may still be amenable to curative-intent therapy, including salvage surgery and definitive chemoradiotherapy (CRT). Selection of optimal treatment should consider tumor burden, performance status, and prior radiation exposure. Salvage surgery offers favorable long-term outcomes in carefully selected patients, particularly when recurrence occurs in non-dissected regions. CRT remains a central treatment strategy for unresectable disease, whereas re-irradiation after prior radiotherapy carries a substantial risk of severe toxicity and requires cautious patient selection. Advances in radiotherapy techniques, including intensity-modulated radiotherapy and particle therapy, may improve therapeutic efficacy while reducing toxicity. In parallel, systemic therapies, particularly immune checkpoint inhibitors, have expanded treatment options; however, their role in locoregional recurrence remains to be fully defined. Importantly, prognostic factors should not only be considered descriptive variables but also integrated into clinical decision-making to distinguish candidates for curative versus palliative treatment. Future strategies integrating precision oncology and multimodal approaches are expected to further improve outcomes. Prospective studies are needed to establish optimal treatment algorithms.
Esophageal squamous cell carcinoma (ESCC) remains a significant clinical challenge in Japan. Real-world data on treatment patterns and outcomes, particularly for patients unfit for cisplatin, remain limited. This study evaluated characteristics, treatments, and outcomes of patients newly diagnosed with metastatic ESCC (mESCC) or recurrent ESCC (rESCC). A retrospective cohort analysis was conducted using the Millennial Medical Record database (December 2021–June 2024), including patients with m/rESCC. Patients receiving first-line (1 L) systemic therapy were categorized into cisplatin or non–cisplatin groups. Key outcomes included time-to-treatment discontinuation and overall survival (OS). Among 155 patients, 52.3
Acid suppression with proton pump inhibitors (PPIs) or a potassium-competitive acid blocker (P-CAB) is the first-line treatment for gastroesophageal reflux disease (GERD); however, a significant proportion of patients exhibit symptomatically refractory GERD. Here, we investigated whether distinct serum miRNA profiles exist in individuals with persistent symptoms despite acid suppression, given that serum miRNAs are promising biomarkers for cancer detection and various pathophysiological conditions. We also examined the relationship between anxiety/depression and serum miRNAs associated with symptomatic refractoriness. GERD patients taking PPIs/P-CAB for at least 8 weeks were enrolled and were classified into symptomatically refractory and symptomatically responsive groups using a GerdQ questionnaire. Comprehensive serum miRNA profiling was performed for all participants. Logistic LASSO/Elastic Net regression analysis was used to identify miRNAs associated with symptomatic refractoriness to PPIs/P-CAB, and a discriminant model was developed. Associations of the identified miRNAs with the presence of reflux esophagitis (RE) and items on the Hospital Anxiety and Depression Scale (HADS) were assessed. A combination of four serum miRNAs (miR-4294, miR-4725-3p, miR-3679-5p, and miR-6893-5p) was able to distinguish the symptomatically refractory group from the responsive group (sensitivity, 0.83; specificity, 0.66; AUC, 0.79). This AUC was higher than that for the presence of RE. The serum levels of three of the four miRNAs were associated with items on the HADS-A subscales. Distinct serum miRNA profiles are associated with symptom persistence despite acid suppression, potentially reflecting neuropsychological factors. These findings may provide new insights into the complex pathophysiology of symptomatically refractory GERD.
Endoscopic balloon dilation (EBD) is the standard treatment for benign esophageal stenosis (BES), but restenosis is common. Although EBD with triamcinolone acetonide injection (EBD-TA) reduces restenosis, dense fibrotic stenoses often show limited distensibility. We introduced a modified endoscopic dilation technique, radial incision and balloon dilation (RIBD), which integrates longitudinal incisions with balloon dilation and adjunctive TA injection, and evaluated its initial clinical outcomes in patients with BES. This retrospective single-center study included 66 patients who underwent endoscopic treatment for BES. RIBD was introduced in 2022, and its initial clinical outcomes were assessed with historical comparison with EBD and EBD-TA. The primary outcome was restenosis. Secondary outcomes were the number of dilation sessions, refractory stenosis, and adverse events. RIBD was used as the sole treatment in 15 patients and as secondary treatment in 12. Restenosis after RIBD occurred in 1/15 patients (6.7
Postoperative pulmonary complications (PPCs) after esophageal cancer surgery remain a major concern. Preoperative exercise capacity has emerged as an important predictor. This study examined the clinical use of practical predictors—the 30-s chair stand test (CS-30) and the 6-min walk test (6MWT). We retrospectively analyzed patients with esophageal cancer from three institutions who underwent preoperative physical therapy between July 2021 and June 2023. Data completeness for the CS-30 and 6MWT was compared using McNemar’s test. Three logistic regression models predicting PPCs were developed: Model 1 (established risk factors), Model 2 (risk factors plus CS-30), and Model 3 (risk factors plus 6MWT). PPCs were defined as pneumonia or sputum retention requiring intervention (Clavien–Dindo grade ≥ 2). Model performance was evaluated using the area under the curve (AUC), and incremental predictive value was assessed using net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Among 213 patients (median age 68 years; 83
Esophagectomy is associated with a higher incidence of venous thromboembolism, including pulmonary embolism (PE), than other gastrointestinal cancer surgeries. However, the true incidence of asymptomatic PE remains unclear. This study aimed to determine the incidence and associated factors of PE using routine contrast-enhanced computed tomography (CECT) after minimally invasive esophagectomy (MIE). A total of 134 consecutive patients who underwent MIE between May 2022 and December 2023 under a standardized postoperative CECT protocol were retrospectively analyzed. Routine CECT was performed on or after postoperative day (POD) 5 in all patients. Prophylactic anticoagulation was initiated based on bleeding risk. Study endpoints included PE incidence, identification of factors associated with PE, and the discriminative performance of postoperative coagulation and fibrinolysis biomarkers. PE developed in 13 patients (9.7
Reflux after curative esophagectomy is common and may persist, disrupting eating, sleep, and recovery, yet most prediction tools estimate risk only at a single late time point. We retrospectively analyzed an esophagectomy derivation cohort (2018–2021; n = 488) and a temporal validation cohort (2023–2024; n = 143). Clinically significant reflux was defined as an EORTC QLQ-OES18 item 14 or 15 score ≥ 2. Time to first event within 12 months was modeled using a time-varying coefficient Cox model, and longitudinal symptom severity (1–4) was modeled using an ordinal mixed-effects model. Predictors were prespecified from routine pre-discharge variables. Model performance was assessed using time-dependent AUC and calibration. Cox analysis linked distal/esophagogastric junction tumors and higher BMI to increased early reflux risk, while neoadjuvant therapy, older age, and a longer oral-to-solid diet interval were protective. The ordinal mixed model showed greater symptom severity in women and in patients with distal/esophagogastric junction tumors, but lower severity with neoadjuvant therapy. Interactions suggested slower early symptom escalation with older age and steeper escalation with higher BMI or shorter oral-to-intake intervals. The time-varying Cox model showed good discrimination, with time-dependent AUCs at 1, 3, and 6 months of 0.702, 0.766, and 0.794 in the development cohort, and 0.708, 0.767, and 0.716 in the external validation cohort, with good calibration. A pre-discharge, time-sensitive risk model with a web-based calculator may support risk-stratified early screening, education, and targeted supportive care after discharge to reduce reflux-related morbidity and protect postoperative health-related quality of life.
BACKGROUND:Multimodal esophageal cancer treatment carries substantial perioperative risks. Although centralization has improved outcomes, variability may persist even among high-volume centers. This study aimed to evaluate inter-institutional heterogeneity in perioperative and survival outcomes using data from JCOG1109. METHODS:JCOG1109, a phase III multicenter trial, compared neoadjuvant cisplatin plus 5-fluorouracil (CF); docetaxel, cisplatin, and 5-fluorouracil (DCF); and cisplatin and 5-fluorouracil combined with radiotherapy (CF-RT) for stage IB-III esophageal squamous cell carcinoma. Individual patient data and institutional survey results were analyzed. Mixed-effects models with random intercepts and slopes, incorporating institutions as random effects, were applied to quantify heterogeneity in DCF and CF-RT's treatment effects on postoperative complications, progression-free survival (PFS), and overall survival (OS), separated from baseline institutional risks in the CF arm. RESULTS:From 44 institutions, 580 patients were eligible and 546 underwent surgery. PFS treatment effect variance was smaller than baseline risk variability (CF: 0.062, standard deviation [SD]: 0.069; DCF: 0.044, SD: 0.053; CF-RT: 0.051, SD: 0.057), whereas OS variance exceeded baseline risk (CF: 0.058, SD: 0.068; DCF: 0.080, SD: 0.094; CF-RT: 0.072, SD: 0.079). Complication variance was lower in both experimental arms (CF: 0.342, SD: 0.432; DCF: 0.111, SD: 0.168; CF-RT: 0.190, SD: 0.326), although it was greater in the CF-RT arm than in the DCF arm. CONCLUSIONS:Multimodal treatment was delivered with high consistency across specialized centers, as reflected by minimal heterogeneity in PFS. In contrast, moderate heterogeneity in OS indicated institutional influences, particularly post-recurrence management, which should be considered in trial designs and clinical practice.
Adjuvant therapy after neoadjuvant treatment and R0 esophagectomy for esophageal squamous cell carcinoma (ESCC) remains controversial, and benefit may vary by post-neoadjuvant pathology. We evaluated heterogeneity of adjuvant benefit across prespecified pathologic strata and quantified absolute survival gains. In this two-center retrospective cohort (January 2018–May 2023), patients with ESCC who underwent neoadjuvant therapy followed by R0 resection were classified as pCR (ypT0N0), ypT+N0, or ypT0–4N+. The exposure was early postoperative adjuvant therapy initiated within 8 weeks after surgery. To reduce immortal-time bias, we used an 8-week landmark design with follow-up from the landmark. Confounding was addressed using stabilized inverse probability of treatment weighting (sIPTW) based on preoperative covariates, center, and surgical approach. Outcomes were overall survival (OS) and disease-free survival (DFS) using weighted Cox models with robust standard errors; absolute differences in survival probability (ΔS) were derived from weighted Kaplan–Meier curves. Among 781 patients (pCR 142, ypT+N0 317, ypT0–4N+ 322), survival for pCR and ypT+N0 largely overlapped, whereas ypT0–4N+ had consistently worse outcomes. In the overall cohort, adjuvant therapy was not associated with improved OS (HR 0.99, 95
Risk assessment is essential for planning esophagectomy in patients with esophageal or gastro-esophageal junction (GEJ) cancers. However, previous reports using only preoperative variables (preoperative risk models) have poorly predicted postoperative anastomotic leakage. This study aimed to develop a novel risk model for anastomotic leakage using a combination of preoperative, intraoperative, and postoperative variables (perioperative risk model). Clinical data of 20,113 patients with esophageal or GEJ cancer who underwent esophagectomy followed by reconstruction between 2016 and 2019 were retrieved from the National Clinical Database (NCD), a Japanese web-based nationwide registry. Preoperative and perioperative risk models for anastomotic leakage were developed using only preoperative variable and a combination of preoperative, intraoperative, and postoperative variables within 72 h, respectively. The performance of the perioperative risk model was validated using NCD data of 5,147 esophagectomies registered in 2020. In the overall population, 11,360 (45.0
We previously reported that specific endoscopic soft palate findings, including a whitish epithelium, were associated with esophageal squamous cell carcinoma (ESCC) history. In the present post hoc analysis of the same cohort, we re-evaluated endoscopic images to identify lesions corresponding to leukoplakia and further characterize their endoscopic features and clinical relevance in relation to ESCC. This single-center retrospective study included 284 patients who underwent upper gastrointestinal endoscopy at the Osaka International Cancer Institute between January and May 2020. This analysis was based on the identical dataset used in our previous study. Associations between leukoplakia and an ESCC history were analyzed; moreover, the diagnostic performance was compared with conventional risk factors such as alcohol consumption, smoking, and flushing reactions. Leukoplakia was observed in 15.9
