To evaluate the dissemination and real-world implementation of recommendations from the 5th Edition of the Japanese Esophageal Cancer Practice Guidelines and to inform development of the upcoming 6th Edition, the Guideline Committee of the Japanese Esophageal Society conducted a nationwide Quality Indicator (QI) survey in Japan. A nationwide, cross-sectional, web-based questionnaire survey was distributed to 381 certified institutions participating in the 2023 National Registry of Esophageal Cancer in Japan. Conducted in November 2024, the survey covered six domains-epidemiology, surgery, endoscopy, chemotherapy, radiation therapy, and pathology-reflecting key recommendations of the 5th Edition. Responses were summarized descriptively at the institutional level. Valid responses were obtained from 190 institutions (49.9%). Smoking cessation guidance was implemented in more than 90% of institutions, and over 90% also provided guidance on alcohol abstinence or moderation, although complete alcohol abstinence was less uniformly recommended. Minimally invasive, including robot-assisted, esophagectomy was adopted by over 90% of institutions. The proportion of institutions performing prophylactic cervical lymph node dissection varied by tumor location and stage, reflecting contemporary staging concepts. The DCF regimen was the predominant neoadjuvant therapy for stage II/III disease (94.7%), and immune checkpoint inhibitor-based chemotherapy was widely used for unresectable or recurrent disease. Advanced endoscopic diagnostic modalities, including magnifying and image-enhanced endoscopy, were widely adopted. This nationwide QI survey demonstrates broad adherence to guideline-based multidisciplinary management of esophageal cancer in Japan and provides an evidence base for refining recommendations in the 6th Edition of the Japanese Esophageal Cancer Practice Guidelines.
We investigated the developmental process of thin membranous dense connective tissue (TMDCT) surrounding the esophagus. Horizontal mediastinal sections at 1-mm intervals were prepared from 2 fetal cadavers fixed in 10% formalin at 4 and 8 months of gestation. The sections were stained with hematoxylin and eosin, elastica van Gieson, and Azan. The structures of the dense connective tissues in the cervical and mediastinal regions were compared with those in adult cadavers. In the superior mediastinum, at 4 months of gestation, homogeneous non-dense fibrous collagenous fibers were observed around the trachea, esophagus, and great vessels. At 8 months of gestation, the difference in collagen fiber density became evident around the great vessels and in parts of the peritracheal and periesophageal regions, forming structures homologous to the vascular and visceral sheaths observed in adults. In the middle-to-lower mediastinum, homogeneous collagen fibers at 4 months of gestation became more organized and denser at 8 months of gestation, especially around the descending aorta and azygos vein. A membranous structure extending bilaterally from the esophagus toward the pulmonary hila was also identified. During the mid-to-late fetal development period, regional differentiation of collagen fiber density in the mediastinum becomes apparent, forming the structural basis for the vascular and visceral sheaths in adults. Vascular pulsations and esophageal peristaltic movements are presumed to be the driving forces behind this process.
Particle therapy is gaining interest for treating esophageal cancer due to its ability to target tumors while minimizing radiation exposure to surrounding organs compared to X-ray therapy. While simulations show a favorable distribution with particle therapy, there is ongoing discussion regarding its impact on the prognosis of esophageal cancer. This study sought to assess the effectiveness of particle therapy in treating esophageal cancer by comparing it with previous clinical trials of X-ray therapy in Japan. This was a multicenter, prospective, observational registry study, and particle therapy was performed in accordance with a unified treatment policy. For stage I and II/III cases, cases that met the eligibility criteria for the Japan Clinical Oncology Group 0502 and 0909 clinical trials were extracted, and the clinical results were compared. The three-year overall survival rates were 94.7% and 84.9% for stage I and stage II/III cases, respectively. The three-year progression-free survival rates were 90.4% in stage I patients and 60.3% in stage II/III patients. No statistically significant differences were observed in overall survival or progression-free survival when comparing registry data with the two Japan Clinical Oncology Group studies. No grade 3 or higher cardiopulmonary toxicities were observed in the registry data. This study analyzed nationwide registry data, and particle therapy is a safe treatment regarding toxicity for esophageal cancer, although further investigation into its effectiveness is needed.
In Japan, endoscopic submucosal dissection (ESD) is the standard treatment for superficial esophageal squamous cell carcinoma (ESCC). Although clinical guidelines outline indications, additional treatment, and stricture prevention, real-world practice patterns remain insufficiently characterized. The present nationwide survey aimed to clarify the current endoscopic management of ESCC in Japan. A web-based, 20-item multiple-choice questionnaire was distributed to endoscopists performing upper gastrointestinal endoscopy at least weekly. Invitations were disseminated through the mailing lists of the Japan Esophageal Society and the individual mailing lists of core study members. The survey assessed diagnostic strategies, endoscopic treatment selection, indications for additional therapy after ESD, and approaches to stricture prevention. Altogether, 303 endoscopists who had performed endoscopic treatment for ESCC within the preceding year were enrolled. Most respondents reported using ESD exclusively. For clinical muscularis mucosa (MM) or shallow submucosa (SM1) lesions, treatment selection depended on circumferential extent, with ESD performed on 95.0% of patients with lesions involving < 1/2 of the circumference and ESD, chemoradiotherapy, and surgery conducted at similar frequencies for circumferential lesions. Decisions regarding additional treatment post-ESD for pathological MM or SM1 lesions were strongly influenced by lymphovascular invasion. Stricture prevention strategies varied according to the extent of mucosal defect, with steroid injection preferred for defects involving ≥ 1/2 but < 3/4 of the circumference and combined local steroid injection and oral steroids for circumferential defects. Although most practices align with guideline recommendations, substantial variability persists in areas lacking explicit guidance, highlighting the need for stronger evidence to support standardized clinical decision-making.
Barrett's mucosa in the remnant esophagus (BMRE) is often identified after gastric pull-up reconstruction after esophagectomy. This study aimed to determine the clinical characteristics of BMRE and the factors that affect the development of BMRE. The characteristics of BMRE and factors affecting its occurrence were studied in patients with subtotal esophagectomy and gastric pull-up reconstruction who survived at least 3 years after esophageal cancer surgery and who were evaluated by endoscopy. A total of 187 eligible patients were identified, BMRE was found in 105 (56.1%) patients. The mean time from esophagectomy to confirmation of BMRE was 667.4 days. Ninety-four (89.5%) patients had ultra-short segment BMRE, nine (8.6%) had short segment BMRE, and one (1.0%) had long segment BMRE. Patients with BMRE were significantly younger than those without BMRE (p < 0.001). The incidence of gastro-esophageal reflux disease (GERD) and the frequency of severe GERD (Grade C and D) were significantly higher in the BMRE-positive group than in the BMRE-negative group (both p < 0.001). BMRE was less frequent in patients who were taking potassium-competitive acid blockers than in those who were not (p = 0.047). A logistic regression analysis showed that a younger age (≤ 67 years) (p = 0.002) and GERD (p < 0.001) were independent risk factors for BMRE. BMRE frequently occurs in patients with gastric pull-up reconstruction. The presence of GERD at a young age and more severe GERD increase the incidence of BMRE, and the administration of potassium-competitive acid blockers may decrease BMRE.
In the global phase 3 RATIONALE-306 study (NCT03783442), first-line tislelizumab plus chemotherapy showed significant overall survival (OS) benefit versus chemotherapy alone for unresectable locally advanced/metastatic esophageal squamous cell carcinoma (ESCC). We report post hoc results for the Japanese subgroup. Eligible Japanese patients were randomized (1:1) to tislelizumab 200 mg or placebo every 3 weeks plus chemotherapy (cisplatin plus fluoropyrimidine) and included in the Japanese analysis set. Endpoints included OS, progression-free survival (PFS), objective response rate (ORR), OS in patients with programmed death-ligand 1 (PD-L1) Tumor Area Positivity (TAP) score ≥ 10%, and safety. Overall, 66/649 (10.2%) patients were randomized in Japan (n = 33 per arm). After a minimum follow-up of 37.9 months (data cutoff November 24, 2023), tislelizumab plus chemotherapy showed improvements in median OS versus placebo plus chemotherapy (24.5 vs. 15.1 months; hazard ratio [HR]: 0.75; 95% CI 0.43-1.30). An improvement in OS was also seen in patients with PD-L1 TAP score ≥ 10% (HR: 0.79; 95% CI 0.26-2.36). There was improvement in median PFS (HR: 0.77; 95% CI 0.45-1.32) and a higher ORR (63.6% vs. 45.5%) in the tislelizumab plus chemotherapy versus placebo plus chemotherapy arm, respectively. Treatment-related adverse events (TRAEs) with tislelizumab plus chemotherapy versus placebo plus chemotherapy occurred in, respectively, 45.5% versus 36.4% (any-grade) and 27.3% versus 6.1% (grade ≥ 3) of patients. No TRAE-related deaths occurred. After 3 years, first-line tislelizumab plus chemotherapy demonstrated sustained efficacy and a tolerable safety profile in Japanese patients with unresectable locally advanced/metastatic ESCC, consistent with the global RATIONALE-306 population.
We occasionally experience incomplete resection of esophageal cancer due to the surrounding organ invasion. The efficacy of additional treatment in these cases is unknown. We studied 445 patients with esophageal squamous cell carcinoma who were unable to undergo curative esophagectomy due to cancer invasion to the surrounding organs at 45 esophageal centers in Japan. Survival outcomes were compared based on the additional treatment modalities. Postoperatively, 175 (40.0%) received no additional treatment, while 59 (13.5%), 153 (35.0%), and 50 (11.4%) received additional chemotherapy, chemoradiotherapy, or radiotherapy, respectively. The three-year disease progression and overall survival rates were 90.6% (95% confidence interval 87.2-93.1%) and 15.4% (95% confidence interval 12.2-19.3%), respectively. Multivariable analysis revealed that chemotherapy, chemoradiotherapy, and radiotherapy were all independently associated with reduced disease progression (hazard ratios [95% confidence intervals]: 0.57 [0.40-0.81], 0.52 [0.39-0.69], and 0.48 [0.33-0.72], respectively). Meanwhile, additional treatment with chemotherapeutic agents (chemotherapy and chemoradiotherapy) was independently associated with better overall survival (hazard ratios [95% confidence intervals]: 0.51 [0.35-0.73] and 0.59 [0.44-0.79], respectively); however, radiotherapy alone had a limited impact (hazard ratio [95% confidence interval]: 0.74 [0.50-1.10]). Any additional treatment could suppress disease progression after incomplete resection, but radiotherapy alone has a limited effect. Additional systemic chemotherapeutics may increase patient survival.
After a median study follow-up of 36.6 months, first-line pembrolizumab plus chemotherapy numerically improved overall survival (OS) and progression-free survival (PFS) versus placebo plus chemotherapy in Japanese participants with advanced esophageal cancer in the phase 3 KEYNOTE-590 study. The 5-year follow-up is presented. Participants with previously untreated advanced esophageal cancer were randomly assigned 1:1 to pembrolizumab 200 mg or placebo every 3 weeks up to 35 cycles plus chemotherapy (cisplatin 80 mg/m2 and 5-fluorouracil 800 mg/m2/day). Primary end points were OS and PFS per RECIST v1.1 by investigator; objective response rate (ORR) and safety were secondary. The data cutoff date was July 10, 2023. In total, 141 of 794... participants were enrolled in Japan. Median study follow-up was 60.6 months (range, 53.8-69.7). Median OS was 17.7 months (95% CI, 13.9-28.5) with pembrolizumab plus chemotherapy versus 11.7 months (95% CI, 9.5-19.0) with placebo plus chemotherapy (HR, 0.65; 95% CI, 0.45-0.94); 60-month rates were 24.0% and 8.5%. Median PFS was 6.3 months (95% CI, 6.0-8.2) versus 6.0 months (95% CI, 4.2-6.2) (HR, 0.57; 95% CI, 0.39-0.83); 60-month rates were 16.9% and 0%. ORRs were 56.8% (95% CI, 44.7-68.2) and 38.8% (95% CI, 27.1-51.5). The median DOR was 8.3 months for pembrolizumab plus chemotherapy and 6.1 months for placebo plus chemotherapy. No new treatment-related adverse events occurred since the prior analysis. After a median follow-up of 5 years, pembrolizumab plus chemotherapy continues to provide long-term survival outcomes among Japanese participants with advanced esophageal cancer. No new safety signals were observed. Clinical trial registration ClinicalTrials.gov, NCT03189719.
Potassium-competitive acid blockers (PCABs), a new class of potent and sustained acid-suppressing drugs, have emerged as an alternative to proton pump inhibitors (PPIs) for gastroesophageal reflux disease (GERD) management. However, the specific benefits of PCABs for nocturnal GERD symptoms remain unclear. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of PCAB therapy compared with PPIs or placebo for managing nighttime heartburn and related symptoms in adults with GERD. We systematically searched the MEDLINE, EMBASE, and Cochrane CENTRAL databases from inception to August 8, 2024. We included randomized controlled trials (RCTs) that compared any PCAB (vonoprazan, tegoprazan, or fexuprazan) with either a PPI or placebo in adult GERD patients. The primary outcome was the proportion of patients with complete resolution of nighttime heartburn throughout the treatment period; the secondary outcome was the treatment-emergent adverse events (TEAEs). Meta-analyses were performed using random-effects models with risk ratios (RRs). Sensitivity analyses were used to assess the robustness of the results. Risk of bias was evaluated using the Cochrane RoB 2 tool. Three RCTs were included in the meta-analysis. PCABs significantly increased the likelihood of complete nighttime heartburn resolution compared with PPIs (RR2.29, 95% CI 1.36-3.87; p = 0.002), with no heterogeneity. Safety analysis of the three trials showed no significant difference in TEAE risk (RR0.88, 95% CI 0.53-1.45; p = 0.62). The findings were consistent across all sensitivity analyses. Our study results suggest that PCABs therapy may provide better nighttime heartburn resolution than PPIs.
Recent advances in multimodal treatments indicate that conversion therapy (CT) is a viable option for metastatic esophageal cancer (EC). JCOG1314 was a randomized phase III trial to confirm the survival benefit of docetaxel plus cisplatin plus 5-fluorouracil (DCF) versus cisplatin plus 5-fluorouracil (CF) for metastatic EC. The purpose of this analysis was to evaluate the safety and survival of CT in patients enrolled in JCOG1314. CT was defined as surgery or chemoradiotherapy (CRT) aimed at cure following initial treatment for tumors that were initially unresectable because of distant metastasis. Clinicopathological factors, surgical outcomes, toxicities during CRT, and survival were compared between the CT and non-CT groups. Of 240 patients enrolled in JCOG1314, excluding patients with recurrent disease, 154 with initially unresectable EC because of distant metastasis were selected. Of these patients, 21 received CT, which included conversion surgery (n = 5) and conversion CRT (n = 16). There was no significant difference in the number of metastatic organs or chemotherapy regimen between the CT and non-CT groups. The most common M1 factor in the CT group was the thoracic lymph node. The 3-year overall survival (OS) for the CT and non-CT groups was 52.4 and 14.3%, respectively. Multivariable analysis revealed that CT patients showed significantly better OS compared with the non-CT group (HR 0.36, 95% CI 0.19-0.67, p < 0.01). CT may be safely performed with a favorable prognosis in EC. A prospective study is warranted to determine whether CT improves survival in metastatic EC.
In patients with esophageal cancer, pulmonary complications such as pneumonia and pleural effusion after esophagectomy are a major concern in terms of the short- and long-term prognosis. The relationship between these postoperative complications and preservation of the bronchial artery and the azygos arch in McKeown esophagectomy is unclear. This meta-analysis was performed to compare short-term outcomes between the preservation group (PG) and the dissection group (DG) of each vessel in McKeown esophagectomy. Studies published prior to December 2024 that compared preservation with dissection of the bronchial artery and azygos vein in patients undergoing McKeown esophagectomy were identified through an electronic literature search. A meta-analysis was performed using a Mantel-Haenszel fixed effects model to calculate odds ratios (ORs) with 95% confidence intervals (CIs). Six studies involving 767 patients met the inclusion criteria. For the bronchial arteries, the incidence of postoperative pneumonia was lower in the PG compared to the DG (OR 0.55; 95% CI, 0.33-0.91). Regarding the azygos vein, the duration of chest tube drainage and hospital stay was shorter in the PG compared to the DG (Mean difference: -1.15; 95% CI, -1.81 to -0.49) and (Mean difference: -0.91; 95% CI, -1.81 to -0.02), respectively. Anastomotic leak, recurrent laryngeal nerve palsy, and the number of dissected mediastinal lymph nodes did not differ significantly between the groups. Preservation of the bronchial arteries and azygos vein in McKeown esophagectomy was associated with individual short-term benefits, contributing to decrease the invasiveness of esophageal cancer surgery.
Esophageal cancer (EC) represents a significant disease burden in China, exhibiting unique age distribution patterns. Previous research has primarily focused on overall epidemiological characteristics of EC, lacking systematic comparisons of the disease burden between early-onset esophageal cancer (EOEC) and late-onset esophageal cancer (LOEC). The study aims to understand the trends in incidence and death rates of EOEC and LOEC in China from 1990 to 2021. Data on incidence, mortality, and attributable risk factors for EOEC and LOEC in China were sourced from the 2021 Global Burden of Disease study. Joinpoint regression analysis was used to describe temporal trends over the past 32 years. Bayesian Age-Period-Cohort (BAPC) modeling was employed to forecast both EOEC and LOEC's trends for the next 14 years. From 1990 to 2021, the age-standardized incidence rates (ASIRs) of EOEC and LOEC in China decreased by 55.52% and 65.16%, respectively, while their age-standardized death rates (ASDRs) fell by 37.65% and 44.06%. Compared to 1990, the peak age group for EC incident cases and deaths shifted to 70-74 years in 2021. BAPC projections revealed that the burden of EOEC would continue to increase in the future, and the burden of LOEC would increase in males (ASIR2022-2035 = 5.53%) but decrease in females (ASIR2022-2035 = - 9.93%). The male burden was projected to consistently exceed the female burden. Risk factor analysis showed that in LOEC, deaths attributed to chewing tobacco, high alcohol use, and smoking increased, but ASDR decreased. The burden attributable to a diet low in vegetables decreased for both EOEC and LOEC. Despite the EC burden in China falling between 1990 and 2021, EOEC and male LOEC burdens will keep rising. Special attention should be given to elderly males as a key demographic, with effective primary prevention measures targeting critical behavioral risk factors such as smoking and alcohol consumption.
The standard neoadjuvant therapy for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC) is a combination of docetaxel, cisplatin (CDDP), and 5-fluorouracil in Japan. However, patients with renal or cardiac dysfunction and elderly patients were unfit for CDDP-containing regimens due to toxicity. In this context, 5-fluorouracil and leucovorin, oxaliplatin, docetaxel (FLOT) therapy, which is the standard neoadjuvant therapy for esophagogastric adenocarcinoma in Western countries, offers an alternative that can be administered to the patients who are unfit for CDDP. However, the safety and short-term efficacy of neoadjuvant FLOT therapy in patients with LA-ESCC remain unclear. This retrospective study analyzed patients with resectable LA-ESCC who received neoadjuvant FLOT from February 2021 to December 2023. Four cycles of FLOT were administered every 2 weeks, and then the subjects underwent esophagectomy. Adverse events were evaluated according to the CTCAE version 5.0, and pathological response and survival outcomes were evaluated for efficacy. Forty-six patients were included in this study. Median age was 76 years (range 57-84 years). Clinical stage III and IVB were the most frequent, at 61% and 20%, respectively. During the neoadjuvant therapy, the most common grade 3 or higher adverse events were neutropenia (65%) and leukopenia (50%). Of 36 patients who underwent surgery, pathologic complete response (ypT0N0) was observed in 5 patients (13.9%). The median progression-free survival and overall survival were 15.0 and 25.2 months, respectively. Neoadjuvant FLOT demonstrated manageable safety profiles and promising efficacy in patients with resectable LA-ESCC who were CDDP-unfit.
The presence of multiple Lugol-voiding lesions (LVLs) in the esophagus and pharynx is indicative of an increased risk for metachronous cancer. However, it is unclear whether esophageal LVLs can predict the development of head and neck squamous cell carcinoma (HNSCC). This retrospective observational study focused on patients who underwent transoral surgery for hypopharyngeal squamous cell carcinoma. Endoscopic images were categorized into three groups based on the number of unstained lesions in the pharyngeal mucosa: Group A had no lesions, Group B had 1 to 4 lesions, and Group C had 5 or more lesions per endoscopic view. Similarly, esophageal unstained lesions were classified into three groups based on the number of Lugol-unstained lesions: Group A had no lesions, Group B had 1 to 9 lesions, and Group C had 10 or more lesions. A total of 313 patients were included in the study. Among them, 157 patients (50.2%) had matching grades between pharyngeal and esophageal LVLs. The concordance between esophageal and pharyngeal LVL grades was weak (κ = 0.21, 95% confidence interval [CI]: 0.125-0.295, p < 0.001). The 3-, 5-, and 10-year cumulative incidences of metachronous HNSCC in esophageal LVL grades A, B, and C were 25.9%, 23.2%, and 21.5%; 35.2%, 33.2%, and 33.2%; and 51.4%, 48.6%, and 52.0%, respectively (log-rank test, p = 0.99). In a multivariate Cox regression analysis, esophageal LVL grade was not significantly associated with the development of metachronous HNSCC (hazard ratio: 0.76, 95% CI: 0.51-1.14, p = 0.182). Pharyngeal, rather than esophageal, LVLs serve as a more reliable indicator of metachronous HNSCC risk in patients with primary hypopharyngeal cancer.
Nivolumab plus ipilimumab (Nivo + Ipi) is recommended as the first-line standard treatment for patients with advanced esophageal squamous cell carcinoma (aESCC), taking into consideration the patient's general condition and Programmed cell death ligand 1 (PD-L1) expression. In the CheckMate 648 (CM648) trial, the incidence of treatment-related adverse events (TRAEs) of any grade and grade ≥ 3 were reported to be 80% and 32%, respectively, among patients who received Nivo + Ipi Still, it is occasionally given to patients with frail general conditions or as salvage-line treatment. However, there was little data on safety and efficacy in real-world settings. We retrospectively analyzed the data of patients who received Nivo + Ipi for aESCC between 2022 and 2023 in our hospital. We evaluated immune-related AEs (irAEs), overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Thirty patients were subjected to this study. The patients' characteristics were as follows: median age (range): 63.5 (36-80) years, ECOG PS 0/1 ≤ : 16/14, treatment-line 1st/2nd or later: 6/24. Eight of 30 patients who experienced grade 2 or higher irAE required systemic steroid therapy. Four of 8 patients required additional treatment following the initial steroid therapy, two with increased steroid dose, one with mycophenolate mofetil (MMF), and one with steroid pulse therapy plus MMF. The ORR, median PFS, and median OS were 66.7%, 11.0 months, and 15.4 months in the 1st-line group and 36.8%, 2.6 months, and 10.2 months in the 2nd or later-line group, respectively. Our study showed a safety profile comparable to that of CM648 trial. Nivo + Ipi as 2nd or later-line treatment demonstrated promising efficacy.
The CROC trial assessed a response-guided approach using endoscopic criteria to identify candidates for definitive chemoradiotherapy (dCRT) as an alternative to surgery for resectable thoracic esophageal squamous cell carcinoma (ESCC). Precise evaluation of treatment response following induction chemotherapy is essential for determining curative strategies. This post hoc analysis of the CROC trial investigated the interobserver concordance of endoscopic response evaluation and its clinical implications. Eighty-seven patients with resectable thoracic ESCC underwent three cycles of induction chemotherapy with docetaxel, cisplatin, and 5-fluorouracil. Endoscopic responses were centrally reviewed by three expert oncologists and categorized as remarkable response (RR), limited partial response, or poor response. Patients were classified as having definitive RR, definitive non-RR, or uncertain response based on reviewer agreement. A comprehensive consensus was achieved, with 51.7% (45/87) and 31.0% (27/87) of patients categorized as definitive RR and definitive non-RR, respectively, whereas 17.2% (15/87) were classified as uncertain response. Patients with definitive RR and uncertain response exhibited high complete response (CR) rates to dCRT at 89.7% (35/39) and 90.9% (10/11), respectively, whereas those with definitive non-RR demonstrated a lower CR rate of 25.0% (1/4). 18F-fluorodeoxyglucose positron emission tomography revealed a progressive decrease in maximum standardized uptake value in the RR and uncertain response groups compared with the non-RR group. Among the surgical cases with definitive RR, the positive predictive value for pathological findings was 83.3% (5/6). High interobserver concordance supports standardizing endoscopic evaluation criteria. Furthermore, an uncertain response may indicate the suitability of dCRT because of favorable outcomes.
This study compared the efficacy and complications of biodegradable stents (BDS) versus self-expandable fully covered metal stents (SEMS) in pediatric patients with strictures after esophageal atresia repair. The charts of children with esophageal atresia (EA) undergoing stent treatment for anastomotic stricture were retrospectively reviewed. Primary outcomes included time to reintervention (TTR) and procedural success, defined as no necessity of further intervention with a patent esophageal lumen at the time of follow-up. Secondary outcomes included stent-related complications. From November 2016 to March 2024, a total of 22 BDS and 26 SEMS were placed in 15 patients for strictures. Median TTR was 77 days for BDS vs. 49 days for SEMS. BDS-treated patients had a 64% lower relapse risk (HR: 0.36, CI: 0.19-0.7, p < 0.003). At the end of individual follow-up (median: 6 months), exclusive stenting succeeded in 4 patients, stenting with other minimally invasive procedures in 2, and with surgery in 2. Migration (18.8%) was more less frequent with BDS compared to SEMS (OR: 0.11, CI: 0.00-0.97, p < 0.028), while there was a trend towards more granulation tissue formation with BDS (OR: 3.48, CI: 0.99-24.2, p = 0.052). Although relapse occurs frequently in the long term, stenting may offer an alternative to assure esophageal patency in the medium term with only few and minor associated complications, notably stent migration and granulation tissue potentially causing restenosis. If placed for recalcitrant stricture, longer periods free of interventions are achieved in comparison to iterative dilatation, particularly when using BDS.
In Western countries, the standard perioperative treatment for resectable locally advanced esophagogastric junction adenocarcinoma (EGJ-AC) is 5-fluorouracil, oxaliplatin, and docetaxel (FLOT) therapy based on the results of the FLOT4 and ESOPEC trials. On the other hand, there was little evidence based on optimal perioperative treatment for resectable locally advanced EGJ-AC in Japan. Our previous report showed that neoadjuvant docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy demonstrated modest efficacy for resectable locally advanced EGJ-AC. Therefore, we compared neoadjuvant DCF to FLOT therapy in terms of efficacy and safety in this study. We retrospectively analyzed the data of patients who received DCF or FLOT therapy for resectable EGJ-AC between 2015 and 2024 in our hospital. We assessed the R0 resection rate, histopathological response, disease-free survival (DFS), overall survival, and adverse events. Thirty-two patients in the DCF therapy group and 20 patients in the FLOT therapy group were analyzed. The patients' characteristics in the DCF group and FLOT group were as follows: median age, 63/59 years; ECOG PS 0, 66%/85%, respectively. The pCR rate was numerically higher in the FLOT group (20%) compared with the DCF group (3%) (p = 0.07). Similarly, the 1-year DFS rate was higher in the FLOT group (93%) than in the DCF group (68%) (p = 0.02), although this difference did not remain statistically significant after adjustment for baseline factors. Febrile neutropenia was significantly lower in the FLOT group (0%) than in the DCF group (12.5%). Neoadjuvant FLOT therapy is well-tolerated and has comparable short-term efficacy to DCF therapy.
Myxoid stroma in the tumor stroma has been suggested to play a key role in cancer progression; however, its underlying mechanisms remain unclear. This study aimed to examine the relationship between myxoid stroma, identified in hematoxylin and eosin (HE)-stained tissue, and tumor-infiltrating lymphocytes (TILs), assessed through immunohistochemical staining. Automated image analysis was employed to evaluate these features, and their clinical significance in esophageal squamous cell carcinoma (ESCC) was investigated. A total of 139 ESCC patients who underwent esophagectomy were included. From each patient, three serial sections from paraffin blocks were prepared and stained with CD3, HE, and CD8, respectively. An algorithm for identifying myxoid stroma was applied to HE slides, and the resulting data were mapped onto the corresponding CD3 and CD8 slides to analyze the spatial relationship between these pathological findings. The myxoid-high group, comprising 76 cases, had significantly deeper tumor depth compared to the myxoid-low group, which included 63 cases (p < 0.05). CD3+ cell density was significantly lower in the myxoid-high group compared to the myxoid-low group (p < 0.01). Within the myxoid stroma regions, CD3+ cell density was significantly lower than in regions outside the stroma (p < 0.01). The mean distance of all CD3+ cells from the edges of the myxoid stroma was significantly greater than that from the tumor margin (p < 0.01). Similar results were observed for CD8+ cells. In conclusion, this study demonstrated that myxoid stroma in the invasive front of ESCC is closely associated with the density of CD3+ and CD8+ positive lymphocytes.
The robotic single-port surgical system (SPS) presents several potential advantages over conventional multiport (MP) robotic systems; however, its feasibility in esophageal cancer surgery remains unclear. This study compared the outcomes of transthoracic robotic SPS esophagectomy via an intercostal approach with conventional robotic-assisted minimally invasive esophagectomy (RAMIE). Between December 2024 and November 2025, 104 cases of MP RAMIE and 21 cases of transthoracic robotic esophagectomy via an intercostal approach using the SPS for esophageal cancer were compared. Baseline demographics were comparable between groups. Although clinical stage distribution did not differ significantly, patients in the SPS group more frequently had earlier-stage disease. Neoadjuvant therapy was more commonly administered in the MP group. Operative outcomes were comparable between the two approaches. Total operation time and robotic console time did not differ significantly. Estimated blood loss was significantly lower in the SPS group. The number of dissected lymph nodes (LNs), including bilateral recurrent laryngeal nerve LN, and R0 resection rates were similar. Postoperative hospital stay and peak pain scores during admission were also comparable. Major postoperative complications (Clavien-Dindo grade ≥ III) occurred in 34.4% of patients, with no significant difference between groups. Postoperative vocal cord palsy occurred less frequently in the SPS group. One postoperative death occurred in the SPS group due to acute myocardial infarction, which was considered unrelated to the surgical procedure. Transthoracic robotic SPS esophagectomy via the intercostal approach was feasible and safe, and enabled sufficient upper mediastinal lymph node dissection compared to MP RAMIE.