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.
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.
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.
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.
Patients with a history of esophageal squamous cell carcinoma or pharyngeal cancer are at high risk of laryngopharyngeal cancers, particularly in the hypopharynx. However, adequate hypopharyngeal visualization during esophagogastroduodenoscopy is challenging because of anatomical constraints. We evaluated the utility of the Modified Killian method for hypopharyngeal visualization during esophagogastroduodenoscopy in high-risk patients. The Modified Killian method had previously been used at our institution for high-risk patients with esophageal and head and neck cancers. In this retrospective comparative study, data were collected from 45 high-risk patients who underwent pharyngeal examination using the Modified Killian method after the conventional method during a single esophagogastroduodenoscopy session. The primary endpoint was the hypopharyngeal visibility score (scale 1-5). Secondary endpoints included visibility of other pharyngeal areas, procedure time, lesion detection, and adverse events. The Modified Killian method without the Valsalva maneuver yielded higher hypopharyngeal visibility scores than the conventional method (median [interquartile range, IQR]: 2.0 [2.0-4.0] vs. 1.0 [1.0-2.0]; p < 0.001). The Modified Killian method further improved visibility (median [IQR]: 4.0 [3.0-5.0]; p < 0.001 vs. conventional). No significant differences were observed in visibility of the oropharynx or vallecula. The procedure time was longer for the Modified Killian method (237 vs. 134 s; p < 0.001). Three intraepithelial hypopharyngeal carcinomas missed by the conventional method were detected with the Modified Killian method. No adverse events occurred. The Modified Killian method, particularly its positional component alone, improves hypopharynx visualization and may contribute to early cancer detection without compromising observation of other pharyngeal areas.
Although a strong volume-outcome association for esophagectomy has been reported in Japan, no national policy for regionalization currently exists. This study simulated the impact of regionalization on operative mortality, patient travel distance, and geographic disparities using a nationwide clinical database. Patients who underwent esophagectomy with reconstruction for malignant tumors were identified from the Japanese National Clinical Database. Four simulation scenarios were established by setting minimum volume standards (MVSs) at 2, 5, 10, and 15 cases annually. Operative mortality in each simulation scenario was estimated using a model that incorporated both the post-regionalization hospital case volume and the characteristics of reassigned patients. Changes in travel distance were also evaluated across the metropolitan, provincial, and rural regions. Among 27,476 patients treated across 1,041 hospitals, 76% of hospitals performed < 5 cases annually. The operative mortality decreased with increasing hospital volume (< 2 cases/year: 4.8%, ≥ 15 cases/year: 1.6%). Based on the simulations, applying MVSs of 2, 5, 10, and 15 reduced the mortality rates to 2.7%, 2.1%, 1.8%, and 1.7%, respectively-corresponding to 8-29 fewer deaths annually. However, 7%-38% of patients would need to travel to the nearest eligible hospital. In metropolitan areas, an MVS of 15 would increase the median travel distance by 2.6 km only. In rural areas, the distance would increase by 24 km at an MVS of 2 and by 43 km at an MVS of 15. Regionalization of esophagectomy in Japan could significantly reduce operative mortality. However, it would increase travel burdens among patients in rural areas. Therefore, balancing outcome improvement and accessibility will be essential for policy implementation.
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.
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.
Photodynamic therapy (PDT) is a salvage endoscopic treatment option for local failure after chemoradiotherapy for esophageal squamous cell carcinoma (ESCC). PDT is usually performed using ordinary-sized conventional endoscopes (CEs); however, some patients with local failure have esophageal stenosis caused by chemoradiotherapy or endoscopic resection. In such cases, an ultra-thin endoscope (UTE) is sometimes used, but the efficacy and safety of PDT performed with UTEs (UTE-PDT) remain unclear. In this study, we compared the treatment outcomes of UTE-PDT with those of PDT using CEs (CE-PDT). This retrospective study analyzed patients who underwent talaporfin sodium-based PDT for histologically confirmed local ESCC failure between October 2015 and June 2022. Short-term outcomes, including the local complete response (L-CR) rate and adverse events, were compared between UTE-PDT and CE-PDT. In total, eight patients underwent UTE-PDT and 81 underwent CE-PDT. L-CR rates were 50.0% and 59.3% for the UTE-PDT and CE-PDT groups, respectively. The L-CR rates for lesions ≤ 20 mm were 50.0% (4/8) and 63.4% (45/71) in the UTE-PDT and CE-PDT groups, and for cT1 lesions, they were 57.1% (4/7) and 63.2% (43/68), respectively. Adverse events included esophageal pain (12.5% and 39.5%) and esophageal stenosis (12.5% and 4.9%) in the UTE-PDT and CE-PDT groups, respectively; however, all were grade ≤ 2. UTE-PDT for local failure after chemoradiotherapy for ESCC showed short-term outcomes that did not differ substantially from those of CE-PDT and may represent a potential therapeutic option for patients with no alternative treatment options.
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.
Boerhaave's syndrome, a spontaneous transmural rupture of the esophagus, is associated with high mortality and requires left thoracotomy. Minimally invasive surgery (MIS) is an alternative. Although most reports on thoracoscopic repair describe the procedure being performed in the lateral decubitus position, there are few reports of repairs conducted in the prone position. We hereby describe a left-sided thoracoscopic technique for primary esophageal repair, in the prone position. Patients are positioned prone and procedure is conducted under general anesthesia with carbon dioxide pneumothorax, avoiding one-lung ventilation. The esophageal muscular layer is incised for complete visualization of the mucosal defect after exposing the lower esophagus. The rupture is closed with layer-to-layer sutures. The procedure is performed with adequate mediastinal and pleural drainage. The technique was performed on two patients with surgical times of 143 and 208 min, and both patients had uneventful recovery. In the prone position, this procedure offers excellent exposure of the lower mediastinum and might reduce pulmonary burden. This approach appears safe in selected stable patients.
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% and 3.1% of the patients in the ESCC and non-ESCC groups (P < 0.01), respectively. The interobserver agreement for leukoplakia was substantial (κ = 0.71, 95% confidence interval: 0.56-0.86). Leukoplakia demonstrated a high specificity (96.9%) and a positive likelihood ratio of 5.21 for ESCC history, which were higher than for alcohol consumption and smoking. Leukoplakia was more easily evaluated using narrow band imaging/blue light imaging compared with white light imaging (P = 0.02). In this post hoc analysis, soft palate leukoplakia was found to be an endoscopic finding associated with ESCC history, supporting the concept of field cancerization of the upper aerodigestive tract. Careful inspection of the soft palate during routine endoscopy may provide additional information for ESCC risk assessment, although prospective validation is warranted.
The impact of histological subtypes on distant organ metastasis remains insufficiently elucidated in patients with esophageal cancer. This study aims to discuss the risk of distant organ metastasis and its effect on survival in esophageal cancer patients. Patients with esophageal cancer, including adenocarcinoma (AC), squamous cell carcinoma (SCC), adenosquamous carcinoma (ASC), neuroendocrine carcinoma (NECS), and signet-ring cell carcinoma (SRCC), were selected from the SEER database. Logistic regression was employed to assess the risk of esophageal cancer metastasis to various organs, while Cox proportional hazards regression, Kaplan-Meier curves and the Log-rank test was used for survival analysis. Compared to AC, patients with SCC exhibit a lower risk of developing bone, brain, and liver metastases, SRCC have a reduced risk of brain, liver, and lung metastases, and NECS are more likely to develop liver metastasis. Among patients with bone and lung metastases, those with SRCC or SCC experience poorer survival. SRCC is associated with worse prognosis in cases of brain metastasis, while SCC predicts inferior outcomes in liver metastasis. Among patients with AC or SCC, those with lung metastasis demonstrate better survival compared to those with bone or liver metastases. In patients with esophageal cancer, organ-specific metastasis and post-metastatic survival are histology-dependent. Among the two most common histological types, AC and SCC, SCC shows a lower risk of distant metastasis. However, once metastasis occurs, patients with SCC have poorer survival compared to those with AC.
Conventional classifications of T1 adenocarcinoma at the esophagogastric junction (T1-AEGJ) rely on lymph node metastasis patterns and define AEGJ according to the distance between the tumor epicenter and esophagogastric junction (EGJ). However, their significance in T1-AEGJs remains unclear due to the low frequency of lymph node metastasis. Thus, classifications based solely on tumor epicenter may encompass tumors with distinct biological behaviors, particularly those in the stomach. Therefore, we aimed to elucidate the characteristics of T1-AEGJs localized in the stomach. We retrospectively analyzed 266 patients with pT1-AEGJs who underwent endoscopic or surgical resection between 2010 and 2023. Tumors were classified into Groups E (confined to the esophagus or crossing the EGJ) and G (localized in the stomach). Clinicopathological features were compared between the groups, and risk factors for deep submucosal invasion (SM > 500 μm) were evaluated using multivariate analysis. Patients in Group G were older and had a higher prevalence of Helicobacter pylori infection (64.9% vs. 30.8%) and intestinal metaplasia (71.6% vs. 43.1%). Conversely, patients in Group E had more incidences of hiatal hernia (42.5% vs. 20.3%), gastroesophageal reflux disease (43.4% vs. 22.4%), Barrett's esophagus (47.6% vs. 9.0%), and deep submucosal invasion (45.4% vs. 27.8%). Tumor size ≥ 20 mm, EGJ extension, depressed or protruded morphology, and undifferentiated biopsy histology were identified as independent risk factors for deep invasion. T1-AEGJ tumors in the stomach demonstrate distinct clinicopathological features. Therefore, a classification based on EGJ extension, and not just epicenter, may improve their risk assessment and treatment decisions.
Neoadjuvant chemoradiotherapy (NCRT) followed by surgery is a standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC). However, the survival outcomes remain suboptimal. Immune checkpoint inhibitors have shown promising efficacy in advanced ESCC, suggesting their potential to improve treatment outcomes when combined with NCRT and surgery. A single-arm prospective multicenter phase II trial was conducted in clinical stage II or III ESCC. Patients received 5-week cycles of neoadjuvant treatment of weekly intravenous paclitaxel, 45 mg/m2 and carboplatin at area under curve 2 mg/mL/min; 2 doses of pembrolizumab 200 mg every 3 weeks; radiation of 44.1 G. After the completion of neoadjuvant treatment, patients underwent surgery, followed by 2 years of adjuvant pembrolizumab 200 mg, every 3 weeks. Primary endpoint was the pathologic complete response (pCR) rate. Secondary endpoints included tumor regression score, event-free survival (EFS), overall survival (OS), disease-free survival (DFS), and safety. Comprehensive biomarker analysis, including PD-L1 expression, whole-exome sequencing (WES), RNA sequencing, and tumor mutation burden (TMB), was performed to identify potential predictive markers for treatment response. Among 28 enrolled patients, 27 completed NCRT and 26 underwent surgery. The pCR rate was 23.1% (6 of 26; 95% CI, 10.7-42.4%). Median EFS was 11.0 months (95% CI, 0.9-27.6 months), OS was 33.6 months (95% CI, 23.8-36.0 months), and DFS was 17.9 months (95% CI, 0-46.2 months). Grade 3-4 adverse events occurred in 25% of patients during neoadjuvant therapy. There were no treatment-related deaths. Biomarker analyses revealed that higher tumor mutation burden and specific gene expression profiles were associated with better treatment outcomes. Adding pembrolizumab to NCRT followed by surgery and adjuvant pembrolizumab in patients with locally advanced ESCC was safe and feasible. Although the pCR rate did not meet the prespecified threshold, the treatment regimen was safe and feasible, but its efficacy was lower than expected. Comprehensive biomarker analyses identified potential predictors of treatment response. Further investigation in larger trials is warranted. NCT02844075.
Numerous studies have investigated prognostic factors for esophageal cancer after curative surgery; however, little is known about the risk factors for non-esophageal cancer-related death. This study identifies predictors of non-esophageal cancer mortality following esophagectomy. We retrospectively analyzed 398 patients who underwent thoracic subtotal esophagectomy for thoracic esophageal or esophagogastric junction cancer from 2009 to 2022. Patients with non-curative resection, special histology, or in-hospital death were excluded. Cause-specific Cox regression was used to assess predictors of non-esophageal cancer-related death. The cumulative incidence function (CIF) was estimated while taking competing risks into account, and Gray's test was applied for group comparisons. During follow-up, 181 patients died: 118 from esophageal cancer, and 63 from other causes. Non-esophageal cancer-related deaths were due to respiratory diseases (n = 23), second cancers (n = 15), and other causes (n = 25). Patients who died of non-esophageal cancer-related causes had lower Geriatric Nutritional Risk Index (GNRI) and body mass index, were older, and more frequently had hypertension compared with the other groups. CIF analysis revealed that non-esophageal cancer-related deaths increased gradually over 10 years and beyond, while respiratory-related deaths tended to occur within the first 10 years. Multivariable analysis revealed that age, percent vital capacity (%VC), and GNRI were independent predictors. Lower GNRI and %VC were independent predictors of non-esophageal cancer-related death among patients undergoing curative esophagectomy for esophageal cancer. Assessment of preoperative nutritional and pulmonary status may help identify vulnerable patients and guide postoperative management and supportive care.