BackgroundCircular stapler (CS) anastomosis is widely used in McKeown esophagectomy; however, anastomotic stenosis remains a significant concern. This study aimed to compare stenosis rates between newly introduced 23- and 25-mm powered CSs in cervical esophagogastric anastomosis.MethodsFrom May 2022 to February 2024, 126 patients who underwent thoracoscopic McKeown esophagectomy with retrosternal gastric conduit reconstruction were retrospectively analyzed. They were categorized into the 23-mm (n = 52) and 25-mm (n = 74) CS groups. The primary endpoint was the comparison of anastomotic stricture rates. Propensity score matching was performed to adjust for potential confounders.ResultsAfter propensity score matching, 39 pairs were selected. The incidence of anastomotic stricture was 18.0% (7 cases) and 12.8% (5 cases) in the 23- and 25-mm CS groups, respectively (p = not significant [NS]). The incidence of anastomotic leakage and the leakage location revealed no significant differences between the two groups. A two one-sided test for equivalence was performed to compare the risk difference in stricture rates between the groups, resulting in a risk difference of 5.1% with a 90% confidence interval of − 0.087 to 0.191 and a p value of 0.041, suggesting potential equivalence.ConclusionIn this study, 23- and 25-mm powered CSs achieved comparable anastomotic stricture rates in cervical esophagogastric anastomosis during McKeown esophagectomy. The newly introduced 23-mm powered CS can be a useful option, considering its easier anvil insertion into the residual esophagus when insertion of the 25-mm CS anvil is technically challenging.

Anti-PD-1 therapy plus chemotherapy (immunochemotherapy) has become standard first-line treatment for high PD-L1-expressing advanced esophageal squamous cell carcinoma (ESCC). Benefits of immunochemotherapy for low PD-L1-expressing ESCC remain debatable. The Cochrane, PubMed, and Embase databases were systemically searched from inception till 10 August 2024. Randomized trials comparing first-line immunochemotherapy with chemotherapy in ESCC were identified and evaluated association of platinum plus paclitaxel (TP) or fluoropyrimidine (PF) chemotherapy regimen, stratified by PD-L1 expression levels, with progression-free survival (PFS) and overall survival (OS) benefits. Pooled study-level hazard ratios (HRs) with 95% confidence intervals (CIs) for PFS and OS were calculated with a random-effects model. Eight studies involving 4733 participants were included. In high PD-L1 group, PFS (HR of TP: 0.56 [95% CI, 0.45–0.69] vs HR of PF: 0.53 [95% CI, 0.45–0.62]) and OS benefits (HR of TP: 0.60 [95% CI, 0.46–0.78] vs HR of PF: 0.59 [95% CI, 0.50–0.69]) did not significantly differ between two regimen subgroups (P = 0.75 and 0.90, respectively). In low PD-L1 group, TP regimen was associated with a significantly greater PFS benefit than PF regimen (HR of TP: 0.59 [95% CI, 0.48–0.74] vs HR of PF: 0.82 [95% CI, 0.72–0.94]; P = 0.01) and TP regimen trended to associate with greater OS benefit over PF regimen (HR of TP: 0.72 [95% CI, 0.55–0.93] vs HR of PF: 0.84 [95% CI, 0.72–0.97]; P = 0.32). In patients with low PD-L1-expressing advanced ESCC, immunochemotherapy with TP may confer a greater PFS benefit than that with PF.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10388-025-01167-y.

BackgroundsIn 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.MethodsWe 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.ResultsThirty-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%).ConclusionsNeoadjuvant FLOT therapy is well-tolerated and has comparable short-term efficacy to DCF therapy.

BackgroundsNivolumab 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.MethodsWe 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).ResultsThirty 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.ConclusionsOur study showed a safety profile comparable to that of CM648 trial. Nivo + Ipi as 2nd or later-line treatment demonstrated promising efficacy.

BackgroundsThe 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.Materials and methodsThis 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.ResultsForty-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.ConclusionsNeoadjuvant FLOT demonstrated manageable safety profiles and promising efficacy in patients with resectable LA-ESCC who were CDDP-unfit.

BackgroundPatients with esophageal cancer (EC) usually have multiple comorbidities, particularly, high cachexia incidence, which may lead to increased postoperative complications. A novel inflammatory marker, growth differentiation factor 15 (GDF15), was recently reported to be associated with cancer cachexia. This study evaluated the correlation between clinical data suggestive of cachexia in patients with EC and circulating GDF15 levels.MethodsEighty patients with EC were enrolled in this study. Plasma samples were collected before initiating any cancer treatment. GDF15 was quantified using ELISA. Clinical information, including age, comorbidities, biochemical data, Controlling Nutritional Status score, and Psoas muscle index (PMI), was collected from the clinical records. Clinical impact of GDF15 was then evaluated and compared with cachectic indicators or postoperative results.ResultsThe median value of GDF15 was 1168 pg/mL (range 298–9100 pg/mL). GDF15 values statistically correlated with age, prevalence of diabetes, serum level of aspartate aminotransferase/γ-glutamyltransferase/creatinine/blood sugar/albumin, and PMI. Sixty-three patients finally underwent curative esophagectomy with right thoracic approach and gastric tube reconstruction. Patients with infectious complications had a statistically higher GDF15 than those without. The cut-off value was 930 pg/mL for detecting infectious complications, with an area under the receiver operating characteristic curve value of 0.685, and high GDF15 was detected as an independent risk factor for postoperative infectious complications.ConclusionsGDF15 is potentially suggestive of general condition deterioration from aging, organ dysfunction, and decreased muscle mass, which may lead to cachexia in patients with EC. Moreover, patients with higher GDF15 are at a risk of postoperative infectious complications.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10388-025-01157-0.

BackgroundWe aimed to identify an acceptable waiting period between the diagnosis of superficial esophageal squamous cell carcinoma (SESCC) and endoscopic submucosal dissection (ESD).MethodsThis retrospective, single-center study included 423 patients with 514 SESCC lesions. All patients underwent image-enhanced magnifying endoscopy at initial evaluation and on the day of ESD. Following three outcomes were assessed: the diagnostic accuracy of tumor invasion depth on the day of ESD using the Japanese Esophageal Society classification; changes in diagnosis between initial and final evaluations across different waiting intervals; and 5-year survival rates based on intrapapillary capillary loop patterns (B1 vs. B2) and waiting duration.ResultsThe diagnostic accuracy was 96.6% for B1 vessels (EP/LPM), 59.6% for B2 vessels (MM/SM1), and 84.6% for B3 vessels (SM2 or deeper). Among B1 lesions, 100% remained B1 on the day of ESD across all time groups. For B2 lesions, stability was observed in 100% of cases within one month, 98.2% in one to two months, 92.9% in two to three months, and 100% after three months. Five-year survival rates showed no significant differences among waiting period groups in both B1 and B2 categories.ConclusionsA waiting period of 3 months is acceptable for patients with SESCC classified as B1 vessels, provided the diagnostic accuracy is maintained. Thorough endoscopic evaluation supports safe scheduling flexibility without adversely affecting long-term outcomes.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10388-025-01156-1.

BackgroundThe cluster of differentiation 47 (CD47)-signal regulatory protein alpha (SIRPα) axis is a key regulator of innate immune surveillance, facilitating the neoplastic evasion of macrophage-mediated phagocytosis. Although this pathway has been implicated in tumor immune escape in multiple malignancies, its clinical and prognostic significance in esophageal squamous cell carcinoma (ESCC) remain to be fully elucidated.MethodsWe retrospectively analyzed 100 patients who underwent esophagectomy for resectable ESCC. Immunohistochemical testing determined SIRPα expression in peritumoral immune infiltrates and CD47 expression in tumor and immune cells, while tumor proportion score (TPS) and combined positive score (CPS) were used to evaluate CD47 staining. Survival outcomes and correlations with clinicopathological factors were also analyzed.ResultsIncreased expression of SIRPα, CD47 CPS, and CD47 TPS was detected in 47, 50, and 47% of patients, respectively. Elevated SIRPα expression was significantly associated with decreased overall survival. Also increased CD47 CPS and TPS was significantly associated with decreased overall survival and relapse-free survival. CD47 CPS was identified as an independent prognostic indicator for overall survival in multivariate Cox regression analysis (hazard ratio [HR] = 3.89; 95% confidence interval [CI] = 1.57–9.61; P = 0.003). Patients with concurrent high expression of both SIRPα and CD47 CPS demonstrated the poorest survival outcomes.ConclusionOverexpression of SIRPα and CD47, especially in tandem, is associated with poor clinical outcomes in ESCC, suggesting that the CD47-SIRPα axis may serve as a useful prognostic biomarker and a potential therapeutic target for newly immune checkpoint blockade in ESCC.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10388-025-01152-5.

Delayed gastric conduit emptying (DGCE) is a significant and prevalent complication following esophagectomy, adversely affecting recovery and quality of life. The true burden of DGCE remains uncertain due to considerable variability in reported incidence rates. This study aimed to determine the incidence of DGCE following esophagectomy and how this is impacted with varying diagnostic criteria. A systematic review was conducted across major databases, including PubMed, MEDLINE, Embase, Web of Science, and Cochrane, to identify studies reporting the incidence of DGCE following esophagectomy. The incidence rates were pooled and analyzed using a random-effects model, with subgroup analyses for potential sources of heterogeneity such as pyloric interventions, conduit dimensions, and anastomotic height. Among 5176 screened records, 125 studies met the eligibility criteria. The pooled incidence of early DGCE was 15.9% (95% CI 11–21%), and late DGCE was 9.4% (95% CI 7.1–11.9%). Significant heterogeneity was observed across studies, driven by variations in diagnostic methods. Subgroup analysis indicated that prophylactic pyloric drainage was not associated with a statistically significant effect on early DGCE (OR 0.76; p = 0.38) or late DGCE (OR 0.71; p = 0.44). DGCE represents a significant burden for esophageal cancer survivors, with considerable variability in its reported incidence, underscoring the urgent need for a standardized diagnostic criterion. The adoption of the recently published international consensus definition is crucial for reducing the heterogeneity, as well as improving the identification and management of DGCE.

BackgroundPreoperative treatment has become widely recognized for improving survival in patients with esophageal cancer. The present study aimed to compare the prognosis between patients with pathological node-negative status treated with surgery alone (SA-pN0) and those who were clinically node-positive but converted to ypN0 following neoadjuvant chemotherapy (NAC-ypN0) in cases of advanced thoracic esophageal squamous cell carcinoma (ESCC).MethodsThis retrospective analysis used a multicenter database of 4849 consecutive patients who underwent treatment for esophageal cancer. Patients with clinical T2 or more advanced ESCC who underwent standard subtotal esophagectomy between 1990 and 2017 were included. The NAC-ypN0 group was compared with the SA-pN0 group in terms of patient characteristics, recurrence patterns, and survival outcomes using propensity score-matched analysis.ResultsIn total, 109 patients were classified as NAC-ypN0 and 137 as SA-pN0. Propensity score matching resulted in the selection of 87 patients per group. Compared with the SA-pN0 group, the NAC-ypN0 group had a significantly more advanced clinical TNM stage and underwent significantly more three-field lymphadenectomies. Pathological findings showed downstaging of the pT stage in the NAC-ypN0 group, resulting in an equivalent distribution between the two groups. Additionally, the NAC-ypN0 group had significantly lower rates of lymphatic invasion (33% vs. 56%) and venous invasion (21% vs. 52%). Recurrence rates (21% vs. 22%) and survival outcomes (5-year overall survival: 83.9% vs. 76.1%, P = 0.110) were comparable between the two groups.ConclusionsThe NAC-ypN0 group demonstrated reduced lymphovascular invasion and showed a prognosis comparable to that of the SA-pN0 group.