This prospective, two-cohort phase 2 trial with random allocation was conducted to evaluate the safety and efficacy of neoadjuvant tislelizumab combined with nab-paclitaxel/paclitaxel and cisplatin (TP) in patients with esophageal squamous cell carcinoma (ESCC). Patients were enrolled and randomly assigned to the nab-paclitaxel or paclitaxel cohorts at a 1:1 ratio, and received intravenous tislelizumab (200 mg, day 1) combined with cisplatin (25 mg/m2, days 1-3) and either nab-paclitaxel (125 mg/m2, days 1 and 8) or paclitaxel (150 mg/m2, day 1) in a 21-day cycle for two cycles before surgery. The primary endpoint was the major pathological response (MPR) rate. From March 01, 2022 to April 10, 2023, 46 patients were enrolled (n = 23 in each cohort), with 42 patients receiving the full two-cycle treatments and undergoing surgery (n = 22 in the nab-paclitaxel cohort, n = 20 in the paclitaxel cohort). The MPR rate and the pCR rate in the total cohort were 44.2% (19/42) and 19.0% (8/42), respectively, with 59.1% (13/22) and 31.8% (7/22) in the nab-paclitaxel cohort and 30.0% (6/20) and 5.0% (1/20) in paclitaxel cohorts. The most common treatment-related adverse events (TRAEs) were anemia (89.1%) and alopecia (71.7%), and no significant difference in TRAEs was observed between the two cohorts. Up until March 28, 2024, the median follow-up time was 15.5 months (range of 6.0-24.3 months), and the survival analysis revealed that the patients in the nab-paclitaxel cohort had a higher event-free survival (p = .002). In conclusion, neoadjuvant tislelizumab combined with cisplatin and nab-paclitaxel, rather than cisplatin and paclitaxel, is a more effective neoadjuvant strategy for locally advanced thoracic ESCC.

The 5‑year survival rate of patients with esophageal squamous cell carcinoma (ESCC) is <20%, highlighting the need for the development of novel therapeutic targets. Neuregulin‑1 (NRG1), a transmembrane protein involved in cell proliferation and survival signaling, has unclear biological functions and clinical value in ESCC. The present study investigated the association between NRG1 expression and ESCC by analyzing data from both patients with ESCC and The Cancer Genome Atlas database. Reverse transcription‑quantitative PCR and immunohistochemistry staining were used to determine the levels of gene and protein in the tissue. The findings revealed that NRG1 gene and protein levels were significantly higher in tumor tissues compared with the normal tissues. Elevated expression of NRG1 was associated with poor outcomes, particularly in patients with advanced ESCC. Silencing NRG1 decreased both its mRNA and protein levels, disrupting key signaling pathways, such as phosphorylated (p‑)AKT and cellular rapidly accelerated fibrosarcoma (p‑cRAF), which led to decreased cancer cell proliferation, migration and tumor sphere formation, along with increased cell death. High expression levels of NRG1 and cRAF were significantly associated with poor prognosis. Additionally, silencing NRG1 promoted autophagosome and autolysosome formation, decreasing LC3B levels. The use of the autophagy inhibitor chloroquine significantly enhanced cell death induced by NRG1 silencing, suggesting that autophagy functions as a survival mechanism in ESCC cells in which NRG1 is silenced. Furthermore, high co‑expression of NRG1 and LC3B was associated with a worse prognosis. On the whole, the present study demonstrated that targeting NRG1 with autophagy inhibitors may serve as a potential therapeutic strategy for ESCC.

Long non-coding RNA HOXC cluster antisense RNA 1 (HOXC-AS1) exhibits elevated expression in gastric and prostate cancers, yet its involvement in esophageal cancer (EC) remains unexplored. This investigation assessed the expression patterns and functional implications of HOXC-AS1 in EC. Quantitative real-time PCR was employed to evaluate HOXC-AS1 expression in EC cell lines, while its impact on cell proliferation, migration, invasion, tumor growth, and metastasis was examined through MTT, EdU, transwell, wound healing assays, and animal models. Mechanistic insights into HOXC-AS1 were pursued using dual-luciferase reporter assays and RNA immunoprecipitation. Analysis of TCGA data demonstrated significant upregulation of HOXC-AS1 in EC tissues, consistent with its enriched expression in EC cell lines. Knockdown experiments revealed that suppressing HOXC-AS1 reduced proliferation, migration, and invasion of EC cells in vitro and inhibited tumor growth and metastasis in vivo. Mechanistically, HOXC-AS1 acted as a molecular sponge for miR-195-5p, with anillin actin-binding protein (ANLN) identified as a direct downstream target of miR-195-5p. Functional rescue experiments showed that inhibiting miR-195-5p or overexpressing ANLN counteracted the suppressive effects induced by HOXC-AS1 silencing on the aggressive phenotypes of EC cells. These findings establish HOXC-AS1 as a promoter of EC progression via regulation of the miR-195-5p/ANLN axis, suggesting its utility as a prospective therapeutic target for EC management.

Esophageal cancer is a major cause of cancer-related death, often preceded with chronic inflammation and injuries. The NFκB/IKKβ pathway plays a central role in inflammation, yet its role in early esophageal carcinogenesis remains unclear. This study investigated the role of epithelial IKKβ in early esophageal carcinogenesis. Mice were treated with the carcinogen 4-nitroquinoline-1-oxide (4-NQO) or a vehicle for one month to induce precancerous lesions. Esophagi were harvested and examined through histological, protein, flow cytometry, and RNA analyses. Histological analysis revealed that 4-NQO treatment led to increased inflammation, intraepithelial CD45+ immune cells, and elevated IKKβ phosphorylation levels. Mice with esophageal epithelial-specific Ikkβ deletion (4-NQO/ Ikkβ EEC-KO ) showed delayed progression to a precancerous state, with reduced immune cell recruitment compared to 4-NQO/controls. Immunophenotyping showed decreased recruitment of T cells, including CD4+, CD8+ and regulatory (Tregs) T cells, and increased recruitment of macrophages in 4-NQO/ Ikkβ EEC-KO mice compared to 4-NQO/controls. RNA sequencing data identified 262 differentially expressed genes in 4-NQO/ Ikkβ EEC-KO mice, implicating pathways related to inflammation and wound healing. Notably, the chemokine CXCL9, a T cell chemoattractant, was significantly upregulated in 4-NQO control mice, but not in 4-NQO/ Ikkβ EEC-KO mice. Further analysis identified IFNγ as an upstream regulator of Cxcl9 expression, and neutralization of IFNγ reduced Cxcl9 expression levels in 4-NQO treated mice. Additionally, in vitro studies demonstrated that IFNγ upregulates Cxcl9 in an NF-ĸB dependent manner in esophageal keratinocytes. These findings suggest that epithelial IKKβ regulates the immune microenvironment in early esophageal carcinogenesis through the IFNγ/CXCL9 axis and influencing T cell recruitment and inflammatory responses.

In a mouse model of early esophageal squamous cell carcinogenesis, loss of epithelial Ikkβ reduced inflammation and T cell recruitment, increased macrophage recruitment, inhibited IFNγ/CXCL9 signaling, and delayed the transition to a precancerous state.

Esophageal squamous-cell carcinoma (ESCC) is a highly aggressive cancer, predominantly affecting populations in Eastern Asia and parts of Africa. Its pathogenesis is influenced by both genetic and environmental factors. Despite recent therapeutic advances, survival rates remain dismal, underscoring an urgent need for novel therapeutic targets.

To investigate the role of hypoxia-inducible factor 1-alpha (HIF1A) in the progression of ESCC and its impact on the metabolic enzyme lactate dehydrogenase A (LDHA), which is crucial for the glycolytic pathway in hypoxic tumor environments.

Utilizing transcriptomic data from multiple public databases, we analyzed differential gene expression and conducted gene ontology and transcription factor network analyses. The regulatory impact of HIF1A on LDHA was specifically examined through integrative analysis with HIF1A ChIP-seq data and confirmed via siRNA-mediated knockdown experiments in ESCC cell lines.

Our findings reveal a significant upregulation of HIF1A in ESCC tissues, associated with poor prognosis. HIF1A directly regulates LDHA, enhancing glycolysis under hypoxic conditions and contributing to tumor aggressiveness. Knockdown of HIF1A in cell lines not only reduced LDHA expression but also altered key pathways related to cell cycle and apoptosis.

The critical role of the HIF1A-LDHA axis in ESCC highlights its potential as a therapeutic target, underscoring the need for future clinical trials to validate the efficacy of HIF1A inhibitors in enhancing treatment outcomes.

Endoscopic radiofrequency ablation (ERFA) is a treatment option for superficial esophageal squamous cell neoplasia (ESCN), with a relatively low risk of stenosis; however, the long-term outcomes remain unclear. We aimed to compare the long-term outcomes of patients with widespread superficial ESCN who underwent endoscopic submucosal dissection (ESD) or ERFA.

We retrospectively analyzed the clinical data of patients with superficial ESCN who underwent ESD or ERFA between January 2015 and December 2021. The primary outcome measure was recurrence-free survival.

Ninety-two and 33 patients with superficial ESCN underwent ESD and ERFA, respectively. The en bloc, R0, and curative resection rates for ESD were 100.0%, 90.2%, and 76.1%, respectively. At 12 months, the complete response rate was comparable between the two groups (94.6% vs 90.9%, p=0.748). During a median follow-up of 66 months, recurrence-free survival was significantly longer in the ESD group than in the ERFA group (p=0.004), while no significant differences in overall survival (p=0.845) and disease-specific survival (p=0.494) were observed. Preoperative diagnosis of intramucosal cancer (adjusted hazard ratio, 5.55; vs high-grade intraepithelial neoplasia) was an independent predictor of recurrence. Significantly fewer patients in the ERFA group experienced stenosis compare to ESD group (15.2% vs 38.0%, p=0.016).

The risk of recurrence was higher for ERFA than ESD for ESCN but overall survival was not affected. The risk of esophageal stenosis was significantly lower for patients who underwent ERFA.

The progression of Esophageal Squamous Cell Carcinoma (ESCC) can be dissected with greater precision using multi-omics and single-cell RNA sequencing (scRNA-seq) compared to traditional methodologies. These advanced approaches enable a comprehensive understanding of cellular heterogeneity and molecular dynamics, offering higher resolution insights into cancer development. Moreover, analyzing transcription factor regulatory networks provides innovative avenues for identifying cancer biomarkers and therapeutic targets, driving new perspectives in cancer research.

To explore the molecular mechanisms and cellular dynamics of ESCC.

Utilizing bulk-RNA-seq and single-cell transcriptomics, our study identify major cell types, transcriptomic gene and function changes during ESCC progression. Validation experiments in clinical sample tissues and ESCC cell lines to confirm core regulation factor in ESCC.

We identified six major cell types in the ESCC scRNA-seq dataset and revealed profound shifts in cellular composition and transcriptional profiles. Notably, STAT3 was found to be a core regulator in ESCC and negatively regulated LHPP expression at promoter sites. Elevated STAT3 and reduced LHPP expression were consistently observed in patient samples, highlighting their inverse relationship in ESCC pathogenesis.

This study integrates bulk-seq and scRNA-seq data to reveal the pivotal role of STAT3 in ESCC. STAT3 negatively regulates LHPP expression, driving tumor progression. These findings underscore the therapeutic potential of targeting STAT3 in ESCC.

ESCC, single-cell transcriptomics, ESCC microenvironment, STAT3.

We previously reported that high tumoral expression of Toll-like receptor 3 (TLR3) and CXCL10, a member of the CXC chemokine family, was an independent positive prognostic factor in patients with advanced thoracic esophageal squamous cell carcinoma (ESCC). However, the direct relationships between TLR3 and CXCL10 in ESCC cells was not fully understood. Here, we analyzed TLR3 mRNA and protein expression in two ESCC lines (TE8 and KYSE180) and one esophageal adenocarcinoma (EAC) line (OE19). We also assessed the effect of the TLR3 agonist poly(I:C) on production of downstream adapter proteins and cytokines, including CXCL10, and further tested its effects on cell viability and caspase 3/7 activity with and without siRNA-induced knockdown of TLR3 and the TICAM-1 or MAVS adapter protein. Both ESCC lines, but not the EAC line, showed high expression of TLR3 mRNA and protein. TICAM-1 and MAVS were also expressed, and their knockdown suppressed responsiveness to poly(I:C) in the ESCC lines. Poly(I:C) induced strong CXCL10 production, resulting in significantly upregulated caspase3/7 activity and downregulated cell proliferation in both ESCC lines but not the EAC line. The effect of poly(I:C) on CXCL10 production was attenuated after transfecting the cells with siRNAs targeting TICAM-1 or MAVS. TLR3 is thus highly expressed in ESCC cells, where it induces strong CXCL10 production and significantly upregulates caspase3/7 activity and downregulates cell proliferation. TLR3 signaling and the resultant downstream CXCL10 production have the potential to serve as useful prognostic markers and therapeutic targets for the treatment of ESCC.

The clinical outcomes and optimal treatment of esophageal squamous cell carcinoma (ESCC) in elderly patients are unclear. This study aimed to assess the clinical outcomes of ESCC in patients aged ≥ 80 years.

Medical records of patients diagnosed with ESCC between December 2008 and February 2024 were retrospectively reviewed. In total, 479 patients with ESCC were included and divided into the elderly (n = 52) and younger (n = 427) groups based on age. The clinical outcomes and survival rates, according to treatment, were compared between the two groups.

The median ages of the two groups were 82 years (range, 80-95 yr) and 66 years (41-79 yr). The overall survival was slightly lower in the elderly group; however, no statistical significance (hazard ratio [HR] 1.27, 95% confidence interval [CI] 0.85-1.91; p = 0.238) was observed. No differences were observed in the outcomes or survival between the two groups according to the treatment method (surgery, chemoradiotherapy or radiotherapy alone, and endoscopic resection). The elderly group was more likely to receive no treatment for cancer (30.8% vs. 13.6%, p = 0.002) than the younger group. However, when there was no treatment for cancer in the elderly group, survival was significantly lower than when treatment was administered (HR 0.08, 95% CI 0.03-020; p < 0.001).

In patients with ESCC aged ≥ 80 years, active cancer treatment was beneficial, and the results did not differ from those of younger patients.

Aberrantly expressed LINC00942 is participated in the progression of several cancers. However, the function of LINC00942 in esophageal cancer (ESCA) is unclear. The objective of this study was to explore the effect of LINC00942 on ESCA and its possible molecular mechanisms. First, differentially expressed lncRNAs in ESCA were analyzed using GSE192662 microarray. catRAPID omics v2.1 was applied to predict the proteins that might interact with LINC00942. SDS-PAGE silver staining assay, RNA pull down, and RIP assay were utilized to validate proteins interacting with LINC00942. Then, RNA seq was applied to detect the downstream targets of PTBP1, and KEGG enrichment analysis was used to analyze the genes involved in proliferation and migration-related signaling pathways. In addition, CCK-8, EdU and transwell were used to detect the impact of LINC00942 on ESCA cell function. Bioinformatics revealed that LINC00942 was significantly overexpressed in ESCA. Patients in low-expression of LINC00942 had an obviously better prognosis. After LINC00942 knockdown, the proliferation and migration of TE-1 and OE19 were dramatically reduced. Subsequently, PTBP1 was found to interact with LINC00942, and PRKDC was a downstream target of PTBP1. Functional analysis showed that TE-1 and OE19 cell proliferation and migration were markedly elevated after LINC00942 overexpression, and knockdown of PRKDC significantly reversed this effect. Mechanistically, LINC00942 promoted PRKDC expression by interacting with PTBP1. In summary, LINC00942 facilitated the proliferation and migration of ESCA cells via binding to PTBP1 to promote PRKDC expression.

Esophageal squamous cell carcinoma (ESCC) is a highly aggressive malignancy with a poor prognosis and limited effective treatment options. This study investigates the therapeutic potential of Deferasirox (DFO), an iron chelator, in ESCC by targeting TAOK1, an STE20-type kinase implicated in cancer development. We demonstrate that DFO significantly inhibits the proliferation and colony formation of ESCC cells in a dose- and time-dependent manner. Mechanistic investigations reveal that DFO binds directly to TAOK1 and reduces its kinase activity. Proteomics and phosphorylated proteomic sequencing analysis further reveal that TAOK1 knocking down dramatically increased p53-mediated apoptosis. Moreover, the inhibition of TAOK1 by DFO or lenti-virus infection induces apoptosis in ESCC cells, as evidenced by the increased expression of p53, p-p53 (S15), p-p53 (S46), Puma, Noxa, and Bax, and the decreased expression of Bcl-2. Furthermore, in vivo studies using patient-derived xenograft (PDX) mouse models show that DFO treatment significantly reduces tumor volume without observable toxicity. Histological and immunohistochemical analyses confirm the down-regulation of TAOK1 and Ki-67, and the up-regulation of p53 expression in DFO-treated tumors. Our findings suggest that DFO exerts its antitumor effects in ESCC by targeting TAOK1, providing a potential therapeutic strategy for ESCC patients.

At present, the application of magnetic resonance imaging (MRI) in the prediction of response to neoadjuvant therapy and concurrent chemoradiotherapy for the treatment of esophageal cancer still needs to be further explored, and its early differential value remains controversial, thus we carried out this systematic review with a meta-analysis. In the application, different MRI sequences and corresponding parameters are used for the differential diagnosis of the response to neoadjuvant therapy and concurrent chemoradiotherapy.

All relevant studies evaluated the efficacy and response to MRI in neoadjuvant therapy or concurrent chemoradiotherapy for esophageal cancer on Pubmed, Embase, Cohrane Library, and Web of Science databases published before October 10, 2023 (inclusive) were systematically searched. A revised tool was used to assess the quality of diagnostic accuracy studies (QUADAS-2) to assess the risk of bias in the included original studies. A subgroup analysis of MRI sequences diffusion weighted imaging (DWI), dynamic contrast enhanced (DCE) and their corresponding different parameters, as well as the acquisition timepoints (before and after treatment) for different parameters, was performed during the meta-analysis. The bivariate mixed-effects model was used for meta-analysis.

21 studies were finally included, involving 1128 patients with esophageal cancer. The sensitivity, specificity, and area under receiver operating characteristic curve (ROC curve) of DWI sequence for identifying response to concurrent chemoradiotherapy were 0.82 (95% CI: 0.74-0.87), 0.81 (95% CI: 0.72-0.87) and 0.88 (95% CI: 0.56-0.98), respectively. The sensitivity, specificity, and area under ROC curve of DCE sequence for identifying response to concurrent chemoradiotherapy were 0.78 (95% CI: 0.70-0.84), 0.65 (95% CI: 0.59-0.70) and 0.73 (95% CI: 0.50-0.88), respectively. In patients with esophageal cancer, the sensitivity, specificity, and area under the ROC curve of DWI sequences for identifying response to neoadjuvant therapy were 0.80 (95% CI: 0.69 - 0.88), 0.81 (95% CI: 0.69 - 0.89), and 0.88 (95% CI: 0.34 - 0.99), respectively; the sensitivity, specificity, and area under the ROC curve of DCE sequences for identifying response to neoadjuvant therapy were 0.84 (95% CI: 0.76 - 0.90), 0.61 (95% CI: 0.53 - 0.68), and 0.70 (95% CI: 0.27 - 0.94), respectively.

Based on the available evidence, MRI had a very good value in the early identification of response to neoadjuvant therapy and concurrent chemoradiotherapy for esophageal cancer, especially DWI. Apparent diffusion coefficient (ADC) value changes before and after treatment could be used as predictors of pathological response. Also, ADC value changes before and after treatment could be used as a tool to guide clinical decision-making.

The prognostic impact of human leukocyte antigen-E (HLA-E) expression and the proportion of natural killer (NK) cells in esophageal squamous cell carcinoma (ESCC) was investigated.

This study retrospectively evaluated 397 ESCC patients across two centers. The cumulative incidence of recurrence (CIR) and the incidence of tumor-related death (CID) were analyzed in various groups. An immunosuppression score (ISS) was developed based on HLA-E expression and NK cell proportion. Differences between groups were adjusted using inverse probability treatment weighting (IPTW). The factors influencing cancer-specific survival (CSS) and recurrence-free survival (RFS) were also examined.

Patients with low HLA-E expression had significantly higher five-year CIR and CID compared to those with high expression (CIR: 20.7% vs. 45.1%, CID: 19.3% vs. 40.1%; p< 0.001). Similarly, NK cell-positive patients had significantly better five-year CIR and CID than NK cell-negative patients (CIR: 16.3% vs. 59.6%, CID: 13.9% vs. 53.7%; p < 0.001). The Sankey diagram indicated that the low ISS group had a lower recurrence and tumor-related mortality rate (p < 0.05). After IPTW adjustment, the low ISS group showed improved five-year RFS (80.1% vs. 35.4%, p < 0.001) and five-year CSS (82.3% vs. 42.5%, p < 0.001) compared to the high ISS group.

ESCC with different ISS statuses represents two distinct biological subtypes, underscoring the need for personalized treatment strategies tailored to varying tumor behaviors.

Definitive chemoradiotherapy (dCRT) is the standard treatment for unresectable (T4) esophageal squamous cell carcinoma (ESCC), but the prognosis is poor. Borderline resectable (T3br) ESCC has been discussed, but its clinical features and appropriate treatment are unclear. The effects of docetaxel plus cisplatin and 5-fluorouracil (DCF) therapy and subsequent surgery for potentially unresectable ESCC remain controversial. This was a single-center retrospective cohort study. Patients with T3 or deeper ESCC lesions between January 2017 and June 2020 were examined. We identified T3br/T4 ESCC patients who initially received DCF therapy or dCRT, and analyzed the long-term outcomes of these patients. Seventy-four patients with T3br/T4 ESCC were identified. Forty-four patients initially received DCF therapy, while thirty initially received dCRT. The 3-year overall survival of T3br/T4 patients in the DCF group was better than that in the dCRT group (62.9% vs. 34.1%, P = 0.001). In the T3br cohort, 95.8% of patients underwent surgery after DCF therapy, with an R0 resection rate of 78.3%. In the T4 group, 40% of patients underwent surgery after DCF, with a 75.0% R0 resection rate. No cases of reoperation or in-hospital death occurred. For both subgroups, T3br and T4, the prognosis tended to be better in the DCF group than in the dCRT group. This study explored real-world data from T3br/T4 ESCC patients who initially received DCF and subsequent surgery and revealed that DCF is a promising treatment strategy.

Esophageal malignancies, constituting 3% of global cancers, pose significant health challenges with poor survival rates. Squamous Cell Carcinoma (SCC) and Adenocarcinoma (AC) are predominant subtypes, with shifting incidences globally. This analysis will focus primarily on the demographics of survival trends for Squamous cell carcinoma of esophagus (SCCE). This retrospective study, utilizing the SEER database, examined demographic factors influencing survival trends in SCC of the upper esophagus. Variables included age, sex, race, income, and rurality. Statistical analyses included chi-square tests and multivariable models, specifically logistic regression and conditional inference tree models. A total of 2821 patients were included in this study. Demographic disparities were evident with race (p < 0.001), age (p = 0.002), and sex (p = 0.048) significantly impacting survival when holding other variables constant, with Non-Hispanic Black individuals exhibiting the greatest odds of mortality compared to other racial groups. Median household income (p = 0.344) and Rural-Urban Continuum (p = 0.100) were not significantly associated with improved survival rates when controlling for other demographics. Our findings align with previous research on sex-based survival disparities and racial variations in SCCE incidence and outcomes. Socioeconomic and biological factors contribute to these disparities, highlighting the need for tailored interventions and equitable healthcare access. Understanding demographic determinants in SCCE survival is crucial for personalized treatment and policy reforms to address disparities. Future research should focus on prospective, diverse cohorts to further elucidate these complex interactions and improve esophageal SCCE management and outcomes.

EP300 mutation is common in esophageal squamous cell carcinoma (ESCC). We aimed to analyze the influence of EP300 mutation on treatment effect and prognosis in ESCC patients underwent neoadjuvant chemoradiotherapy.

Thirty ESCC patients treated with neoadjuvant chemoradiotherapy (nCRT) were enrolled in this study. After assessment of treatment response, transcriptome analyses and immunochemistry were performed for cases in well response or poor response group.

Four of thirty patients harbor EP300 mutation and have poor response to nCRT. Of the remaining 26 nonmutated patients, fifteen patients have a well response, and seven patients have a poor response to nCRT. The EP300-mutated poor response cases have significantly higher immune score than EP300 wild-type poor response cases (P = 0.002), but have no difference from EP300 wild-type well response cases (P = 0.360). Up-regulated B cell related pathways and more CD20 + B cells are in EP300-mutated poor response group, when compared with EP300 wild-type poor response group (P < 0.050). Whereas up-regulated negative regulation of cell death related pathway and higher bcl2 expression level was observed in EP300 mutated poor response group than these in EP300 wild-type well response group (P < 0.050). In prognosis, cases in EP300-mutated poor response group have worse disease-free survival (P = 0.019) and overall survival (P = 0.004) than EP300 wild-type well response group.

EP300 mutated cases have high immune activity in tumor microenvironment. The high anti-apoptosis activity of tumor cells may contribute to resistance to nCRT in EP300-mutated cases.

Numerous studies have described positive relationships between hospital volume (HV) and clinical outcomes in highly complex procedures, including esophagectomies. Although the centralization of surgery has been considered a possible solution for improving clinical outcomes, the HV impact on perioperative healthcare costs is unknown. This study aimed to determine the relationship between HV and perioperative healthcare costs for patients undergoing esophagectomy for esophageal cancer.

This retrospective, nationwide cohort study used Japanese Administrative Claims Database data. Data on esophagectomies performed nationwide in 2015 were extracted. The outcome measure was perioperative healthcare costs per person from the perspective of the insurer. The healthcare costs in outpatient or inpatient settings of any hospital and clinic where patients received treatment were summed up from the month the surgery was performed to 3 months after. Linear regression analyses were conducted to assess the risk-adjusted effects of the HV category (1-4/5-9/10-14/15-) on perioperative costs.

A total of 5232 patients underwent an esophagectomy at 584 hospitals. The overall perioperative cost was 20.834 billion Japanese yen (JPY). The median perioperative costs per person for each HV category (1-4/5-9/10-14/15-) were 3.728 (709 patients), 3.740 (658 patients), 3.760 (512 patients), and 3.760 (3253 patients) million JPY, respectively (P = 0.676). Multivariate analyses revealed that each HV category had no significant impact on perioperative costs.

There were no significant differences in the perioperative costs between high- and low-volume centers. Esophageal cancer surgery centralization may be achievable without increasing healthcare costs.

Esophageal cancer (EC) is a malignancy with a poor prognosis and a five-year survival rate of less than 20%. It is the ninth most frequent cancer globally and the sixth leading cause of cancer-related deaths. The incidence of EC has been found to vary significantly by geography, indicating the importance of environmental and lifestyle factors along with genetic factors in the onset of the disease. In this work, we investigated mycotoxin exposure in a case-control study from the Arsi-Bale districts of Oromia regional state in Ethiopia, where there is a high incidence of EC while alcohol and tobacco use - two established risk factors for EC - are very rare.

Internal exposure to 39 mycotoxins and metabolites was assessed by liquid chromatography-tandem mass spectrometry in plasma samples of EC cases (n = 166) and location-matched healthy controls (n = 166) who shared similar dietary sources. Demographic and lifestyle data were collected using structured questionnaires. Principal Component Analysis and machine learning models were used to identify the most relevant demographic, lifestyle, and mycotoxin (co-)exposure variables associated with EC. Multivariate binary logistic regression analysis was used to assess EC risk.

Evidence of mycotoxin exposure was observed in all plasma samples, with 10 different mycotoxins being detected in samples from EC cases, while only 6 different mycotoxins were detected in samples from healthy controls. Ochratoxin A was detected in plasma from all cases and controls, while tenuazonic acid was detected in plasma of 145 (87.3%) cases and 71 (42.8%) controls. Using multivariable logistic regression analysis, exposure to tenuazonic acid (AOR = 1.88 [95% CI: 1.68-2.11]) and to multiple mycotoxins (AOR = 2.54 [95% CI: 2.10-3.07]) were positively associated with EC.

All cases and controls were exposed to at least one mycotoxin. Cases were exposed to a statistically significantly higher number of mycotoxins than controls. Exposure to tenuazonic acid and to multiple mycotoxins were associated with increased risk of EC in the study population. Although aflatoxin B1-lysine and the ratio of sphinganine to sphingosine (as a biomarker of effect to fumonisin exposure) were not assessed in this study, our result emphasizes the need to characterize the effect of mycotoxin co-exposure as part of the exposome and include it in risk assessment, since the current mycotoxin safety levels do not consider the additive or synergistic effects of mycotoxin co-exposure. Moreover, a prospective study design with regular sampling should be considered in this high incidence area of EC in Ethiopia to obtain conclusive results on the role of mycotoxin exposure in the onset and development of the disease.

To assess the impact of the definition of the Global Leadership Initiative in Sarcopenia (GLIS) on mortality in esophageal cancer (EC) patients, postesophagectomy, within a Chinese cohort and to validate the effectiveness of a new GLIS framework in oncology.

We performed an observational real-world cohort study in a single center at Daping Hospital of the Army Medical University in China, spanning from December 2014 to July 2022. We used the combined definition of muscle mass and muscle strength in a new GLIS framework for the diagnosis of sarcopenia. Potential covariates were identified through univariate and multivariate analyses. The association between GLIS-defined sarcopenia and mortality was estimated using Kaplan-Meier curves and Cox models. We also conducted stratified analyses to assess the stability of multivariable Cox models.

A total of 520 EC patients were included in the study, with a median follow-up of 48.7 months. A total of 229 EC patients (44.0%) were identified with GLIS-defined sarcopenia. Patients with GLIS-defined sarcopenia had significantly worse overall survival in Kaplan-Meier curves (log-rank P = 0.015). Age; sex; tumor, node, metastasis stage; blood glucose; bleeding volume in operation; and operating time were introduced as covariates in a fully adjusted Cox model. Multivariable-adjusted Cox models revealed that GLIS-defined sarcopenia was an independent prognostic factor for EC patients postesophagectomy (hazard ratio, 1.87, 95% confidence interval, 1.28-2.74, P = 0.001). Stratified analyses confirmed the stability of the relationship between GLIS-defined sarcopenia and mortality in EC patients.

GLIS-defined sarcopenia is prevalent among Chinese EC patients and is linked to increased mortality risk postesophagectomy. This finding offers compelling evidence and serves as a valuable reference for the establishment of an operational definition of GLIS sarcopenia.

The role of concurrent pyloroplasty with esophagectomy is unclear. Available literature on the impact of pyloroplasty during esophagectomy on complications and weight loss is varied. Data on the need for further pyloric intervention are scarce. Our study compares the clinical outcomes after esophagectomy with or without pyloroplasty and investigates the role of post-operative pyloric dilatation.

Consecutive patients (n = 207) undergoing Ivor Lewis esophagectomy performed by two surgeons at our institution were included. Data on patient demographics, mortality rate, anastomotic leak, respiratory complications (Clavien-Dindo grade ≥ 3), anastomotic stricture rate, and percentage weight loss at 1 and 2 year post-operatively were evaluated. For weight analysis at 1 and 2 year post-operatively, patients were excluded if they had been diagnosed with recurrence or died prior to the 1 or 2 year timepoints.

Ninety-two patients did not have a pyloroplasty, and 115 patients had a pyloroplasty. There were no complications resulting from pyloroplasty. There was no significant demographic difference between the groups except for age. Mortality rate, anastomotic leak, respiratory complications, anastomotic stricture rate, and percentage weight loss at 1 and 2 years were statistically similar between the two groups. However, 14.1% of patients without pyloroplasty required post-operative endoscopic pyloric balloon dilatation to treat respiratory complications or gastroparesis. Subgroup analysis of patients without pyloroplasty indicated that patients requiring dilatation had greater weight loss at 1 year (15.8% vs 9.4%, p = 0.02) and higher respiratory complications rate (27.3% vs 4.7%, p = 0.038).

Overall results from our study that pyloroplasty during Ivor Lewis esophagectomy is safe and useful to prevent the need for post-operative pyloric dilatation.

Altered glucose metabolism is a critical characteristic from the beginning stage of esophageal squamous cell carcinoma (ESCC), and the phenomenon is presented as a pink-color sign under endoscopy after iodine staining. Therefore, calculating the metabolic score based on the glucose metabolic gene sets may bring some novel insights, enabling the prediction of prognosis and the identification of treatment choices for ESCC.

A total of 8, 99, and 140 individuals from The Gene Expression Omnibus database, The Cancer Genome Atlas database, and the Memorial Sloan Kettering Cancer Center, respectively, were encompassed in the investigation. Patients diagnosed with ESCC after surgery were enrolled for further validation.

A total of 13 kinds of cell clusters were screened, and the squamous epithelium was identified with the highest score. And 558 differential genes were selected from the single-cell RNA sequencing (scRNA-seq) dataset. Four glucose metabolism-related genes, namely, SERP1, CTSC, RAP2B, and SSR4, were identified as hub genes to develop a risk prognostic model. The model was validated in another external cohort. According to the risk score (RS) determined by the model, the patients were categorized into low- and high-risk groups (LRG and HRG). Compared with LRG, HRG indicated poor survival and decreased drug sensitivity. Additionally, the immune microenvironment and pathway enrichment were different between the two groups. Immunohistochemical staining revealed that hub genes were expressed differently in ESCC tissues, high- and low-grade intraepithelial neoplasia, and adjacent normal tissues.

Four hub genes (SERP1, CTSC, RAP2B, and SSR4) screened based on glucose metabolism developed a predictive model in ESCC patients. The RS was established as an independent risk factor for predicting prognosis. These findings may enhance understanding of ESCC's molecular profile and serve as a new prognostic tool for better patient stratification and treatment planning in clinical practice.

Patient-derived organoids (PDOs) represent a promising approach for replicating the characteristics of original tumors and facilitating drug testing for personalized treatments across diverse cancer types. However, clinical evidence regarding their application to esophageal cancer remains limited. This study aims to evaluate the efficacy of implementing PDOs in clinical practice to benefit patients with esophageal squamous cell carcinoma (ESCC).

Fresh surgical biopsies were obtained from patients with esophageal cancer for the establishment of PDOs. These PDOs were subsequently characterized through histological analysis. A customized drug panel, based on standard-of-care chemotherapy regimens, was applied to the PDOs. The resulting drug sensitivity profiles were then correlated with the clinical responses observed in individual patients undergoing actual treatment.

A total of 34 PDOs were successfully established with a 61.8% success rate. The classification method based on chemotherapy sensitivity closely corresponded to clinical responses. The paclitaxel plus cisplatin (TP)-sensitive group demonstrated significantly longer progression-free survival (PFS) compared to the resistant groups, Hazard ratio (HR), 5.12; 95% confidence intervals (CI 0.58-44.71; p < 0.05), thus illustrating the potential of this approach for guiding personalized treatment strategies.

Organoid biobanks were established across multiple institutes to facilitate PDOs-based functional precision medicine. The findings demonstrate that this framework offers robust predictive value in clinical settings, enhances precision therapeutics, and advances drug discovery for esophageal cancer.

The incidence of oesophageal adenocarcinoma (OAC) has risen six-fold in western countries over the last forty years but survival rates have only marginally improved. Hyperactivation of the PI3K-AKT-mTOR pathway is a common occurrence in OAC, driving cell survival, proliferation and resistance to chemotherapeutic agents. Inhibition of AKT has been explored as a treatment strategy with limited success and current inhibitors have failed to progress through clinical trials. Our study, describes a novel allosteric AKT inhibitor, ALM301, and demonstrates an enhancement of the efficacy of conventional chemotherapy when combined with ALM301 in OAC. Reduced sensitivity to ALM301 is associated with high expression of the Inhibitor of Apoptosis (IAP) family of proteins, particularly XIAP. Combined AKT and IAP inhibition synergistically enhanced OAC cell death and successfully re-sensitized ALM301 and chemotherapy resistant cell lines. A high degree of synergism was also observed in patient-derived OAC organoids indicating the potential clinical relevance of the combination. This study demonstrates the role for dual AKT/IAP inhibition in OAC and provides a strong rationale for the further investigation of this highly efficacious combination strategy.

ZNF468 is a zinc finger protein that plays a key role in the occurrence and development of tumors. However, no studies have demonstrated whether ZNF468 is involved in the progression of esophageal squamous cell carcinoma (ESCC).

The expression of ZNF468 in ESCC tumor and normal samples was analyzed by the TCGA database and confirmed by tissue immunohistochemistry. Subsequently, we established the lentivirus ZNF468 knockdown and ZNF468 overexpression models using ESCC cell lines. The effect of ZNF468 on ESCC was assessed by in vivo and in vitro experiments. The latter included CCK8, colony formation, wound healing, and transwell assays. Additionally, we also explored the underlying mechanism.

The mRNA and protein expression of ZNF468 were significantly increased in the tumor tissue of ESCC patients compared to normal para-cancerous tissue. Patients with high ZNF468 level were significantly related to shorter overall survival and disease-specific survival. Overexpression of ZNF468 increased the ability of proliferation, migration, and invasion of ESCC cells. In vivo experiments indicated that ZNF468 inhibition could also decrease the ESCC tumor growth. At last, we found that ZNF468 might affect ESCC progression through the AKT/mTOR signaling pathway.

These findings showed that increased ZNF468 expression might promote ESCC progression via the AKT/mTOR pathway, which might be a potential biomarker and drug target for ESCC.

Esophageal squamous cell carcinoma (ESCC) remains a significant global health challenge, being the sixth leading cause of cancer mortality with pronounced geographic variability. The incidence rates range from 125 per 100,000 in northern China to 1-1.5 per 100,000 in the United States, driven by environmental and lifestyle factors such as tobacco and alcohol use, dietary habits, and pollution. Major modifiable risk factors include tobacco and alcohol consumption, with a synergistic risk increase when combined. Nonmodifiable risk factors include previous diagnoses of head and neck squamous cell carcinoma (H&N SCC), achalasia, and prior radiotherapy. Prevention strategies must be tailored to specific regional burdens to efficiently allocate medical and financial resources. Gastrointestinal endoscopy is crucial in reducing ESCC burden through early detection and characterization of neoplastic changes, such as high-grade dysplasia. Early diagnosis significantly improves survival rates, while endoscopic resection of noninvasive dysplasia can prevent ESCC onset, reducing treatment burden for advanced disease. Postresection surveillance can detect high-risk metachronous lesions. Despite these benefits, endoscopic prevention faces challenges, including the lack of high-level evidence supporting its efficacy, opportunity costs, the need for specialized training and techniques, and the requirement for advanced technology investments. This Position Statement from the World Endoscopy Organization (WEO) aims to address these challenges, supplying recommendations for the exploitation of endoscopic resources regarding the possible role of screening, quality, and training for the detection, characterization, resection, and surveillance of ESCC.

The prognosis of esophageal squamous cell carcinoma (ESCC) with obstruction is unclear. This study aimed to analyze clinical outcomes and prognosis of patients with ESCC and obstruction.

Patients with advanced ESCC were included and divided into obstructive and non-obstructive groups. Clinical outcomes and survival according to treatment were compared between these groups.

Among 353 patients with advanced ESCC, obstruction was present in 105 (29.7%). ESCC with obstruction was more common in the upper thoracic location (23.8% vs. 14.5%, p = 0.036) and had a higher stage (7.6% vs. 32.7%, p < 0.001 in stage 2; 41.0% vs. 24.2%, p = 0.002 in stage 4) than those without obstruction. The median survival time of patients with obstruction was significantly shorter than that of patients without obstruction (7.6 months vs. 20.2 months, p < 0.001). Patients with obstruction had a significantly lower survival rate regardless of treatment. When surgery was performed first on patients with obstruction, the R0 resection rate was significantly lower (33.3% vs. 88.5%, p < 0.001). For patients with obstruction in resectable stages, surgery after neoadjuvant chemoradiotherapy resulted in the best survival (HR: 0.48; 95% CI: 0.15 - 1.49; p = 0.201). When only chemoradiotherapy was performed in resectable stages, clinically complete response rate was significantly lower (35.3% vs. 64.9%, p = 0.035) in the obstructive group.

ESCC with obstruction was at a more advanced stage and had a poor prognosis regardless of treatment. Surgery first or chemoradiotherapy alone is not recommended for these patients. Neoadjuvant chemoradiotherapy prior to surgical resection is recommended for those with ESCC and obstruction at resectable stages.

Esophageal squamous cell carcinoma (ESCC) remains a significant challenge in oncology due to its aggressive nature and heterogeneity. As one of the deadliest malignancies, ESCC research lags behind other cancer types. The balance between ubiquitination and deubiquitination processes plays a crucial role in cellular functions, with its disruption linked to various diseases, including cancer.

Our study utilized diverse analytical approaches, encompassing Cox regression models, single-cell RNA sequencing, intercellular communication analysis, and Gene Ontology enrichment. We also conducted mutation profiling and explored potential immunotherapeutic agents. Furthermore, in vitro cellular experiments and in vivo mouse models were performed to validate findings. These methodologies aimed to establish deubiquitination-related gene signatures (DRGS) for predicting ESCC patient outcomes and response to immunotherapy.

By integrating datasets from TCGA-ESCC and GSE53624, we developed a DRGS model based on 14 deubiquitination-related genes (DUBGs). This signature effectively forecasts ESCC prognosis, drug responsiveness, and immune cell infiltration patterns. It also influences the mutational landscape of patients. Those classified as high-risk exhibited reduced survival rates, increased genetic alterations, and more complex cellular interactions, potentially explaining their poor outcomes. Notably, in vitro and in vivo experiments identified MTOR, a key component of the signature, as a promising therapeutic target for ESCC treatment.

Our research highlights the significance of 14 DUBGs in ESCC progression. The risk score derived from this gene set enables clinical stratification of patients into distinct prognostic groups. Moreover, MTOR emerges as a potential target for personalized ESCC therapy, offering new avenues for treatment strategies.

Poor oral health is an independent risk factor for upper-aerodigestive tract cancers, including esophageal squamous cell carcinoma (ESCC); thus, good oral health may reduce the risk of ESCC. We previously reported that high expression of Toll-like receptor (TLR) 6, which recognizes peptidoglycan (PGN) from Gram-positive bacteria correlates with a good prognosis after esophagectomy for ESCC. Most beneficial bacteria in the mouth are Gram-positive. We therefore hypothesized that PGN affects cancer cell proliferation and disease progression in ESCC. To test that idea, we assessed the expression of cytokine and chemokine mRNA and protein in eight ESCC cell lines. We also employed a mouse xenograft model to investigate the effect of PGN on ESCC tumor progression in vivo. We then investigated the relationship between the combined expression profiles of TLR6 and C-X-C motif chemokine ligand 10 (CXCL10) in clinical samples and 5-year overall survival (OS) and disease-specific survival (DSS) in ESCC patients after curative esophagectomy. We found that PGN significantly inhibited cell proliferation in six of eight ESCC lines and upregulated CXCL10 production via NF-κB2. In vivo, subcutaneous PGN administration tended to decrease ESCC tumor volume in mice. Combined high expression of TLR6 and CXCL10 correlated with a better prognosis in ESCC patients. This suggests that PGN reduces cell proliferation and tumor progression through a PGN-TLR-CXCL10 cascade, thereby influencing prognosis after esophagectomy for ESCC, and that improving the oral environment could potentially improve the prognosis of ESCC patients after esophagectomy.

Esophageal cancer (EC) often occurs in the elderly, with approximately 33% of patients aged ≥ 75 years at the time of diagnosis.

To evaluate the prognostic factors for radiotherapy (RT) in elderly patients with unresectable EC.

We retrospectively analyzed the clinical characteristics, toxic reactions, and survival information of EC patients aged ≥ 75 years who underwent intensity-modulated RT at Lu'an Hospital of Anhui Medical University between January 2016 and September 2023. Kaplan-Meier analysis was used to draw the overall survival (OS) curves, and Cox regression analysis was employed to evaluate the influence of various clinical factors on the prognosis.

A total of 139 patients were enrolled. The median follow-up time was 52.0 months. The median OS was 20.0 months. The 1-year, 2-year, 3-year, and 5-year OS rates were 69.8%, 38.7%, 28.2%, and 17.5%, respectively. Univariate analysis showed that age, radiation dose, and chemotherapy had no significant impact on prognosis. Multivariate analysis indicated that clinical stage [III-IVa vs I-II, hazard ratio (HR) = 2.421, 95% confidence interval (CI): 1.242-4.718, P = 0.009; IVb vs I-II, HR = 4.222, 95%CI: 1.888-9.438, P < 0.001), Charlson comorbidity index (CCI) (0 vs ≥ 1, HR = 1.539, 95%CI: 1.015-2.332, P = 0.042), and nutritional risk screening 2002 (NRS2002) (< 3 vs ≥ 3, HR = 2.491, 95%CI: 1.601-3.875, P < 0.001) were independent prognostic factors for OS.

Our results suggest that CCI and NRS2002 were independent prognostic factors of OS for unresectable elderly EC patients undergoing RT. For elderly patients with EC, full attention should be given to biological age-related indicators, such as comorbidities and nutrition, when formulating treatment protocols. These factors should be considered in future clinical practice.

To develop and validate an online individualized model for predicting local recurrence-free survival (LRFS) in esophageal squamous cell carcinoma (ESCC) treated by definitive chemoradiotherapy (dCRT).

ESCC patients from three hospitals were randomly stratified into the training set (715) and the internal testing set (179), and patients from the other hospital as the external testing set (120). The important radiomic features extracted from contrast-enhanced computed tomography (CECT)-based subregions clustered from the whole volume of tumor and peritumor were selected and used to construct the subregion-based radiomic signature by using COX proportional hazards model, which was compared with the tumor-based radiomic signature. The clinical model and the radiomics model combing the clinical factors and the radiomic signature were further constructed and compared, which were validated in two testing sets.

The subresion-based radiomic signature showed better prognostic performance than the tumor-based radiomic signature (training: 0.642 vs. 0.621, internal testing: 0.657 vs. 0.638, external testing: 0.636 vs. 0.612). Although the tumor-based radiomic signature, the subregion-based radiomic signature, the tumor-based radiomics model, and the subregion-based radiomics model had better performance compared to the clinical model, only the subregion-based radiomics model showed a significant advantage (p < 0.05; training: 0.666 vs. 0.616, internal testing: 0.689 vs. 0.649, external testing: 0.642 vs. 0.604). The clinical model and the subregion-based radiomics model were visualized as the nomograms, which are available online and could interactively calculate LRFS probability.

We established and validated a CECT-based online radiomics nomogram for predicting LRFS in ESCC received dCRT, which outperformed the clinical model and might serve as a powerful tool to facilitate individualized treatment.

This retrospective study was approved by the ethics committee (KY20222145-C-1).

Oral and esophageal cancers are globally prevalent, especially in East Asia. Over half of head and neck cancer patients developing second primary esophageal cancer (SPEC) were initially diagnosed with oral cavity cancer (OCC). This study assessed the cost-effectiveness of universal endoscopic screening for early SPEC prevention in newly diagnosed OCC patients at different stages.

This study employed Markov cohort models to evaluate the cost-effectiveness of endoscopic SPEC screening post-OCC diagnosis (stages 0 to IV) between screened and non-screened groups. Four surveillance frequencies were assessed: (i) one time, (ii) annual for 3 years, (iii) annual for 10 years, and (iv) annual for life. A hypothetical cohort of 100 000 cases across stages was compared for costs and quality-adjusted life-years (QALYs), discounted annually at 3%.

All four screening strategies were beneficial for all OCC stages, especially for early-stage patients, resulting in higher QALYs. Lifetime/annual screening from the payer's perspective proved most favorable, with incremental QALYs of 1.23 at stage 0 and 0.06 at stage IV. Incremental costs for this strategy ranged from NTD 121 331 (USD 4044) at stage 0 to NTD 13 032 (USD 434) at stage IV. Both incremental costs and incremental cost-effectiveness ratio (ICER) values indicated cost savings from a societal perspective. The ICER values ranged from NTD -626 440 (USD -20 881) at stage 0 and NTD -475 021 (USD -15 834) at stage IV.

Overall, our study provided cost-effectiveness evidences to understanding the cost-effectiveness of endoscopic screening in OCC patients, particularly emphasizing the benefits of early and consistent screening.

Oesophageal cancer is the seventh leading cause of cancer mortality worldwide. Two major pathological subtypes exist: oesophageal squamous cell carcinoma and oesophageal adenocarcinoma. Epidemiological studies in the last decade have shown a gradual increase in the incidence of oesophageal adenocarcinoma worldwide. The prognosis of oesophageal cancer has greatly improved due to breakthroughs in screening, surgical procedures, and novel treatment modalities. The success achieved with combined modality therapies, including surgery, chemotherapy, and radiotherapy, to treat locally advanced oesophageal cancer is particularly notable. Immunotherapy has become a crucial treatment for oesophageal cancer, with immune checkpoint inhibitor-based therapies now established as the standard of care in adjuvant and metastatic first-line settings. This Seminar provides an overview of advances in the screening, diagnosis, and treatment of oesophageal squamous cell carcinoma and oesophageal adenocarcinoma, with a particular focus on neoadjuvant therapies for locally advanced oesophageal cancer and immune checkpoint inhibitor-based therapies.

Robot-assisted minimally invasive esophagectomy (RAMIE) is increasingly adopted in centers worldwide, with ongoing refinements to enhance results. This study aims to assess the current state of RAMIE worldwide and to identify potential areas for improvement.

This descriptive study analyzed prospective data from esophageal cancer patients who underwent transthoracic RAMIE in Upper GI International Robotic Association (UGIRA) centers. Main endpoints included textbook outcome rate, surgical techniques, and perioperative outcomes. Analyses were performed separately for intrathoracic (Ivor-Lewis) and cervical anastomosis (McKeown), divided into three time cohorts (2016-2018, 2019-2020, 2021-2023). A sensitivity analysis was conducted with cases after the learning curve (> 70 cases).

Across 28 UGIRA centers, 2012 Ivor-Lewis and 1180 McKeown procedures were performed. Over the time cohorts, textbook outcome rates were 39%, 48%, and 49% for Ivor-Lewis, and 49%, 63%, and 61% for McKeown procedures, respectively. Fully robotic procedures accounted for 66%, 51%, and 60% of Ivor-Lewis procedures, and 53%, 81%, and 66% of McKeown procedures. Lymph node yield showed 27, 30, and 30 nodes in Ivor-Lewis procedures, and 26, 26, and 34 nodes in McKeown procedures. Furthermore, high mediastinal lymphadenectomy was performed in 65%, 43%, and 37%, and 70%, 48%, and 64% of Ivor-Lewis and McKeown procedures, respectively. Anastomotic leakage rates were 22%, 22%, and 16% in Ivor-Lewis cases, and 14%, 12%, and 11% in McKeown cases. Hospital stay was 13, 14, and 13 days for Ivor-Lewis procedures, and 12, 9, and 11 days for McKeown procedures. In Ivor-Lewis and McKeown, respectively, the sensitivity analysis revealed textbook outcome rates of 43%, 54%, and 51%, and 47%, 64%, and 64%; anastomotic leakage rates of 28%, 18%, and 15%, and 13%, 11%, and 10%; and hospital stay of 11, 12, and 12 days, and 10, 9, and 9 days.

This study demonstrates favorable outcomes over time in achieving textbook outcome after RAMIE. Areas for improvement include a reduction of anastomotic leakage and shortening of hospital stay.