crossing96/oncoscreening huggingface dataset:
TRIM21 promotes K63-linked ubiquitination of ALKBH5 and suppresses cuproptosis via down-regulation of LIAS in esophageal squamous cell carcinoma.	Cuproptosis is a newly discovered programmed cell death regulated by lipoic acid synthase (LIAS) in cancer cells. However, its functions in Esophageal squamous cell carcinoma (ESCC) and the underlying mechanism remains unclear. Here, we show that in human ESCC cells, TRIM21 facilitates the K63-linked ubiquitination dependent translocation of ALKBH5 from cytosol to nucleus and augments its m6A demethylase activity. LIAS mRNA was demethylated by ALKBH5, and then further identified by reader IGF2BP3, which comprehensively caused the lower expression of LIAS. Moreover, O-GlcNAc transferase OGT facilitated TRIM21-mediated K63-ubiquitination of ALKBH5. Combined treatment with an OGT inhibitor OSMI-1 and copper ionophore elesclomol eliminates tumor growth and remarkably enhances the sensitivity of tumor cells to cisplatin. Together, our study identifies TRIM21 Ubiquitinated-ALKBH5 as a critical gatekeeper to restrict cuproptosis, and such mechanism may contribute to tumor development and drug resistance in ESCC.	esophagus
Research trends in neoadjuvant therapy for esophageal cancer: a bibliometric and meta-analysis.	BACKGROUND: Neoadjuvant treatment followed by radical surgery has become the standard treatment approach for locally advanced esophageal cancer. We aimed to explore the development trends, research hotspots, and differences among treatment regimens in this field using bibliometric analysis and meta-analysis. METHODS: Literature on neoadjuvant therapy for esophageal cancer was retrieved from PubMed, Embase, Cochrane Library, and Web of Science. Bibliometric analysis and visualization were conducted on publications since 2000 from Web of Science Core Collection (WoSCC) using CiteSpace, VOSviewer, and the bibliometrix package in RStudio. A meta-analysis of phase III randomized controlled trials (RCTs) involving different treatment regimens was performed using Stata/MP, based on studies screened from all four databases. RESULTS: A total of 1,324 and 27 studies were included in the bibliometric analysis and meta-analysis, respectively. Overall, there was an increasing trend in the volume of publications in this field. The United States and the Karolinska Institute emerged as the leading country and institution in terms of publication volume. The most frequently cited journals and authors were Annals of Surgery and van Hagen P, respectively. Research hotspots have primarily focused on neoadjuvant chemotherapy (NCT) and chemoradiotherapy (NCRT), with a recent shift toward neoadjuvant immunotherapy (NIT). The pooled complete pathological response (pCR) rates were 0.08 for NCT, 0.29 for NCRT, 0.22 for neoadjuvant chemoimmunotherapy (NCIT), and 0.27 for NCRT combined with targeted therapy (NCRT+NTT). The pooled rates of tumor regression grade 1 (TRG1) were 0.09, 0.25, 0.30, and 0.37, respectively. The R0 resection rates were 0.87, 0.96, 0.99, and 0.96, while the incidence of grade ≥3 treatment-related adverse events (TRAEs) was 0.37, 0.66, 0.25, and 0.69, respectively. CONCLUSIONS: Neoadjuvant therapy for esophageal cancer has evolved significantly over the past decades. Recently, NIT has emerged as a key area of research interest. However, its clinical efficacy and safety require validation through long-term follow-up data from future phase III RCTs.	esophagus
The comprehensive oral microbiome landscape unveils its interplay with poor oral health in esophageal squamous cell carcinoma risk.	Growing evidence links poor oral health to an increased esophageal squamous cell carcinoma (ESCC) risk, with the oral microbiome recognized as a key contributor. However, human-based evidence remains limited. Here, we analyze salivary shotgun metagenomic data from 390 ESCC case-control pairs and 16S rRNA sequencing data from 206 incident esophageal cancer (EC) case-control pairs. We identify 50 bacterial species altered in ESCC (e.g., enriched Porphyromonas catoniae and depleted Campylobacter rectus) and disruptions in 54 biochemical pathways (e.g., inosine 5'-phosphate degradation). These features potentially mediate the association between poor oral health and ESCC. Notably, this association is stronger among individuals with lower Streptococcus mitis levels, implicating pathways related to thiamine salvage and energy metabolism. Consistent findings in the validation dataset further support the interplay between the oral microbiome and oral health in EC risk. Our results highlight the promise of precision-targeted microbial interventions to improve oral health for ESCC prevention and management.	esophagus
First-line pembrolizumab plus chemotherapy for advanced HER2-negative gastric or gastroesophageal junction adenocarcinoma: Health-related quality of life from the randomized phase III KEYNOTE-859 trial.	BACKGROUND: The objective with cancer treatment is prolonging survival; however, treatment should also not negatively impact health-related quality of life (HRQoL). Therefore, the KEYNOTE-859 trial compared the impact of pembrolizumab plus chemotherapy against placebo plus chemotherapy on HRQoL in participants with advanced or metastatic HER2-negative gastric or gastroesophageal (GEJ) adenocarcinoma. METHODS: Overall, 1579 participants were randomly assigned 1:1 to pembrolizumab 200 mg or placebo plus chemotherapy every 3 weeks. We report prespecified exploratory patient-reported outcomes (PROs), including change from baseline to week 18, and time to deterioration (TTD) assessed in EORTC QLQ-C30 scales/items, EORTC QLQ-STO22 pain scale, and EQ-5D-5L visual analog scale (VAS). RESULTS: Among 1531 participants in the PRO full analysis set (FAS) population for the QLQ-C30 and EQ-5D-5L VAS assessments, least squares mean (LSM) changes from baseline to week 18 were similar between treatments for both assessments. For the 1516 participants in the PRO FAS population for the QLQ-STO22 pain scale, LSM change favored pembrolizumab plus chemotherapy (LSM difference, -2.58; 95 % CI, -4.73 to -0.43). TTD was similar between treatments for the QLQ-C30 scales/items; TTD favored pembrolizumab plus chemotherapy (HR, 0.77; 95 CI, 0.59-1.00) for the QLQ-STO22 pain scale. CONCLUSIONS: HRQoL was similar between groups during treatment; the addition of pembrolizumab maintained HRQoL with a numerical trend toward improvement. Combined with safety and efficacy results published at the interim analysis for KEYNOTE-859, HRQoL data support a favorable benefit-to-risk profile for pembrolizumab plus chemotherapy as a first-line treatment option for advanced or metastatic HER2-negative gastric or GEJ adenocarcinoma.	esophagus
Potentially Causal Associations Between Extensive Gastric Atrophy and Esophageal Squamous Cell Carcinoma: A Nationwide Retrospective Cohort Study in Japan.	OBJECTIVES: A potential association between esophageal squamous cell carcinoma (ESCC) and gastric atrophy (GA) has been reported. However, most published studies have used case-control designs, leading to selection bias. This study aimed to investigate the causal association between ESCC and GA using a nationwide cohort. METHODS: A retrospective cohort study was conducted on consecutive participants who underwent endoscopy at 17 health check-up institutes in Japan between 2013 and 2017, with at least one follow-up endoscopy by December 2022. GA was evaluated endoscopically and classified into atrophy-free, closed-type, and open-type GA. The association between ESCC incidence and GA was estimated using the Kaplan-Meier method and Cox regression. RESULTS: Among 33,461 participants, 17,398 (52.0%), 8257 (24.7%), and 7804 (23.3%) were classified into atrophy-free, closed-type GA, and open-type GA, respectively. Seventy-seven ESCCs were identified during a median 6-year follow-up period. The incidence of ESCC was 24 cases (0.024%/year) in the atrophy-free group, 15 cases (0.031%/year) in the closed-type GA group, and 38 cases (0.089%/year) in the open-type GA group, with a significantly higher incidence observed in the open-type GA group (p < 0.001). After adjusting for established risk factors (e.g., age, sex, drinking, and smoking), open-type GA, but not closed-type GA, was an independent risk factor for ESCC (adjusted hazard ratio: 2.72, 95% confidence interval: 1.58-4.69). CONCLUSIONS: This Japanese nationwide cohort study provides new evidence suggesting a causal association between extensive GA and the subsequent development of ESCC.	esophagus
Strategies to prevent Barrett's esophagus associated esophageal adenocarcinoma.	There has been a rise in the incidence of esophageal adenocarcinoma (EAC) over the past five decades in the United States, and it remains a highly lethal malignancy due to frequent late-stage diagnosis. Barrett's esophagus (BE), a well-established precursor to EAC, presents a critical window for early intervention through screening, surveillance, and endoscopic eradication therapy. Despite gastrointestinal society guideline recommendations for screening, the majority of patients with BE or early EAC remain undiagnosed until symptoms of late-stage cancer emerge. This review outlines current challenges and evolving strategies in the United States in BE detection and management, including risk stratification models, non-endoscopic screening tools, high-quality endoscopic techniques, tissue-based biomarkers, and artificial intelligence-enhanced imaging. We highlight best practices for surveillance, emphasizing the importance of thorough inspection of high-risk anatomic zones and the integration of advanced imaging. Endoscopic eradication therapy, including endoscopic mucosal resection and ablation, achieves high rates of complete eradication when performed with meticulous technique, especially with comprehensive treatment of the gastroesophageal junction and gastric cardia. Long-term surveillance remains essential due to the risk of recurrence. As new technologies continue to emerge, integrating precision tools into routine practice will be key to improving outcomes and reducing EAC mortality.	esophagus
Opening the black box: defining true-negative outcomes in esophageal cancer screening - a population-based study.	BACKGROUND: Current negativity definition in esophageal cancer screening overlooks the risk heterogeneity between individuals with non-dysplastic Lugol's unstained lesions (ND-LULs) and normal-stained epithelium. We aimed to define the screening negativity by the incidence risk of severe dysplasia and above lesions (SDAs) after chromoendoscopy and ascertain their re-screening interval. METHODS: We enrolled 815 participants with ND-LULs and 14,123 with normal-stained epithelium from the screening arm of a community-based randomized controlled trial (RCT). The control groups included the RCT's unscreened arm (n = 16,473), and population controls matched 1:5 by birth year, sex, and village (4075 controls for ND-LULs group, 70,615 controls for normal-stained group). All participants were followed up for up to 10 years. Poisson regression and the cumulative incidence function compared the cumulative incidence of SDA between groups. RESULTS: Compared with the RCT control, the cumulative incidence of SDAs was significantly higher in the ND-LULs group over 10 years (adjusted IRR = 3.16, 95% CI: 2.02-4.76) but lower in the normal-stained group (adjusted IRR = 0.52, 95% CI: 0.37-0.72). Similar results were achieved using the general population control. The cumulative incidence of SDAs in the ND-LULs group significantly exceeded controls after 2-3 years while remaining consistently lower in the normal-stained group over 10 years. CONCLUSIONS: Individuals with normal Lugol staining should be considered the genuinely screening-negative population for esophageal cancer. A 10-year screening interval is recommended for normal-stained individuals, while 2-3 years are necessary for ND-LULs.	esophagus
Impact of staging investigations on nodal upstaging in early esophago-gastric adenocarcinoma: multicenter CONGRESS dataset analysis.	Current recommendations for the clinical staging of patients undergoing resection for early esophago-gastric (OG) cancer are variable and the value of staging investigations is unclear. The aim of this study was to assess current practice for staging early OG cancers across the UK, and the accuracy of staging with reference to nodal disease at surgery. Data for surgical patients was extracted from the CONGRESS database, a large UK-based multicenter dataset for patients with T1N0 OG cancer between 2015 and 2022. Logistic regression analysis was performed to assess the association of different staging investigations on subsequent nodal upstaging. Cox regression analysis was used to analyze for impact on overall survival (OS). In total, 497 patients from 28 centers were included, 13.1% of which underwent N upstaging from clinical to pathological staging. The rate of unexpected LNM was 12.7% in patients who underwent a CT pre-treatment, compared to 18.2% in patients with no staging investigations. Patients that underwent no staging investigations were also more likely to have unexpected nodal metastases at surgery (OR 6.66 [95%CI 1.34-33.24], P = 0.021). The addition of PET-CT, EUS and staging laparoscopy had no significant impact on N upstaging (P = 0.062, 0.053, and 0.690, respectively). No combination of staging modality had a significant impact on OS. Current guidelines are variable in their recommendation of pre-operative staging investigations for early OG cancer. This study suggests CT plays an important role in the staging of this population. Other staging modalities could be considered selectively, rather than routinely, to preserve resources and accelerate treatment pathways.	esophagus
The Impact of Worsening Nutritional Status in Neoadjuvant Chemotherapy on Postoperative Outcomes in Esophageal Cancer.	BACKGROUND/AIM: Esophageal squamous cell carcinoma (ESCC) significantly affects nutritional status. While neoadjuvant chemotherapy (NAC) is the standard treatment for clinical stage II/III ESCC, its impact on nutritional status and postoperative outcomes remains unclear. This study investigated the relationship between nutritional deterioration during NAC and outcomes following esophagectomy. PATIENTS AND METHODS: This single-center retrospective study included 85 patients with thoracic ESCC who received NAC followed by esophagectomy between January 2019 and December 2023. The NAC regimens included cisplatin plus 5-fluorouracil (CF), administered with or without radiation, and docetaxel, cisplatin, and fluorouracil (DCF). Nutritional status and postoperative outcomes were evaluated. RESULTS: Of the 85 patients, 20 received DCF, 36 received CF alone, and 29 received CF with radiation. Nutritional deterioration was noted during NAC with significant decreases in Prognostic Nutritional Index (PNI), Geriatric Nutritional Risk Index (GNRI), and hemoglobin-albumin-lymphocyte-platelet (HALP) score. Grade 3-4 hematologic toxicities correlated with reductions in GNRI and increases in neutrophil-lymphocyte ratio (NLR) (p=0.004 and 0.020, respectively). An increase in NLR post-NAC and decrease in PNI post-NAC were associated with prolonged hospital stays (p=0.024 and 0.042, respectively). Post-NAC NLR of 2.3 or over and HALP score below 20 were significantly associated with poorer overall survival (p=0.012 and <0.001, respectively). CONCLUSION: Although NAC reduces tumor burden and eliminates micrometastases, it potentially worsens nutritional status. Chemotherapy-induced hematologic toxicities are a risk factor for this decline. Therefore, comprehensive nutritional assessment and timely intervention during NAC are essential to optimize patient outcomes.	esophagus
Trastuzumab Deruxtecan Versus Ramucirumab-Paclitaxel as Second-Line Therapy for Patients With HER2-Positive Gastric or GEJ Adenocarcinoma.	BACKGROUND: The single-arm phase II DESTINY-Gastric02 (DG-02) study investigated trastuzumab deruxtecan (T-DXd) as second-line therapy in Western patients with HER2-positive unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma that progressed during or after trastuzumab-based first-line therapy. The aim of the current study was to compare patients in the DG-02 study with a real-world reference group of patients who received ramucirumab and paclitaxel (Ram + Pac) as second-line therapy. METHODS: A total of 71 of 79 patients from DG-02 who had received trastuzumab in the metastatic setting were included. A comparable cohort of patients with HER2-positive esophageal, gastric, or GEJ adenocarcinoma who received trastuzumab in the first-line setting and Ram + Pac in the second-line setting was identified from the Netherlands Cancer Registry (NCR; n=120). Propensity score trimming and propensity score were used to select a reference group for DG-02 from patients in the NCR, based on sex, age, ECOG performance status, primary tumor location, body mass index, renal function, number of metastatic sites, presence of liver metastases, and duration of first-line therapy. RESULTS: Propensity score trimming led to the exclusion of 12 patients from the DG-02 group and 33 patients from the NCR group. Thereafter, propensity score matching resulted in a balanced group of patients from the NCR (n=78) and the DG-02 trial (n=58). Median overall survival was significantly longer among patients treated with T-DXd (11.6 months; 95% CI, 9.0-20.5) compared with those treated with the Ram + Pac reference regimen (6.2 months; 95% CI, 4.5-10.0; P<.0001). CONCLUSIONS: Compared with patients with metastatic, trastuzumab-pretreated HER2-positive gastric or GEJ adenocarcinoma who received Ram + Pac, those who received T-DXd as second-line therapy had improved overall survival.	esophagus
Application of artificial intelligence in esophageal surgery: a systematic review.	The aim of this systematic review was to summarize and analyze the available literature on the application of artificial intelligence systems in esophageal surgery, focusing on anatomy recognition, instrument detection, and surgical phase recognition. Esophageal cancer poses a significant global health challenge, ranking as the seventh most common cancer worldwide. Esophagectomy is the only curative treatment for non-metastatic esophageal cancer. While the introduction of minimally invasive esophagectomy and later robot-assisted minimally invasive esophagectomy significantly improved surgical precision and patient outcome, this development promoted a transition to increasing digitalization and video processing. Subsequently facilitating the integration of artificial intelligence is a promising tool in the enhancement of esophageal surgery. A systematic search was conducted following the PRISMA guidelines in the Medline and Web of Science databases. Studies published between January 2019 and June 2025 published in English and without restrictions to study type were included. Inclusion criteria focused on artificial intelligence-based anatomy recognition, instrument recognition, and phase recognition in esophageal surgery. Studies addressing preoperative and postoperative risk prediction or artificial intelligence applications not directly related to the surgical procedure were excluded. The systematic literature search yielded 7063 results. After screening, we identified six studies examining artificial intelligence applications in esophagectomy focusing on anatomy, instrument, and phase recognition. Artificial intelligence can be a useful tool-especially for intraoperative anatomy recognition-reaching detection rates comparable to trained surgeons in real time as seen in one study, reaching a Dice coefficient of 0.58, which was close to that of an expert esophageal surgeon (0.62) and significantly higher than the general surgeon (0.47, p= 0.0019). Due to the heterogeneity of study aims, utilized algorithms and outcome measures direct comparison between studies was not feasible. Artificial intelligence has demonstrated significant potential in enhancing esophageal surgery by improving anatomical recognition and optimizing surgical workflow. Despite these advancements, challenges remain in standardizing datasets, refinement of annotation methodologies, and seamless integration into real-time surgical navigation systems. To ensure clinical applicability, future research should focus on large-scale validation and prospective clinical trials to establish artificial intelligence's clinical utility and safety in minimally invasive esophagectomy.	esophagus
Camrelizumab plus chemotherapy versus chemoradiotherapy as neoadjuvant therapy for resectable esophageal squamous cell carcinoma: Phase 2 randomized trial (REVO).	Several studies have evaluated PD-1 inhibitors plus chemotherapy as neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma (ESCC), but comparative data with chemoradiotherapy (CRT) remain limited. This multicenter, randomized, open-label, phase 2 non-inferiority trial (REVO, NCT05007145) assessed the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy (ICT) versus CRT in patients with resectable, locally advanced ESCC. A total of 104 patients were randomized to ICT (camrelizumab, nab-paclitaxel, cisplatin) or CRT (nab-paclitaxel, cisplatin, radiotherapy). The primary endpoint was pathologic complete response (pCR). ICT achieved a pCR rate of 32.7% versus 34.6% with CRT (rate ratio 0.94, 90% CI 0.6-1.49), demonstrating non-inferiority and meeting the pre-specified primary endpoint. Major pathologic response was observed in 42.3% of ICT patients and 57.7% of CRT patients, with R0 resection achieved in 100% of both groups. 1-year disease-free survival was 89.1% versus 78.2%, and 1-year overall survival was 100% versus 92.3% for ICT and CRT, respectively. Grade ≥3 treatment-related adverse events occurred in 19.2% of ICT patients and 33.3% of CRT patients, and surgical complications were reported in 31.1% and 35.9%, respectively. These findings indicate that ICT is a safe and effective neoadjuvant strategy for resectable ESCC with a more favorable safety profile.	esophagus
Zinc Finger Protein 82 regulates p53 protein stability through histone deacetylase and enhances neo-adjuvant chemotherapy in esophageal cancer.	Tumor suppressor genes silenced by CpG methylation uncover the molecular mechanism of tumorigenesis and potential tumor biomarkers. Our previous research found that the promoter of zinc-finger protein 82 (ZFP82) was highly methylated in multiple cancers, including esophageal cancer, which induces the occurrence and development of tumors. Here, we describe the frequent detection of methylation of the ZFP82 promoter CpG Island in patients who did not respond to neoadjuvant chemotherapy, indicating that ZFP82 may related to esophageal cancer chemo-resistance. We further verified that in esophageal cancer cells expressing wild-type p53, ZFP82 bound to the HDAC3 promoter and mediated its interaction with p53, leading to HDAC3 cleavage and reduction of p53 ubiquitin-dependent proteasomal degradation, thus enhancing wild-type p53 stability. In cells expressing mutant p53, ZFP82 interacted with HDAC3 to regulate the down-regulation of HSP 70, leading to degradation of mutant p53. Through both mechanisms, the restoration of ZFP82 enhanced the chemosensitivity in esophageal cancer cells expressing wild-type p53 or mutant p53, significantly inhibiting in vivo tumorigenicity of these cells. Analyses of the expression of ZFP82 and clinical data indicated that ZFP82 expression correlated with improved prognosis. Our results define a mechanism for p53 stabilization via ZFP82-dependent HDAC3 decay under genotoxic stress conditions and validate a candidate bio-marker of early prediction of patients who will respond to esophageal cancer neoadjuvant chemotherapy.	esophagus