Background Familial adenomatous polyposis (FAP) requires lifelong surveillance for duodenal lesions due to increased cancer risk. Aims This study evaluated the effectiveness, safety, and long-term impact of endoscopic surveillance and treatment of duodenal and ampullary lesions, focusing on lesion detection, dysplasia grade, Spigelman stage evolution and adverse events. Methods This retrospective study analyzed prospectively collected data from 233 genetically confirmed FAP patients undergoing esophagogastroduodenoscopy (EGD) at the National Cancer Institute between 2013 and 2023. Demographics, endoscopic procedures, histology, Spigelman staging, treatment techniques, and outcomes were assessed. Results A total of 862 EGDs were performed, with 208 duodenal lesions treated. Structured surveillance was associated with increased lesion treatment and reduced high-grade dysplasia rates. Cold snare polypectomy was the most commonly used technique (41.9%). Histology showed low-grade dysplasia in 72.4% of lesions, high-grade dysplasia in 25.9%, and adenocarcinoma in 1.7%. Forty-seven ampullary lesions were identified; most were managed with surveillance (78.7%), while 21.3% underwent papillectomy. Conclusions Endoscopic management of duodenal lesions in FAP is safe and effective. Papillectomy for selected ampullary lesions carries low morbidity and low risk of progression. A multidisciplinary approach may reduce progression to advanced Spigelman stages and high-grade dysplasia.
INTRODUCTION AND OBJECTIVES:Steatotic liver disease (SLD) is a leading cause of liver disease worldwide. Itsstratified into metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol-associated liver disease (MetALD), and alcohol-associated liver disease (ALD) based on self-reported alcohol use remains a challenge. We developed the Steatosis Liver Index (SLI), an ordinal machine-learning model that distinguishes these phenotypes using SLD clinical and laboratory variables without alcohol quantification data MATERIALS AND METHODS: National Health and Nutrition Examination Survey (NHANES) data cycles (1999 to 2006 and 2017 to March 2020) were analyzed. Participants meeting eligibility criteria (age ≥20 years and elevated alanine aminotransferase) were stratified into MASLD, MetALD, and ALD. Using an ordinal forest framework, SHAP-guided variable selection, and the Synthetic Minority Oversampling Technique (SMOTE) to address class imbalance, the model was derived from survey cycles 1999-2006 (n=3452) and validated on survey cycles 2017-2020 (n=1013) RESULTS: Of 57,034 participants, 4465 met eligibility criteria, 4145 MASLD, 245 MetALD, and 75 ALD. We derived a model including 15 variables (high-density lipoprotein, mean corpuscular volume, gamma glutamyl transferase, glycohemoglobin, height, mean diastolic blood pressure, ferritin, total cholesterol, monocyte percentage, globulin, iron, hemoglobin, mean systolic blood pressure, sex, and aspartate aminotransferase) with an accuracy of 0.855 in training and 0.848 in validation sets. In the validation dataset, c-statistics were 0.770 and 0.802 for distinguishing MASLD from MetALD and from ALD, respectively. CONCLUSION:This novel SLI may provide a clinical tool for both practice and research settings to stratify SLD phenotypes.
Background Rectal bleeding in infants younger than 3 months may arise from benign conditions but can also represent an early sign of necrotizing enterocolitis (NEC). Aims We aimed to describe etiology, management, and outcomes of rectal bleeding in early infancy. Methods We retrospectively analysed data from patients presenting with rectal bleeding between 2015 and 2024, collecting demographics, comorbidities, diagnostic work-up, treatments, recurrence, and outcomes. Results Ninety-one infants were included, with a median age at onset of 20 days; 34 (37.4%) were preterm and 43 (47.3%) had congenital heart disease (CHD). NEC was the most frequent diagnosis (35.1%), followed by isolated rectal bleeding (IRB, 22.0%) and infectious gastroenteritis (16.5%). Among infants diagnosed with NEC, 25.0% required surgery; it occurred predominantly in those with CHD (25/32, 78.1%) and preterm infants (7/32, 21.9%). Stool pathogens were detected in 25.3% of cases. Bleeding recurrence occurred in 16.5% of infants. In-hospital mortality was 2.2%. Conclusions NEC is the leading cause of rectal bleeding in early infancy, followed by IRB. Although IRB is often benign, rectal bleeding should always prompt careful evaluation, particularly in high-risk infants such as those with CHD and those born preterm, in whom rectal bleeding may represent an early manifestation of NEC. Early recognition and close monitoring are essential to optimize outcomes.
BACKGROUND & AIMS:The rising prevalence of cirrhosis, driven by non-viral etiologies, strains healthcare systems and necessitates personalized hepatocellular carcinoma (HCC) surveillance. We conducted a head-to-head comparison of the Toronto HCC risk index (THRI) and aMAP score within an etiology-diverse Western population to evaluate their performance in identifying low-risk patients. METHODS:We included adults with cirrhosis from 3 sites in the Netherlands. The exclusion criteria were follow-up <6 months, missing risk score data, or prior HCC. THRI and aMAP were calculated as previously reported. Performance was assessed using time-dependent AUC analysis and cumulative HCC incidence using Kaplan-Meier analysis. RESULTS:In a cohort of 1531 patients, the median age was 53 years (IQR: 44-61), 63% were male, the median CTP was 5 (IQR: 5-7). The etiology of liver disease was non-viral in 60% of patients, with the majority having steatotic liver disease (SLD: 453, 30%). Over a median follow-up of 5.4 years (IQR: 3.0-9.1), 196 patients developed HCC. Overall 5-year cumulative HCC incidence was 7.2% (95%CI: 5.7-8.7). THRI offered superior discrimination over aMAP at 3 years (AUC 0.74 vs 0.64) and at 5 years (0.73 versus 0.70). Patients identified by THRI as low-risk (n = 269, 18%) had a lower 5-year risk of HCC (0.5%) than those identified as low risk by aMAP (2.9%). Among the patients considered low-risk by aMAP (n = 437), two-thirds were assigned a higher risk category by THRI and had a substantially higher 5-year HCC incidence than low-risk THRI and low-risk aMAP (4.3%vs. 0%, p = 0.009). CONCLUSION:THRI appears more effective than aMAP in identifying patients with negligible 5-year HCC risk and may inform personalized HCC surveillance strategies, particularly in supporting deferral decisions in low-risk patients.
BACKGROUND:While the addition of Ivonescimab to chemotherapy has demonstrated promising results in non-small cell lung cancer compared with chemotherapy alone, its efficacy as a first- or second-line treatment in advanced/metastatic gastric cancer remains to be established. AIMS:GRACIE aims to evaluate the efficacy and safety of Ivonescimab combined with FOLFOX chemotherapy as first-line treatment (Arm-1) or as second-line when combined with paclitaxel or irinotecan or FOLFIRI following progression (Arm-2), in patients with advanced/metastatic gastric cancer and esophageal adenocarcinoma, regardless of actionable targets' presence (PD-L1/HER2/CLDN-18.2). METHODS:This multicenter, two-arm, non-randomized, open-label exploratory phase II study is recruiting 88 patients, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, over 18 French centers. The primary objective is the Objective Response Rate (ORR) after central review according to RECIST v1.1 in HER2- and CLDN-18.2-negative, treatment-naïve patients (Arm-1) and patients with a single previous line for advanced disease, regardless of biomarkers expression (Arm-2). Secondary objectives are investigator-assessed ORR, Duration-of-Response, Progression-Free Survival, Overall Survival, time to ECOG performance status deterioration, Safety and Quality-of-life. DISCUSSION:GRACIE will provide crucial information about Ivonescimab plus chemotherapy regimens efficacy either as a first- or second-line treatment in molecularly defined advanced/metastatic gastric and esophageal adenocarcinomas to inform future phase III trials. TRIAL REGISTRATION:EU-CTIS: 2025-520694-39-00, ClinicalTRials.gov: NCT06846346.
BACKGROUND AND AIMS:Selection criteria for liver transplant allocation are crucial for benefit-risk assessment of every patient evaluated for liver transplantation (LTx). Currently, Milan criteria are the key decision tool in several countries to assess whether a patient with hepatocellular carcinoma (HCC) is eligible for LTx. In this post-hoc analysis of the SiLVER Study, we analysed the performance of Milan criteria compared to the broader criteria UCSF, Up-to-7 and MT 2.0 to assess whether there is need to reform the selection process of HCC patients evaluated for LTx. METHODS:Outcomes of 485 patients of the multicentre and randomized SiLVER Study were analysed determined by recurrence-free survival (RFS), overall survival (OS) and freedom of tumor (FoT). RESULTS:Discrimination was modest for all four criteria and showed no statistically significant differences across OS (C-index 0.55-0.57), RFS (0.57-0.59) or FoT (0.62-0.64), with Metroticket 2.0 numerically highest. In the competing-risks analysis, being outside any criterion was associated with an increased subdistribution hazard of recurrence (sHR 2.7-3.6, all p < 0.001). The broader criteria classified substantially more patients as eligible (Up-to-7 83.9% vs Milan 65.6%). CONCLUSIONS:Our data based on explant histopathology suggest that Milan criteria exclude patients with HCC evaluated for LTx without demonstrable benefit, questioning Milan criteria as sole selection tool in many regions doing liver transplants.
BACKGROUND:Gastrointestinal stromal tumors (GISTs) are tumors with malignant potential. This research aims to develop an artificial intelligence (AI)-based system for analyzing endoscopic ultrasonography (EUS) visuals and generating risk scores. AIMS:This system is designed to better predict GIST risk levels by identifying risk factors. METHODS:An internal dataset comprising 504 EUS images from 226 patients with pathologically confirmed GISTs was collected from Yuzhong Hospital and Jiangnan Hospital of the Second Affiliated Hospital of Chongqing Medical University, Sichuan Provincial People's Hospital between 2018 and 2024. Multiple AI-based machine learning models were developed and tested. Six machine learning models were compared, and the optimal diagnostic model was selected based on statistical results. RESULTS:For the best-performing model, XGBoost, the internal test set results were as follows: overall accuracy 83.17%, sensitivity 75.68%, specificity 93.72%, positive predictive value (PPV) 73.21%, negative predictive value (NPV) 93.52%, F1 score 0.74, and area under the curve (AUC) 0.97. The external validation set results were: overall accuracy 80.68%, sensitivity 71.53%, specificity 92.72%, PPV 70.44%, NPV 92.78%, F1 score 0.70, and AUC 0.94. CONCLUSIONS:This model utilizes machine learning algorithms on EUS images to accurately predict GIST risk stratification.
BACKGROUND:Computer-aided detection (CADe) improves adenoma detection rate (ADR) in randomised trials; however, translation into routine practice remains uncertain, with real-world studies showing inconsistent results. AIMS:To evaluate CADe in a pragmatic multicentre setting using a within-endoscopist design, with endoscopists serving as their own comparators under routine clinical conditions. METHODS:Pragmatic multicentre observational study analysing prospectively recorded data from 13 units. Six endoscopists performed procedures in a unit with routine CADe use and in units without CADe, enabling within-operator comparisons under naturalistic conditions. The primary outcome was ADR. Secondary outcomes included combined adenoma plus clinically significant serrated polyp detection rate (A+CSSPDR) and additional polyp-related metrics. RESULTS:Of 3161 colonoscopies, 2973 were analysed (947 CADe; 2026 non-CADe). ADR was higher with CADe (34.4%vs 30.7%; p = 0.042). A+CSSPDR was also higher (40.3%vs 35.8%; p = 0.018), with consistent improvements across other metrics. In multivariable analysis, CADe remained independently associated with higher ADR (aOR 1.31, 95%CI 1.11-1.55; p = 0.002) and A+CSSPDR (aOR 1.33, 95%CI 1.13-1.56; p = 0.001), with attenuation after adjustment for endoscopist. CONCLUSION:In a pragmatic real-world setting, CADe improved detection of colorectal neoplasia. This within-endoscopist design provides a balanced estimate of effectiveness by minimising behavioural bias affecting both trial and real-world studies.
BACKGROUND:EUS-guided FNB is crucial in the management of solid pancreatic lesions (SPLs). Very little is known about SPLs and the risk of pancreatic cancer (PDAC) in young patients. METHODS:All consecutive patients who have undergone EUS-guided FNB for non-metastatic SPLs between July 1st 2021 and June 30th 2025 at the Gastroenterology Unit of the University of Verona were evaluated retrospectively. Demographical, clinical, radiological and endoscopic data were extrapolated from a prospectively maintained database. RESULTS:Among the 1250 included patients, 65 (5.2%) were younger than 40 years. The proportion of PDAC was 12.3% compared with 55.9% of patients older than 40 (p < 0.001). The most frequent SPLs were NET (44.6%) and solid pseudopapillary neoplasms (24.6%). Hypovascular pattern, dilation of the main pancreatic duct (MPD), and of the common bile duct (CBD) were associated with a significant increase of PDAC likelihood in both, general population and patients younger than 40 years. Finally, in 39 patients (60%) the SPLs required surgical resection and in 8 patients (12.3%) the SPLs were benign. DISCUSSION:The proportion of SPLs in patients younger than 40 is remarkable in a tertiary center. Despite the probability of malignancy is lower in this setting, ruling out PDAC is crucial, particularly in case of hypovascular lesions with dilation of MPD and/or CBD.
BACKGROUND:Endoscopic resection is the standard treatment for rectal neuroendocrine tumors (r-NETs) ≤10 mm, yet the optimal technique remains debated. Modified endoscopic mucosal resection (m-EMR) has been proposed as an alternative to endoscopic submucosal dissection (ESD), but prior evidence is mainly retrospective and recent randomized controlled trials (RCTs) are inconclusive. METHODS:We systematically searched CENTRAL, PubMed, Embase, and WanFang from January 1, 1970 to December 23, 2025, for RCTs comparing m-EMR and ESD in r-NETs ≤10 mm. Evidence certainty was evaluated using GRADE, and trial sequential analysis (TSA) was conducted to support the statistical stability of the pooled estimate. RESULTS:Six RCTs involving 440 patients were included. No significant differences were found between m-EMR and ESD in histologic complete resection (RR = 1.00, 95% CI 0.97-1.03; I² = 0%), en bloc resection (P = 0.75), or procedure-related adverse events (P = 0.94). m-EMR was associated with significantly shorter procedure time and lower hospitalization cost. Evidence certainty was moderate; TSA confirmed the reliability of the findings, and both cumulative and sensitivity analyses supported the robustness. CONCLUSION:m-EMR provides comparable short-term histologic efficacy to ESD, while being associated with shorter procedure time and lower hospitalization costs, supporting its consideration as a reasonable first-line option for r-NETs ≤10 mm.
AIMS:To characterize the progression patterns and analyze the efficacy of immune checkpoint inhibitors (ICIs) in unresectable, recurrent, or metastatic cholangiocarcinoma (CCA). METHODS:A retrospective analysis was conducted in CCA patients treated with ICIs between September 2019 and September 2024. The progression patterns of ICIs were assessed, and survival and prognostic factors were analyzed using Kaplan-Meier and Cox regression models. RESULTS:Among 131 eligible patients, the median overall survival (OS) and progression-free survival (PFS) were 14.1 and 7.9 months, respectively. Multivariable Cox analysis identified lung metastasis, absent abdominal lymph node/retroperitoneal lymph node (LN/RPLN) metastasis, and CA199 ≥ 35 U/ml as independent predictors of shorter PFS, and smoking, no surgery, and CA199 ≥ 35 U/ml as predictors of shorter OS (all p < 0.05). Rising CA199 correlated with poorer PFS (p < 0.05). Progression occurred in 80 patients, 77.5% within 12 months. Oligo-progression was the main pattern (53.8%). Liver (43.8%) and abdominal LN/RPLN (38.8%) were the most common sites of progression. Oligo-progression was associated with superior OS versus systemic progression (median 22.7 vs. 11.7 months, p = 0.003). Among oligo-progression patients, local plus systemic therapy showed a trend toward better OS than systemic therapy alone (28.9 vs. 15.8 months, p = 0.062). CONCLUSIONS:ICIs demonstrate meaningful efficacy in CCA. Oligo-progression represents the predominant failure pattern and is associated with favorable prognosis.
