BACKGROUND:The fecal immunochemical test (FIT) is widely implemented as a first-line tool in organized colorectal cancer (CRC) screening programs, including Italy. Following a positive FIT, colonoscopy is recommended. Computer-aided detection (CADe) systems have the potential to enhance adenoma detection, particularly in FIT-positive populations where identifying advanced adenomas is critical for cancer prevention. This study evaluated the diagnostic performance of CADe-assisted colonoscopy versus standard colonoscopy (SC) in a FIT-based screening cohort. METHODS:In this multicenter, randomized controlled trial, patients with a positive FIT result were randomized to undergo either CADe-assisted or standard colonoscopy. The primary endpoint was the advanced adenoma detection rate (AADR). Secondary endpoints included overall adenoma detection rate (ADR), adenomas per colonoscopy (APC), and mean withdrawal time (WT). RESULTS:Of 1077 patients enrolled, 68 were excluded due to inadequate bowel preparation, leaving 1009 patients for analysis (CADe: n = 506; SC: n = 503). AADR was comparable between the groups (21.3% vs. 20.5%, p = 0.794). However, CADe significantly improved ADR (67.6% vs. 59.8%, p = 0.012) and APC (1.82 ± 2.12 vs. 1.34 ± 1.81, p < 0.001). Mean WT was longer in the CADe group (17.10 ± 8.28 min vs. 16.13 ± 8.28 min, p = 0.016). CONCLUSIONS:In a FIT-based organized CRC screening setting, CADe did not enhance detection of AADR with a modest increase in withdrawal time. NCT04441580.

Colorectal cancer (CRC) remains a major global health burden, and early detection through population-based screening programs significantly reduces both incidence and mortality. Although gut microbiome-based biomarkers have emerged as promising non-invasive tools for CRC detection, limited evidence is available regarding patient acceptance and compliance with microbiome-based screening studies, factors that may influence their future implementation in clinical practice. We conducted a preliminary analysis of an ongoing multicenter, prospective observational study designed to develop a gut microbiome-based diagnostic tool for CRC and advanced colorectal adenomas in fecal immunochemical test (FIT)-positive individuals. The primary objective of this preliminary analysis was to evaluate patient acceptance and compliance with participation in a microbiome-based study within an organized CRC screening setting. Secondary objectives included describing the clinical, endoscopic, and histopathological characteristics of the enrolled cohort. FIT-positive individuals referred for screening colonoscopy at participating Italian centers were screened for eligibility, underwent colonoscopy, and were invited to provide a stool sample for microbiome analysis. A total of 315 individuals were screened, of whom 212 (67%) were enrolled. Among eligible patients, 90% agreed to enroll after receiving study information. Overall, 200 (94%) of enrolled individuals completed the required study activities, including stool sample collection and colonoscopy, indicating high compliance with study procedures. Colonoscopy was performed in 209 patients (99% of enrolled patients). CRC was detected in 7 patients (3%), and advanced colorectal adenomas in 39 (18%), while 86 (41%) colonoscopies were negative. The positive predictive value of FIT was 3.35% for CRC and 18.66% for advanced adenomas. In our preliminary analysis, patient acceptance and compliance with microbiome-based sampling were high among FIT-positive individuals undergoing CRC screening. These findings support the feasibility of conducting microbiome-based studies within organized screening programs. Analyses aimed at developing and validating the microbiome-based diagnostic tool are currently ongoing and are beyond the scope of the present report.

Malignancy-related gastrointestinal bleeding (GIB) remains a significant clinical challenge, contributing substantially to morbidity, mortality, and healthcare utilization in patients with cancer. Up to 10% of individuals with advanced malignancies develop GIB during their disease, and these episodes are frequently characterized by a high risk of rebleeding and poor long-term hemostatic control. Tumor-associated bleeding typically arises from friable, infiltrative, and highly vascular lesions that respond suboptimally to conventional endoscopic techniques such as thermal coagulation or mechanical clipping. These limitations underscore the need for improved diagnostic accuracy and more reliable therapeutic options. Recent advances in imaging modalities, including contrast-enhanced CT studies, have enhanced the ability to localize and characterize bleeding sources in complex oncologic cases. Parallel developments in endoscopic hemostasis—such as over-the-scope clips and contact-free coagulation devices—have expanded the therapeutic armamentarium for managing malignant bleeding. Clinically, topical hemostatic powders—particularly TC-325—represent a highly effective option for achieving rapid endoscopic hemostasis, supported by the strongest comparative evidence and the highest rates of immediate bleeding control among currently available technologies. In this review, we synthesize contemporary diagnostic approaches to GIB and place particular emphasis on the evolving and emerging therapeutic strategies for malignancy-related bleeding. We also highlight innovative technologies that are reshaping clinical practice and improving management options in this challenging clinical domain.

Early rectal cancer represents a challenging setting in which accurate locoregional staging is essential to guide appropriate treatment. Current diagnostic strategies primarily include magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS). However, both modalities show significant limitations in early-stage disease, particularly in T staging. This diagnostic gap impacts therapeutic decision-making, particularly in patients with lesions suggestive of deep submucosal invasion. In these cases, endoscopic submucosal dissection (ESD) may be insufficient to achieve adequate vertical negative margins, whereas radical surgery is associated with considerable morbidity and potential impairment of quality of life. In this gray zone, endoscopic intermuscular dissection (EID) has recently emerged as a novel therapeutic approach designed to overcome the limitations of standard endoscopic resection. By enabling dissection within the deeper intermuscular plane, it can achieve curative resections while preserving rectal wall integrity. This narrative review aims to explore the current diagnostic gaps in early rectal cancer and to define the potential role of EID within the current therapeutic algorithm.

Background: Up to one-third of patients with gastroesophageal reflux disease (GERD) have persistent symptoms despite proton-pump inhibitor (PPI) therapy. E-Gastryal® + MgAlg (Aurora Biofarma, Italy) is a mucosal protective agent that enhances barrier function against acid and non-acidic reflux. This study assessed its efficacy in combination with omeprazole versus omeprazole alone and as maintenance therapy. Methods:Patients with symptomatic GERD and Grade A reflux esophagitis confirmed by endoscopy were randomized to receive omeprazole 20 mg plus E-Gastryal® + MgAlg or omeprazole 20 mg alone. The primary endpoint was the number of rescue medications used over 28 days. Secondary endpoints included symptom relief and quality-of-life assessments using the Reflux Symptom Index (RSI), Gastroesophageal Reflux Disease Impact Scale (GIS), GERD-Health-Related Quality of Life (GERD-HRQL), and Global Assessment of Performance (IGAP). Results: Ninety-six patients were included. The combination group used significantly fewer rescue medications (mean: 21 vs. 40.9 tablets; p = 0.002). At week 4, the combination group showed greater improvement in RSI, GIS, and GERD-HRQL scores (p < 0.001). Symptom relief was sustained during weeks 5–26 with E-Gastryal® + MgAlg alone. Conclusions: E-Gastryal® + MgAlg combined with omeprazole improves symptom control compared to PPI monotherapy. Continued use as maintenance therapy supports its role in long-term GERD management (NCT04130659).

Background and aim Endoscopic mucosal resection (EMR) of superficial nonampullary duodenal epithelial tumors (SNADETs) is challenging, and to date, only a few studies assessed the clinical outcomes of EMR in the duodenum. The aim of this study was to evaluate the efficacy and safety of EMR for the treatment of SNADETs >10 mm. Patients and methods This is a single-center retrospective study reporting data from a cohort of consecutive patients undergoing EMR of large (>1 cm) SNADETs between January 2017 and December 2021. Results A total of 81 patients with 83 lesions underwent EMR (70 conventional EMR, 13 underwater EMR). The median size was 20 mm (range: 10–60 mm). The mean procedure time was 45 ± 30 min, and the en-bloc resection rate was 47%. In all patients, SNADETs were successfully removed (i.e. technical success). Delayed bleeding occurred in 5 (6%) of EMRs. One delayed perforation occurred, which was managed surgically. Recurrence rate was 20% with a median follow-up period of 20.5 months. Recurrence was detected at the first endoscopic follow-up in 88% of cases, and all recurrences were successfully treated endoscopically. Lesion size ( P = 0.04), previous endoscopic resection ( P = 0.05), and piecemeal resection ( P = 0.05) were independent risk factors of local recurrence after EMR on multivariate-adjusted analysis. Conclusion Large duodenal adenomas can be effectively managed by EMR. However, duodenal EMR of large lesions carries a significant risk of early recurrence, with a nonnegligible risk of adverse events. Lesion dimension, piecemeal resection, and previous endoscopic resection were associated with a higher recurrence rate. Close endoscopic follow-up is recommended given the high incidence of early recurrence, which can be successfully treated endoscopically.

BACKGROUND:Endoscopic variceal band ligation (EVBL) represents a pivotal treatment in the prophylaxis of esophageal varices bleeding in patients with cirrhosis, but in some cases a single session of EVBL is unable to eradicate esophageal varices completely, and a control endoscopy after 2-4 weeks is required to assess eradication and/or the need for another band ligation. Liver stiffness measurement (LSM) is being increasingly used as a screening non-invasive tool to predict varices according to Baveno VII criteria. However, to date, there are no instruments able to non-invasively predict the outcome of EVBL. AIM:To identify non-invasive predictors of varices eradication (VE) after EVBL through multiparametric ultrasound (US). Secondary aim was to develop a prediction model of successful variceal eradication based on non-invasive parameters. METHODS:We prospectively enrolled consecutive cirrhotic patients intolerant or with contraindications to beta-blockers undergoing EVBL for bleeding prophylaxis. Patients underwent multiparametric US with LSM, spleen stiffness measurement (SSM) and dynamic contrast-enhanced US (DCE-US) on liver parenchyma and portal vein, at baseline (T0) and one month (T1) after EVBL. Each US parameter and their variations from baseline were correlated with VE evaluated by control endoscopy performed at T1. RESULTS:We enrolled 41 patients (median age 64 years, 75.6% males). At T1 28 patients (68.3%) reached VE, whereas 13 (31.7%) required a second EVBL. Patients who achieved VE showed a significant decrease in SSM (P = 0.018), and a significant increase in peak enhancement, area under the curve and wash-in rate of both liver parenchyma and portal vein after treatment (P < 0.001). Statistically significant differences between the two groups of patients were incorporated in a multivariate analysis and used to develop three prediction models. CONCLUSION:A multimodal US approach based on DCE-US parameters, LSM and SSM might become a reliable predictor of VE and a useful non-invasive alternative to endoscopy.

Background and study aims:Hybrid argon plasma coagulation (H-APC) is a novel technique for ablation of neoplastic Barrett's esophagus (BE), consisting in submucosal fluid injection and subsequent APC of visible BE. The aim of this study was to assess H-APC efficacy, safety, and tolerability. Patients and methods:We prospectively included patients undergoing H-APC ablation at four Italian Hospitals from September 2022 to March 2024. Patients with BE C3M5 maximum extent, low- or high-grade dysplasia (LGD, HGD) or residual BE after endoscopic resection (ER) of visible lesions were included. Patients who had undergone previous ablative treatments were excluded. The primary endpoints were complete eradication of intestinal metaplasia (CE-IM) and dysplasia (CE-D). Secondary endpoints were safety in terms of major and minor adverse events (AEs) and tolerability, assessed using pain (0-10) and dysphagia (0-5) scores within 7 days post-ablation (NCT05645679). Results:Among the 51 enrolled patients (mean circumferential 0.43 cm; standard deviation [SD] 0.72, mean maximum longitudinal 2.20 cm; SD 1.09) who completed treatment (80 H-APC sessions), 45.1% (23/51) had prior ER of visible lesions. All patients achieved both CE-IM and CE-D (51/51), requiring a mean of 1.51 sessions (SD 0.83). Only one case of fever and absolute dysphagia was observed (1/51; 1.96% AEs). Regarding tolerability, mean pain score was 1.3 (SD 1.99) whereas mean dysphagia score was 1.28 (SD 0.56). Conclusions:The H-APC technique showed promising results in terms of effectiveness and safety with good tolerability in achieving initial CE-IM and CE-D in a selected population of BE patients.

Patients with long-standing inflammatory bowel disease (IBD) are at increased risk of developing colitis-associated neoplasia (CAN), requiring a comprehensive approach from surveillance to endoscopic management. This narrative review provides an integrated overview of the entire pathway, including surveillance strategies for dysplasia detection, characterization of lesion types, and selection of appropriate resection techniques. Real-life examples and a proposed step-up approach are presented to guide clinical practice. The choice of endoscopic resection technique depends on lesion size, morphology, and the degree of fibrosis. Conventional EMR is suitable for small, lifting lesions, while ESD is preferred for larger or fibrotic lesions to achieve en bloc resection. In addition, emerging approaches—like underwater techniques—can also provide valuable options in complex cases. However, integrating effective surveillance with personalized resection techniques is essential to improve outcomes and reduce the need for surgery in patients with IBD-associated neoplasia.

Background and study aims:Esophagogastric junction (EGJ) lesions are uncommon and histologically diverse. Among these, EGJ hyperplastic lesions are rare and generally considered benign. However, their nonspecific appearance makes accurate endoscopic identification challenging. Endoscopic resection is both a diagnostic and therapeutic approach, yet risk factors for neoplastic transformation in EGJ lesions remain unclear. This study aimed to identify predictive factors for neoplastic transformation in hyperplastic EGJ lesions. Patients and methods:This multicenter, retrospective study included patients with hyperplastic EGJ lesions endoscopically resected across 13 European hospitals. Data were collected from endoscopy and pathology reports. Neoplastic transformation was defined by presence of dysplasia or adenocarcinoma. A multivariable logistic regression model was conducted to assess predictive factors for neoplastic transformation in resected hyperplastic lesions. Results:From January 2015 to October 2024, 91 EGJ hyperplastic lesions were included. Polypectomy/endoscopic mucosal resection (EMR) was performed in 86% of cases, endoscopic submucosal dissection (ESD) in 19%. En bloc resection was successfully achieved in 93% of cases, whereas R0 resection rates were confirmed in 84% of cases. Twenty-one lesions (23%) showed neoplastic transformation on histology. Independent predictive factors for neoplastic transformation in hyperplastic lesions included non-polypoid morphology (odds ratio [OR] 5.48; P = 0.025), presence of surface ulceration (OR 11.5; P = 0.0005) and lesion size (OR 5.48; P = 0.021). Lesion size > 12 mm was identified as a significant predictor of neoplastic transformation in hyperplastic lesions. Conclusions:EGJ hyperplastic lesions showed a non-negligible risk of neoplastic transformation. These findings highlight the need for careful endoscopic assessment to predict malignancy while promoting appropriate management strategies to ensure adequate R0 resection in case of undetected local malignancy.

INTRODUCTION:Colorectal cancer (CRC) represents a global public health challenge, ranking as the third most prevalent cancer globally. Population-based screening programs for average-risk populations have proven effective in reducing incidence and mortality of CRC through early detection of cancer. The fecal immunochemical test (FIT), the standard diagnostic method in many nations, still falls short in diagnostic effectiveness, resulting in undetected adenomas and, more significantly, unnecessary colonoscopies. AREAS COVERED:One of the primary research focuses in the field of CRC is the discovery of new, noninvasive biomarkers. Recent studies, including metagenomic meta-analyses, have discovered common microbial signatures able to reproducibly discriminate between patients with CRC and healthy controls. Based on this evidence, international guidelines have recently recommended the use of microbiome-based biomarkers for CRC screening in clinical settings, although such studies have yet to be conducted. EXPERT OPINION:This field of research needs considerable multidisciplinary efforts, including large and geographically different meta-cohorts, and the application of state-of-the-art computational approaches, to identify reproducible signatures able to predict early lesions. Such diagnostic tool would revolutionize CRC screening. More widely, it would provide a mind-set shift in the clinical and scientific community promoting the exploitation of diagnostic and therapeutic microbiome tools in clinical practice.

Purpose: This national survey aimed to evaluate current clinical practices for managing pT1 rectal cancer post-local excision (LE) in Italian radiotherapy (RT) centers, focusing on high-risk cases. Materials and methods: Conducted from July to October 2024, a cross-sectional survey with 40 questions was distributed to 183 heads of radiation oncology departments. Quantitative data were collected through closed-ended questions, while qualitative feedback was grouped thematically. Results: The survey yielded responses from 54 centers. Multidisciplinary team discussions were common (96.2 %). Surgical re-excision or total mesorectal excision (TME) was the primary management for high-risk cases, with RT used in only 7.4 % of cases, primarily for patients declining surgery. Key local recurrence risks identified by respondents include deep margin <1 mm (96.2 %), high tumor grading (72.2 %), lymphovascular infiltration (64.8 %), and tumor budding (51.9 %). For regional recurrence, the main risk factors identified were lymphovascular infiltration (90.7 %), high tumor grading (83.3 %), and perineural infiltration (72.2 %). Significant variability was observed in RT techniques and target volumes. Elective volume recommendations were split between 45 Gy and 50 Gy, while surgical bed doses ranged from 50-50.4 Gy to 54-55 Gy. Most centers included the complete mesorectum and elective lymph nodes in treatment volumes, though some limited treatment to the surgical scar and mesorectum. Follow-up practices also showed considerable heterogeneity. Conclusion: This survey highlights significant variability in pT1 rectal cancer management post-LE across Italian centers, underscoring the necessity for standardized guidelines, and providing a foundation for future multicenter studies to optimize patient care.

BACKGROUND AND AIMS:Adenoma detection rate (ADR) serves as a primary quality metric in colonoscopy. Various computer-aided detection (CADe) tools have emerged, yielding diverse impacts on ADR across different demographic cohorts. This study aims to evaluate a new CADe system in patients undergoing colonoscopy. METHODS:This is an Italian multicenter randomized control trial (RCT) that included patients aged 40-85 scheduled for screening, surveillance or diagnostic colonoscopy randomly assigned to CADe or standard colonoscopy (SC). Patients with a Boston Bowel Preparation Scale < 2 in any segment were excluded. The primary outcome was ADR in both groups. Secondary outcomes included adenoma per colonoscopy (APC), polyp per colonoscopy (PPC) and sessile serrated lesion detection rate (SSLDR). RESULTS:1228 patients were enrolled of whom 70 were excluded for inadequate bowel cleansing or missed cecal intubation. Therefore, 1158 subjects (578 CADe vs 580 SC) were included in the final analysis. ADR was significantly higher in CADe than in the control group (50.2 % vs 40.5 %, p = 0.001). CADe also significantly increased PPC and APC (1.64 ± 2.03 vs 1.23 ± 1.72, p < 0.001; 1.16 ± 1.82 vs 0.80 ± 1.46 p < 0.001; respectively). No significant differences were found in SSLDR between CADe and SC (12.1 % vs 11.0 %, p = 0.631). CONCLUSIONS:The results of this RCT indicate that AI-assisted colonoscopy significantly improved ADR in a non-selected population undergoing colonoscopy without causing any significant delay in procedure time or increasing the detection of nonneoplastic lesions. (Ethical committee approval: NCT05862948).

Aims Preliminary data from a prospective, single-arm, multicenter observational study to evaluate the initial treatment success of the Hybrid-APC (H-APC) technique, which combines argon plasma coagulation (APC) with a previous saline injection for ablation therapy of neoplastic Barrett's esophagus (BE). This technique is being evaluated as an alternative to radiofrequency (RFA), the current gold standard.