Mutations Targeted by Nous-209 Immunotherapy Occur Early in Lynch Syndrome Carriers’ Precancer Lesions with Microsatellite Instability Elisa Micarelli, Lorenzo De Marco, Paola Spaggiari, Anna Morena D’Alise, Arianna Dal Buono, et al. Cancer Prevention Research, 2026 This study provides a molecular characterization of precancerous colorectal lesions in Lynch syndrome (LS) carriers to assess the preventive potential of Nous-209 immunotherapy against colorectal cancer development. A total of 50 adenomas and 12 advanced adenomas (AA) were collected from 26 LS carriers with pathogenic variants in either MLH1 or MSH2. Molecular analyses included assessment of mismatch repair (MMR) status, microsatellite instability (MSI), and detection of mutations targeted by Nous-209. We found that 83% of AAs and 58% of adenomas were MMR-deficient (dMMR). Notably, although all dMMR AA were MSI-high (MSI-H), only 66% of dMMR adenomas showed MSI-H. The presence of Nous-209 mutations correlated strongly with MSI status, with mutation counts ranging from 15 to 57 in dMMR/MSI-H lesions. dMMR adenomas classified as MSI-low carried a limited number of mutations (6–19), whereas microsatellite-stable lesions harbored very few (0–2) Nous-209 mutations, regardless of MMR proficiency. These findings confirm the molecular heterogeneity of precancerous lesions and support the potential of Nous-209 immunotherapy to prevent MSI colorectal cancer in LS by targeting the adenoma–carcinoma sequence at the time of MSI acquisition. Prevention Relevance: Our study shows that MSI and neoantigen accumulation emerge during the evolution of precancerous lesions in LS. These findings support the clinical evaluation of Nous-209, a shared neoantigen vaccine, as an immunoprevention strategy for MSI-driven colorectal carcinogenesis, with important implications for cancer prevention research.
Peri-operative fasting in adults: an international, multidisciplinary consensus statement Anne Rüggeberg, Kariem El‐Boghdadly, Federico Bilotta, Marta Dias Vaz, Anne Marie Camilleri Podesta, et al. Anaesthesia, 2026 Summary Introduction Evidence suggests that existing pre‐operative fasting guidelines are associated with prolonged fasting times. Prolonged fasting, particularly from clear liquids, has the potential to harm patients through reduced peri‐operative wellbeing; impaired glucose metabolism and peri‐operative inflammatory response; delayed return of bowel function; and reduced muscle strength. Liberalisation of fasting practices has, therefore, become increasingly common. Such a change in practice dictates the need for updated practice guidance. We aimed to develop recommendations on peri‐operative fasting that reflect increasing global awareness of the adverse effects of prolonged fasting. Methods Following a systematic literature review, 13 draft recommendations related to peri‐operative fasting were developed iteratively. These were modified during a three‐round Delphi process by an international, multidisciplinary stakeholder panel, which included: patients; anaesthetists; surgeons; physicians; nurses; and members of relevant international organisations from five continents. Results Sixty‐eight stakeholders participated in the Delphi consensus process. The panel subsequently agreed on eight recommendations. We recommend continuing current practices on pre‐operative fasting for solid food and non‐clear liquids. We recommend encouraging clear liquids until 2 h before the start of anaesthesia or sedation, unless institutional protocols allow for more liberal liquid intake. We further recommend implementation of institutional protocols that allow more liberal clear liquid intake < 2 h before the start of anaesthesia or sedation. Salivation stimulants can be used until transfer for the procedure. Oral intake should be resumed as soon as clinically feasible. Preprocedural gastric ultrasound performed by a trained provider may be used to guide clinical decisions when additional information is required. Discussion This international, multidisciplinary consensus statement aims to improve the quality of patient care by minimising periprocedural fasting times, within safe margins. To achieve this, liberalised pre‐operative clear liquid intake regimens may be implemented with institutional protocols.
Learning curve in intestinal ultrasound: advancing from basic skills to advanced competencies–insights from the IUS IG-IBD Master program Cristina Bezzio, Luisa Bertin, Simone Saibeni, Davide Giuseppe Ribaldone, Federica Furfaro, et al. Journal of Crohn S and Colitis, 2026 Background Intestinal ultrasound (IUS) is increasingly valuable in inflammatory bowel disease (IBD) management. Objective This study aimed to determine the learning curve for basic and advanced IUS parameters and establish the minimum number of examinations required for diagnostic proficiency. Design We conducted a prospective, multicenter study across eight Italian tertiary IBD centers. Eight gastroenterology trainees with extensive abdominal ultrasound experience but limited IUS exposure completed standardized training comprising theoretical education, 30 supervised examinations, and 99 independent assessments. Expert sonographers independently and blindly reassessed all independent examinations using identical protocols. Interobserver agreement was quantified using Cohen’s kappa coefficients across 12 predefined categories, stratified into basic (bowel wall thickness, vascularity, stratification) and advanced (fistulas, collections, strictures) findings. Results Following initial training, trainees demonstrated substantial baseline competency. Basic parameters achieved consistently high performance throughout the study period (from κ = 0.792 to κ = 0.842), while advanced findings showed more pronounced learning curves, improving from κ = 0.728 to κ = 0.854. Small bowel dilation exhibited the steepest learning trajectory (κ = 0.674 to κ = 0.921, 36.6% improvement, P = .204). Sustained primary competence (κ ≥ 0.8) was achieved by 37.5-62.5% of trainees for basic parameters within 99 examinations, with bowel wall stratification proving most challenging (37.5% success rate). Conclusion This study establishes the first comprehensive, parameter-specific learning thresholds for IUS competency in IBD. Our findings demonstrate that structured training enables basic IUS proficiency within 69-112 examinations for experienced ultrasonographers, while advanced skills require extended practice. These data represent an important step toward defining evidence-based benchmarks for IUS training, supporting the development of standardized international curricula and safe clinical implementation.
New Technologies for IBD Endoscopy Cristina Bezzio, Valeria Farinola, Giuseppe Privitera, Arianna Dal Buono, Roberto Gabbiadini, et al. Journal of Clinical Medicine, 2026 Background: Endoscopic assessment is central to the management of inflammatory bowel disease (IBD), particularly within treat-to-target strategies. However, conventional high-definition white-light endoscopy (HD-WLE) is limited by interobserver variability and its inability to reliably reflect microscopic inflammation or predict long-term outcomes. Over the last decade, multiple technological innovations have reshaped the role of endoscopy in both disease activity monitoring and dysplasia surveillance. Methods: This narrative review provides a comprehensive and clinically oriented overview of emerging endoscopic technologies in IBD, including image-enhanced endoscopy, ultra-high-magnification techniques, artificial intelligence (AI), and molecular imaging. We discuss their diagnostic performance, prognostic implications, and potential integration into clinical practice. Results: Image-enhanced endoscopy improves visualization of subtle mucosal and vascular alterations and demonstrates stronger correlation with histological activity compared with HD-WLE alone. Confocal laser endomicroscopy and endocytoscopy enable in vivo microscopic assessment of epithelial architecture and barrier integrity, redefining remission beyond macroscopic healing. AI systems have shown expert-level performance in grading inflammatory severity in ulcerative colitis and high sensitivity in capsule endoscopy for Crohn’s disease, supporting objective and reproducible assessment. In surveillance, targeted high-definition inspection has replaced random biopsies, while adjunctive optical and AI-based tools enhance lesion detection and characterization. Molecular imaging introduces a predictive dimension by enabling visualization of drug–target engagement and dysplasia-specific pathways. Conclusions: Endoscopy in IBD is evolving from a descriptive modality toward a multimodal precision tool integrating enhanced imaging, AI-driven standardization, and molecular profiling. Although further validation and cost-effectiveness studies are required, these innovations have the potential to improve therapeutic stratification, surveillance strategies, and long-term patient outcomes.
Treat-to-target optimization of biologic therapy is effective on endoscopic and histologic outcomes in a real-life cohort of ulcerative colitis—the TACTIC-UC study Giuseppe Privitera, Cristina Bezzio, Arianna Dal Buono, Roberto Gabbiadini, Laura Loy, et al. Journal of Crohn S and Colitis, 2026 Background & Aims In ulcerative colitis (UC), therapeutic goals are evolving beyond symptom control toward endoscopic and histologic healing. However, optimal strategies to achieve these targets are undefined, and the implementation of treat-to-target (T2T) in patients with minimal symptoms despite ongoing intestinal inflammation remains unexplored. This study evaluated the real-world effectiveness of endoscopy-guided optimization in this population. Methods TACTIC-UC is a retrospective, single-centre study including UC patients undergoing endoscopy-guided optimization of anti-TNF agents, vedolizumab, or ustekinumab. Eligible cases had quiescent or mild symptoms (partial Mayo score 0-4) but moderate-to-severe endoscopic activity (endoscopic Mayo Score, eMS ≥ 2) and underwent treatment optimization within 1 month after index endoscopy. The primary outcome was mucosal healing (MH, eMS ≤ 1) within 1 year. Secondary endpoints included endoscopic remission (ER, eMS = 0), histo-endoscopic mucosal remission (HEMR, eMS = 0 + Nancy Index = 0-1), biomarker trends, steroid use, adverse events, and treatment persistence. Results A total of 164 optimization episodes were analysed in 142 patients. The 1-year cumulative probabilities of MH, ER, and HEMR were 54.2%, 28.8%, and 20.9%, respectively. In weighted analyses, anti-TNF-α therapies outperformed non-anti-TNF-α agents (vedolizumab and ustekinumab pooled together) across all outcomes: 66.3% versus 45.0% for MH, 39.3% versus 19.8% for ER, and 33.2% versus 8.1% for HEMR (all P-values &lt; 0.05); consistent trends were confirmed in an exploratory 3-arm analysis incorporating synthetic data augmentation. Baseline steroid use and an eMS of 3 were independently associated with reduced probability of achieving endoscopic and histologic outcomes. No safety signals emerged. Endoscopic and histologic outcomes were associated with improved treatment persistence. Conclusions In UC patients with quiescent or mild symptoms but active endoscopic inflammation, endoscopy-guided optimization of biologics is effective in achieving deeper inflammatory control, supporting its integration into T2T strategies.
Discovering Hereditary Risk Through Surveillance: A Prospective Genetic Analysis of Individuals With Familial Pancreatic Cancer Salvatore Paiella, Erica Secchettin, Livia Archibugi, Raffaele De Luca, Cristiana Bonifacio, et al. United European Gastroenterology Journal, 2026 Background Little is known about the genetic background of individuals with familial pancreatic cancer (PC). Integrating germline testing into surveillance may uncover previously unrecognized hereditary susceptibility and expand prevention strategies beyond BRCA testing alone. This study evaluated the genetic landscape of high‐risk individuals due to familiality (HRI‐FHs) enrolled in a national surveillance program. Methods Five hundred HRI‐FHs from seven centers underwent surveillance and germline testing with a 41‐gene NGS panel. Pathogenic/likely pathogenic variants (PGVs) and variants of unknown significance (VUS) were identified and correlated with clinical and imaging findings. Results Overall, forty‐four (8.8%) out of 500 HRI‐FHs carried at least one PGV, including 3.4% in high‐penetrance genes ( ATM, BRCA1/2, PALB2, BRIP1 ). Notably, 8 out of 17 (47%) of ATM , BRCA1/2, PALB2 carriers would not have met the national testing criteria based solely on their family history. An additional 5.4% (27/500) carried PGVs in genes linked to other hereditary conditions ( CFTR, MUTYH, CTRC, SPINK1, APC ), and 39.6% harbored at least one VUS. PGV status, age, and female gender were independent predictors of radiological abnormalities. Two PCs were diagnosed, both in mutation‐negative individuals. Discussion Integrating germline testing into surveillance redefines the management of familial PC. It uncovers hereditary susceptibility beyond classical criteria and supports cascade testing. PC also arises in mutation‐negative HRI. #NCT05724992.
Juvenile polyposis syndrome: An overview Arianna Dal Buono, Federica Gaiani, Laura Poliani, Luigi Laghi Best Practice and Research Clinical Gastroenterology, 2022
JAK inhibitors in crohn’s disease: ready to go? Cecilia Dell’Avalle, Ferdinando D’Amico, Roberto Gabbiadini, Arianna Dal Buono, Nicola Pugliese, et al. Expert Opinion on Investigational Drugs, 2022
