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Abstract A large proportion of colorectal carcinomas (CRC) evolve from colorectal adenomas. However, not all individuals with colonic adenomas have a risk of CRC substantially higher than those of the general population. The aim of the study was to determine the differences or similarities of mutation profile among low- and high-grade adenomas and in situ carcinoma with detailed follow up. We have investigated the mutation spectrum of well-known genes involved in CRC (such as APC, BRAF, EGFR, NRAS, KRAS, PIK3CA, POLE, POLD1, SMAD4, PTEN, and TP53) in a large, well-defined series of 96 adenomas and in situ carcinomas using a high-throughput genotyping technique. Besides, the microsatellite instability and APC and MLH1 promoter methylation were studied as well. We observed a high frequency of pathogenic variants in the studied genes. The APC, KRAS and TP53 mutation frequencies were slightly lower in adenoma samples than in in situ carcinoma samples. Further, when we stratified mutation frequency based on the grade, the frequency distribution was as follows: low-grade adenoma—high-grade adenomas—in situ carcinoma: APC gene 42.9–56.0–54.5%; KRAS gene 32.7–32.0–45.5%; TP53 gene 8.2–20.0–18.2%. The occurrence of KRAS mutation was associated with the presence of villous histology and methylation of the APC promoter was significantly associated with the presence of POLE genetic variations. However, no association was noticed with the presence of any singular mutation and occurrence of subsequent adenoma or CRC. Our data supports the multistep model of gradual accumulation of mutations, especially in the driver genes, such as APC, TP53 and KRAS.

This joint ASGE-ESGE guideline provides an evidence-based summary and recommendations regarding the role of endoscopic bariatric and metabolic therapies (EBMTs) in the management of obesity. The document was developed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. It evaluates the efficacy and safety of EBMT devices and procedures that currently have CE mark or FDA-clearance/approval, or that had been approved within five years of document development. The guideline suggests the use of EBMTs plus lifestyle modification in patients with a BMI of ≥ 30 kg/m 2 , or with a BMI of 27.0-29.9 kg/m 2 with at least 1 obesity-related comorbidity. Furthermore, it suggests the utilization of intragastric balloons and devices for endoscopic gastric remodeling (EGR) in conjunction with lifestyle modification for this patient population., Competing Interests: Disclosure The following authors disclosed financial relationships: P. Jirapinyo: Consultant for Apollo Endosurgery, Boston Scientific Corporation, Erbe, and Spatz Medical; advisory board for Apollo Endosurgery; research support from Apollo Endosurgery, Boston Scientific Corporation, GI Dynamics, Fractyl, and USGI Medical. A. Hadefi: Research support from Endo Tools Therapeutics. C. C. Thompson: Consultant for Apollo Endosurgery, Boston Scientific Corporation, Medtronic, Endoquest Robotics, Fractyl, FujiFilm, GI Dynamics, EnVision Endoscopy, Olympus/Spiration, Softac, USGI Medical, Xenter, Enterasense Ltd, and Lumendi; research support from Apollo Endosurgery, Boston Scientific Corporation, Endoquest Robotics, Erbe, Fractyl, FujiFilm, GI Dynamics, Olympus/Spiration, USGI Medical, and Lumendi; advisory board for Fractyl and USGI Medical; founder of Bariendo, BlueFlame Healthcare Venture Fund, ELLES, EnVision Endoscopy, GI Windows, Society for Metabolic and Bariatric Endoscopy Inc, and Enterasense Ltd, and GI Windows; board member for Bariendo, ELLES, EnVision Endoscopy, GI Windows, and Enterasense Ltd; ownership in Bariendo, ELLES, EnVision Endoscopy, GI Windows, Society for Metabolic and Bariatric Endoscopy Inc, Softac, Xenter, and Enterasense Ltd; partner in BlueFlame Healthcare Venture Fund; president of the Society for Metabolic and Bariatric Endoscopy Inc; Scientific Advisory Board for Xenter. R. Pannala: Research support from Fractyl Labs; general payments from Boston Scientific Corporation; consultant for HCL Technologies; advisory board for Nestle Healthsciences and Bluestar Genomics. S. K. Goelder: Travel compensation from Apollo Endosurgery. V. Kushnir: Consultant for BSCI, Noah Medical, Steres, and ConMed. M. Barthet: Consultant for Boston Scientific Corporation, Endotools, and Taewoong. C. M. Apovian: Advisory board for Altimmune, Inc, CinFina Pharma, Inc, Cowen and Company, LLC, Currax Pharmaceuticals, LLC, EPG Communication Holdings Ltd, Form Health, Inc, Gelesis, Srl, L-Nutra, Inc, NeuroBo Pharmaceuticals, Inc, Novo Nordisk, Inc, OptumRx, Inc, Pain Script Corporation, Palatin Technologies, Inc, Pursuit By You, ReShape Lifesciences Inc, Riverview School, and Xeno Biosciences; research support from the National Institutes of Health, Patient-Centered Outcomes Research Institute, and GI Dynamics, Inc. I. Boskoski: Consultant for Boston Scientific Corporation (Apollo Endosurgery), Nitinotes, and EndoTools. C. G. Chapman: Consultant for Boston Scientific Corporation, Olympus, Steris, and Apollo Endosurgery; speaker for Apollo Endosurgery. V. Kumbhari: Consultant for Boston Scientific Corporation. J. Esker: Consultant for Pendulum Therapeutics. A. D. Pryor: Speaker for Gore, Medtronic, and Stryker. R. Maselli: Consultant for Apollo Endosurgery. A. R. Schulman: Consultant for Apollo Endosurgery, Boston Scientific Corporation, Olympus, and MicroTech; research support from GI Dynamics and Fractyl. N. Thosani: Consultant for Boston Scientific Corporation, Ambu, and Pentax America; royalties from UpToDate; ownership in ROSEAId. V. Huberty: Shareholder in, board member for, and research support from EndoTools Therapeutics. S. Sullivan: Consultant for Allurion Technologies, Biolinq, BariaTek, Pentax, Fractyl, and Endo Tools Therapeutics; research support from Allurion Technologies, ReShape Medical/Obalon Therapeutics, and Rebiotix; stock ownership in Biolinq. All other authors disclosed no financial relationships., (Copyright © 2024 American Society for Gastrointestinal Endoscopy and European Society of Gastrointestinal Endoscopy. Published by Elsevier Inc on behalf of American Society for Gastrointestinal Endoscopy and by Georg Thieme Verlag KG Stuttgart on behalf of European Society of Gastrointestinal Endoscopy. All rights reserved. Published by Elsevier Inc. All rights reserved.)