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Achalasia, characterized by impaired lower esophageal sphincter (LES) relaxation and failed peristalsis, stands out as the most widely recognized primary esophageal motility disorder. It manifests with dysphagia to solid and liquid foods, chest pain, regurgitation, and weight loss, leading to significant morbidity and healthcare burden. Traditionally, surgical Heller myotomy and pneumatic dilation were the primary therapeutic approaches for achalasia. However, in 2009, Inoue and colleagues introduced a groundbreaking endoscopic technique called peroral endoscopic myotomy (POEM), revolutionizing the management of this condition. This review aims to comprehensively examine the recent advancements in the POEM technique for patients diagnosed with achalasia, delving into critical aspects, such as the tailoring of the myotomy, the prevention of intraprocedural adverse events (AEs), the evaluation of long-term outcomes, and the feasibility of retreatment in cases of therapeutic failure., Competing Interests: Declaration of competing interest Cesare Hassan: Fujifilm Co. (consultancy), Medtronic Co. (consultancy); Alessandro Repici: Fujifilm Co. (consultancy), Olympus Corp (consultancy), Medtronic Co. (consultancy); Roberta Maselli: Fujifilm Co. (consultancy). Other authors have no conflict of interest to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background/objectives: Inflammatory bowel disease (IBD) and eosinophilic gastrointestinal diseases (EGIDs) are complex, multifactorial chronic inflammatory disorders affecting the gastrointestinal tract. Their epidemiology, particularly for eosinophilic esophagitis (EoE), is increasing worldwide, with a rise in the co-diagnosis of IBD and EGIDs. Both disorders share common risk factors, such as early exposure to antibiotics or specific dietary habits. Moreover, from a molecular perspective, eosinophilic infiltration is crucial in the diagnosis of eosinophilic disorders, and it also plays a pivotal role in IBD histological diagnosis. Indeed, recent evidence highlights the significant role of eosinophils in the health of the intestinal mucosal barrier and as mediators between innate and acquired immunity, even indicating a potential role in IBD pathogenesis. This narrative review aims to summarize the current evidence regarding the common clinical and molecular aspects of EGIDs and IBD and the current state of knowledge regarding overlap conditions and their pathogenesis., Methods: Pubmed was searched until May 2023 to assess relevant studies describing the epidemiology, pathophysiology, and therapy of EGIDs in IBD., Results: The immune pathways and mechanisms underlying both EGIDs and IBD remain partially known. An improved understanding of the role of eosinophils in overlapping conditions could lead to enhanced diagnostic precision, the development of more effective future therapeutic strategies, and a more accurate prediction of patient response. Consequently, the identification of red flags indicative of an eosinophilic disorder in IBD patients is of paramount importance and must be evaluated on a case-by-case basis.

The present document constitutes Part 2 of the EoETALY Consensus Statements guideline on the diagnosis and management of eosinophilic esophagitis (EoE) developed by experts in the field of EoE across Italy (i.e., EoETALY Consensus Group). Part 1 was published as a different document, and included three chapters discussing 1) definition, epidemiology, and pathogenesis; 2) clinical presentation and natural history and 3) diagnosis of EoE. The present work provides guidelines on the management of EoE in two final chapters: 4) treatment and 5) monitoring and follow-up, and also includes considerations on knowledge gaps and a proposed research agenda for the coming years. The guideline was developed through a Delphi process, with grading of the strength and quality of the evidence of the recommendations performed according to accepted GRADE criteria.This document has received the endorsement of three Italian national societies including the Italian Society of Gastroenterology (SIGE), the Italian Society of Neurogastroenterology and Motility (SINGEM), and the Italian Society of Allergology, Asthma, and Clinical Immunology (SIAAIC). The guidelines also involved the contribution of members of ESEO Italia, the Italian Association of Families Against EoE., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The gender gap in the authorship of scientific research may affect career advancement. Our aim was to assess the potential gender gap in gastrointestinal (GI) journals., Methods: A systematic review was performed of the GI literature and ongoing research in the period 2020-2022. A total 10 GI journals and ongoing research on clinicaltrials.gov were selected for review. The gender gap in first and senior authorship was evaluated for each article and ongoing research project. Associations between the gender gap and possible predictors were measured and results are presented as odds ratios (ORs) with 95%CI., Results: The number of first female authors (FFAs) and senior female authors (SFAs) in published articles were 1408/4207 (33.5%) and 911/4207 (21.7%), respectively. There were 781/2654 (29.4%) female principal investigators (PI)s for the ongoing research. On comparison of non-endoscopic vs. endoscopic topics, the latter were associated with the gender gap (hepatology, OR 2.15 [95%CI 1.83-2.55]; inflammatory bowel disease, OR 2.12 [95%CI 1.60-2.45]; upper and lower GI, OR 1.31 [95%CI 1.18-1.73]); as well as the type of article (original article vs. editorial, OR 1.92 [95%CI 1.58-2.33]). The type of research was also associated with the gender gap (clinical vs. preclinical studies, OR 0.88 [95%CI 0.66-0.91])., Conclusion: Our results demonstrated a correlation between the gender gap and the design and topic of the research. Future strategies for improving equity in career development in GI endoscopy should focus on closing the gender gap in equity of authorship., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Eosinophilic esophagitis (EoE) is a chronic type 2-mediated inflammatory disease of the esophagus that represents the most common eosinophilic gastrointestinal disease. Experts in the field of EoE across Italy (i.e., EoETALY Consensus Group) including gastroenterologists, endoscopists, allergologists/immunologists, and paediatricians conducted a Delphi process to develop updated consensus statements for the management of patients with EoE and update the previous position paper of the Italian Society of Gastroenterology (SIGE) in light of recent evidence. Grading of the strength and quality of the evidence of the recommendations was performed using accepted GRADE criteria. The guideline is divided in two documents: Part 1 includes three chapters, namely 1) definition, epidemiology, and pathogenesis; 2) clinical presentation and natural history, and 3) diagnosis, while Part 2 includes two chapters: 4) treatment and 5) monitoring and follow-up. This document has received the endorsement of three Italian national societies including the SIGE, the Italian Society of Neurogastroenterology and Motility (SINGEM), and the Italian Society of Allergology, Asthma, and Clinical Immunology (SIAAIC). With regards to patients' involvement, these guidelines involved the contribution of members of ESEO Italia, the Italian Association of Families Against EoE., Competing Interests: Declaration of competing interest Nicola de Bortoli: Advisory board member for: AlfaSigma, Sanofi Genzyme, Dr Falk; Lecture grants from Reckitt-Benkiser, Malesci, Dr. Flak, Sofar, Alfa-Sigma, Pharma-Line. Pierfrancesco Visaggi: Has served as speaker for Dr Falk, JB Pharmaceuticals, Malesci. Roberto Penagini: Has served as speaker for Dr Falk, Sanofi. Edda Battaglia: has served as consultant for NZP, GUNA Gaia Pellegatta has served as speaker for Dr Falk, Sanofi Genzyme, Malesci. Paola Iovino: Has served as consultant for Dr Falk Giovanni Marasco: Served as an advisory board member for AlfaSigma, EG Pharma, Monteresearch srl, Recordati, Cineca. Received lecture grants from Agave, AlfaSigma, Bromatech, Clorofilla, Echosens, Ferring, Mayoly Spindler, Menarini and Schwabe Pharma. Salvatore Oliva: Has served as speaker for Sanofi, Medtronic; Has served as consultant for: Sanofi, Medtronic, Brystol; Has received research support from Alfa Sigma, Medtronic. Francesca Racca: has served as speaker for Sanofi; has served as consultant for Dr Falk, Sanofi, GSK Erminia Ridolo: has served as consultant for Dr Falk Edoardo Vincenzo Savarino: has served as speaker for Abbvie, Agave, AGPharma, Alfasigma, Aurora Pharma, CaDiGroup, Celltrion, Dr Falk, EG Stada Group, Fenix Pharma, Fresenius Kabi, Galapagos, Janssen, JB Pharmaceuticals, Innovamedica/Adacyte, Malesci, Mayoly Biohealth, Omega Pharma, Pfizer, Reckitt Benckiser, Sandoz, SILA, Sofar, Takeda, Tillots, Unifarco; has served as consultant for Abbvie, Agave, Alfasigma, Biogen, Bristol-Myers Squibb, Celltrion, Diadema Farmaceutici, Dr. Falk, Fenix Pharma, Fresenius Kabi, Janssen, JB Pharmaceuticals, Merck & Co, Nestlè, Reckitt Benckiser, Regeneron, Sanofi, SILA, Sofar, Synformulas GmbH, Tssakeda, Unifarco; he received research support from Pfizer, Reckitt Benckiser, SILA, Sofar, Unifarco, Zeta Farmaceutici. Bruno Annibale, Federica Baiano Svizzero, Giovanni Barbara, Brigida Barberio, Ottavia Bartolo, Antonio Di Sabatino, Ludovico Docimo, Marzio Frazzoni, Manuele Furnari, Matteo Ghisa, Andrea Iori, Marco Vincenzo Lenti, Elisa Marabotto, Aurelio Mauro, Marcella Pesce, Antonino Carlo Privitera, Ilaria Puxeddu, Mentore Ribolsi, Salvatore Russo, Giovanni Sarnelli, Salvatore Tolone, Patrizia Zentilin, Fabiana Zingone: None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Swallowed topical corticosteroids (tC) are common therapy for patients with eosinophilic esophagitis (EoE). Widely heterogeneous results have occurred due to their active ingredients, formulations and doses., Objective: To assess the effectiveness of topical corticosteroid therapy for EoE in real-world practice., Methods: Cross-sectional study analysis of the multicentre EoE CONNECT registry. Clinical remission was defined as a decrease of ≥50% in dysphagia symptom scores; histological remission was defined as a peak eosinophil count below 15 per high-power field. The effectiveness in achieving clinico-histological remission (CHR) was compared for the main tC formulations., Results: Overall, data on 1456 prescriptions of tC in monotherapy used in 866 individual patients were assessed. Of those, 904 prescriptions with data on formulation were employed for the induction of remission; 234 reduced a previously effective dose for maintenance. Fluticasone propionate formulations dominated the first-line treatment, while budesonide was more common in later therapies. A swallowed nasal drop suspension was the most common formulation of fluticasone propionate. Doses ≥0.8 mg/day provided a 65% CHR rate and were superior to lower doses. Oral viscous solution prepared by a pharmacist was the most common prescription of budesonide; 4 mg/day provided no benefit over 2 mg/day (CHR rated being 72% and 80%, respectively). A multivariate analysis revealed budesonide orodispersible tablets as the most effective therapy (OR 18.9, p < 0.001); use of higher doses (OR 4.3, p = 0.03) and lower symptom scores (OR 0.9, p = 0.01) were also determinants of effectiveness., Conclusion: Reduced symptom severity, use of high doses, and use of budesonide orodispersible tablets particularly were all independent predictors of tC effectiveness., (© 2024 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Benign biliary strictures (BBS) might occur due to different pancreaticobiliary conditions. The etiology and location of biliary strictures are responsible of a wide array of clinical manifestations. The endoscopic approach endoscopic retrograde cholangiopancreatography represents the first-line treatment for BBS, considering interventional radiology and surgery when endoscopic treatment fails or it is not suitable. The purpose of this review is to provide an overview of possible endoscopic treatments for the optimal management of this subset of patients., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The endoscopic submucosal dissection (ESD) is a technically demanding and time-consuming procedure, with an increased risk of adverse events compared to standard endoscopic resection techniques. The main difficulties are related to the instability of the operating field and to the loss of traction. We aimed to evaluate in a pilot trial a new endoscopic platform [tissue retractor system (TRS); ORISE, Boston scientific Co., Marlborough, MA, USA], designed to stabilize the intraluminal space, and to provide tissue retraction and counter traction., Method: We prospectively enrolled all consecutive patients who underwent an ESD for sigmoid/rectal lesions. The primary outcome was the rate of technical feasibility. Further technical aspects such as en-bloc and R0 resection rate, number of graspers used, circumferential incision time, TRS assemblage time, submucosal dissection time, and submucosal dissection speed were provided. Clinical outcomes (recurrence rate and adverse events) were recorded as well., Results: In all, 10 patients (M/F 4/6, age: 70.4 ± 11.0 years old) were enrolled. Eight out of 10 lesions were located in the rectum. Average lesion size was 31.2 ± 2.7 mm, and mean lesion area was 1628.88 ± 205.3 mm 2 . The two sigmoid lesions were removed through standard ESD, because the platform assemblage failed after several attempts. All rectal lesions were removed in an en-bloc fashion. R0 resection was achieved in 7/8 (87.5%) patients in an average procedure time of 60.5 ± 23.3 min. None of the patients developed neither intraprocedural nor postprocedural adverse events., Conclusion: TRS-assisted ESD is a feasible option when used in the rectum, with promising result in terms of efficacy and safety outcomes. Nevertheless, our pilot study underlines few technical limitations of the present platform that need to be overcome before the system could be widely and routinely used., Competing Interests: Drs Roberta Maselli, Andrea Anderloni, Alessandro Fugazza, and Alessandro Repici received consultancy fees from Boston Scientific. Dr Silvia Carrara received in the last 36 months a research Grant from Boston Scientific on FNB Needles. No further conflict of interest to be disclosed., (© The Author(s), 2023.)

Background: Direct comparisons of childhood- and adulthood-onset eosinophilic esophagitis (EoE) are scarce., Aim: To compare disease characteristics, endoscopic and histological features, allergic concomitances and therapeutic choices across ages., Methods: Cross-sectional analysis of the EoE CONNECT registry., Results: The adulthood-onset cohort (those diagnosed at ≥18y) comprised 1044 patients and the childhood-onset cohort (patients diagnosed at <18 y), 254. Vomiting, nausea, chest and abdominal pain, weight loss, slow eating and food aversion were significantly more frequent in children; dysphagia, food bolus impaction and heartburn predominated in adults. A family history of EoE was present in 16% of pediatric and 8.2% of adult patients (p<0.001). Concomitant atopic diseases did not vary across ages. Median±IQR diagnostic delay (years) from symptom onset was higher in adults (2.7 ± 6.1) than in children (1 ± 2.1; p<0.001). Esophageal strictures and rings predominated in adults (p<0.001), who underwent esophageal dilation more commonly (p = 0.011). Inflammatory EoE phenotypes were more common in children (p = 0.001), who also presented higher eosinophil counts in biopsies (p = 0.015) and EREFS scores (p = 0.017). Despite PPI predominating as initial therapy in all cohorts, dietary therapy and swallowed topical corticosteroids were more frequently prescribed in children (p<0.001)., Conclusions: Childhood-onset EoE has differential characteristics compared with adulthood-onset, but similar response to treatment., Competing Interests: Conflict of Interest AJ Lucendo has served as a speaker, and/or has received research and/or education funding and/or consulting fees from Adare/Ellodi, Dr. Falk Pharma, Regeneron, Dr. Falk Pharma and EsoCap. C. Santander received honoraria as consultant and trainer at Laborie/MMS and Medtronic Covidien AG, and received research funding from AstraZeneca, EsoCap Biotech, Regeneron Pharmaceuticals Inc., Adare Pharmaceuticals Inc., and Dr. Falk Pharma GmbH. J. Alcedo has served as a speaker, consultant and advisory member for or has received research funding from Adare Pharmaceuticals Inc, Abbvie, MSD, Allergan, and Shire Pharmaceuticals. C Gutiérrez-Junquera has received research funding from Dr. Falk Pharma. The remaining authors have no conflict of interest., (Copyright © 2022. Published by Elsevier Ltd.)

Background: The long-term outcomes of esophageal peroral endoscopic myotomy (POEM) are still unknown., Methods: We searched electronic databases (MEDLINE/PubMed, EMBASE, Scopus) for studies assessing outcomes after POEM for esophageal achalasia with a minimum median follow-up duration of 36 months. Pooled rates of clinical success and postoperative reflux were calculated and compared with the same values at 12/24/36 months when available. Subgroup analyses were performed to explore the interstudy heterogeneity., Results: From 1528 initial records, 11 studies (2017-2021) were included. A total of 2342 patients (age 48.1 [SD 6.8] years; 50.1 % males) with a median follow-up of 48 months (interquartile range 45-60) were analyzed. The pooled clinical success rate was 87.3 % (95 %CI 83.6 %-91.0 %; I2  = 73.1 %). The symptomatic reflux pooled rate was 22.0 % (95 %CI 14.4 %-29.5 %; I2  = 92.7 %). Three cases of peptic strictures and one Barrett's esophagus were reported. The pooled rate of severe adverse events was 1.5 % (95 %CI 0.5 %-2.5 %; I2  = 52.8 %)., Conclusions: Long-term clinical efficacy of POEM persisted in 87 % of patients with achalasia. Post-POEM symptomatic reflux remained stable over time. The risk for Barrett's esophagus and peptic strictures appeared minimal., Competing Interests: R. Maselli: consulting for Fujifilm, ERBE. P. Sharma: consultant for Medtronic, Olympus, Boston Scientific, Fujifilm, and Lumendi. He receives grant support from Ironwood, Erbe, Docbot, Cosmo pharmaceuticals, and CDx labs. C. Hassan: consulting fees from Fujifilm, Medtronic. A. Repici: consulting fees from Medtronic, Fujifilm, Boston Scientific, ERBE. All other authors declare that no conflicts of interest exist., (Thieme. All rights reserved.)

Background and Objectives: EUS-guided biliary drainage (BD) through hepaticogastrostomy (HGS) is an option in case of ERCP failure. Available data suggest that this procedure may be challenging with possible severe adverse events (AEs) mainly due to stent migration. The aim of our pilot study was to prospectively assess the technical and clinical outcomes of EUS-HGS using a new dedicated partially covered self-expandable metal stent with anti-migratory systems., Methods: This is a single-center prospective study enrolling patients with malignant biliary obstruction undergoing EUS-HGS after failed ERCP, between June 2020 and March 2021. The primary endpoint was the technical success rate. Evaluation of specific stent-related technical features as compared with commonly used self-expandable metal stent, clinical success rate, and procedure-related AEs was also assessed., Results: Twenty-two patients (15%-68.2%, female; mean age, 66.0 ± 10.0) were enrolled in the study analysis. Different causes of ERCP failure were infiltration of papilla by neoplastic tissue (4, 18.2%), unreachable papilla for duodenal stricture (9, 40.9%), surgically altered anatomy with Roux-en-Y reconstruction (4, 18.2%), and incomplete BD after transpapillary stent placement (5, 22.7%). Technical success was achieved in all patients, in a mean procedural time of 43.3 ± 26.8 min. Technical features were graded as high or medium in all cases. The clinical success rate was 91% (20/22, mean follow-up: 10.8 ± 3.1 months). There were no cases of stent misplacement or stent migration. Three (13.6%) cases of a hepatic abscess requiring percutaneous drainage and systemic antibiotics were reported, with no impact on clinical success and following oncologic treatments. No deaths occurred., Conclusion: EUS-HGS with a new dedicated stent with anti-migratory systems is feasible and effective, preventing stent migration, and misplacement. Although the persistent procedural challenges, dedicated devices may contribute to outcomes improvement and procedure diffusion., Competing Interests: None

The peroral endoscopic myotomy (POEM) procedure, as described over 10 years ago, is a submucosal endoscopy procedure that allows access to the muscle layers throughout the gastrointestinal (GI) tract. With this access, and ability to cut the muscle fibers, POEM can be performed not only for motility disorders but for structural pathology as well, such as Zenker diverticulum. Regardless of the location, there are 4 steps to the procedure: mucosotomy, submucosal tunneling, myotomy, and mucostomy closure. This review outlines these key components as well as variations in techniques for POEM throughout the GI tract., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background and study aims  Artificial intelligence (AI) is set to impact several fields within gastroenterology. In gastrointestinal endoscopy, AI-based tools have translated into clinical practice faster than expected. We aimed to evaluate the status of research for AI in gastroenterology while predicting its future applications. Methods  All studies registered on Clinicaltrials.gov up to November 2021 were analyzed. The studies included used AI in gastrointestinal endoscopy, inflammatory bowel disease (IBD), hepatology, and pancreatobiliary diseases. Data regarding the study field, methodology, endpoints, and publication status were retrieved, pooled, and analyzed to observe underlying temporal and geographical trends. Results  Of the 103 study entries retrieved according to our inclusion/exclusion criteria, 76 (74 %) were based on AI application to gastrointestinal endoscopy, mainly for detection and characterization of colorectal neoplasia (52/103, 50 %). Image analysis was also more frequently reported than data analysis for pancreaticobiliary (six of 10 [60 %]), liver diseases (eight of nine [89 %]), and IBD (six of eight [75 %]). Overall, 48 of 103 study entries (47 %) were interventional and 55 (53 %) observational. In 2018, one of eight studies (12.5 %) were interventional, while in 2021, 21 of 34 (61.8 %) were interventional, with an inverse ratio between observational and interventional studies during the study period. The majority of the studies were planned as single-center (74 of 103 [72 %]) and more were in Asia (45 of 103 [44 %]) and Europe (44 of 103 [43 %]). Conclusions  AI implementation in gastroenterology is dominated by computer-aided detection and characterization of colorectal neoplasia. The timeframe for translational research is characterized by a swift conversion of observational into interventional studies., Competing Interests: Competing interets The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background and Aims: Sporadic non-ampullary duodenal adenomas (SNDAs) are often referred to tertiary centers because of the challenges in endoscopic resection. There is a paucity of data on both technical and clinical outcomes. The aim of our study was to evaluate the efficacy and safety of endoscopic resection for the treatment of SNDA in two western centers., Methods: This is a retrospective study reporting data of a cohort of patients referred for resection of SNDA between 2013 and 2017. Patients with familial adenomatous polyposis or ampullary lesions were excluded from present analysis. Outcomes considered for this study were technical success, adverse events, recurrence and need for surgery., Results: 120 patients (mean age 66 ± 11.9 years, 64male) were enrolled in the study. Mean size of the lesions was 23.3 mm (range 5-80). Fifty-six en-bloc endoscopic mucosal resection (EMR) (46.6%), 41 piecemeal EMR (pEMR) and 23 endoscopic submucosal dissection were performed. Intra-procedural perforation was observed in 4 patients (3.3%). Fourteen post-procedural (11.6%) adverse events were recorded. All post-procedural perforations occurred in lesions > 30 mm. Recurrence was observed in 11 patients (9.5%) during a mean follow-up of 29 months. All recurrences were successfully managed endoscopically. 119 patients were still alive at last follow-up., Conclusion: Endoscopic resection can be successfully carried out in majority of patients. Size > 30 mm seems to be the predictor of high adverse events risk., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Poor adherence to clinical practice guidelines for eosinophilic esophagitis (EoE) has been described and the diagnostic delay of the disease continues to be unacceptable in many settings., Objective: To analyze the impact of improved knowledge provided by the successive international clinical practice guidelines on reducing diagnostic delay and improving the diagnostic process for European patients with EoE., Methods: Cross-sectional analysis of the EoE CONNECT registry based on clinical practice. Time periods defined by the publication dates of four major sets of guidelines over 10 years were considered. Patients were grouped per time period according to date of symptom onset., Results: Data from 1,132 patients was analyzed and median (IQR) diagnostic delay in the whole series was 2.1 (0.7-6.2) years. This gradually decreased over time with subsequent release of new guidelines (p < 0.001), from 12.7 years up to 2007 to 0.7 years after 2017. The proportion of patients with stricturing of mixed phenotypes at the point of EoE diagnosis also decreased over time (41.3% vs. 16%; p < 0.001), as did EREFS scores. The fibrotic sub-score decreased from a median (IQR) of 2 (1-2) to 0 (0-1) when patients whose symptoms started up to 2007 and after 2017 were compared (p < 0.001). In parallel, symptoms measured with the Dysphagia Symptoms Score reduced significantly when patients with symptoms starting before 2007 and after 2012 were compared. A reduction in the number of endoscopies patients underwent before the one that achieved an EoE diagnosis, and the use of allergy testing as part of the diagnostic workout of EoE, also reduced significantly over time (p = 0.010 and p < 0.001, respectively)., Conclusion: The diagnostic work-up of EoE patients improved substantially over time at the European sites contributing to EoE CONNECT, with a dramatic reduction in diagnostic delay., (© 2022 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Nutritional support is essential in patients who have a limited capability to maintain their body weight. Therefore, oral feeding is the main approach for such patients. When physiological nutrition is not possible, positioning of a nasogastric, nasojejunal tube, or other percutaneous devices may be feasible alternatives. Creating a percutaneous endoscopic gastrostomy (PEG) is a suitable option to be evaluated for patients that need nutritional support for more than 4 wk. Many diseases require nutritional support by PEG, with neurological, oncological, and catabolic diseases being the most common. PEG can be performed endoscopically by various techniques, radiologically or surgically, with different outcomes and related adverse events (AEs). Moreover, some patients that need a PEG placement are fragile and are unable to express their will or sign a written informed consent. These conditions highlight many ethical problems that become difficult to manage as treatment progresses. The aim of this manuscript is to review all current endoscopic techniques for percutaneous access, their indications, postprocedural follow-up, and AEs., Competing Interests: Conflict-of-interest statement: All the authors declare that they have no competing interests related to the topic., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background and Aims: Artificial intelligence has been shown to be effective in polyp detection, and multiple computer-aided detection (CADe) systems have been developed. False-positive (FP) activation emerged as a possible way to benchmark CADe performance in clinical practice. The aim of this study was to validate a previously developed classification of FPs comparing the performances of different brands of approved CADe systems., Methods: We compared 2 different consecutive video libraries (40 video per arm) collected at Humanitas Research Hospital with 2 different CADe system brands (CADe A and CADe B). For each video, the number of CADe false activations, cause, and time spent by the endoscopist to examine the area erroneously highlighted were reported. The FP activations were classified according to the previously developed classification of FPs (the NOISE classification) according to their cause and relevance., Results: In CADe A 1021 FP activations were registered across the 40 videos (25.5 ± 12.2 FPs per colonoscopy), whereas in CADe B 1028 were identified (25.7 ± 13.2 FPs per colonoscopy; P = .53). Among them, 22.9 ± 9.9 (89.8% in CADe A) and 22.1 ± 10.0 (86.0% in CADe B) were because of artifacts from the bowel wall. Conversely, 2.6 ± 1.9 (10.2% in CADe A) and 3.5 ± 2.1 (14% in CADe B) were caused by bowel content (P = .45). Within CADe A each false activation required .2 ± .9 seconds, with 1.6 ± 1.0 FPs (6.3%) requiring additional time for endoscopic assessment. Comparable results were reported within CADe B with .2 ± .8 seconds spent per false activation and 1.8 ± 1.2 FPs per colonoscopy requiring additional inspection., Conclusions: The use of a standardized nomenclature provided comparable results with either of the 2 recently approved CADe systems. (Clinical trial registration number: NCT04399590.)., (Copyright © 2022. Published by Elsevier Inc.)

Background and Aims: Artificial intelligence has been shown to increase adenoma detection rate (ADR) as the main surrogate outcome parameter of colonoscopy quality. To which extent this effect may be related to physician experience is not known. We performed a randomised trial with colonoscopists in their qualification period (AID-2) and compared these data with a previously published randomised trial in expert endoscopists (AID-1)., Methods: In this prospective, randomised controlled non-inferiority trial (AID-2), 10 non-expert endoscopists (<2000 colonoscopies) performed screening/surveillance/diagnostic colonoscopies in consecutive 40-80 year-old subjects using high-definition colonoscopy with or without a real-time deep-learning computer-aided detection (CADe) (GI Genius, Medtronic). The primary outcome was ADR in both groups with histology of resected lesions as reference. In a post-hoc analysis, data from this randomised controlled trial (RCT) were compared with data from the previous AID-1 RCT involving six experienced endoscopists in an otherwise similar setting., Results: In 660 patients (62.3±10 years; men/women: 330/330) with equal distribution of study parameters, overall ADR was higher in the CADe than in the control group (53.3% vs 44.5%; relative risk (RR): 1.22; 95% CI: 1.04 to 1.40; p<0.01 for non-inferiority and p=0.02 for superiority). Similar increases were seen in adenoma numbers per colonoscopy and in small and distal lesions. No differences were observed with regards to detection of non-neoplastic lesions. When pooling these data with those from the AID-1 study, use of CADe (RR 1.29; 95% CI: 1.16 to 1.42) and colonoscopy indication, but not the level of examiner experience (RR 1.02; 95% CI: 0.89 to 1.16) were associated with ADR differences in a multivariate analysis., Conclusions: In less experienced examiners, CADe assistance during colonoscopy increased ADR and a number of related polyp parameters as compared with the control group. Experience appears to play a minor role as determining factor for ADR., Trial Registration Number: NCT:04260321., Competing Interests: Competing interests: Conflict of interest statement/disclosure(s): All authors for equipment loan by Medtronic. AR and CH received consultancy fee from Medtronic. MBW provides consulting activity to Medtronic and Cosmo on behalf of Mayo Clinic and has equity interest in Virgo., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Extraesophageal reflux symptoms are increasingly common in the Western population and their clinical management is still controversial. Although therapy with proton-pump inhibitors (PPIs) represents the gold standard, to date, many patients are refractory to this treatment. The aim of this study was to evaluate, in patients with a recent diagnosis of GERD experiencing extraesophageal symptoms, the efficacy and safety of a 6-week treatment with PPI acid suppression in combination with Gerdoff ® (a hyaluronic acid and chondroitin sulphate-based medical device) compared to PPI monotherapy. The trial verified the reduction in symptom frequency and severity by evaluating the proportion of Responders and Non-Responder patients after 6 weeks of treatment, compared to baseline. The effects of Gerdoff ® + PPI treatment on extraesophageal symptoms were also evaluated after a 12-week follow up only in Responder patients. The analysis of the change in total Reflux Symptoms Index (RSI) score from baseline to the other time points showed that the extent of the decrease from baseline was higher in the Gerdoff ® + PPI group than in the PPI group at any time point. However, the comparison between groups did not show statistically significant differences at any time point. A statistically significant difference, in favor of the Gerdoff ® + PPI group, was observed for individual RSI items. Even if the trial showed some limitations, this is the first published study on the efficacy of a medical device containing hyaluronic acid and chondroitin sulphate with antacid in the treatment of extraesophageal reflux symptoms.

Background: Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is emerging as a complementary therapeutic approach for pancreatic solid masses. However, results of published data are difficult to interpret because of a retrospective design and small sample size., Aim: To systematically review data on EUS-RFA for solid lesions and to pool the results of the different experiences in order to provide more consistent evidence in terms of safety and efficacy., Methods: A comprehensive systematic literature search on the main databases was performed to identify articles in which patients with pancreatic solid lesions underwent EUS-RFA. The primary outcomes were procedure-related adverse events (AEs) and mortality. Secondary outcomes were the technical success rate and the effects on primary tumor growth. Statistical analyses were performed using Stata version 14.0., Results: In total, 14 studies were included, with 120 patients undergoing 153 ablations of 129 solid pancreatic lesions. The STARmed technology was used in seven studies, the Habib system in six studies, and the HybridTherm probe in one study. The pooled technical success rate was 99.0% ( I 2 : 25.82%). The pooled overall AE rate was 8.0% ( I 2 : 11.46%). Excluding mild AEs, the pooled rates of serious AEs was 1.0% ( I 2 : 0%). No mortality related to the procedure was reported., Conclusion: The present pooled analysis confirms the safety and feasibility of EUS-RFA., Competing Interests: Conflict-of-interest statement: All the authors declare that they have no competing interests related to the topic., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background and study aims  The role of endoscopic submucosal dissection (ESD) for colorectal lesions in Western communities is unclear and its adoption is still limited. The aim of this study is to assess the long-term outcomes of a large cohort of patients treated with colorectal ESD in a tertiary Western center. Patients and methods  A retrospective analysis was conducted on patients treated by ESD for superficial colorectal lesions between February 2011 and November 2019. The primary outcome was the recurrence rate. Secondary outcomes were en-bloc and R0 resection rates, procedural time, adverse events (AEs), and need for surgery. The curative resection rate was assessed for submucosal invasive lesions. Results  A total of 327 consecutive patients, median age 69 years (IQR 60-76); 201 men (61.5 %) were included in the analysis. Of the lesions, 90.8 % were resected in an en-bloc fashion. The rate of R0 resection was 83.1 % (217/261) and 44.0 % (29/66) for standard and hybrid ESD techniques, respectively. Submucosal invasion and piecemeal resection independently predicted R1 resections. A total of 18(5.5 %) intra-procedural AEs (perforation:11, bleeding:7) and 12(3.7 %) post-procedural AEs occurred (perforation:2, bleeding: 10). Eighteen adenoma recurrences per 1,000 person-years (15cases, 5.6 %) were detected after a median follow-up time of 36 months. All recurrences were detected within 12 months. No carcinoma recurrences were observed. R1 resection status and intra-procedural AEs independently predicted recurrences with seven vs 150 recurrences per 1,000 person-years in the R0 vs R1 group, respectively. Conclusions  Colorectal ESD is a safe and effective option for managing superficial colorectal neoplasia in a Western setting, with short and long-terms outcomes comparable to Eastern studies. En-bloc R0 resection and absence of intra-procedural AEs are associated with reduced risk of recurrence., Competing Interests: Competing interests The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease of the esophagus characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation, whose incidence is rising. It significantly affects patients' quality of life and, if left untreated, results in fibrotic complications. Although broad consensus has been achieved on first-line therapy, a subset of patients remains non-responder to standard therapy. The pathogenesis of EoE is multifactorial and results from the complex, still mostly undefined, interaction between genetics and intrinsic factors, environment, and antigenic stimuli. A deep understanding of the pathophysiology of this disease is pivotal for the development of new therapies. This review provides a comprehensive description of the pathophysiology of EoE, starting from major pathogenic mechanisms (genetics, type 2 inflammation, epithelial barrier dysfunction, gastroesophageal reflux, allergens, infections and microbiota) and subsequently focusing on the single protagonists of type 2 inflammation (involved cells, cytokines, soluble effectors, surface proteins and transcription factors) that could represent present and future therapeutic targets, while summarizing previous therapeutic approaches in literature., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a past collaboration with several of the authors GWC and EH., (Copyright © 2022 Racca, Pellegatta, Cataldo, Vespa, Carlani, Pelaia, Paoletti, Messina, Nappi, Canonica, Repici and Heffler.)

Background: Eosinophilic oesophagitis (EoE) may lead to severe complications if not promptly recognised., Aims: To assess the diagnostic delay in patients with EoE and to explore its risk factors., Methods: EoE patients followed-up at eight clinics were included via retrospective chart review. Diagnostic delay was estimated as the time lapse occurring between the appearance of the first likely symptoms indicative of EoE and the final diagnosis. Patient-dependent and physician-dependent diagnostic delays were assessed. Multivariable regression models were computed., Results: 261 patients with EoE (mean age 34±14 years; M:F ratio=3:1) were included. The median overall diagnostic delay was 36 months (IQR 12-88), while patient- and physician-dependent diagnostic delays were 18 months (IQR 5-49) and 6 months (IQR 1-24). Patient-dependent delay was greater compared to physician-dependent delay (95% CI 5.1-19.3, p<0.001). A previous misdiagnosis was formulated in 109 cases (41.8%; gastro-oesophageal reflux disease in 67 patients, 25.7%). The variables significantly associated with greater overall diagnostic delay were being a non-smoker, >1 episode of food impaction, previous endoscopy with no biopsies, regurgitation, and ≥2 assessing physicians. Being single was significantly associated with lower overall and patient-dependent diagnostic delay., Conclusion: EoE is burdened by substantial diagnostic delay, depending on both patient-related and physician-related factors., Competing Interests: Declaration of Competing Interest None to disclose for all authors., (Copyright © 2021. Published by Elsevier Ltd.)

Background and Aims: Peroral endoscopic myotomy (POEM) has been recommended for achalasia treatment. To prevent the potential of infective risk, antibiotic prophylaxis is usually administered, whereas the additional need of antibiotic therapy after POEM is uncertain. The primary endpoint was to determine whether prophylaxis versus prophylaxis plus short therapy was needed after POEM., Methods: Consecutive patients scheduled for POEM were randomly assigned (1:1) to group A (prophylactic cefazolin 2 g IV) or group B (prophylaxis + cefazolin 2 g IV × 3 followed by oral amoxicillin/clavulanate 3 g/day). Infective risk was assessed by means of host response, namely body temperature and serum levels of white blood cells and C-reactive protein; immune response (the cytokines interleukin [IL]-6, IL-1β, and tumor necrosis factor-α and microbial translocation mediators lipopolysaccharide binding protein and soluble CD14); and blood cultures at time points before (t0) and after (t1, t2) POEM., Results: After POEM, none of the 124 enrolled patients (54.6 ± 12.6 years old; 64 men) developed any fever (body temperature: t0, 36.56± .49°C; t1, 36.53± .52°C; t2, 36.48± .41°C), without any differences between groups at any time point. Regarding systemic inflammation, no difference was reported between groups in serum levels of C-reactive protein and white blood cells. Considering microbial translocation mediated response, lipopolysaccharide binding protein (group A: t0, 1539 ± 168.6 pg/mL; t1, 1321 ± 149.1 pg/mL; t2, 2492 ± 283.2 pg/mL; group B: t0, 1318 ± 115.9 pg/mL; t1, 1492 ± 163.8 pg/mL; t2, 2600 ± 328.2 pg/mL) and soluble CD14 (group A: t0, 2.16 ± .15 μg/mL; t1, 1.89 ± .15 μg/mL; t2, 2.2 ± .15 μg/mL; group B: t0, 2.1 ± .13 μg/mL; t1, 2 ± .13 μg/mL; t2, 2.5 ± .2 μg/mL) were similar between the 2 groups; the immune response cytokines IL-6, IL-1β, and tumor necrosis factor-α also were similar in the 2 groups. In relation to blood cultures, at t1 the group B bacteremia rate was 3.2% (2/62) and group A was 1.6% (1/62) with no difference (P = .6). All subsequent blood cultures were negative at t2., Conclusions: According to our study, postprophylactic short-term antimicrobial therapy after POEM is not required because of a very low residual infective risk. (Clinical trial registration number: NCT03587337.)., (Copyright © 2021 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Adequate bowel cleansing is critical to ensure quality and safety of a colonoscopy. A novel 1-L polyethylene glycol plus ascorbate (1L-PEG+ASC) regimen was previously validated against low-volume regimens but was never compared with high-volume regimens., Methods: In a phase IV study, patients undergoing colonoscopy were randomized 1:1 to receive split-dose 1L PEG+ASC or a split-dose 4-L PEG-based regimen (4L-PEG) in 5 Italian centers. Preparation was assessed with the Boston Bowel Preparation Scale (BBPS) by local endoscopists and centralized reading, both blinded to the randomization arm. The primary endpoint was noninferiority of 1L-PEG+ASC in colon cleansing. Secondary endpoints were superiority of 1L-PEG+ASC, patient compliance, segmental colon cleansing, adenoma detection rate, tolerability, and safety., Results: Three hundred eighty-eight patients (median age, 59.8 years) were randomized between January 2019 and October 2019: 195 to 1L-PEG+ASC and 193 to 4L-PEG. Noninferiority of 1L-PEG+ASC was demonstrated for cleansing in both the entire colon (BBPS ≥ 6: 97.9% vs 93%; relative risk [RR], 1.03; 95% confidence interval [CI], 1.001-1.04; P superiority = .027) and in the right-sided colon segment (98.4% vs 96.0%; RR, 1.02; 95% CI, .99-1.02; P noninferiority = .013). Compliance was higher with 1L-PEG+ASC than with 4L-PEG (178/192 [92.7%] vs 154/190 patients [81.1%]; RR, 1.10; 95% CI, 1.05-1.12), whereas no difference was found regarding safety (moderate/severe side effects: 20.8% vs 25.8%; P = .253). No difference in adenoma detection rate (38.8% vs 43.0%) was found., Conclusions: One-liter PEG+ASC showed noninferiority compared with 4L-PEG in achieving adequate colon cleansing and provided a higher patient compliance. No differences in tolerability and safety were detected. (Clinical trial registration number: NCT03742232.)., (Copyright © 2021 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: Computer-aided detection (CADe) techniques based on artificial intelligence algorithms can assist endoscopists in detecting colorectal neoplasia. CADe has been associated with an increased adenoma detection rate, a key quality indicator, but the utility of CADe compared with existing advanced imaging techniques and distal attachment devices is unclear., Methods: For this systematic review and network meta-analysis, we did a comprehensive search of PubMed/Medline, Embase, and Scopus databases from inception to Nov 30, 2020, for randomised controlled trials investigating the effectiveness of the following endoscopic techniques in detecting colorectal neoplasia: CADe, high definition (HD) white-light endoscopy, chromoendoscopy, or add-on devices (ie, systems that increase mucosal visualisation, such as full spectrum endoscopy [FUSE] or G-EYE balloon endoscopy). We collected data on adenoma detection rates, sessile serrated lesion detection rates, the proportion of large adenomas detected per colonoscopy, and withdrawal times. A frequentist framework, random-effects network meta-analysis was done to compare artificial intelligence with chromoendoscopy, increased mucosal visualisation systems, and HD white-light endoscopy (the control group). We estimated odds ratios (ORs) for the adenoma detection rate, sessile serrated lesion detection rate, and proportion of large adenomas detected per colonoscopy, and calculated mean differences for withdrawal time, with 95% CIs. Risk of bias and certainty of evidence were assessed with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach., Findings: 50 randomised controlled trials, comprising 34 445 participants, were included in our main analysis (six trials of CADe, 18 of chromoendoscopy, and 26 of increased mucosal visualisation systems). HD white-light endoscopy was the control technique in all 50 studies. Compared with the control technique, the adenoma detection rate was 7·4% higher with CADe (OR 1·78 [95% CI 1·44-2·18]), 4·4% higher with chromoendoscopy (1·22 [1·08-1·39]), and 4·1% higher with increased mucosal visualisation systems (1·16 [1·04-1·28]). CADe ranked as the superior technique for adenoma detection (with moderate confidence in hierarchical ranking); cross-comparisons of CADe with other imaging techniques showed a significant increase in the adenoma detection rate with CADe versus increased mucosal visualisation systems (OR 1·54 [95% CI 1·22-1·94]; low certainty of evidence) and with CADe versus chromoendoscopy (1·45 [1·14-1·85]; moderate certainty of evidence). When focusing on large adenomas (≥10 mm) there was a significant increase in the detection of large adenomas only with CADe (OR 1·69 [95% CI 1·10-2·60], moderate certainty of evidence) when compared to HD white-light endoscopy; CADe ranked as the superior strategy for detection of large adenomas. CADe also seemed to be the superior strategy for detection of sessile serrated lesions (with moderate confidence in hierarchical ranking), although no significant increase in the sessile serrated lesion detection rate was shown (OR 1·37 [95% CI 0·65-2·88]). No significant difference in withdrawal time was reported for CADe compared with the other techniques., Interpretation: Based on the published literature, detection rates of colorectal neoplasia are higher with CADe than with other techniques such as chromoendoscopy or tools that increase mucosal visualisation, supporting wider incorporation of CADe strategies into community endoscopy services., Funding: None., Competing Interests: Declaration of interests AA reports consulting fees for Olympus and Medtronic. SC reports consulting fees for Olympus and Medtronic. AF reports consulting fees for Olympus. AR reports consulting fees for Fuji, Olympus, and Medtronic. CH reports consulting fees for Fuji and Medtronic. RM reports consulting fees for Fuji. DKR reports consulting fees for Olympus, Boston, Aries Pharmaceutical, Braintree Laboratories, Norgine, Endokey, GI Supply, and Medtronic. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The novel Coronavirus (SARS-CoV-2) has caused almost 2 million deaths worldwide. Both Food and Drug Administration and European Medicines Agency have recently approved the first COVID-19 vaccines, and a few more are going to be approved soon., Methods: Several different approaches have been used to stimulate the immune system in mounting a humoral response. As more traditional approaches are under investigation (inactivated virus vaccines, protein subunit vaccines, recombinant virus vaccines), more recent and innovative strategies have been tried (non-replicating viral vector vaccines, RNA based vaccines, DNA based vaccines)., Results: Since vaccinations campaigns started in December 2020 in both the US and Europe, gastroenterologists will be one of the main sources of information regarding SARS-CoV 2 vaccination for patients in their practice, including vulnerable patients such as those with Inflammatory Bowel Disease (IBD), patients with chronic liver disease, and GI cancer patients., Conclusions: Thus, we must ourselves be well educated and updated in order to provide unambiguous counseling to these categories of vulnerable patients. In this commentary, we aim to provide a comprehensive review of both approved COVID-19 vaccines and the ones still under development, and explore potential risks, benefits and prioritization of vaccination., (© 2021 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC. on behalf of United European Gastroenterology.)

Introduction: Multiple therapeutic modalities including surgery and rigid and flexible endoscopy have been adopted to manage Zenker's diverticulum (ZD). Minimally invasive flexible endoscopic septotomy (FES) techniques have been increasingly favored over the past 20 years; however, long-term data are still scanty. The aim of this study is to evaluate early and long-term outcomes of FES for naive ZD in a single-center setting., Methods: From 2010 to 2017, ZD patients treated with FES were included in a prospectively maintained database (NCT03948438). Those who had already been treated surgically or endoscopically were excluded from the analysis. The Dakkak and Bennett dysphagia scale was used to rate the dysphagia. Persistent complete or near-complete resolution of symptoms (Dakkak and Bennett 0 or 1) was defined as clinical success. Postprocedural adverse events were reported according to ASGE lexicon., Results: Overall, 256 consecutive patients were treated. Mean pouch size was 29.8 ± 11.3 mm. The procedure was successfully completed in all scheduled patients, with an early clinical success of 96.1%. Adverse events occurred in 3.5% (9/256) of patients. Eight of them were mild/moderate with no fatal events, whereas one patient required surgery. Recurrences occurred in 31.3% (80/256) of treated patients after a mean time of 9 ± 3 months and 95% of recurrences were treated by a second FES. At an average follow-up of 5.5 years, 95.3% of patients were asymptomatic after a mean number of 1.3 procedures., Discussion: FES is a safe and effective treatment modality for patients with ZD. Recurrence rate is significant; however, endoscopic reintervention is associated with long-term relief of dysphagia., (Copyright © 2021 by The American College of Gastroenterology.)