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Pierfrancesco Visaggi,1,* Matteo Ghisa,2,* Edoardo Vespa,3 Alberto Barchi,3 Amir Mari,4 Andrea Pasta,5 Elisa Marabotto,5,6 Nicola de Bortoli,1 Edoardo Vincenzo Savarino2 1Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy; 2Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy; 3Gastroenterology and Digestive Endoscopy, IRCCS Ospedale San Raffaele, Milan, 20132, Italy; 4Gastroenterology Unit, Nazareth Hospital EMMS, Azrieli Faculty of Medicine, Bar Ilan University, Ramat Gan, Israel; 5Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy; 6IRCCS Policlinico San Martino, Genoa, Italy*These authors contributed equally to this workCorrespondence: Edoardo Vincenzo Savarino, Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Via Giustiniani 2, Padua, 35128, Italy, Tel +39-049-8217749, Email edoardo.savarino@unipd.itAbstract: Eosinophilic esophagitis (EoE) is a chronic type 2 inflammation-mediated disease characterized by an eosinophil-predominant inflammation of the esophagus and symptoms of esophageal dysfunction. Relevant treatment outcomes in the setting of EoE include the improvement of histology, symptoms, and endoscopy findings, quality of life (QoL), and the psychological burden of the disease. Established validated tools for the assessment of EoE include questionnaires on dysphagia and QoL (ie, DSQ, EEsAI, and EoE-IQ). More recently, esophageal symptom-specific anxiety and hypervigilance, assessed using the esophageal hypervigilance and anxiety scale (EHAS), have emerged as contributors to disease burden, confirming the importance of psychological aspects in EoE patients. The EoE endoscopic reference score (EREFS) is the only validated endoscopy score in EoE and can quantify mucosal disease burden. However, esophageal panometry using the functional lumen imaging probe (FLIP) and high-resolution manometry (HRM) have shown potential to optimize the assessment of fibrostenotic features of EoE, providing novel insights into the pathophysiology of symptoms. There is a growing number of licenced and off-label therapeutic options in EoE, with various randomized controlled trials demonstrating the efficacy of proton pump inhibitors, topical steroids, food elimination diets, biological drugs, and esophageal dilatation. However, standardized optimal management strategies of EoE are currently lacking. In this review, we provide an overview of established and novel assessment tools in EoE including patient reported outcomes, FLIP panometry, HRM, endoscopy, and histology outcome measures to improve the outcomes of EoE patients. In addition, we summarize available therapeutic options for EoE based on the most recent evidence.Keywords: eosinophilic esophagitis, treatment, monitoring

Arianna Dal Buono,1 Roberto Gabbiadini,1 Virginia Solitano,1,2 Edoardo Vespa,1,2 Tommaso Lorenzo Parigi,1,2 Alessandro Repici,2,3 Antonino Spinelli,1,2,4 Alessandro Armuzzi1,2 1IBD Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy; 2Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; 3Endoscopy Unit, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy; 4Colon and Rectal Surgery Division, IRCCS Humanitas Research Hospital, Rozzano, Milan, ItalyCorrespondence: Alessandro Armuzzi, IBD Center, Humanitas Research Hospital – IRCCS, Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Rozzano, Milan, Italy, Tel +39(0)282245555, Fax +39(0)282242591, Email alessandro.armuzzi@hunimed.euBackground and Aims: Patients affected by moderate-to-severe Ulcerative Colitis (UC) demand a challenging management. Small molecules, administrated as oral agents, have the ambition of overcoming the limitations of the biologic agents (ie, parenteral administration, rapidity of action, primary and secondary non-responsiveness). Beyond tofacitinib, a pan-Janus kinase (JAK) inhibitor already approved for the treatment of moderate-to-severe UC, novel more selective molecules like filgotinib are being currently evaluated in randomized clinical trials. We aimed to review the current evidence on filgotinib, a JAK-1 preferential inhibitor, in the treatment of UC and its place in therapy in the current scenario.Methods: PubMed and EMBASE were searched to identify relevant studies: those investigating the efficacy and safety of filgotinib in the treatment of UC patients were included in this narrative review.Results: The current preliminary data have shown that filgotinib is safe and effective in inducing clinical end endoscopic response in both biologic-naïve and biologic-experienced patients with moderate-to-severe UC, also with high inflammatory burden at baseline. In the SELECTION trial, one case of pulmonary embolism occurred with filgotinib 200 mg induction, and three venous thrombosis cases were observed in the placebo maintenance/LTE; the incidence of herpes zoster was ≤ 1% in all UC treated patients. Filgotinib represents an appealing treatment option for its high selectiveness, route of administration and rapidity of action; cost-effectiveness studies and head-to-head trials are needed to better define its place in therapy.Keywords: ulcerative colitis, filgotinib, Janus kinase inhibitors, efficacy, safety

Background/Objectives : Delayed gastric conduit emptying (DGCE) occurs in 15-39% of patients who undergo esophagectomy. Intra-Pyloric Injection of Botulinum Toxin (IPBT), Pneumatic Balloon Dilation (PBD), and the same session combination (BTPD) represent the main endoscopic procedures, but comparative data are currently unavailable. Methods : We retrospectively analyzed prospectively collected data on all consecutive patients with DGCE treated endoscopically with IPBT, PBD, or BTPD. ISDE Diagnostic Criteria were used for DGCE diagnosis and classification. A Gastric Outlet Obstruction Score was used for clinical staging. All patients undergoing IPBT received 100 UI of toxin, while those undergoing PBD were dilated up to 20 mm. Clinical success (CS) was defined as the resolution of symptoms/resumption of feeding at discharge or expanding dietary intake at any rate. Recurrence was defined as symptom relapse after more than 15 days of well-being requiring endoscopic/surgical intervention. Results : A total of 64 patients (81.2% male, 90.6% Ivor-Lewis esophagectomy, 77.4% adenocarcinoma) with a median age of 62 years (IQR 55-70) were enrolled: 18 (28.1%) in the IPBT group, 24 (37.5%) in the PBD group, and 22 (34.4%) in the BTPD group. No statistically significant differences were found in the baseline characteristics, surgical techniques, and median follow-up among the three groups. BTPD showed a higher CS rate (100%) compared to the PD and BTPD groups ( p = 0.02), and a Kaplan-Meier analysis with a log-rank test revealed that the BTPD group was associated both with a significatively shorter mean time to refeed of 1.16 days (95% CI 0.8-1.5; p = 0.001) and a shorter median time to discharge of one day (95% CI 1-3; p = 0.0001). Conclusions : Endoscopic management of DGCE remains challenging. Waiting for further strong evidence, BTPD can offer patients a higher clinical efficacy rate and a shorter time to refeed and be discharged.

Introduction: Although gastric peroral endoscopic myotomy (G-POEM) has shown substantial efficacy in patients with medically refractory gastroparesis (GP), comprehensive long-term data on its effectiveness are lacking., Methods: We conducted a systematic review and meta-analysis including observational studies assessing long-term efficacy after G-POEM in patients with refractory GP. Our primary outcome was the pooled rate of clinical success 1-year after G-POEM. Secondary outcomes included clinical success at 2 and 3 years and the rate of adverse events according to the American Society for Gastrointestinal Endoscopy classification., Results: Thirteen studies, involving 952 patients with refractory GP undergoing G-POEM, were eligible. The pooled 1 year-clinical success was 0.72 (95% confidence interval [CI]: 0.56, 0.85, I 2 = 94.9%). The clinical success was 0.67 (95% CI: 0.47, 0.97, I 2 = 95.8%) when considering only studies defining success as 1 point decrease in Gastroparesis Cardinal Symptoms Index score and at least 25% decrease in two subscales. For patients who had 1-year success, the pooled clinical success at 2 and 3 years were 0.71 (95% CI: 0.45, 0.92, I 2 = 94.9%) and 0.58 (95% CI: 0.19, 0.92, I 2 = 97.1%), respectively. The pooled rate of adverse events was 0.08 (95% CI: 0.06, 0.10, I 2 = 0%)., Conclusion: G-POEM is associated with successful outcomes in about 70% of treated cases after 1 year, with durable long-term effects lasting up to 3 years. In the future, new uniform outcome definitions and strict patient selection criteria are warranted to delineate G-POEM outcomes more accurately., Competing Interests: None., (© 2024 The Author(s). DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Zenker's Diverticulum (ZD) is the most common hypopharyngeal diverticulum; however, it is often underdiagnosed. It results from the herniation of the mucosa and submucosa through Killian's Triangle. Dysphagia is the primary symptom, occurring in 80-90% of cases. The primary goal of treatment is to transect the cricopharyngeal muscle (CM) and connect the ZD cavity to the esophageal lumen. Traditional treatments include surgical open transcervical diverticulectomy and CM septomyotomy, using rigid or flexible endoscopes. However, surgery is burdened by technical difficulties and not negligible rates of adverse events (AEs). For this reason, endoscopic techniques for ZD treatment have gained traction in recent years. Flexible endoscopic septum division (FESD), introduced nearly 20 years ago, involves a full-thickness incision of the diverticular septum. The advent of third-space endoscopy has led to the application of these techniques to ZD treatment as well. Zenker-POEM (Z-POEM) and, subsequently, Per Oral Endoscopic Septomyotomy (POES) have been developed. Hybrid techniques, such as Peroral Endoscopic Diverticulotomy (POED) and tunneling-free methods, represent additional ZD treatment options. This review outlines the armamentarium of ZD endoscopic management, summarizing the characteristics of these techniques, their benefits and limitations, and highlighting future research directions.

Peroral endoscopic myotomy (POEM) is an established treatment for achalasia, yet there is still a lack of technical standardization. No clear definition of 'long', 'standard', or 'short' POEM exists to date. We conducted a systematic review with meta-analysis to analyze current POEM length standards. We included studies reporting technical details of POEM, in which no definite or comparative myotomy length was intentionally adopted (standard myotomy). The primary outcome was the pooled mean total myotomy length. Sub-group analyses were performed to explore heterogeneity across studies. From the initial 7172 records, 31 studies with 3023 patients were included. Pooled mean of total myotomy length was 10.39 cm (95% CI 10.06-10.71; I2 99.3%). Pooled mean of esophageal and gastric myotomy length, provided by 17 studies, was 7.11 cm (95% CI 6.51-7.71; I2 99.8%) and 2.81 cm (95% CI 2.41-3-22; I2 99.8%), respectively. On subgroup analysis for achalasia subtypes, pooled mean length in non-spastic achalasia (type I and II) was 10.17 cm (95% CI 9.91-10.43; I2 94.2%), while in type III it was 14.02 cm (95% CI 10.59-17.44; I2 98.9%). Pooled mean myotomy length for studies conducted between 2014-2020 was 10.53 cm (95% CI, 10.22-10.84; I2 99.1%) and 9.74 cm (95% CI, 7.95-11.54; I2 99.7%) in 2021-2022. Myotomy length during a 'standard' POEM is 10.4 cm, remaining over 10 cm in non-spastic achalasia. The high heterogeneity across studies confirms that the POEM technique needs further standardization. We found no significant time trend towards adopting short POEM, despite recent evidence supporting its use., (© The Author(s) 2024. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus.)

Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder of the esophagus. EoE shares a common pathogenetic mechanism with other chronic disorders pertaining to the type 2 inflammatory spectrum, such as atopic dermatitis (AD), allergic rhinitis (AR), asthma, and chronic rhinosinusitis with nasal polyps (CRSwNP). The recent advancements in EoE pathogenesis understanding have unveiled new molecular targets implied within the "atopic march" picture as well as specific to EoE. These discoveries have led to the clinical evaluation of several novel drugs (monoclonal antibodies and immune modulators), specifically aimed at the modulation of Th2 inflammation. In this comprehensive review, we have focused on the subtle mechanisms of type 2 inflammatory disorders, highlighting the similarities and differences with EoE, taking a deeper look into the evolving field of biologic therapies, already approved or under current investigation.

Background: Despite the established efficacy of achalasia treatments on symptomatic outcomes, there are limited data evaluating the treatment effect on esophageal dilatation. This study aimed to assess the effect achalasia treatment on esophageal dilatation and the effect of esophageal width reduction ("recoil") on clinical outcomes., Methods: Patients with type I or type II achalasia that completed high-resolution manometry (HRM), functional lumen imaging probe (FLIP), and timed barium esophagram (TBE) pre and post treatment were included. Esophageal width was measured using TBE. Focused subgroup analysis was performed on patients with normal posttreatment EGJ opening on FLIP. Good clinical outcomes were defined as barium column height of <5 cm at 5 min and Eckardt Score ≤3., Key Results: Sixty-nine patients (41% type I and 59% type II) were included. Esophageal width decreased from pre to post treatment mean (SD) 4.2 (1.3) cm-2.8 (1.2) cm; p < 0.01. In the normal post treatment EGJ opening subgroup, esophageal width was less in patients with good TBE outcome compared to poor outcome mean (SD) 2.2 (0.7) cm versus 3.2 (1.4) cm (p < 0.01), but did not differ in good versus poor symptomatic outcome groups. Esophageal width recoil >25% posttreatment was associated with a greater rate of good TBE outcome (71% vs. 50%, p = 0.04) and good symptomatic outcome (88% vs. 50%; p = 0.04)., Conclusions and Inferences: Esophageal recoil was associated with good achalasia treatment outcome in patients without posttreatment EGJ obstruction. This suggests that mechanical properties of the esophageal wall, likely associated with tissue remodeling, play a role in clinical outcomes following achalasia treatment., (© 2024 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Endoscopic treatments such as peroral endoscopic myotomy (POEM) and pneumatic dilation (PD) are commonly used to treat achalasia. Although POEM has gained popularity due to its high efficacy, the technique is more complex and may be associated with a higher risk of long-term complications compared to PD. This narrative review will focus on efficacy and safety of PD and POEM, and their suitability for different patient populations. While evidence suggests that POEM may be preferred for type III achalasia, PD remains a valuable alternative for patients with a straight, non-dilated esophagus, who prioritize the preservation of anatomical integrity and a lower risk of post-procedural gastroesophageal reflux disease (GERD). While PD carries a non negligibile risk of perforation, it has an excellent safety profile in terms of GERD and is minimally likely to cause permanent esophageal deformation. PD can be repeated with minimal risks to maintain symptom relief, whereas reversing permanent anatomical modifications related to POEM is difficult. The choice of treatment for achalasia should be patient-tailored, considering benefits and drawbacks of each intervention. The importance of personalized approach in the "POEM era" is highlighted, emphasizing the reasons why PD should still be considered a valuable option in the therapeutic armamentarium for achalasia. Areas requiring further research will be also outlined., Competing Interests: Conflict of interest Edoardo Vespa, Alberto Barchi and Sandro Passaretti have no disclosures. Silvio Danese has served as speaker and consultant for Schering-Plough, AbbVie, Actelion, Alphawasserman, AstraZeneca, Cellerix, Cosmo Pharmaceuticals, Ferring, Genentech, Grunenthal, Johnson and Johnson, Millenium Takeda, MSD, Nikkiso Europe GmbH, Novo Nordisk, Nycomed, Pfizer, Pharmacosmos, UCB Pharma and Vifor. 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, Takeda, Unifarco; he received research support from Pfizer, Reckitt Benckiser, SILA, Sofar, Unifarco, Zeta Farmaceutici., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Eosinophilic Gastrointestinal Disorders (EGIDs) are a group of conditions characterized by abnormal eosinophil accumulation in the gastrointestinal tract. Among these EGIDs, Eosinophilic Esophagitis (EoE) is the most well documented, while less is known about Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), and Eosinophilic Colitis (EoC). The role of endoscopy in EGIDs is pivotal, with applications in diagnosis, disease monitoring, and therapeutic intervention. In EoE, the endoscopic reference score (EREFS) has been shown to be accurate in raising diagnostic suspicion and effective in monitoring therapeutic responses. Additionally, endoscopic dilation is the first-line treatment for esophageal strictures. For EoG and EoN, while the literature is more limited, common endoscopic findings include erythema, nodules, and ulcerations. Histology remains the gold standard for diagnosing EGIDs, as it quantifies eosinophilic infiltration. In recent years, there have been significant advancements in the histological understanding of EoE, leading to the development of diagnostic scores and the identification of specific microscopic features associated with the disease. However, for EoG, EoN, and EoC, precise eosinophil count thresholds for diagnosis have not yet been established. This review aims to elucidate the role of endoscopy and histology in the diagnosis and management of the three main EGIDs and to analyze their strengths and limitations, their interconnection, and future research directions.

Background and Aims: Some achalasia patients exhibit esophageal contractile activity on follow-up after treatment, yet its importance remains unclear. We aimed to identify factors associated with presence of contractility after treatment and to assess its impact on timed barium esophagram (TBE) and clinical outcomes., Methods: Patients with type I or II achalasia on baseline high-resolution manometry (HRM) who completed HRM, TBE, and functional lumen imaging probe (FLIP) after treatment were retrospectively identified. Contractility was defined on post-treatment HRM as presence of at least 1 supine swallow with DCI ≥100 mmHg s cm., Key Results: One hundred twenty-two patients were included (mean age 48 ± 17 years, 50% female). At follow-up evaluation after treatment (54% peroral endoscopic myotomy, 24% pneumatic dilation, 22% laparoscopic Heller myotomy), 61 (50%) patients had contractility on HRM. Patients with contractility (compared to those without) more frequently had type II achalasia (84% vs 57%, p = 0.001) and a post-treatment normal EGJ opening classification on FLIP (69% vs 49%; p < 0.001). In the subgroup of patients with post-treatment integrated relaxation pressure <15 mmHg and normal EGJ opening on FLIP (n = 53), those with contractility had a lower median column height on TBE at 1 min (4 vs 7 cm, p = 0.002) and 5 min (0 vs 5 cm, p = 0.001). In patients with "abnormal" EGJ metrics, patients with contractility showed lower symptom scores (median Eckardt score 2 vs 3, p = 0.03)., Conclusions & Inferences: Occurring more frequently in type II achalasia, and if adequate EGJ opening is achieved after treatment, esophageal contractility may contribute to improved esophageal emptying and improved symptoms in non-spastic achalasia. Preservation of esophageal body muscle could improve outcomes in these patients., (© 2023 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Introduction: Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus with increasing prevalence worldwide. It is a multifactorial disease caused by a combination of immunologic, genetic, and environmental factors. The clinical presentation of EoE varies largely, especially between different age groups. While diagnostic criteria and therapeutic goals are similar in children and adults, there are differences in treatment, with a more cautious approach in children to avoid growth disturbances. In addition, close monitoring and follow-up are essential in children to ensure uninterrupted growth., Areas Covered: A search in PubMed/MEDLINE, EMBASE, and SCOPUS databases was conducted to identify relevant studies published between January 2010 and January 2023 to give an overview of the state-of-the-art of EoE epidemiology, diagnosis, and treatment while focusing on similarities and differences between the adult and the pediatric population., Expert Opinion: The current state of research indicates that while significant progress has been made in understanding and treating EoE, further research and advances are needed to optimize diagnostic strategies, tailored treatment approaches, monitoring, and follow-up, and improve long-term outcomes for patients. With further innovation, the management of EoE can become more precise and tailored, leading to better patient outcomes and improved quality of life.

Gut microbiota is recognized nowadays as one of the key players in the development of several gastro-intestinal diseases. The first studies focused mainly on healthy subjects with staining of main bacterial species via culture-based techniques. Subsequently, lots of studies tried to focus on principal esophageal disease enlarged the knowledge on esophageal microbial environment and its role in pathogenesis. Gastro Esophageal Reflux Disease (GERD), the most widespread esophageal condition, seems related to a certain degree of mucosal inflammation, via interleukin (IL) 8 potentially enhanced by bacterial components, lipopolysaccharide (LPS) above all. Gram - bacteria, producing LPS), such as Campylobacter genus, have been found associated with GERD. Barrett esophagus (BE) seems characterized by a Gram - and microaerophils-shaped microbiota. Esophageal cancer (EC) development leads to an overturn in the esophageal environment with the shift from an oral-like microbiome to a prevalently low-abundant and low-diverse Gram - -shaped microbiome. Although underinvestigated, also changes in the esophageal microbiome are associated with rare chronic inflammatory or neuropathic disease pathogenesis. The paucity of knowledge about the microbiota-driven mechanisms in esophageal disease pathogenesis is mainly due to the scarce sensitivity of sequencing technology and culture methods applied so far to study commensals in the esophagus. However, the recent advances in molecular techniques, especially with the advent of non-culture-based genomic sequencing tools and the implementation of multi-omics approaches, have revolutionized the microbiome field, with promises of implementing the current knowledge, discovering more mechanisms underneath, and giving insights into the development of novel therapies aimed to re-establish the microbial equilibrium for ameliorating esophageal diseases.., Competing Interests: Professor Silvio Danese declares the following conflicts of interest: has served as a speaker, consultant, and advisory board member for Schering-Plough, AbbVie, Actelion, Alphawasserman, AstraZeneca, Cellerix, Cosmo Pharmaceuticals, Ferring, Genentech, Grunenthal, Johnson and Johnson, Millenium Takeda, MSD, Nikkiso Europe GmbH, Novo Nordisk, Nycomed, Pfizer, Pharmacosmos, UCB Pharma and Vifor. The other authors declare no conflicts of interest. A.Barchi, L. Massimino, F.V. Mandarino, E. Vespa, O. Almolla, S. Passaretti, E. Sinagra, T.L. Parigi, S. Cagliani, S. Spanò, F. Ungaro declares no conflict of interest. S Danese has served as a speaker, consultant, and advisory board member for Schering-Plough, AbbVie, Actelion, Alphawasserman, AstraZeneca, Cellerix, Cosmo Pharmaceuticals, Ferring, Genentech, Grunenthal, Johnson and Johnson, Millenium Takeda, MSD, Nikkiso Europe GmbH, Novo Nordisk, Nycomed, Pfizer, Pharmacosmos, UCB Pharma and Vifor., (© 2024 The Authors.)

Our review delves into the realm of peroral endoscopic myotomies (POEMs) in the upper gastrointestinal tract (UGT). In recent years, POEMs have brought about a revolution in the treatment of UGT motility disorders. Esophageal POEM, the first to be introduced, has now been validated as the primary treatment for achalasia. Subsequently developed, G-POEM displays promising results in addressing refractory gastroparesis. Over time, multiple endoscopic myotomy techniques have emerged for the treatment of Zenker's diverticulum, including Z-POEM, POES, and hybrid approaches. Despite the well-established efficacy outcomes, new challenges arise in the realm of POEMs in the UGT. For esophageal POEM, the future scenario lies in customizing the myotomy extent to the minimum necessary, while for G-POEM, it involves identifying patients who can optimally benefit from the treatment. For ZD, it is crucial to validate an algorithm that considers various myotomy options according to the diverticulum's size and in relation to individual patients. These challenges align with the concept of precision endoscopy, personalizing the technique for each subject. Within our text, we comprehensively examine each myotomy technique, analyzing indications, outcomes, and adverse events. Additionally, we explore the emerging challenges posed by myotomies within the context of the evolving field of precision endoscopy.

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease characterized by eosinophilic infiltration of the esophagus. It arises from a complex interplay of genetic predisposition (susceptibility loci), environmental triggers (allergens and dietary antigens), and a dysregulated immune response, mainly mediated by type 2 T helper cell (Th2)-released cytokines, such as interleukin (IL)-4, IL-5, and IL-13. These cytokines control eosinophil recruitment and activation as well as tissue remodeling, contributing to the characteristic features of EoE. The pathogenesis of EoE includes epithelial barrier dysfunction, mast cell activation, eosinophil degranulation, and fibrosis. Epithelial barrier dysfunction allows allergen penetration and promotes immune cell infiltration, thereby perpetuating the inflammatory response. Mast cells release proinflammatory mediators and promote eosinophil recruitment and the release of cytotoxic proteins and cytokines, causing tissue damage and remodeling. Prolonged inflammation can lead to fibrosis, resulting in long-term complications such as strictures and dysmotility. Current treatment options for EoE are limited and mainly focus on dietary changes, proton-pump inhibitors, and topical corticosteroids. Novel therapies targeting key inflammatory pathways, such as monoclonal antibodies against IL-4, IL-5, and IL-13, are emerging in clinical trials. A deeper understanding of the complex pathogenetic mechanisms behind EoE will contribute to the development of more effective and personalized therapeutic strategies.

Background: Panesophageal pressurization (PEP) defines type II achalasia on high-resolution-manometry (HRM) but some patients exhibit spasm after treatment. The Chicago Classification (CC) v4.0 proposed high PEP values as predictor of embedded spasm, yet supportive evidence is lacking., Methods: Fifty seven type II achalasia patients (47 ± 18 years, 54% males) with HRM and LIP Panometry before and after treatment were retrospectively identified. Baseline HRM and FLIP studies were analyzed to identify factors associated with post-treatment spasm, defined on HRM per CC v4.0., Results: Seven patients (12%) had spasm following treatment (peroral endoscopic myotomy 47%; pneumatic dilation [PD] 37%; laparoscopic Heller myotomy 16%). At baseline, greater median maximum PEP pressure (MaxPEP) values on HRM (77 vs 55 mmHg, p = 0.045) and spastic-reactive contractile response pattern on FLIP (43% vs 8%, p = 0.033) were more common in patients with post-treatment spasm while absent contractile response on FLIP was more common in patients without spasm (14% vs 66%, p = 0.014). The strongest predictor of post-treatment spasm was the percentage of swallows with MaxPEP ≥70 mmHg (best cut-off: ≥30%), with AUROC of 0.78. A combination of MaxPEP <70 mmHg and FLIP 60 mL pressure < 40 mmHg identified patients with lower rates of post-treatment spasm (3% overall, 0% post-PD) compared to those with values above these thresholds (33% overall, 83% post-PD)., Conclusions: High maximum PEP values, high FLIP 60 mL pressures and contractile response pattern on FLIP Panometry prior to treatment identified type II achalasia patients more likely to exhibit post-treatment spasm. Evaluating these features may guide personalized patient management., (© 2023 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Competing Interests: A. Repici is a consultant for Medtronic, Fujifilm, Boston Scientific and ERBE.

Introduction: Functional luminal imaging probe (FLIP) Panometry evaluates the esophageal response to distension involving biomechanics and motility. We have observed that hiatus hernia (HH) is evident during FLIP studies as a separation between the crural diaphragm (CD) and lower esophageal sphincter (LES) like what is seen with high-resolution manometry (HRM). The aim of this study was to compare FLIP findings to endoscopy and HRM in the detection of HH., Methods: A total of 100 consecutive patients that completed FLIP during sedated endoscopy and HRM were included. LES-CD separation was assessed on FLIP and HRM with the presence of HH defined as LES-CD ≥1 cm. The agreement was evaluated using the kappa (κ) statistic., Results: Hiatal hernia was detected in 32% of patients on HRM and 44% of patients on FLIP with a substantial agreement between studies (84% agreement; κ = 0.667). On FLIP, a 'new' HH (i.e. HH not observed on HRM) occurred in 14 patients and an "enlarged" HH (i.e., LES-CD ≥2 cm larger than on HRM) occurred in 11 patients. Among patients that also completed, timed barium esophagogram (TBE), delayed esophageal emptying on TBE was more common in patients with new or enlarged HH on FLIP than those without: 7/11 (64%) versus 2/12 (17%); p = 0.017., Conclusion: FLIP can detect HH with a substantial agreement with HRM, though esophageal distension with FLIP testing appeared to elicit and/or enlarge a HH in an additional 25% of patients. Although this unique response to esophageal distension may represent a mechanism of dysphagia or susceptibility to reflux, additional study is needed to clarify its significance., (© 2022 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons 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: Eosinophilic esophagitis (EoE) is a chronic immune-mediated rare disease, characterized by esophageal dysfunctions. It is likely to be primarily activated by food antigens and is classified as a chronic disease for most patients. Therefore, a deeper understanding of the pathogenetic mechanisms underlying EoE is needed to implement and improve therapeutic lines of intervention and ameliorate overall patient wellness., Methods: RNA-seq data of 18 different studies on EoE, downloaded from NCBI GEO with faster-qdump ( https://github.com/ncbi/sra-tools ), were batch-corrected and analyzed for transcriptomics and metatranscriptomics profiling as well as biological process functional enrichment. The EoE TaMMA web app was designed with plotly and dash. Tabula Sapiens raw data were downloaded from the UCSC Cell Browser. Esophageal single-cell raw data analysis was performed within the Automated Single-cell Analysis Pipeline. Single-cell data-driven bulk RNA-seq data deconvolution was performed with MuSiC and CIBERSORTx. Multi-omics integration was performed with MOFA., Results: The EoE TaMMA framework pointed out disease-specific molecular signatures, confirming its reliability in reanalyzing transcriptomic data, and providing new EoE-specific molecular markers including CXCL14, distinguishing EoE from gastroesophageal reflux disorder. EoE TaMMA also revealed microbiota dysbiosis as a predominant characteristic of EoE pathogenesis. Finally, the multi-omics analysis highlighted the presence of defined classes of microbial entities in subsets of patients that may participate in inducing the antigen-mediated response typical of EoE pathogenesis., Conclusions: Our study showed that the complex EoE molecular network may be unraveled through advanced bioinformatics, integrating different components of the disease process into an omics-based network approach. This may implement EoE management and treatment in the coming years., (© 2023. The Author(s).)

Background: Since it was first described in 2001, endoscopic ultrasonography-guided biliary drainage (EUS-BD) has emerged as an alternative procedure for achieving an endoscopic internal drainage in case of endoscopic retrograde cholangiopancreatography (ERCP) failure. Biliary drainage can be achieved by either a transduodenal extrahepatic approach through EUS-guided choledochoduodenostomy (EUS-CDS), or a transgastric intrahepatic approach, namely EUS-guided hepaticogastrostomy (EUS-HGS) which already holds a remarkable place in the treatment of patients with malignant biliary obstruction., Data Sources: For this review we did a comprehensive search of PubMed/MEDLINE from inception to May 31, 2021 for papers with a significant sample size (at least 20 patients enrolled) dealing with EUS-HGS. Data on technical success, clinical success and rate of adverse events were collected., Results: A total of 22 studies with different design, comprising 874 patients, were included. Technical success was achieved in about 96% of cases (ranging from 65% to 100%). Clinical success was obtained in almost 91% of cases (ranging from 76% to 100%). Overall rate of adverse events was 19% (ranging from 0% to 35%). Abdominal pain, self-limiting pneumoperitoneum, bile leak, cholangitis, bleeding, perforation and intraperitoneal migration of the stent were the most common., Conclusions: Despite both safety and efficacy profile, at the moment HGS still remains a challenging procedure at every single step and must therefore be conducted by a very experienced endoscopist in interventional EUS and ERCP procedures, who is able to deal with the possible severe adverse events of this procedure. A rapid introduction in clinical practice of dedicated devices is desiderable., (Copyright © 2022 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.)

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.)

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.

Barrett's esophagus (BE) is a well-established risk factor for esophageal adenocarcinoma. It is recommended that patients have regular endoscopic surveillance, with the ultimate goal of detecting early-stage neoplastic lesions before they can progress to invasive carcinoma. Detection of both dysplasia or early adenocarcinoma permits curative endoscopic treatments, and with this aim, thorough endoscopic assessment is crucial and improves outcomes. The burden of missed neoplasia in BE is still far from being negligible, likely due to inappropriate endoscopic surveillance. Over the last two decades, advanced imaging techniques, moving from traditional dye-spray chromoendoscopy to more practical virtual chromoendoscopy technologies, have been introduced with the aim to enhance neoplasia detection in BE. As witnessed in other fields, artificial intelligence (AI) has revolutionized the field of diagnostic endoscopy and is set to cover a pivotal role in BE as well. The aim of this commentary is to comprehensively summarize present evidence, recent research advances, and future perspectives regarding advanced imaging technology and AI in BE; the combination of computer-aided diagnosis to a widespread adoption of advanced imaging technologies is eagerly awaited. It will also provide a useful step-by-step approach for performing high-quality endoscopy in BE, in order to increase the diagnostic yield of endoscopy in clinical practice., Competing Interests: Conflict-of-interest statement: Maselli R reports consulting fees for Fuji; Anderloni A reports consulting fees for Olympus and Medtronic; Carrara S reports consulting fees for Olympus and Medtronic; Fugazza A reports consulting fees for Olympus; Hassan C reports consulting fees for Fuji and Medtronic; Repici A reports consulting fees for Fuji, Olympus, and Medtronic; All other authors declare no competing interests., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Video 1At preoperative esophagram, a typical bird's beak image is shown at the gastroesophageal junction. A gastro-gastric fistula, opening from cardia to fundus, is also shown. A scope fitted with a distal clear cap is introduced. At the cardia, we see the proximal opening of the fistula. Here, we see the gastric fundus. As we go down, the gastric pouch is regular, and further down we reach the pylorus. In the retroflexed view, we recognize the neo-pylorus and the distal opening of the fistula. After submucosal injection on the anterior wall of the esophagus, a longitudinal mucosal incision is made. Submucosal tunnelling is performed using the endoscopic submucosal dissection technique. The gastroesophageal junction is reached, as confirmed by the finding of typical spindle veins. Here, we show submucosal tunnelling across the cardia, extending 2 cm into the gastric pouch. No obstacles from past surgery are encountered. Correct extension of the tunnel down into the cardia is also confirmed by visualizing a blue cushion. Dissection of a circular layer (of the muscularis) is performed and carried into the cardia. Submucosal tunnel is smoothy performed with no issues related to past surgery. Here, we demonstrate myotomy being carried into the gastric pouch across the cardia. We can see the more complex organization of muscular fibers. Again, no obstacles from past surgery are encountered. Myotomy is then completed along the entire length of the submucosal tunnel. Clip closure of the mucosal incision is eventually performed., (© 2022 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc.)

The histological assessment has been advocated as a detailed and accurate measure of disease activity in inflammatory bowel diseases (IBD). In ulcerative colitis (UC), histological activity has been demonstrated to be associated with higher rates of relapse, prolonged corticosteroid use and long-term complications, even when endoscopic remission is achieved. Therefore, histological healing may represent a potential treatment target. Several histological scores have been developed and are available today. The Robarts histopathology index (RHI) and the Nancy index (NI) are the only two recommended by the European Crohn's and Colitis Organization (ECCO) for use in patients with UC. Conversely, in Crohn's disease (CD), the discontinuous nature of lesions has limited standardized histological assessment. Most of the available histological scoring systems in CD are complex and not validated. The aim of this review is to comprehensively summarize the latest evidence regarding histological scoring systems in IBD. We guide the reader through understanding the importance of an accurate microscopic evaluation using validated scoring systems, highlighting the strengths and pitfalls of each score. The priorities of future research needs are also addressed.

Objective: Endoscopic submucosal dissection (ESD) in a curative intent for submucosa-invasive early (T1) colorectal cancers (T1-CRCs) often leads to subsequent surgical resection in case of histologic parameters indicating higher risk of nodal involvement. In some cases, however, the expected benefit may be offset by the surgical risks, suggesting a more conservative approach., Design: Retrospective analysis of consecutive patients with T1-CRC who underwent ESD at 13 centres ending inclusion in 2019 (n=3373). Cases with high risk of nodal involvement (non-curative ESD: G3, submucosal invasion>1000 µm, lymphovascular involvement, budding or incomplete resection/R1) were analysed if follow-up data (endoscopy/imaging) were available, regardless of the postendoscopic management (follow-up vs surgery) selected by the multidisciplinary teams in these institutions. Comorbidities were classified according to Charlson Comorbidity Index (CCI). Outcomes were disease recurrence, death and disease-related death rates in the two groups. Rate of residual disease (RD) at both the previous resection site and regional lymph nodes was assessed in the surgical cases as well as from follow-up in the follow-up group., Results: Of 604 patients treated by colorectal ESD for submucosally invasive cancer, 207 non-curative resections (34.3%) were included (138 male; mean age 67.6±10.9 years); in 65.2% of cases, no complete resection was achieved (R1). Of the 207 cases, 60.9% (n=126; median CCI: 3; IQR: 2-4) underwent surgical treatment with RD in 19.8% (25/126), while 39.1% (n=81, median CCI: 5; IQR: 4-6) were followed up by endoscopy in all cases. Patients in the follow-up group had a higher overall mortality (HR=3.95) due to non-CRC causes (n=9, mean survival after ESD 23.7±13.7 months). During this follow-up time, tumour recurrence and disease-specific survival rates were not different between the groups (median follow-up 30 months; range: 6-105)., Conclusion: Following ESD for a lesion at high risk of RD, follow-up only may be a reasonable choice in patients at high risk for surgery. Also, endoscopic resection quality should be improved., Trial Registration Number: NCT03987828., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)