No abstract

Background: Five to ten percent of all patients undergoing radiofrequency ablation (RFA), which is the most established technique for Barrett's esophagus (BE) ablation-develop strictures. Hybrid-argon plasma coagulation (APC) combines APC with submucosal saline injection that was recently developed to tackle this problem. The aims of this pilot study were to evaluate the feasibility, tolerance, safety and long-term efficacy of hybrid-APC for the treatment of BE. Methods: Patients with histological proven BE were selected for hybrid-APC. Prior to APC thermal ablation the mucosa was lifted using a submucosal high-pressure water jet injection system (Erbejet 2; Erbe, Tuebingen, Germany). Short-term (< 48 hours) and long-term (> 48 hours) safety were evaluated. Efficacy of ablation was measured at 3, 6, 12 and 24 months at follow-up endoscopy by evidence of macroscopically complete resolution of BE mucosa and/or histologically complete resolution of intestinal metaplasia (CRIM). Results: Eleven patients were included in the study (average age, 68.2 years; male 72.7%). Eight patients (72.7%) were treatment naive, 9.1% (n = 1) had prior RFA and 18.2% (n = 2) had prior endoscopic mucosal resection. Two patients were excluded from the study. Nine patients (100%) had macroscopic remission and 88.9% (n = 8) had macroscopic remission and microscopic CRIM at 24 months after hybrid-APC ablation. No treatmentrelated stricture or other major complications were observed, 1 patient (11.1%) reported minor adverse effects. Conclusion: In this prospective pilot study, hybrid-APC appears safe, feasible and effective after 24 months, which has not been evaluated so far. Further large, multi-centre trials are warranted to confirm the present results.

Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exomesequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P < 4 × 10 −10 ), and replicate this finding in an independent cohort of VEO-IBD cases and controls (117 patients and 2,603 controls; P < 5 × 10 −10 ). This discovery indicates that a polygenic component operates in VEO-IBD pathogenesis.

Summary ▪ Obesity is reaching pandemic proportions globally, with overweight or obesity affecting at least two‐thirds of Australian adults. ▪ Bariatric surgery is an effective weight loss strategy but is constrained by high resource requirements and low patient acceptance. ▪ Multiple endoscopic bariatric therapies have matured, with well established and favourable safety and efficacy profiles in multiple randomised controlled trials (RCTs), and are best used within a multidisciplinary setting as an adjuvant to lifestyle intervention. ▪ Three types of intragastric balloon are currently in use in Australia offering average total weight loss ranging from 10% to 18%, with others available internationally. ▪ Endoscopic sleeve gastroplasty produces average total weight loss of 15–20% with low rates of severe complications, with RCT data anticipated in December 2021. ▪Bariatric and metabolic endoscopy is rapidly evolving, with many novel, promising therapies currently under investigation.