Bariatric endoscopic antral myotomy: first-in-human proof of concept of a novel therapeutic method to delay gastric emptying and induce weight loss

摘要

As knowledge regarding the pathophysiology of obesity and mechanisms of action for bariatric procedures has evolved, opportunities have been created to develop new interventions that more directly address these mechanisms. One potential target is gastric emptying. This is a critical step in digestion that has been found to be more rapid after prolonged exposure to a high-fat diet in both animal and human studies, with rapid emptying also being more common in young people with obesity in some studies.1Pajot G. Camilleri M. Calderon G. et al.Association between gastrointestinal phenotypes and weight gain in younger adults: a prospective 4-year cohort study.Int J Obes. 2020; 44: 2472-2478Crossref Scopus (8) Google Scholar,2Little T.J. Horowitz M. Feinle-Bisset C. Modulation by high-fat diets of gastrointestinal function and hormones associated with the regulation of energy intake: implications for the pathophysiology of obesity.Am J Clin Nutr. 2007; 86: 531-541Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar Medications, such as GLP-1 receptor agonists, and interventions, such as intragastric balloons (IGBs), have been shown to delay gastric emptying as part of their mechanism to treat obesity. This appears to be effective even in those with normal baseline emptying rates. More recently, gastroplasty with endoscopic myotomy (GEM) has been shown to consistently delay gastric emptying without triggering symptoms of gastroparesis and to produce substantial weight loss.3Thompson C.C. Jirapinyo P. Shah R. et al.Gastroplasty with endoscopic myotomy (GEM) for the treatment of obesity: preliminary efficacy and physiologic results.Gastroenterology. 2022; 163: 1173-1175Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar This procedure involves submucosal tunneling, similar to a typical gastric peroral endoscopic myotomy procedure; however, the tunnel is substantially longer and the myotomy only involves the antrum, leaving the pylorus intact. A modified endoscopic sleeve gastroplasty (ESG) is also performed proximal to the myotomy. Based on our experience with GEM, we hypothesized that a pylorus-sparing antral myotomy alone, referred to as bariatric endoscopic antral myotomy (BEAM), would produce a consistent delay in gastric emptying and lead to reproducible and durable weight loss independent of ESG. This is an initial case report from a single-arm, prospective, first-in-human pilot study undertaken to examine the effects of the BEAM procedure (clinical trial registration number: NCT05725967). Patients with body mass indices ≥30 kg/m2 who were unable or unwilling to undergo bariatric surgery were recruited from a weight management clinic. Exclusion criteria were diabetes, gastroparesis, severe reflux, gastric surgery, and taking GLP-1 receptor agonists, anticoagulants, or antiplatelet agents. Primary outcomes were technical feasibility and safety, and secondary outcomes were percentage of total weight loss (TWL), gastric emptying assessed using a gastric-emptying breath test (Cairn Diagnostics, Brentwood, Tenn, USA) reported as gastric-emptying half-time, and change in gastroparesis cardinal symptom index (GCSI) at 1, 3, and 6 months. The study was approved by the institutional review board (IRB protocol: 2022P001757). With patients under general anesthesia, an endoscopic pylorus-sparing antral myotomy was performed. Specifically, a mucosal incision was performed us a T-type hybrid knife (Erbe, Tübingen, Germany) at the level of the incisura along the level of the greater curvature using a Carr-Locke needle (Steris, Mentor, Ohio, USA) and 6% hetastarch with diluted methylene blue without epinephrine. Submucosal tunneling was then performed using a T-type hybrid knife and a VIO 3 electrosurgical unit (Erbe, Tübingen, Germany, Endocut Q 2-2-2, PreciseSECT6.0, SoftCoag 6.0 settings). The tunnel was stopped immediately proximal to the pylorus. Two parallel lines of partial-thickness myotomy were then performe