Video 1The endoscopic blind limb reduction with septotomy procedure.

Background and study aims Endoscopic weight loss procedures have gained traction as minimally invasive options for the primary treatment of obesity. Thus far, we have developed endoscopic procedures that reliably address gastric restriction but result in significantly less weight loss than surgical gastrointestinal bypass. The goal of this nonsurvival study was to assess the technical feasibility of an endoscopic procedure, that incorporates both gastric restriction and potentially reversible gastrointestinal bypass. Methods Ultrasound-assisted endoscopic gastric bypass (USA-EGB) was performed in three consecutive live swine, followed by euthanasia and necropsy. Procedure steps were: 1) balloon-assisted enteroscopy that determines the length of the bypassed limb; 2) endoscopic ultrasound-guided gastroenterostomy that creates a gastrointestinal anastomosis using a lumen apposing metal stent; 3) endoscopic pyloric exclusion that disrupts transpyloric continuity resulting in complete gastrointestinal bypass; and 4) gastric restriction that reduces gastric volume. Results Complete gastrointestinal bypass and gastric restriction was achieved in all three swine. The mean total procedure time was 131 minutes (range 113-143), mean length of the bypassed limb was 92.5 cm and 180 cm, using short and long overtubes, respectively. There were no significant complications. Conclusions We successfully described USA-EGB in three consecutive live swine. Further studies are needed to access the procedures safety, efficacy, and clinical use.

Background and study aims Alterations to interstitial cells of Cajal (ICC) and collagen fibrosis have been implicated in the pathogenesis of gastroparesis. We aimed to evaluate the feasibility and safety of pyloric muscle sampling during gastric peroral endoscopic myotomy (G-POEM) and the association between pyloric ICC density and degree of fibrosis with clinical outcomes. Patients and methods This was a single-center prospective study of gastroparetic patients who underwent G-POEM and intraprocedural pyloric muscle biopsies between January 2022 and April 2023. ICC count was estimated using CD117 stain and trichome for collagen fibrosis. Clinical response to G-POEM was defined as an improvement of ≥ 1 point on the Gastroparesis Cardinal Symptom Index. Results Fifty-six patients (median age 60 years, 71.4% women) underwent G-POEM (100% technical success; 71.4% clinical response). ICC depletion (< 10/high-power field) and fibrosis were encountered in 70.4% and 75% of the cases, respectively. There was no difference in mean ICC count between G-POEM responders vs. non-responders (7±3.6 vs. 7.7±3.3; P = 0.9). There was no association between ICC density or degree of fibrosis with the etiology of gastroparesis, duration of symptoms, gastric emptying rate, or pyloric impedance planimetry. Patients who did not respond to G-POEM had a significantly higher degree of moderate/severe fibrosis when compared with those who responded (81.3% vs. 25%; P = 0.0002). Conclusions Pyloric muscle biopsies during G-POEM was feasible and safe. ICC depletion and pyloric muscle fibrosis are common in gastroparetic patients. The degree of fibrosis may be related to pyloric dysfunction and clinical response to G-POEM. Additional studies are needed to confirm these results.