Abstract
Background: Ghrelin is an enteric peptide that is synthesized mainly in the stomach fundus and has strong orexigenic and adipogenic effects. Several studies have shown that reduction in plasma ghrelin level (PGL) after gastric bypass surgery is one of the important mechanisms by which it induces weight loss. Also, recent studies suggest that ghrelin help to control plasma glucose and could contribute to the metabolic syndrome (MS). Therefore, the ghrelin signaling system is a promising target for the development of new methodology for the treatment of obesity and diabetes. Objective: To develop a minimally invasive endoscopic procedure that may result in PGL reduction in obese and diabetic patients. Main study outcome: To measure feasibility, safety and changes in PGL after EMR of the stomach fundus. Design: Two obese Ossabaw pigs having MS were randomly assigned to fundoplasty (EMR of 10 cm diameter circle of the fundus) or to sham procedure (endoscopy only). A multi-band mucosectomy (Duette; DT-6; Cook Endoscopy, Winston-Salem, NC) was used to perform the EMR. Endoscopy and PGLs (fasting, immediately post-meal and 2 hour-post meal) were performed in both pigs at baseline and at month 2. Results: The procedure was feasible and safe (no perforation, immediate or delayed bleeding or death). Stellate scar was seen at the site of EMR in fundoplasty pig (Fig.1). At the end of follow up, the fundoplasty pig's PGLs (fasting, immediately post-meal and 2 hours-post meal) were decreased by 67%, 64% and 52% respectively compared to their baseline levels. In contrast, the sham pig's PGLs (fasting, immediately-post meal and 2 hour-post meal) were increased by 56%, 98% and 42% respectively compared to their baseline levels. Conclusions: Our preliminary results suggest that EMR of the stomach fundus is technically feasible, safe and associated with marked reduction in PGLs in MS Ossabaw swine. Recommendations: A large-scale study is needed to confirm these results.
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