돼지 모델에서 체중 감소를 위한 새로운 식욕억제 위장관 장치의 개발

Abstract

Introduction: Minimally invasive procedures can impact the treatment of obesity by bridging the gap between medical and surgical therapy. Therefore, we developed a device that can be placed under endoscopic guidance to reduce the rate of weight gain and promote weight loss and evaluated its safety and efficacy in a porcine model. Methods: The intra-gastric satiety inducing device (ISD) is a modified partially covered self-expandable esophageal stent connected to a star-shaped disk part. Eight juvenile pigs were randomly divided into ISD (n=5) and control (n= 3) groups. The ISD was placed under endoscopic and fluoroscopic guidance and fixed to the pig’s nose by a string. Animal behavior, body weight, serum ghrelin hormone, and the ISD position were monitored weekly. Four pigs were sacrificed 6 weeks after ISD placement or in case of complications. One pig had the ISD removed at 6 weeks and was followed up for an additional 4 weeks to check for rebound effects (rebound pig). Hematoxylin& eosin and Masson's trichrome staining, and immunostaining for the interstitial cell of Cajal (ICC) were performed after sacrifice. Results: The ISD placement was technically successful in all pigs without any immediate complications. Two ISDs (40%) migrated at 4 and 5 weeks after placement and their data were included in the analysis at the respective time points. The ISD group had significantly lower median percentage weight gain ratio from week 1 to week 6 compared to the control group: 4% vs 26% at week 1 (p=0.025), 15% vs 47% at week 2 (p=0.025), 29% vs 49% at week 3 (p= 0.024), 49% vs 71% at week 4 (p=0.043), 56% vs 82% at week 5 (p=0.034), and 46% vs 88% (p = 0.05), respectively. The rebound pig showed a higher rate of weight gain compared to the control from week 7 to week 10: 105%, 126%, 142%, and 157% vs 97%, 99%, 102%, and 107%, respectively. The median ghrelin hormone levels in the ISD group from week 1 to week 6 were 20.9, 32.3, 28.3, 41.4, 47, 39.7 ng/L. The ISD induced reversible inflammatory changes in the distal esophagus and the fundus of the stomach. The number of the ICCs (median, range) was lower in the ISD (3, 1-4) compared to the control (9.5, 7-16), and the rebound (11.5, 8-15) pigs. Conclusion: The ISD reduces the rate of weight gain in juvenile pigs and induces reversible inflammation and tissue hyperplasia. The mechanism of action of the ISD may be related to pressure effect on the gastric fundus or alteration of gastric motility.