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Comparison of Different Surgical Procedures in Animal Models for a Better Consideration of Personalized Bariatric Surgery
Magnus K. Olsen*1, Helene Johannessen1, Yosuke Kodama1, Marianne W. Furnes1, Baard Kulseng1, 2, Chun-Mei Zhao1, Duan Chen1, 2

1Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway; 2Center for Obesity, Department of Surgery, St. Olav's Hospital, Trondheim, Norway

Background/Aim: Personalized bariatric surgery should be derived from evidence-based practice, which is an integration of patient's preferences, clinical expertise (surgical skills and experience) and research evidence. In the present study, different surgical procedures were compared in animal models and the underlying mechanisms were characterized to facilitate a move towards personalized treatment.
Methods: Normal chow-fed (ND) and high-fat-diet induced obese (DIO) rats were subjected to Roux-en-Y-gastric bypass (RYGB), Omega-Loop gastric bypass (ΩGB) and Sleeve Gastrectomy (SG), Vagal Blocking for Obesity Control (VBLOC) or gastric Botulinum Toxin Type A injection (Botox): RYGB and sham-operated (SO) (n=12 and 18, respectively), ΩGB and SO (n=14 and 6), SG and SO (n=14 and 6), VBLOC and SO (n=13 and 8) and Botox and SO (n=10 and 6). RYGB, ΩGB and SG were performed according to the rat anatomy. VBLOC was performed by subdiaphragmatic vagal nerve stimulation. Botox was injected into the subserosa layer of the antrum once per month. In addition, bilateral subdiaphragmatic truncal vagotomy plus pyloroplasty (VTPP) was performed in rats that were later subjected to Botox (n=10). %total weight loss (%TWL) and eating behavior and metabolic parameters were continuously monitored using the Comprehensive Laboratory Animal Monitoring System for a postoperative period of 7 weeks. Gastric emptying time (GET) was measured after Botox.
Results: In comparison to SO controls, %TWL was 13% after RYGB, 16% after ΩGB, 11% after SG, 10% after VBLOC, and 17% after Botox. VTPP per se was without %TWL, but prevented Botox-induced %TWL. GET was unchanged after Botox. Food intake was reduced after VBLOC or Botox. Energy expenditure (kcal/h/100g BW) was increased after Botox or ΩGB. Meal duration (min/meal) and satiety ratio (min/g) were increased after Botox. Rate of eating (g/min) was decreased after ΩGB. Intermeal interval (min) was increased after VBLOC. There were no mortality and surgical complications after Botox, VBLOC, and/or VTPP. However, the mortality rates were 8-36% after RYGB, ΩGB or SG due to the experience curve effect and surgical complications.
Conclusions: The present study using animal models showed %TWL in the following order: Botox > ΩGB > RYGB > SG > VBLOC, which was associated with a combination of reduced food intake and increased energy expenditure and satiety ratio. Botox-induced %TWL was dependent of intact vagus nerve but not GET. In consideration of individual patients' preferences as well as individual surgeons' skills and experience, we suggest that Botox injection can be used as "the first line bariatric surgery". A clinical phase II trial of Botox-treatment of obesity has started at our hospital (http://clinicaltrials.gov/show/NCT02035397).


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