Histologic assessment of the intestinal wall following duodenal mucosal resurfacing (DMR): a new procedure for the treatment of insulin-resistant metabolic disease

Abstract

Background and study aims Minimally invasive procedures that replicate aspects of bariatric surgery with more favorable safety and tolerability offer an attractive alternative in management of metabolic disease. Duodenal mucosal resurfacing (DMR), an endoscopic procedure using hydrothermal ablation, is designed to remove surface epithelium to allow subsequent epithelial regeneration and a reset to a more insulin-sensitive state.

Materials and methods DMR was performed on a healthy pig under general anethesia, approximating the procedure designed for use in humans. Immediately post-DMR, analysis of the histological landscape was conducted in distinct duodenal areas that received ablation treatment.

Results DMR submucosal lift and hydrothermal ablation elicited disruption of villous tips and partial disruption of the crypt base with no damage to deeper tissue. Excessive ablation (purposeful double ablation exposure) did incur damage to the underlying muscle layer.

Conclusion Our results confirmed that DMR elicits superficial ablation of duodenal villi and crypts. Defining the cellular consequences of ablation and regeneration of the epithelium will aid our understanding of how and why DMR affects metabolic homeostasis.

• References

• 1 Pories WJ, Swanson MS, MacDonald KG. et al. Who would have thought it? An operation proves to be most effective therapy for adult onset diabetes mellitus. Ann Surg 1995; 222: 339-350 ; Discussion 350 – 352
• 2 Ikramuddin S, Korner J, Lee W-J. et al. Roux-en-Y gastric bypass vs intensive medical management for the control of type 2 diabetes, hypertension, and hyperlipidemia: the Diabetes Surgery Study randomized clinical trial. JAMA 2013; 309: 2240-2249
• 3 Buchwald H, Estok R, Fahrbach K. et al. Weight and type 2 diabetes after bariatric surgery: systematic review and meta-analysis. Am J Med 2009; 122: 248-256.e5
• 4 Schauer PR, Kashyap SR, Wolski K. et al. Bariatric surgery versus intensive medical therapy in obese patients with diabetes. N Engl J Med 2012; 366: 1567-1576
• 5 Flum DR, Belle SH, King WC. et al. Perioperative safety in the longitudinal assessment of bariatric surgery. N Engl J Med 2009; 361: 445-454
• 6 Obeid NR, Malick W, Concors SJ. et al. Long-term outcomes after Roux-en-Y gastric bypass: 10- to 13-year data. Surg Obes Relat Dis 2016; 12: 11-20
• 7 Yan Y, Sha Y, Yao G. et al. Roux-en-Y gastric bypass versus medical treatment for type 2 diabetes mellitus in obese patients: a systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore) 2016; 95: e3462
• 8 Kindel TL, Yoder SM, Seeley RJ. et al. Duodenal-jejunal exclusion improves glucose tolerance in the diabetic, Goto-Kakizaki rat by a GLP-1 receptor-mediated mechanism ligament of Treitz. J Gastrointest Surg 2009; 10: 1762-1772
• 9 De Jonge C, Rensen SS, Verdam FJ. et al. Endoscopic duodenal-jejunal bypass liner rapidly improves type 2 diabetes. Obes Surg 2013; 9: 1354-1360
• 10 Rajagopalan H, Cherrington AD, Thompson CC. et al. Endoscopic duodenal mucosal resurfacing for the treatment of type 2 diabetes: 6-month interim analysis from the first-in-human proof-of-concept study. Diabetes Care 2016; 39: 2254-2261
• 11 Van Baar ACG, Nieuwdorp M, Holleman F. et al. Duodenal mucosal resurfacing elicits improvement in glycemic and hepatic parameters in type 2 diabetes – one-year multicenter study results. Diabetes 2018; 67 [http://diabetes.diabetesjournals.org/content/67/Supplement_1/1137-P.abstract]
• 12 Machado CJS, Tereza A, Filipecki P. et al. Current Brazilian law on animal experimentation. Science 2009; 324: 10-12
• 13 Cummings DE, Rubino F. Metabolic surgery for the treatment of type 2 diabetes in obese individuals. Diabetologia 2018; 61: 257-264
• 14 Cummings DE, Bloom SR. Community corner at the heart of the benefits of bariatric surgery Francesco Rubino. 2012; 18: 2011-2012
• 15 Rubino F, Forgione A, Cummings DE. et al. The mechanism of diabetes control after gastrointestinal bypass surgery reveals a role of the proximal small intestine in the pathophysiology of type 2 diabetes. Ann Surg 2006; 244: 741-749