LONGITUDINAL COMPRESSION THERAPY FOR SMALL BOWEL STRICTURE CROHN'S DISEASE: DURABLE RESOLUTION IN SWINE MODEL

Abstract INTRODUCTION Small bowel stricture is common in Crohn’s disease (CD), both de novo and after resection. With all standard treatments having high recurrence rates, CD patients would benefit greatly from a novel and highly durable non-surgical intervention. We report the first long-term study of longitudinal compression therapy (LCT) for the treatment of anastomotic strictures in an animal CD stricture model. LCT entails progressive endoluminal compression of stricture tissue between two flange-like device components. The goal is to gradually bring about necrosis of fibrotic tissue interposed between the two flanges while allowing remodeling with minimal iatrogenic inflammation around the periphery. METHODS Stable anastomotic strictures with hallmarks of CD small bowel strictures were created in 6 pigs, using an established method entailing ileocolonic anastomosis creation with a bypassed ileal segment to maintain patency of the gastrointestinal tract followed by serial injections of phenol/trinitrobenzenesulfonic acid at the anastomosis site. Instead of using LCT devices deployed wholly endoscopically, to best study stricture response to LCT in this model, we used devices with magnetic elements for compressive force generation and integrated ultraminiature sensor arrays for monitoring treatment progression; one 23 mm diameter device component was placed via a surgical enterotomy and a second was deployed endoscopically. Animals were followed for 9 weeks after LCT to gauge post-treatment stricture response. RESULTS LCT device placement was successful in all animals. Five animals reached the 9-week timepoint. One animal was sacrificed on day 12 due to urinary tract complications unrelated to the device. The initial therapeutic response took place over a 3-hour period after device placement, with LCT devices applying increasing force from 3 to 10 Newtons. In endoscopic assessments, widened lumens were noted, with openings 3.3-fold larger at 2 weeks and 3.7-fold larger at 9 weeks. In comparison, for endoscopic balloon dilation in the same animal stricture model, the openings were 2.3-fold larger at 2 weeks, declining to 1.9-fold at 9 weeks. Endoscopic and macroscopic evaluation after euthanasia demonstrated newly patent lumens after excision of stricture tissue, with healthy-appearing mucosa and no macroscopic findings of stricture. CONCLUSION Prior work by our group and others--in animal models and in a small number of treated patients--has provided f