MeSenteric SpAring Versus High Ligation Ileocolic Resection for the Prevention of REcurrent Crohn's DiseaSe (SPARES)

There is increasing evidence to suggest that the mesentery may play an active role in the pathophysiology of Crohn's disease. There is significant clinical, endoscopic, and surgical recurrence of disease following ileocolic resection at the site of the anastomosis. The study is seeking to understand if the mesentery plays a role in recurrence following ileocolic resection.

Crohn's disease (CD) is a chronic inflammatory disease of the intestinal tract with an unknown etiology and an unknown cure. The characteristic transmural inflammation can progress to refractory inflammatory disease, stricturing disease, and fistulizing disease - all potential indications for surgery when medical management has been exhausted. An important tenant to remember is that surgery is not curative but is rather an adjunct to maximal medical therapy.

One third of patients with Crohn's disease (CD) will require a major abdominal resection within 5 years of their diagnosis, and two-thirds will ultimately require operative management at least once during the course of their disease.

Unfortunately, surgery for Crohn's disease (CD) is not curative and disease recurrence is common with 62% having endoscopic recurrence at six months, and 80% and 30% of patients having endoscopic and clinical recurrence, respectively, at one year. A third of these patients will require a reoperation at 10 years and up to 80% will require an additional operation by 15 years.This undoubtedly leads to an increased probability of malabsorption syndrome and decreased quality of life.

A significant volume of research has been conducted in attempt to determine how to prevent postoperative recurrence of CD following an ileocolic resection. Some studies have focused on the timing of resuming postoperative medical therapy. Others have looked at surgical technique at the time of ileocolic resection including anatomic configuration of the anastomosis and performing a stapled versus handsewn anastomosis. Various configurations include a side to side anastomosis, end to end, and Kono-S anastomosis. A randomized clinical trial compared a side to side versus an end to end, and found endoscopic recurrence rates were similar in the two groups (42.5% versus 37.9%) at a mean follow up of 11.9 months. A later multi-institution international trial of the Kono S anastomosis determined that the anastomosis was associated with a decreased surgical recurrence rate as compared to conventional anastomoses; 5 and 10 year surgical recurrence-free survival was 98.6%.15 Several Cochrane Database reviews have reported no difference in a stapled versus handsewn anastomosis for an ileocolic resection. Therefore, other than the potential decreased recurrence with the Kono-S anastomosis, no other surgical techniques have altered the postoperative recurrence rate of CD following an ileocolic resection.

Interestingly there is recent evidence to suggest that CD may be a disease of the mesentery rather than just the mucosa of the bowel alone. In CD, the transmural inflammation facilitates increased bacterial translocation into the creeping fat. These translocating antigens and activate adipocytes which are cells than have complex metabolic and immunologic functions. Additionally, it is thought that functional abnormalities in the mesenteric structures exert an inflammatory effect: the secretion of adipokines that have endocrine functions contribute to immunomodulation through a response to afferent signals, neuropeptides, and functional cytokines; mesenteric nerves are involved in the pathogenesis through neuropeptides; and lymphatics in the mesentery may obstruct, remodel, and impair contraction, contributing to the irregularly thickened mesentery seen in CD. Interestingly, the interaction between neuropeptides, adipokines, and vascular and lymphatic endothelia leads to adipose tissue remodeling. This makes the mesentery an active participant in CD, seemingly as much as the bowel itself. However, the mesentery is typically spared, or left in situ, during resection for CD, unlike resections for adenocarinocma of the colon. In adenocarcinoma, a 'high ligation' is performed, where the feeding vessel is taken at its origin in order to take sufficient mesentery and lymph nodes with the colon specimen. However, in operations for CD, the mesentery is spared and typically taken close to the bowel wall despite enlarged lymph nodes and thickened diseased mesentery. A high ligation of the ileocolic artery in order to sample an increased volume of mesentery and lymph nodes to prevent postoperative CD has never been evaluated in a randomized control trial. A recent retrospective study comparing surgical recurrence following a mesenteric sparing versus mesenteric resection approach with ileocecal resection found cumulative reoperation rates were significantly lower in the mesenteric resection group (40% versus 2.9%; p=0.003).

The endoscopic recurrence of CD typically precedes clinical symptoms, and the severity of lesions can predict the subsequent symptomatic course of the disease. Over a four year follow-up period, 100% of patients with severe endoscopic recurrence (Rutgeerts score of i2-i4) developed symptomatic recurrence compared to only 9% of patients with a low score (i0-i1). With such a high rate of endoscopic recurrence, it is thought that post-surgical evaluation should be performed at six months rather than one year when considering adequate early treatment.