Increased enteric glial cells in proximal margin of resection is associated with postoperative recurrence of Crohn's disease

Abstract

Background and aim: The enteric nervous system can amplify or modulate intestinal inflammation through secretion of neuropeptides, and enteric glial cells have been implicated in the pathophysiology of Crohn's disease. The goal of the study was to search for an association between the density of neurons, neuropeptides, and enteric glial cells and postoperative recurrence.

Methods: The ileal proximal uninflamed section from ileocolonic sample was studied using immunohistochemistry with antibodies directed against vasoactive intestinal polypeptide (VIP), substance P (SP), neuron-specific enolase (NSE), and the glial marker protein S100. The density in the submucosa was calculated, and the relationship of the density of VIP, SP, NSE, and S100 and postoperative disease recurrence was assessed.

Results: There were no significant differences between patients with and without postoperative endoscopic recurrence or clinical recurrence for the density of NSE-positive, VIP-positive, or SP-positive neurons in the proximal margin. Interestingly, the density of S100-positive enteric glial cells was significantly increased in patients with endoscopic and clinical recurrence than in subjects without disease recurrence (P ˂ 0.001). The density of S100-positive enteric glial cells was independently associated with postoperative disease recurrence.

Conclusions: Increased S100-positive enteric glial cells are associated with a high risk of both endoscopic and clinical recurrence after surgery. These findings have implications in individualized postoperative prophylaxis for Crohn's disease.

Keywords: Crohn's disease; enteric glial cells; postoperative recurrence; substance P; vasoactive intestinal peptide.