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Date
2017
Abstract
Background Mesenteric manifestations are of pathobiologic relevance in Crohn’s disease. Clarification of mesenteric morphology provides an opportunity to re-appraise their pathogenic significance. Therefore, we examined the relationship between mesenteric, mucosal and systemic manifestations in Crohn’s disease. Methods A multi-institutional study was conducted in which mesenteric disease was quantified (mesenteric disease score) in patients undergoing resection (n=34) for CD. The mesenteric disease score was correlated with a mucosal disease score, and Crohn’s Disease Activity Index (CDAI). The relationship between mesenteric manifestations and surgical recurrence was retrospectively determined in a second cohort (n=94). Local mesenteric and systemic fibrocyte levels were determined using a combination of histology, immunohistochemistry and flow cytometry. Mesenteric and mucosal gene expressions were compared in Crohn’s disease patients, in silico using Chipster©, an R based bio-informatic software. Results Mesenteric disease scores correlated with mucosal disease scores (r=0.8, p<0.0001) and CDAI (r=0.7, p<0.0001) and were significantly increased in smokers (p<0.04). Mesenteric disease manifestations independently predicted increased risk of surgical recurrence (HR 4.7, 95% CI: 1.71-13.01, p=0.003) and reduced time to recurrence (p<0.001). Mesenchymal abnormalities included fibrocytosis and adipocyte hyperplasia and were contiguous between mesentery and adjacent intestine. The fibrocyte proportion of circulating monocytes was increased in Crohn’s disease compared with healthy controls (6.4 ± 2.82% vs. 2.0 ± 1.04%, p<0.001). Levels normalized following ileocolic resection (5.7 ± 2.12% vs. 1.7 ± 1.20%, p=0.005), in patients with ileocolic disease. Fibrocyte percentages correlated with mesenteric and mucosal disease scores as well as with the CDAI (r=0.94, p<0.0001). Mesenteric, but not mucosal, gene expression profiles were associated with connective tissue, immunologic and inflammatory disorders. Conclusions Mesenteric manifestations are an important part of the pathogenesis of Crohn’s disease; they are associated with smoking and disease severity, and have predictive value for surgical recurrence. Therefore, they should be formally scored and recorded at the time of surgery.
Supervisor
Calvin J. Coffey
Colum P. Dunne
Colum P. Dunne
Description
peer-reviewed