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P547 Distribution of mesenteric macrophage polarisation: a guide for surgical resections in Crohn’s disease?

J. van der Meer*1, K. Wasmann2, J. van der Bilt3, M. Becker1, W. Bemelman2, M. Wildenberg1,4, C. Buskens2

1Amsterdam UMC, Tytgat Institute for Liver and Intestinal Research, Amsterdam, The Netherlands, 2Amsterdam UMC, Department of Surgery, Amsterdam, The Netherlands, 3Flevoziekenhuis, Department of Surgery, Almere, The Netherlands, 4Amsterdam UMC, Department of Gastroenterology and Hepatology, Amsterdam, The Netherlands

Background

Mesenteric involvement in Crohn’s disease (CD) has been suggested as a potential factor in post-surgical disease recurrence. Although surgical guidelines recommend a limited ileocaecal resection for CD, preliminary data suggest a benefit of resecting more mesentery. Aberrancies in macrophage polarisation in the mesorectum are found to be related to post-operative complications after proctectomy for Crohn’s colitis, with improved outcomes after mesorectal excision. Trials are currently evaluating wide mesenteric excision vs. sparing of the mesentery for ileocaecal resections. The aim of this study was to assess the distribution of mesenteric macrophages in Crohn’s disease as a potential guide for mesenteric excision in rectal and ileocaecal resections.

Methods

In 39 CD patients and 5 non-IBD controls undergoing ileocaecal resection, three mesenteric tissue samples were obtained: adjacent to the inflamed terminal ileum (creeping fat), adjacent to the non-inflamed ileal resection margin, and centrally along the ileo-colic artery (where a wide mesenteric resection would end). In 10 CD patients undergoing proctectomy for therapy-refractory perianal fistulas and in 5 controls with ulcerative colitis, mesenteric tissue specimens were also sampled at three locations: distal (rectum), mid, and proximal (sigmoid) (Figure 1). Tissue specimens were cultured for 48 h and analysed by flow cytometry. The primary outcome was the ratio between regulatory (CD206+) and pro-inflammatory macrophages (CD206-).

Results

In the mesorectum an unfavourable ratio of CD206 expression (predominantly pro-inflammatory macrophages) was observed at the distal site, with an increased presence of regulatory macrophages towards the proximal sigmoid. No such gradient was found in the control group. In contrast, in the ileo-colic mesentery close to the affected small bowel, a favourable ratio of CD206 comparable to that of the control group was found. This gradient became more unfavourable towards the central mesentery. In a subset of patients with L3 (ileo-colic) disease, predominance of pro-inflammatory macrophages was found throughout the ileo-colic mesentery.

Figure 1. Diagram of sample locations. Gradients on the right represent macrophage polarisation in relation to anatomic location (red, pro-inflammatory; green, regulatory).

Conclusion

These data indicate that not all parts of the mesentery are affected equally in CD patients. The gradually increasing presence of pro-inflammatory macrophages towards the central ileo-colic mesentery does not support the rationale to perform an extensive mesenteric excision in ileocaecal resections in Crohn’s disease patients.