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P071 The mesentery in Crohn's disease displays mesenchymal abnormalities

Walsh L.*1, Kiernan M.2, Sahebally S.1, Kiely P.2, Waldron D.3, Moloney M.4, Skelly M.4, Hidayat H.3, Faul P.5, O'Leary D.P.3, Lowery A.1, Dunne C.2, Coffey J.C.2

1University of Limerick, Department of Surgery, Limerick, Ireland 2University of Limerick, Graduate Entry Medical School, 4i Centre for Interventions in Infection, Inflammation and Immunity, Limerick, Ireland 3University Hospital Limerick, Department of Surgery, Limerick, Ireland 4University Hospital Limerick, Department of Gastroenterology, Limerick, Ireland 5University Hospital Limerick, Department of Histopathology, Limerick, Ireland

Background

Recent advances in our understanding of mesenteric anatomy have shown that the mesentery is continuous along the intestinal tract at vascular, lymphatic and connective tissue levels [1]. Thus, the mesentery represents a conduit which may propagate disease [2]. This study aimed to investigate abnormalities of the mesentery in Crohn's disease (CD) at a histological level.

Methods

Samples of mesentery, intestine and intestinal hilum were resected from cadavers (n=5) and CD patients (n=5). Haematoxylin and eosin light microscopy (LM) and scanning electron microscopy (SEM) were utilised to examine tissues. Diseased tissue was graded as in Table 1. Surface mesothelium and connective tissue septal thickness were assessed in addition to adipocyte number in areas of mild, moderate and severe mesenteric disease. Primary mesenteric fibroblast cultures were developed from CD patients (n=3). Adhesion and proliferation of mesenteric-derived fibroblasts and a human dermal fibroblast cell line were characterised using real-time cell analysis (xCELLigence®, ACEA Biosystems).

Table 1. Mesenteric disease activity index in CD

Mesenteric disease scoreSeverityStageScore
FW minimal, MT minimalMildOne1
FW <25%, MT adipovascular pedicle onlyModerate ITwo A2
FW <25%, pan-mesenteric MTModerate IITwo B4
FW >25%, pan-mesenteric MTSevereThree6

Results

Mesenteric surface mesothelium thickness (p<0.001), connective tissue septal thickness (p<0.001) and adipocyte number (p<0.05) were all increased with respect to CD severity (Table 2). Upon appraisal of the intestinal hilum, normal mesentery displayed a distinct serosa between the mesentery and muscularis externa. In CD, however, this could not be identified. Additionally, mesenteric mesenchymal abnormalities extended into the muscularis externa and deeper mural layers. Mesenteric-derived fibroblasts (n=3) adhered (p=0.034) and proliferated (10–30 h, p=0.001) faster than a human dermal fibroblast cell line.

Table 2. Mesenteric abnormalities in CD

NormalMildModerateSevere
Surface mesothelium (μm)24±13.062±16.0215±70.0408±73.0
Connective tissue septae (μm)16±7.053±17.0101±21.0245±100.0
Adipocytes (cell number per high power field)23±628±4.037±7.060±7.0

Conclusion

As severity of mesenteric disease increased; surface mesothelium and connective tissue septae thickened while adipocyte number increased. Mesenteric-derived fibroblasts adhered and proliferated faster than a fibroblast cell line.

References:

[1] Culligan, K. Walsh, S. Dunne, C. Walsh, M. Ryan, S. Quondamatteo, F. Dockery, P. Coffey, J. C., (2014), The mesocolon: a histological and electron microscopic characterization of the mesenteric attachment of the colon prior to and after surgical mobilization, Lippincott, Williams & Wilkins, Annals of Surgery

[2] Coffey J.C., O'Leary D.P., (2016), The mesentery: structure, function, and role in disease. The Lancet Gastroenterology & Hepatology