Inclusion of the Mesentery in Ileocolic Resection for Crohn's Disease is Associated With Reduced Surgical Recurrence

Calvin J Coffey, Miranda G Kiernan, Shaheel M Sahebally, Awad Jarrar, John P Burke, Patrick A Kiely, Bo Shen, David Waldron, Colin Peirce, Manus Moloney, Maeve Skelly, Paul Tibbitts, Hena Hidayat, Peter N Faul, Vourneen Healy, Peter D O'Leary, Leon G Walsh, Peter Dockery, Ronan P O'Connell, Sean T Martin, Fergus Shanahan, Claudio Fiocchi, Colum P Dunne, Calvin J Coffey, Miranda G Kiernan, Shaheel M Sahebally, Awad Jarrar, John P Burke, Patrick A Kiely, Bo Shen, David Waldron, Colin Peirce, Manus Moloney, Maeve Skelly, Paul Tibbitts, Hena Hidayat, Peter N Faul, Vourneen Healy, Peter D O'Leary, Leon G Walsh, Peter Dockery, Ronan P O'Connell, Sean T Martin, Fergus Shanahan, Claudio Fiocchi, Colum P Dunne

Abstract

Background and aims: Inclusion of the mesentery during resection for colorectal cancer is associated with improved outcomes but has yet to be evaluated in Crohn's disease. This study aimed to determine the rate of surgical recurrence after inclusion of mesentery during ileocolic resection for Crohn's disease.

Methods: Surgical recurrence rates were compared between two cohorts. Cohort A [n = 30] underwent conventional ileocolic resection where the mesentery was divided flush with the intestine. Cohort B [n = 34] underwent resection which included excision of the mesentery. The relationship between mesenteric disease severity and surgical recurrence was determined in a separate cohort [n = 94]. A mesenteric disease activity index was developed to quantify disease severity. This was correlated with the Crohn's disease activity index and the fibrocyte percentage in circulating white cells.

Results: Cumulative reoperation rates were 40% and 2.9% in cohorts A and B [P = 0.003], respectively. Surgical technique was an independent determinant of outcome [P = 0.007]. Length of resected intestine was shorter in cohort B, whilst lymph node yield was higher [12.25 ± 13 versus 2.4 ± 2.9, P = 0.002]. Advanced mesenteric disease predicted increased surgical recurrence [Hazard Ratio 4.7, 95% Confidence Interval: 1.71-13.01, P = 0.003]. The mesenteric disease activity index correlated with the mucosal disease activity index [r = 0.76, p < 0.0001] and the Crohn's disease activity index [r = 0.70, p < 0.0001]. The mesenteric disease activity index was significantly worse in smokers and correlated with increases in circulating fibrocytes.

Conclusions: Inclusion of mesentery in ileocolic resection for Crohn's disease is associated with reduced recurrence requiring reoperation.

Figures

Figure 1.
Figure 1.
[A] [Left] Right colon and terminal ileum and line demonstrating mesenteric division flush with the intestinal margin, i.e. mesentery retained. [Right] Postoperative specimen following conventional resection and division of mesentery flush with the intestine. Both images are representative of conventional resection for Crohn’s disease. [B] [Left] Right colon, terminal ileum, and mesentery, with a line demonstrating a mesenteric division wide of the intestinal margin, i.e. mesentery excised. [Right] Postoperative specimen following mesocolic excision. The entire right mesocolon is evident. A substantial volume of small intestinal mesentery is apparent. Both images are representative of concept of mesenteric resection for Crohn’s disease. [C] Mesenteric transition zone in a postoperative specimen following resection for ileocolic Crohn’s disease. [D] Mesenteric transition zone at a skip lesion. [E] Mucosal transition zone adjacent mesenteric transition zone in specimen in [C]. [F] Mucosal transition zone adjacent mesenteric transition zone in specimen in [D]. [G] Kaplan-Meier estimates demonstrating the cumulative incidence of reoperation for a Crohn’s-related indication in patients in Cohort A [i.e. mesentery excluded] and Cohort B [i.e. mesentery included]. Estimates were compared using log-rank analysis.
Figure 2.
Figure 2.
Key: FW refers to fat wrapping, MT refers to mesenteric thickening. [A] Digitally sculpted mesentery and intestinal tract demonstrating fat wrapping and mesenteric thickening. In mild mesenteric disease, thickening was confined to adipovascular regions. Fat wrapping commenced at the intestinal margin of the mesentery and was limited. In moderate mesenteric disease, adipovascular thickening was more pronounced but pedicles could still be differentiated. Fat wrapping increased but covered less than 25% of the bowel circumference. In severe mesenteric disease, thickening was pan-mesenteric. Adipovascular pedicles could not be differentiated. Fat wrapping extended beyond 25% of the circumference. [B–D] Macroscopic features of mesenteric (fat wrapping [B], mesenteric thickening [C]) and mucosal disease [D], as seen in postoperative surgical specimens. [E] Kaplan-Meier estimates demonstrating the percentage of patients reoperation-free following surgery for Crohn’s disease. Patients were subdivided into cohorts with and without fat wrapping of greater than 50% of the intestinal circumference at the index operation.
Figure 3.
Figure 3.
[A] [Left] Digital sculpture demonstrating the junction between the small intestinal mesentery and the right mesocolon, and [right] mesenteric connective tissue lattice [grey]. [B] [Left] Photomicrograph (haematoxylin and eosin [H&E]) demonstrating normal mesentery, surface mesothelium [single arrow], and connective tissue [4X]. A connective tissue septation [double arrows] extended from the submesothelial connective tissue. [Right] H&E photomicrograph demonstrating mesentery in Crohn’s disease [4X]. The surface mesothelium, submesothelial [single arrow], and interlobular connective tissue were thickened [multiple arrows]. [C] H&E photomicrograph demonstrating interface between normal mesentery and longitudinal muscle of adjacent intestine [4X]. The connective tissue serosa [arrows] separated mesentery from longitudinal muscle. The serosa was continuous with mesenteric connective tissue and extended into the outer longitudinal circular layer [asterix]. [D] Scanning electron microscopic [SEM] photomicrograph demonstrating mesentery, serosa [arrows], and adjacent intestine, in normality [30X]. [E] H&E photomicrograph demonstrating serosal thickening in a region of fat wrapping in Crohn’s disease [asterix] [10X]. [F] SEM photomicrograph demonstrating mesentery, serosa [arrows], and adjacent intestine, in Crohn’s disease [45X]. Mesenteric connective tissue thickening extended into the intestinal longitudinal muscle.
Figure 4.
Figure 4.
[A] Scatter plots demonstrating differences in the percentage of fibrocytes in circulating white cells, between a healthy control and a patient with ileocolic Crohn’s disease. [B] Bar chart summarising percentage of fibrocytes in circulating white cells, in all resection types, in ileocolic resections alone [ileocolic Crohn’s disease], and in patients with ‘other’ inflammatory conditions [including ulcerative colitis and diverticular disease]. [C] Bar chart demonstrating preoperative and long-term postoperative percentage of fibrocytes in circulating white cells in patients undergoing ileocolic resection for Crohn’s disease. [D] Photomicrograph [dual staining for CD45+αSMA+ with an eosin counterstain] demonstrating immune-positive cells within and nearby mesenteric vessels [4X]. [E] [Left] Photomicrograph [dual staining for CD45+αSMA+ with an eosin counterstain] demonstrating immune-positive cells clustered at the serosal surface and within connective tissue of the longitudinal muscle layer [2X]. The inset is taken from a corresponding haematoxylin and eosin-stained serial section. [Right] Scanning electron photomicrograph demonstrating a cell cluster at the serosal surface, i.e. interposed between mesentery and adjacent intestinal surface, in Crohn’s disease [700X]. The inset demonstrates a cell cluster at the serosal surface.

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