Combined Clinical and Histopathological Risk Stratification for Prediction of (severe) Endoscopic Postoperative Recurrence in Patients with Crohn’s Disease after Ileocolic Resection

Objective: This study assessed the association of histopathological features in the resection specimen of CD patients with (severe) endoscopic postoperative recurrence (ePOR) in a large prospective, multicenter cohort study. Summary Background Data: The predictive value of histopathologic features of the intestinal resection specimen for the risk of Crohn’s disease (CD) recurrence after ileocolic (re-)resection (ICR) remains a matter of debate. Methods: CD patients (≥16 y) scheduled for ICR (n=293) were included. Outcome measures were ePOR (modified Rutgeerts’ score ≥i2b) and severe ePOR (≥i3) at six months postoperatively. Histopathological assessment of resection margins and mesentery/mesocolon was performed by expert gastrointestinal pathologists. Logistic regression was performed and ROC curves were delineated to explore the association and accuracy of histopathology with (severe) ePOR. Results: ePOR and severe ePOR was observed in 37% and 9% of patients. Only moderate to severe inflammation at the ileal resection margin (OR 2.5; 95%CI 1.1-5.6) was associated with ePOR in multivariable analysis. Area under the curve for individual histopathological risk factors varied between 0.53-0.58 for ePOR (active inflammation at the resection margins, submucosal plexitis and transmural inflammation) and 0.69-0.71 for severe ePOR (submucosal plexitis, transmural inflammation and mesenteric granulomas). Clinical risk factors alone (active smoking and postoperative prophylactic medication) had an AUC of 0.66 and 0.74 for ePOR and severe ePOR. Combined histopathological and clinical risk stratification increased the AUC up to 0.71 for ePOR and up to 0.79 for severe ePOR. Conclusions: Only moderate to severe inflammation at the ileal margin was independently associated with ePOR. A combined approach of clinical risk stratification and assessment of histopathological features in the resection specimen provides an adequate predictive value for (severe) ePOR after ICR in patients with CD.