ORIGINAL ARTICLE Submucosal Plexitis as a Predictor of Postoperative Surgical Recurrence in Crohn’s Disease Aude Bressenot, MD,* ,† Jean-Baptiste Chevaux, MD,* ,‡ Nicolas Williet, MD,* ,‡ Abderrahim Oussalah, MD,* ,‡ Adeline Germain, MD,* ,§ Guillaume Gauchotte, MD,* ,† Marie-Pierre Wissler, MD,* ,† Jean-Michel Vignaud, MD, PhD,* ,† Laurent Bresler, MD, PhD,* ,§ Marc-André Bigard, MD, PhD,* ,‡ Franc¸ois Plénat, MD, PhD,* ,† Jean-Louis Guéant, MD, PhD,* ,‡ and Laurent Peyrin-Biroulet, MD, PhD* ,‡ Background: The presence of submucosal or myenteric plexitis was associated with clinical and endoscopic Crohn’s disease (CD) recurrence after ileocolonic resection. We assessed the value of both submucosal and myenteric plexitis for predicting postoperative surgical recurrence in CD. Methods: We performed a retrospective study using the database of the Department of Pathology of Nancy University Hospital. All patients who underwent CD-related resection between 1996 and 2008 were analyzed. The proximal resection margin was analyzed blindly by 2 expert pathologists. Plexitis was evaluated by counting each cell type (mast cell, plasmocyte, lymphocyte, eosinophil, and neutrophil) in both submucosal and myenteric plexuses. The optimal cut-off value for each cell type was determined by using receiver operating characteristic analysis. Cox proportional hazards regression analysis was used to identify independent predictors of the second CD-related surgery. Results: Sixty-seven patients were included in the study. Median duration of follow-up was 46 months. Using Kaplan–Meier survival analysis, the proportion of patients without second surgery was 68% at 5 years. In multivariate analysis, using Cox proportional hazards regression analysis, early surgical revision after the first ileocecal resection (hazard ratio ¼ 9.56; 95% confidence interval, 2.02–45.19; P ¼ 0.0046), the presence of at least one eosinophil in the submucosal plexus (hazard ratio ¼ 8.02; 95% confidence interval, 1.87–34.47; P ¼ 0.0054), and the presence of more than 6 lymphocytes in the submucosal plexus (hazard ratio ¼ 5.84; 95% confidence interval, 1.23–27.65; P ¼ 0.0269) were independently associated with risk of surgical recurrence. Conclusions: Early surgical revision and submucosal plexitis in proximal margins of ileocolonic resection specimens are independently associated with CD surgical recurrence. (Inflamm Bowel Dis 2013;19:1654–1661) Key Words: Crohn’s disease, plexitis, recurrence, postoperative I n the era of biologics, the need for surgery in referral centers ranged from 18% to 33% within 5 years after diagnosis. 1 Sur- gery is not curative, and postoperative recurrence remains a prob- lem in patients with Crohn’s disease (CD). 2,3 CD lesions often relapse at the anastomosis or in the neoterminal ileum in months or years after surgery. 4 CD is characterized by the presence of inflammatory infiltrates, consisting of plasma cells, lymphocytes, eosinophils, mast cells, and occasion- ally granulomas in both the submucosal and myenteric plexuses. 5–9 Predictors of postoperative CD recurrence have been evaluated on histological analysis of resected specimens including granulomas 10–15 and pathologically involved resection margin. 14,16–20 Histological changes within the enteric nervous system of the resection margin, such as neural fiber hypertrophy and hyperplasia, have been observed in the mucosa, submucosal, and plexus, both in colon and ileum affected by CD. 5,21,22 In a retrospective study, Ferrante et al 23 dem- onstrated that inflammatory activity within the myenteric plexitis was significantly associated with postoperative CD recurrence. Moreover, the severity of myenteric plexitis in the proximal resection margin correlated with the severity of endoscopic recurrence both at 3 months and 1 year. 23 Sokol et al 24 demonstrated an association between submucosal plexitis and early clinical recurrence. No study has evaluated the histological predictors of second surgery after the first CD-related ileocecal resection. The aim of this study was therefore to assess for the first time the value of submucosal and myenteric plexitis for predicting postoperative surgical recurrence after the first CD-related ileocecal resection. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.ibdjournal.org). Received for publication November 19, 2012; Accepted November 28, 2012. From the *Inserm U954, Genetic Nutrition and Exposure to Environmental Risks (NGERE), Henri Poincaré University, Vandoeuvre-lès-Nancy, France; and † Department of Pathology, ‡ Department of Hepato-Gastroenterology, and § Department of Surgery, University Hospital of Nancy, Henri Poincaré Univer- sity, Vandoeuvre-lès-Nancy, France. Institutional grants were obtained from the region Lorraine and from Inserm, France. The authors have no conflicts of interest to disclose. Reprints: Laurent Peyrin-Biroulet, MD, PhD, Department of Gastroenterology, University Hospital of Nancy, Allée du Morvan, 54 511 Vandœuvre-lès-Nancy, France (e-mail: peyrinbiroulet@gmail.com). Copyright © 2013 Crohn’s & Colitis Foundation of America, Inc. DOI 10.1097/MIB.0b013e318281f336 Published online 7 June 2013. 1654 | www.ibdjournal.org Inflamm Bowel Dis  Volume 19, Number 8, July 2013 Copyright © 2013 Crohn’s & Colitis Foundation of America, Inc. Unauthorized reproduction of this article is prohibited.