The Value of Myenteric Plexitis to Predict Early Postoperative Crohn’s Disease Recurrence

Infliximab treatment of postoperative ulcers in Crohn's disease: to inject or not to inject—that is the question

This Month in Gastroenterology

Postoperative Crohn's Disease Recurrence: Time to Adapt Endoscopic Recurrence Scores to the Leading Surgical Techniques

Sa1895 Myenteric Plexitis Is a Risk Factor for Endoscopic and Clinical Postoperative Recurrence After Ileocolonic Resection in Crohn's Disease

Myenteric plexitis is a risk factor for endoscopic and clinical postoperative recurrence after ileocolonic resection in Crohn's disease

Objectives: To assess the predictive values of myenteric and submucosal plexitis for postoperative endoscopic recurrence of Crohn's disease (CD). Methods: A retrospective study of CD patients who underwent intestinal resection between 1995 and 2013 in the Department of Surgery 2, Tokyo Women's Medical University was performed. Proximal resection margins were analyzed and plexitis was evaluated by counting the number of inflammatory cells in myenteric and submucosal plexuses. The sizes of the most severely inflamed ganglion (MIG) were measured. Multiple regression analysis was used to identify independent risk factors for postoperative endoscopic recurrence. Results: Of the 51 included patients, 40 patients underwent colonoscopy after surgery. Endoscopic recurrence was observed in 21 patients (52.5%). Mean duration (±standard deviation) from surgery to recurrence was 49.7±34.7 months. Endoscopic recurrence rates at 1, 3, and 5 years were 5.0%, 24.1%, and 45.1%, respectively. Submucosal plexitis and myenteric plexitis were observed in 36 (90.0%) and 37 patients (92.5%), respectively. On multivariate analysis, initial intestinal resection, rate of plexitis <50%, size of the MIG in the myenteric plexus ≥867 μm2, and total number of inflammatory cells in the submucosal plexus ≥8 were independent risk factors for postoperative endoscopic recurrence. Conclusions: Pathological findings of proximal resection margins, especially submucosal plexitis and large sizes of myenteric plexus, are predictive of postoperative endoscopic recurrence in CD.

Is Early Endoscopy-Based Therapy the Best Strategy to Prevent All Crohn’s Disease Postoperative Recurrence?

Active Margins, Plexitis, and Granulomas Increase Postoperative Crohn’s Recurrence: Systematic Review and Meta-analysis

Resections for Crohn's disease should be limited and only resect macroscopically affected bowel. However, recent studies suggest microscopic inflammation at resection margins as a predictor for postoperative recurrence. The clinical impact remains unclear, as non-uniform pathological criteria have been used. The aim of this study was to assess the predictive value of pathological characteristics at ileocecal resection margins for recurrence. Both resection margins of 106 consecutive patients undergoing ileocecal resection for Crohn's disease between 2002 and 2009 were revised and scored for active inflammation, myenteric plexitis, and granulomas. Pathological findings were correlated to recurrence, defined as recurrent disease activity demonstrated by endoscopy (modified Rutgeerts score ≥i2) requiring upscaling medical treatment, using multivariate analysis. Active inflammation was found at the proximal and distal resection margin in 27% and 15% of patients, respectively, myenteric plexitis in 37% and 32%, respectively, and granulomas in 4% and 6%, respectively. In total, 47 out of 106 patients developed recurrence. Only active inflammation at the distal colonic resection margin was an independent significant predictor for recurrence (88% vs 43% vs 51% for distal, proximal, and no involved margins, respectively; P < 0.01). Active inflammation at the distal colonic resection margin after ileocecal resection identifies a patient group at high risk for postoperative recurrence both at the anastomotic site and the colon because it identifies undiagnosed L3 disease. These patients have a different and more aggressive natural history and require more intense medical treatment. Therefore, pathological evaluation of the distal resection margin should be implemented in daily practice.

Prevention and treatment of postoperative Crohn's disease recurrence with anti-TNF therapy: A meta-analysis of controlled trials

Mesenteric hypertrophy has been recognized as an indicator of the complicated course of Crohn's disease. The aim of this study was to investigate whether the visceral fat area (VFA) is associated with postoperative clinical and endoscopic recurrence. Computed tomography was used to measure the subcutaneous fat area and VFA, and the mesenteric fat index (MFI) was defined as the ratio of the VFA to the subcutaneous fat area. Associations between body mass index, subcutaneous fat area, VFA and MFI and postoperative clinical and endoscopic recurrence were investigated. The factors associated with postoperative endoscopic recurrence at 6months after surgery were a high VFA value (P=0.019) and MFI values above the median (P=0.008). VFA values were significantly correlated with endoscopic recurrence (r=0.895, P= 0.040) and endoscopic lesions (r=0.617, P<0.0001). Additionally, MFI values correlated well with endoscopic recurrence (r=0.918, P=0.02) and endoscopic scores (r=0.584, P<0.0001). Multivariate analysis indicated that VFA values above the median (hazard ratio 2.63, 95% CI 1.03-6.74) were predictive of postoperative clinical recurrence in Crohn's disease. A high VFA value is associated with postoperative recurrence of Crohn's disease and has clinical implications with respect to optimizing prophylaxis for each individual. However, further studies are needed to confirm the predictive role of this biomarker in a different data set.

Bowel resection in patients with Crohn's disease (CD) has a high reported rate of postoperative complications and surgical recurrence. A macroscopically normal resection margin is recommended in CD surgery as wider margins do not translate in reduced recurrence rates. The aim of this study was to evaluate the association between resection margin status and anastomotic complications following ileocaecal resection for primary CD. All patients treated with ileocaecal resection for primary CD from 2010 to 2018 were included in this retrospective observational study. Emergency operations and recurrent CD were excluded. Patients in whom an anastomosis was not fashioned at the time of the surgery were also excluded. Histopathology data collected included macroscopic description, presence of macroscopic and microscopic involvement of the proximal and distal resection margins. The primary outcome was the rate of positive resection margin in patients who developed anastomotic complications(anastomotic leaks and intra-abdominal collections), and the secondary outcomes were overall complications rate, length of hospital stay, reoperations and rehospitalisation within 30days. A total of 104 patients were included. The proximal resection margin was microscopically involved in 19 patients (18.2%). Ten patients (9.6%) developed intra-abdominal anastomotic related complications, with 5 patients out of 10 (50%) in the group of postoperative anastomotic complications having a positive microscopic proximal margin at histology, compared to 14 patients (14.9%) in the group that did not develop anastomotic complications (p < 0.0001). Microscopic involvement of the proximal resection margin is more frequent in patients who develop postoperative anastomotic complications following elective ileocaecal resection for primary CD.

P430 Prognostic significance of neuropeptide expression in ileal neural plexuses in Crohn’s disease. A retrospective study

The accumulation of immune cells in and around enteric ganglia, called plexitis, is associated with postoperative recurrence in Crohn's disease. Interaction between T cells and enteric glia is increased at the proximal resection margin in patients with Crohn's disease who suffer from postoperative recurrence. However, little is known about the T cells that interact with enteric glia and contribute to the formation of plexitis. In this work, the number of CD4 and CD8 T cells interacting with enteric glia was quantified in sections of the proximal (ileal) resection margin of patients with Crohn's disease, and in cocultures prepared with rat and human enteric glia. The molecules implicated in these interactions were investigated, as well as the impact of enteric glia on T cell survival. Analyses indicated that both CD4 and CD8 cells were present and in contact with enteric glia in plexitis in patients with Crohn's disease. In vitro studies demonstrated that the adhesion of both human and rat CD4 and CD8 cells to enteric glia was increased after pretreatment of the glial cells with IL1β/TNFα, and that this adhesion was lymphocyte function-associated antigen 1 (LFA-1)-dependent. The interactions between T cells and enteric glia increased the survival of CD4 and CD8 T cells in an ICAM-1/LFA-1-independent manner. In conclusion, both CD4 and CD8 T lymphocytes are present and in contact with enteric glia in plexitis. The in vitro studies demonstrate that they adhere to human and rat enteric glia through LFA-1 and show that interactions with enteric glia promote their survival, independently of LFA-1.NEW & NOTEWORTHY Both CD4 and CD8 T cells adhere to enteric glial cells in patients with Crohn's disease, contributing to the development of plexitis associated with postoperative recurrence. The adhesion of CD4 and CD8 T cells to enteric glial cells is dependent on ICAM-1/LFA-1. Enteric glial cells promote the survival of CD4 and CD8 T cells independently of ICAM-1/LFA-1.

S1107 Plexitis As Predictive Factor of Early Postoperative Clinical Recurrence in Crohn's Disease