Analysis of risk factors - especially different types of plexitis - for postoperative relapse in Crohn’s disease

Abstract

AIMTo evaluate the presence of submucosal and myenteric plexitis and its role in predicting postoperative recurrence.METHODSData from all patients who underwent Crohn’s disease (CD)-related resection at the University of Szeged, Hungary between 2004 and 2014 were analyzed retrospectively. Demographic data, smoking habits, previous resection, treatment before and after surgery, resection margins, neural fiber hyperplasia, submucosal and myenteric plexitis were evaluated as possible predictors of postoperative recurrence. Histological samples were analyzed blinded to the postoperative outcome and the clinical history of the patient. Plexitis was evaluated based on the appearance of the most severely inflamed ganglion or nerve bundle. Patients underwent regular follow-up with colonoscopy after surgery. Postoperative recurrence was defined on the basis of endoscopic and clinical findings, and/or the need for additional surgical resection.RESULTSOne hundred and four patients were enrolled in the study. Ileocecal, colonic, and small bowel resection were performed in 73.1%, 22.1% and 4.8% of the cases, respectively. Mean disease duration at the time of surgery was 6.25 years. Twenty-six patients underwent previous CD-related surgery. Forty-three point two percent of the patients were on 5-aminosalicylate, 20% on corticosteroid, 68.3% on immunomodulant, and 4% on anti-tumor necrosis factor-alpha postoperative treatment. Postoperative recurrence occurred in 61.5% of the patients; of them 39.1% had surgical recurrence. 92.2% of the recurrences developed within the first five years after the index surgery. Mean disease duration for endoscopic relapse was 2.19 years. The severity of submucosal plexitis was a predictor of the need for second surgery (OR = 1.267, 95%CI: 1.000-1.606, P = 0.050). Female gender (OR = 2.21, 95%CI: 0.98-5.00, P = 0.056), stricturing disease behavior (OR = 3.584, 95%CI: 1.344-9.559, P = 0.011), and isolated ileal localization (OR = 2.671, 95%CI: 1.033-6.910, P = 0.043) were also predictors of postoperative recurrence. No association was revealed between postoperative recurrence and smoking status, postoperative prophylactic treatment and the presence of myenteric plexitis and relapse.CONCLUSIONThe presence of severe submucosal plexitis with lymphocytes in the proximal resection margin is more likely to result in postoperative relapse in CD.

T cells show preferential adhesion to enteric neural cells in culture and are close to neural cells in the myenteric ganglia of Crohn's patients

“…As several studies have identified the presence of plexitis in the proximal margin of intestinal resections as a powerful tool to predict relapse (Ryan et al, 2019), the accumulation of immune cells in and around the nerve enteric ganglia or bundle, has been recognized as a marker of post-operative recurrence in case of Crohn's disease (Gionchetti et al, 2017). Attempts to characterize the plexitis describe the presence of mast cells, eosinophils and T lymphocytes infiltrating the submucosal and/or myenteric plexus (Bressenot et al, 2013;Decousus et al, 2016;Ferrante et al, 2006;Lemmens et al, 2017;Milassin et al, 2017;Misteli et al, 2015;Sokol et al, 2009). However, little is known about the enteric neural cells involved in plexitis.…”

Intriguing Role of the Mesentery in Ileocolic Crohn's Disease

“…37,38 Similarly, myenteric plexitis at the proximal resection margin is associated with an increased risk of endoscopic and surgical relapse. 35,36,[39][40][41] Finally, some studies suggest that reduced density of lymphatic vessels is associated with postoperative recurrence. 36,42 Regardless of the extent of surgery, 25 to 75% of patients will develop endoscopic recurrence within one year of surgery, often just proximal to the surgical anastomosis.…”

Proposal of novel staging system CNM (Crohn’s primary site, nodes, mesentery) to predict postoperative recurrence of Crohn’s disease

“…17 Studies have shown that at least 1 eosinophil and 6 lymphocytes in SMP predicted surgical recurrence whereas at least 1 lymphocyte in SMP or MP predict endoscopic, clinical and surgical recurrence. [19][20][21][22] The hazard ratio of surgical, endoscopic, and clinical recurrence were 9, 6, and 4, respectively, in the presence of plexitis on time to event analysis. 1 Overall 4 studies also reported a 30% higher risk of early endoscopic recurrence (<12 months) with plexitis.…”

“…11,[13][14][15][16][17][18] On multivariate analysis, plexitis was associated with 10-fold higher risk of endoscopic recurrence and a 30% higher risk of surgical recurrence. 12,19 Plexitis in MP and not SMP was associated with an increased risk of endoscopic recurrence when assessed by hematoxylin and eosin staining alone. 17 Studies have shown that at least 1 eosinophil and 6 lymphocytes in SMP predicted surgical recurrence whereas at least 1 lymphocyte in SMP or MP predict endoscopic, clinical and surgical recurrence.…”

“…36 It became increasingly evident that factors other than active microscopic disease margins like www.irjournal.org depth of infiltration (transmural and extramural), granuloma and plexitis at Crohn' s primary resection site could predict recurrence. 7,12,15,19,25 Apart from the primary site of involvement, involvement of the adjacent structures like nodes (specially granuloma) and mesentery predict recurrence. This could be due to the fact mesenteric adipose tissue and lymph nodes help in mediating immunological, inflammatory and fibrotic signals in the intestine.…”