You are here
Myenteric plexitis is a risk factor for endoscopic and clinical postoperative recurrence after ileocolonic resection in Crohn's disease
Digestive and Liver Disease
As surgical resection is not curative in Crohn's disease, postoperative recurrence remains a crucial issue. The selection of patients, according to available risk factors, remains disappointing in clinical practice highlighting the need for better criteria, such as histologic features.
To investigate whether submucosal and myenteric plexitis increase the risk of endoscopic, clinical and surgical postoperative recurrence in Crohn's disease.
From the pathology department database, we retrospectively retrieved the data of all the patients who have undergone ileocolonic resection for Crohn's disease. Two pathologists, blinded from clinical data, reviewed all specimens to evaluate the presence of plexitis at the proximal resection margin.
Of the 75 included CD patients, 19 (25.3%) had histological involvement of resection margin. Inflammatory cells count for myenteric and submucosal plexus were performed in 56 patients. In multivariate analysis, the myenteric plexitis was a risk factor for endoscopic postoperative recurrence (HR 8.83 CI95% [1.6–48.6], p = 0.012), and the presence of at least one myenteric lymphocyte (HR 4.02 CI95% [1.4–11.2], p = 0.008) was predictive of clinical postoperative recurrence. We observed no histologic predictor for surgical postoperative recurrence.
Myenteric plexitis in proximal margins of ileocolonic resection specimens is independently associated with endoscopic and clinical postoperative recurrence in Crohn's disease.
Keywords: Crohn's disease, Plexitis, Postoperative recurrence, Risk factors.
Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) involving the digestive tract that could lead to bowel damage  and . In the era of biologics, surgery is still required in half of the patients ten years after diagnosis . Surgical resection is unfortunately not curative in CD, and postoperative recurrence (POR) remains a key point in these patients. Approximately one-third of the patients experience postoperative recurrence, warranting surgery for CD, 10 years after the baseline surgery , , , and . Clinical POR occurs in approximately 25%, 40% and 50%, respectively 1, 5 and 10 years after surgery . From 54% to 75% of the patients present with endoscopic recurrence in the neoterminal ileum within 1 year following surgery .
Many years ago, Rutgeerts et al. showed a wide panel of CD postoperative courses, highlighting the need of predictors to differentiate high-risk patients, requiring top-down strategy immediately after surgery, from low-risk patients, remains a crucial issue in postoperative management . Several factors have been suggested to define high-risk patients such as smoking, perianal lesions, previous intestinal resection, fistulizing phenotype and resection length >50 cm  and . However, the impact of these former factors remains debated and limited, which highlights the need to identify more efficient criteria for selecting the CD patients according to their risk of postoperative recurrence.
Inflammatory infiltrates associated with both the submucosal and myenteric plexus have been observed in CD patients . It remains unclear whether these enteric nervous system changes are the cause or the consequence of inflammation. However, it has been suggested that these histologic modifications may precede mucosal inflammation .
In the last decade, the presence of submucosal or myenteric plexitis in the proximal resection margin of ileocolonic CD resection specimen has been proposed as risk factor of endoscopic, clinical and surgical endoscopic POR in CD , , , and . However, the definition of plexitis was not consensual and widely varies across the different studies published so far  and .
In the present study we aimed to assess the value of submucosal and myenteric plexitis in predicting endoscopic, clinical and surgical POR in CD.
2. Patient and methods
2.1. Ethical considerations
The study was performed in accordance with the Declaration of Helsinki, Good Clinical Practice and applicable regulatory requirements. The study was approved by local Ethics Committee (IRB #00008526–2014/CE86).
We performed a retrospective study of a single-centre cohort, in which standardized evaluation was performed by experienced clinicians, in all patients. From the electronic database of the Pathology Department of the University Hospital Estaing of Clermont-Ferrand, France, we identified 205 patients who underwent an intestinal resection for CD between 1986 and 2015 in our institution. The diagnosis of CD was based on clinical, radiological/endoscopic examination, and histological findings. Inclusion criteria were patients with confirmed diagnosis of CD with ileocolonic or ileocecal resection and ileocolonic anastomosis. Exclusion criteria were diagnosis of ulcerative colitis or unclassified colitis, definitive ileostomy, abdomino-perineal amputation, colo-colonic anastomosis, ileo-ileal anastomosis, absence of labelled proximal margin, absence of macroscopic free resection margin and unavailable postoperative follow-up (Fig. 1). For each patient, the following data were extracted from medical charts: demographic information, CD clinical setting (age at diagnosis, age at the time of inclusion, disease duration, Montreal classification , prior intestinal resection and smoking status, etc.). Data regarding the surgery were also recorded: treatment before surgery and at the time of surgery, type of anastomosis, anastomosis location, anastomosis technique, perioperative complications and postoperative prophylactic or curative treatment.
2.3. Definition of recurrence
Surgical recurrence was defined as symptomatic recurrence warranting re-operation for CD. Clinical POR was defined, according to De Cruz et al. , as recurrence of CD symptoms leading to hospitalization or therapeutic modifications. Endoscopic POR was defined as Rutgeerts’ score ≥i2 . Regarding endoscopies performed before the widespread of Rutgeerts’ score use or with no score specified on the colonoscopy report, the score was evaluated retrospectively based on the content of the colonoscopy report. The endoscopies were performed at the physician's discretion to assess potential subclinical disease.
2.4. Histological examination
The surgical specimens were conserved in either formol or AFA (alcohol–formol–acetic acid). For each patient, the histological specimens were prepared using haematoxylin–eosin–saffran (HES) staining to analyse the proximal margin and to evaluate the presence of neutrophils, eosinophils and plasma cells. Additional immunostainings were performed for lymphocytes labelled in plexus by CD3 antibody, for mast cells labelled by MCT and for macrophages labelled by CD163 antibody. Two pathologists (SD, JJ) retrospectively reviewed all specimens to evaluate the presence or absence of plexitis at the proximal resection margin in selecting the most inflammatory plexus according to pathologist's judgement. Evaluation was made independently for each cellular type and blinded for clinical data. Plexitis was defined as presence of inflammatory cells (neutrophils, lymphocytes, plasma cells, macrophages, eosinophils, mast cells) within or in contact with ganglion cells or nerve bundles , , , , and  (Fig. 2A and B). The grading of severity was undertaken in the most severe areas where Grade 1 was defined as <4 cells/high power field (HPF), Grade 2 as 4–9 cells/HPF and Grade 3 as >10 cells/HPF . Presence of granuloma at the proximal margin was also investigated. Presence of granuloma within the surgical specimen was retrieved from Pathology Department reports. Microscopic proximal margin involvement was defined as histologic features of CD on the proximal margin (inflammatory cells, abscess, fissure, granuloma, etc.). Interobserver disagreement was solved by joint revision of the case with a multiheaded microscope.
2.5. Data management and statistical analysis
Study data were collected and managed using REDCap electronic data capture tools hosted at Clermont-Ferrand University Hospital . REDCap (Research Electronic Data Capture) is a secure, web-based application designed to support data capture for research studies, providing (1) an intuitive interface for validated data entry; (2) audit trails for tracking data manipulation and export procedures; (3) automated export procedures for seamless data downloads to common statistical packages; and (4) procedures for importing data from external sources.
Statistical analysis was performed using Stata 13 software (StataCorp LP, College Station, TX, US). The tests were two-sided, with a type I error set at a = 0.05. Subject's characteristics were presented as mean (±standard-deviation) or median [interquartile range] for continuous data (assumption of normality assessed using the Shapiro–Wilk test) and as the number of patients and associated percentages for categorical parameters. Concerning the censored data, estimates were constructed using the Kaplan–Meier method. The log-rank test was used in a univariate analysis to test the prognostic value of patient characteristics for the occurrence of an event. Cox proportional hazards regression was used to investigate prognostic factors in a multivariate situation by backward and forward stepwise analysis of the factors considered significant in univariate analysis (entered into the model if p < 0.10) and according to clinically relevant parameters. Then, we add systematically the five following risk factors: smoking, perianal lesions, previous intestinal resection, fistulizing phenotype and resection length > 50 cm. The proportional hazard hypotheses were verified using Schoenfeld's test and plotting residuals. The interactions between possible predictive factors were also tested. Results were expressed as hazard ratios (HR) and 95% confidence intervals (CI95%). To study multicollinearity, comparisons between the independent groups were performed using the chi-squared or Fisher's exact tests for categorical variables, and using Student t-test or Mann–Whitney test for quantitative parameters (normality, assumption of homoscedasticity studied using Fisher–Snedecor test).
3.1. Baseline characteristics of the patients
Overall, samples retrieved from 75 CD patients underwent pathological examination. The characteristics of these patients at the time of surgery are given in Table 1. We observed a prevalence of endoscopic, clinical and surgical POR of 69.0%, 61.6%, and 17.9% respectively, five years following surgery. Endoscopic, clinical and surgical POR occurred in, respectively, 80.0%, 76.5% and 38.9% 10 years after surgery.
|Median age at the time of surgery (years), [IQR]||34.0 [25.7–48.2]||Postoperative prophylactic therapy|
|Median age at diagnosis (years) [IQR]||25.5 [20.0–36.9]||None||34 (45.3)|
|Median disease duration (years) [IQR]||3.7 [1.3–11.0]||5-ASA||12 (16.0)|
|Female gender, n (%)||45 (60.0)||Thiopurines, n (%)||17 (22.7)|
|Active smoker, n (%)||22 (29.3)||Methotrexate, n (%)||1 (1.3)|
|Previous intestinal resection, n (%)||14 (18.7)||Anti-TNF, n (%)||11 (14.6)|
|Montreal classification, n (%)||Type of surgery, n (%)|
|Crohn's disease location||Ileocecal resection||57 (76.0)|
|L1, n (%)||36 (48.0)||Ileocolonic resection||18 (24.0)|
|L2, n (%)||6 (8.0)||Site of anastomosis, n (%)|
|L3, n (%)||33 (44.0)||Ileo-colic||75 (100.0)|
|L4, n (%)||3 (4.0)||Stomia, n (%)|
|Crohn's disease behaviour||None||59 (78.7)|
|B1, n (%)||3 (4.0)||Transitory||16 (21.3)|
|B2, n (%)||33 (44.0)||Surgical technique of anastomosis, n (%)|
|B3, n (%)||39 (52.0)||Stapled||39 (52.0)|
|Perianal lesions, n (%)||19 (25.3)||Handsewn||36 (48.0)|
|Medication at the time of surgery||Type of anastomosis, n (%)|
|5-ASA, n (%)||16 (21.3)||Side-to-end||9 (12.0)|
|Steroids/budesonide, n (%)||21 (28.0)/4 (5.3)||Side-to-side||39 (52.0)|
|Thiopurines, n (%)||18 (24.0)||End-to-end||27 (36.0)|
|Methotrexate, n (%)||1 (1.3)||Mean length of ileal resection (cm) ± SD||19.0 [10.5–30.5]|
|Infliximab, n (%)||5 (6.7)||Mean length of colonic resection (cm) ± SD||8.0 [4.0–11.0]|
|Adalimumab, n (%)||11 (14.7)||Mean length of digestive resection (cm) ± SD||29.3 [21.0–42.0]|
|Anti-TNF naive at the time of surgery, n (%)||21 (28.0)||Perioperative complications, n (%)||11 (14.7)|
n = number; cm = centimetres; IQR = interquartile; TNF = tumour necrosis factor.
3.2. Pathological evaluation
Histologic characteristics are listed in Table 2. Of the 75 CD patients included in the study, 19 (25.3%) had histological involvement of resection margins including nine specimens with presence of granuloma on the proximal resection margin. Inflammatory cells count for myenteric and submucosal plexus was performed in 56 patients and are summarized in Table 2. Within the myenteric and submucosal layers of the proximal resection margin, eosinophils, neutrophils and plasma cells were observed in almost no patient. Myenteric plexitis was mainly constituted by lymphocytes with a lymphocyte number per plexus ranging from 0 to 13 and by macrophages with a count ranging from 0 to 20 per plexus. Mast cells were found in few patients (n = 6/56) in the myenteric layer while 49 of the 56 patients had submucosal mast cells on their proximal resection margin with a number varying from 0 to 20 mast cells per plexus. The severity of submucosal and myenteric plexitis, scored according to Ferrante et al. , is given in Table 2.
|Number of patients, %||Median cells count||IQR, 25th to 75th|
|Involved proximal resection margina||19/75 (25.3)||–||–|
|Granuloma within the surgical specimen||28/75 (37.3)||–||–|
|Granuloma on the proximal resection margin||9/75 (12.0)||–||–|
|Myenteric plexitis||51/56 (91.1)|
|Grade of plexitis severityb|
|Grade 0||5/56 (8.9)||–||–|
|Grade I||24/56 (42.9)||–||–|
|Grade II||20/56 (35.7)||–||–|
|Grade III||7/56 (12.5)||–||–|
|Mast cells||6/56 (10.7)||0–0|
|Plasma cells||0/56 (0.0)||0–0|
|Submucosal plexitis||54/56 (96.4)|
|Grade of plexitis severityb|
|Grade 0||2/56 (3.6)||–||–|
|Grade I||24/56 (42.8)||–||–|
|Grade II||22/56 (39.3)||–||–|
|Grade III||8/56 (14.3)||–||–|
|Mast cells||49/56 (87.5)||3||0–2.75|
|Plasma cells||3/56 (5.4)||0–0|
a Histologic features of CD on the proximal margin (inflammatory cells, abscess, fissure, granuloma).
b Ferrante et al. .
IQR = interquartile.
3.3. Risk factors for endoscopic POR
Among the 75 CD patients included in this study, 39 patients underwent a colonoscopy during their follow-up. The median interval for endoscopic POR was 1.1 years [0.5–5.0]. Overall, 12 patients (30.7%) received 5-ASA in prevention of endoscopic POR. In addition, 17 patients (43.6%), 1 patient (2.6%) and 11 patients (30.6%) were treated preventively with thiopurines, methotrexate and anti-TNF, respectively. The severity of postoperative endoscopic evaluation was as follows: 6 patients (15.4%) classified as i0 according to the Rutgeerts’ score , 9 patients (23.1%) as i1, 6 patients (15.4%) as i2, 4 patients (10.3%) as i3 and 14 patients (35.9%) as i4. In univariate analysis, the presence of myenteric plexitis (HR 3.69 CI95% [1.06–12.89], p = 0.04), involved proximal resection margin (HR 2.25 CI95% [0.99–5;13] p = 0.05) and prior anti-TNF exposure before surgery (HR 2.49 CI95% [1.04–5.94], p = 0.04) were associated with increased risk of endoscopic POR. In multivariate analysis, the myenteric plexitis was the only risk factor for endoscopic POR (HR 8.83 CI95% [1.6–48.6], p = 0.012) (Table 3).
|Risk factors||Hazard ratio||Confident interval||p-Value|
|Involved proximal margin||1.64||0.61–4.41||0.319|
|Prior anti-TNF exposure before surgery||1.79||0.51–6.23||0.36|
|Previous intestinal resection||0.76||0.61–4.41||0.36|
|Fistulizing phenotype (B3 according to Montreal classification)||0.56||0.25–1.27||0.17|
|Resection length > 50 cm||1.75||0.62–4.93||0.28|
3.4. Risk factors of clinical POR
Among the 75 included patients, the median time to clinical POR was 1.4 years [0.5–3.6]. Overall 23 patients (30.6%) were treated with 5-ASA in prevention of clinical POR. Anti-TNF therapy was administered to 19 patients (25.3%) while 11 patients (14.7%) were treated with thiopurines to prevent clinical POR. In univariate analysis, we reported that myenteric lymphocytes (HR 2.53 CI95% [1.09–5.89], p = 0.03) and myenteric neutrophils (HR 5.91 CI95% [1.29–27.08], p = 0.02) were associated with increased risk of clinical POR. In multivariate analysis, we confirmed that the presence of myenteric lymphocytes (HR 4.02 CI95% [1.4–11.2], p = 0.008) and neutrophils (HR 23.0 CI95% [3.3–160.4], p = 0.002) were predictive of clinical POR (Table 4).
|Risk factors||Hazard ratio||Confident interval||p-Value|
|Myenteric lympcocytes ≥ 1||4.02||1.4–11.2||0.008|
|Myenteric neutrophils ≥ 1||23.0||3.29–160.4||0.002|
|Previous intestinal resection||1.18||0.41–3.39||0.75|
|Fistulizing phenotype (B3 according to Montreal classification)||0.41||0.14–1.18||0.10|
|Resection length > 50 cm||1.25||0.23–6.79||0.27|
3.5. Risk factors of surgical POR
In our cohort (n = 75), 14 patients experienced re-operation for CD with a median time to surgical POR of 6.2 years [3.2–10.2]. The medications used between the time of surgery and surgical POR were 5-ASA in 25 patients (33.3%), steroids in 29 patients (38.7%), methotrexate in 8 patients (10.7%), thiopurines in 28 patients (37.3%) and anti-TNF in 27 patients (36.0%). In univariate analysis, fistulizing phenotype (B3 according to Montreal classification) (HR 4.87 CI95% [1.27 18.64], p = 0.02) and prior anti-TNF exposure before surgery (HR 2.98 CI95% [0.83–10.67], p = 0.08) were associated with an increased risk of surgical POR. We found no histologic predictor for surgical POR. In multivariate analysis, only fistulizing phenotype (B3 according to Montreal classification) was associated with increased risk of surgical POR (HR 4.29 CI95% [1.0–18.9], p = 0.05).
In the present study, we confirmed the significant value of investigating the presence of myenteric plexitis in the proximal margin of ileo-colonic resection specimen to predict the postoperative course in Crohn's disease patients. In addition, our study confirmed that the identification of plexitis could be performed routinely with the analysis of proximal margin, including routine staining (HES) and immunostaining to label lymphocytes in plexus, by CD3 antibody.
Patients’ stratification according to their risk of postoperative recurrence remains a cornerstone in the postoperative management in CD. From the landmark cohort of Leuven – Belgium – three distinct subgroups have been identified based on their early endoscopic features within the first year after surgery . While the CD patients experiencing no early endoscopic POR (i0 and i1 according to Rutgeerts’ score) had a low risk of clinical POR (<15% at 5years), those with i2 Rutgeerts’ score had an intermediary risk of clinical POR (around 40% at 5 years) and those with severe endoscopic POR (i3 or i4) had a high risk of clinical POR (>80% at 5 years) . However, endoscopic evaluation is often performed from 6 to 12 months after surgery and does not help IBD physicians in choosing the best therapeutic strategy in the very early postoperative period. These data highlighted the need to identify some factors in order to discriminate the high-risk patients, who could receive the most effective therapies to prevent POR . Smoking is the strongest risk factor for POR, increasing the risk of clinical recurrence by twofold  and . Prior intestinal resection, penetrating behaviour, perianal disease and extensive bowel disease (>50 cm) are established risk factors for postoperative recurrence  and . However, the impact of these factors still remains debated and limited . Recently, the POCER trial designed according to patients’ POR risk (smoking or penetrating behaviour or prior intestinal resection defining high-risk patients), reported that almost half of low-risk patients experienced endoscopic POR 18 months after surgery . Indeed these selection criteria appeared disappointing and underlined that better factors are warranted to differentiate low-risk patients from high-risk patients who could benefit from top-down strategy immediately after CD surgery.
In the last decade, a particular focus has been made on histologic features to assess the POR risk in CD, but for most of them, the literature provided conflicting data . Among these factors, inflammatory changes within the enteric nervous system of the resection margin are probably the most promising factor that may be associated with CD recurrence , , , and . In our cohort, we identified myenteric plexitis (presence of at least one inflammatory cell) as risk factor of endoscopic POR. This result confirmed the data from Ferrante et al. reporting, in a retrospective cohort of 59 patients, an increased risk of endoscopic POR in patients presented with myenteric plexitis compared to those with no plexitis (41% vs 75% and 59% vs 93%, at 3 and 12 months after surgery, respectively) . In addition, we reported that the presence of at least one lymphocyte in the myenteric plexus was associated with a higher risk of clinical POR. Recently, a retrospective study showed that myenteric plexitis (mainly lymphocytes infiltrate) was associated with a high risk of clinical POR (n = 86 patients) , while Ng et al. failed to confirm these findings . This negative result could be partly explained by the fact that the authors chose an endpoint (one year after surgery) that was too soon after the surgery to evaluate clinical POR . We also found that the presence of myenteric neutrophils could be associated with an increased risk of clinical POR. Due to the low number of patients presenting with myenteric neutrophils (only 2 patients), we cannot draw any conclusion and this result should be confirmed in another independent cohorts. We showed no impact of submucosal plexitis in our cohort. Two retrospective studies previously reported a role of submucosal plexitis in predicting re-operation in CD  and . However, some authors suggested the role of mast cells (>3 mast cells), and others identified combined criteria (eosinophils count ≥ 1 OR lymphocytes count > 6), using a very rigorous methodology. The wide variety of these definitions makes their use quite difficult in clinical practice. Recently, the preliminary results of a prospective study have been presented at Digestive Disease Week in Washington, DC. Among 74 CD patients, the authors found that submucosal plexitis seemed to be associated with an increased risk of endoscopic POR at 3 and 12 months after surgery .
The prevalence of myenteric plexitis (at least one inflammatory cell) ranged from 69.7% to 88% , , and , while the submucosal plexitis (at least one inflammatory cell) rate was around 85%  and  in the literature. As myenteric and submucosal plexitis occurred in most of the patients, the relevance of these factors themselves, to discriminate the patients according to their POR risk, remains questionable. However, the adjunction of plexitis to clinical established risk factors could be of great value . Although we did not observe any influence of prophylactic therapy in our study due to the sample size, accumulated evidence suggests that anti-TNF agents are the most effective treatments to prevent endoscopic POR in CD, leading IBD physicians to consider these biologics in a growing number of patients , , , , , , , , and . This tendency could lead to over-treat some low-risk patients. Usual clinical risk factors remain disappointing in identifying low-risk patients, since almost 50% of the low-risk patients (treated with antibiotics) experienced endoscopic POR at 6 months, in the POCER trial . In this regard, absence of plexitis could improve the identification of low-risk patients who could benefit from a break in drug therapy following surgery.
All available data, including ours, seems to identify the lymphocyte as the inflammatory cell having the most important role in predicting POR. Accordingly, such authors  suggest to design clinical trial studying therapy influencing lymphocytes gut homing e.g. vedolizumab, to prevent POR in patients with plexitis.
The main limitations of our study were the retrospective and monocentric design, and the absence of fixed time-point for endoscopic evaluation. However, we confirmed, in an independent cohort retrieved from a Pathology Department electronic database (consecutive patients), the impact of myenteric plexitis (especially lymphocytes infiltrates) on the risk of endoscopic and clinical POR in CD.
In conclusion, myenteric plexitis in the proximal resection margins after ileocolonic resection is predictive of endoscopic and clinical POR. Myenteric plexitis research added to clinical risk factors could be very helpful to stratify patients according to their risk and should be encouraged. Further prospective studies are warranted to definitively confirm the role of histologic features in predicting POR. The identification of low-risk patients who could benefit from drug holiday and high-risk patients who could benefit from aggressive medication regimen remains a crucial issue to attempt to modify the CD postoperative course.
Conflict of interest
Thank you to the company “MG translate” for reviewing the manuscript.
-  B. Pariente, J. Cosnes, S. Danese, et al. Development of the Crohn's disease digestive damage score, the Lémann score. Inflammatory Bowel Diseases. 2011;17:1415-1422 Crossref
-  B. Pariente, J.-Y. Mary, S. Danese, et al. Development of the Lémann index to assess digestive tract damage in patients with Crohn's disease. Gastroenterology. 2015;148:52-63
-  L. Peyrin-Biroulet, E.V. Loftus Jr., J.-F. Colombel, et al. The natural history of adult Crohn's disease in population-based cohorts. American Journal of Gastroenterology. 2010;105:289-297 Crossref
-  S. Riss, I. Schuster, P. Papay, et al. Surgical recurrence after primary ileocolic resection for Crohn's disease. Techniques in Coloproctology. 2014;18:365-371 Crossref
-  S. Shivananda, M.L. Hordijk, A.S. Pena, et al. Crohn's disease: risk of recurrence and reoperation in a defined population. Gut. 1989;30:990-995 Crossref
-  M.R. Lock, R.G. Farmer, V.W. Fazio, et al. Recurrence and reoperation for Crohn's disease: the role of disease location in prognosis. New England Journal of Medicine. 1981;304:1586-1588 Crossref
-  N.R. Borley, N.J.M. Mortensen, M.A. Chaudry, et al. Recurrence after abdominal surgery for Crohn's disease: relationship to disease site and surgical procedure. Diseases of the Colon and Rectum. 2002;45:377-383 Crossref
-  A. Buisson, J.-B. Chevaux, P.B. Allen, et al. Review article: the natural history of postoperative Crohn's disease recurrence. Alimentary Pharmacology and Therapeutics. 2012;35:625-633 Crossref
-  P. Rutgeerts, K. Geboes, G. Vantrappen, et al. Predictability of the postoperative course of Crohn's disease. Gastroenterology. 1990;99:956-963
-  G. Van Assche, A. Dignass, W. Reinisch, et al. The second European evidence-based consensus on the diagnosis and management of Crohn's disease: special situations. Journal of Crohn s and Colitis. 2010;4:63-101 Crossref
-  K. Geboes, P. Rutgeerts, N. Ectors, et al. Major histocompatibility class II expression on the small intestinal nervous system in Crohn's disease. Gastroenterology. 1992;103:439-447
-  A. Bressenot, L. Peyrin-Biroulet. Histologic features predicting postoperative Crohn's disease recurrence. Inflammatory Bowel Diseases. 2015;21:468-475 Crossref
-  M. Ferrante, G. de Hertogh, T. Hlavaty, et al. The value of myenteric plexitis to predict early postoperative Crohn's disease recurrence. Gastroenterology. 2006;130:1595-1606 Crossref
-  H. Sokol, V. Polin, A. Lavergne-Slove, et al. Plexitis as a predictive factor of early postoperative clinical recurrence in Crohn's disease. Gut. 2009;58:1218-1225 Crossref
-  A. Bressenot, J.-B. Chevaux, N. Williet, et al. Submucosal plexitis as a predictor of postoperative surgical recurrence in Crohn's disease. Inflammatory Bowel Diseases. 2013;19:1654-1661
-  H. Misteli, C.E. Koh, L.M. Wang, et al. Myenteric plexitis at the proximal resection margin is a predictive marker for surgical recurrence of ileocaecal Crohn's disease. Colorectal Disease. 2015;17:304-310 Crossref
-  S.C. Ng, G.A. Lied, M.A. Kamm, et al. Predictive value and clinical significance of myenteric plexitis in Crohn's disease. Inflammatory Bowel Diseases. 2009;15:1499-1507 Crossref
-  J. Satsangi, M.S. Silverberg, S. Vermeire, et al. The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications. Gut. 2006;55:749-753
-  P. De Cruz, M.-P. Bernardi, M.A. Kamm, et al. Postoperative recurrence of Crohn's disease: impact of endoscopic monitoring and treatment step-up. Colorectal Disease. 2013;15:187-197 Crossref
-  P.A. Harris, R. Taylor, R. Thielke, et al. Research electronic data capture (REDCap) – a metadata-driven methodology and workflow process for providing translational research informatics support. Journal of Biomedical Informatics. 2009;42:377-381 Crossref
-  A. Buisson, J.-B. Chevaux, G. Bommelaer, et al. Diagnosis, prevention and treatment of postoperative Crohn's disease recurrence. Digestive and Liver Disease. 2012;44:453-460 Crossref
-  P. De Cruz, M.A. Kamm, A.L. Hamilton, et al. Crohn's disease management after intestinal resection: a randomised trial. Lancet. 2015;385:1406-1417 Crossref
-  B. Lemmens, G.A. Van Assche, A. de Buck van Overstraeten, et al. Sa1154 plexitis as a predictive factor for early post-operative endoscopic recurrence in patients with Crohn's disease undergoing a right hemicolectomy with ileocolonic anastomosis: results from a prospective, single center trial. Gastroenterology. 2015;148 S–242
-  M. Regueiro, W. Schraut, L. Baidoo, et al. Infliximab prevents Crohn's disease recurrence after ileal resection. Gastroenterology. 2009;136:441-450
-  M. Regueiro, B.G. Feagan, B. Zou, et al. 749 infliximab for prevention of recurrence of post-surgical Crohn's disease following ileocolonic resection: a randomized, placebo-controlled study. Gastroenterology. 2015;148 S-141
-  Y. Qiu, R. Mao, B.-L. Chen, et al. Systematic review with meta-analysis of prospective studies: anti-TNFs for prevention of postoperative Crohn's disease recurrence. Journal of Crohn s and Colitis. 2015;9:918-927
-  A. Carla-Moreau, S. Paul, X. Roblin, et al. Prevention and treatment of postoperative Crohn's disease recurrence with anti-TNF therapy: a meta-analysis of controlled trials. Digestive and Liver Disease. 2015;47:191-196 Crossref
-  K. Yoshida, K. Fukunaga, H. Ikeuchi, et al. Scheduled infliximab monotherapy to prevent recurrence of Crohn's disease following ileocolic or ileal resection: a 3-year prospective randomized open trial. Inflammatory Bowel Diseases. 2012;18:1617-1623 Crossref
-  E. Savarino, G. Bodini, P. Dulbecco, et al. Adalimumab is more effective than azathioprine and mesalamine at preventing postoperative recurrence of Crohn's disease: a randomized controlled trial. American Journal of Gastroenterology. 2013;108:1731-1742 Crossref
-  T. Yamamoto, S. Umegae, K. Matsumoto. Impact of infliximab therapy after early endoscopic recurrence following ileocolonic resection of Crohn's disease: a prospective pilot study. Inflammatory Bowel Diseases. 2009;15:1460-1466 Crossref
-  D. Sorrentino, G. Terrosu, A. Paviotti, et al. Early diagnosis and treatment of postoperative endoscopic recurrence of Crohn's disease: partial benefit by infliximab – a pilot study. Digestive Diseases and Sciences. 2012;57:1341-1348 Crossref
-  P. De Cruz, M.A. Kamm, A.L. Hamilton, et al. Efficacy of thiopurines and adalimumab in preventing Crohn's disease recurrence in high-risk patients – a POCER study analysis. Alimentary Pharmacology and Therapeutics. 2015;42:867-879
a Pathology Department, University Hospital Estaing, Clermont-Ferrand, France
b Gastroenterology Department, University Hospital Estaing, Clermont-Ferrand, France
c DRCI, Biostatistics Unit, GM Clermont-Ferrand University and Medical Center, Clermont-Ferrand, France
d Digestive Surgery Department, University Hospital Estaing, Clermont-Ferrand, France
e Microbes, Intestine, Inflammation and Susceptibility of the Host, UMR 1071 Inserm/Université d’Auvergne, USC-INRA 2018, Clermont-Ferrand, France
⁎ Corresponding author at: University Hospital Estaing, Gastroenterology Department, 1, place Lucie et Raymond Aubrac, 63003 Clermont-Ferrand, France. Tel.: +33 4 73 750 523; fax: +33 4 73 750 524.
© 2016 Editrice Gastroenterologica Italiana S.r.l., Published by Elsevier B.V.