Ileal Crohn's Disease and Post-operative Outcome: Prospective Cohort Study of the REMIND Group

Crohn's disease (CD), a chronic inflammatory process in intestinal segments leads to tissue damage. More than two thirds of CD patients need intestinal resection. Symptomatic clinical recurrence occurs in 60% by 10 years. The principal factors affecting postoperative recurrence are active smoking, penetrating disease, perianal lesions history, prior intestinal resection, small bowel resection extent, and prophylaxis treatment absence. Ileocolonoscopy within one year of surgery can predict clinical recurrence risk. Different therapies are proposed after surgery, to prevent post-operative recurrence : Thiopurines, 6-mercaptopurine (positive for clinical and endoscopic postoperative recurrence prevention), Anti-tumour necrosis factor therapy (anti-TNF), the most effective therapy. Intestinal microbiota acts as a central factor in the CD pathogenesis, and fecal stream role is clearly shown. Various changes in luminal flora with a possible link to local inflammation was also demonstrated. Bacteria associated with postoperative recurrence could be more pathogenic as adherent invasive E coli (AIEC), which could be a pathogen in CD through several mechanisms including increased mucosal colonization, adherence, replication and induction of TNF secretion. Alternatively, postoperative CD recurrence could be linked to a protective commensal species lack, such as Faecalibacterium prausnitzii. Microscopic inflammation occurs as early as 8 days after anastomosis in the neoterminal ileum mucosa. IL6, IL10 and TGFb levels, measured in neoterminal ileum early after surgery are associated with different rates of postoperative recurrence. It suggests cytokines implication in postoperative recurrence. T cells are major players in the intestinal immune response. The presence at time of surgery and persistence of disease inducing T cell clonal expansions could play an important role in post-operative recurrence. The main objective is to define a classification of ileal Crohn's Disease based on data integration on a large cohort of patients.

Crohn's Disease is a major health issue with a complex etiology and despite available medical treatment, patients endure poor quality of life. The disease 's characterization on a molecular level will allow for a better management of patients treatment. To do so, the strategy is to integrate precise prospective clinical records with extensive biological data in a large cohort of patients. All the clinical centers, participating to the study, include patients, with a tight collaboration between Gastroenterology and Surgery departments. Demographics and clinical parameters are collected in an eCRF. Inclusion of patients is performed, before a scheduled ileocecal resection or ileal resection, and after eligibility criteria checking, and consent form signature. During surgery, several samples are collected : blood samples, mucosal biopsies, and surgical specimens. As usual practice, post-operative treatment will be prescribed at investigator's discretion, with help of a pre-established algorithm. Then, an endoscopic exam is scheduled, at least 6 months after surgery, or at least 6 months after intestine continuity restoration, in case of temporary stoma. Several samples are also collected during this exam (blood, ileal and colon biopsies). At the same time as these 2 visits, clinical data regarding medical history, CD history, surgical history, treatments history, post-operative treatment if prescribed, treatments history between surgery and colonoscopy 6 months later, endoscopic score. Clinical data are also collected 18 months after surgery during a scheduled visit organized as usual practice, for long-term study : Clinical relapse, surgical recurrence, change in the therapy, hospitalizations and complications A patient has achieved the study after the endoscopic exam. Several studies will be performed along the cohort setting-up: * Transcriptomic analyses of mucosal tissues: * Identification of a molecular signature predictive of post-operative recurrence * Molecular classification of ileal Crohn's Disease * Study of the mucosa-associated microbiota * Study of association of AIEC * Study of anti-TNF efficacy in post-operative recurrence prevention * Study of new biologics in the treatment of post-operative recurrence All the biologic samples are stored on sites at -80°C, or at room temperature depending on the samples : Samples collected in Formol tubes, are sent immediatly, at room temperature, to the central pathology department in Beaujon Hospital, Paris. All the other samples, stored at -80°C, are sent to a central department, the Bio-Bank of Pasteur Hospital, Nice (every 3 months). Samples analyses are performed by dedicated research centers: DNA, and RNA extraction for transcriptome analysis, Micobiota analysis, Lipids analysis, AIEC analysis : Histological analyzes: Analyzis of the structure and inflammatory status of intestinal tissue of patients of the cohort, particularly at the ileal limit of the surgical specimens. Molecular Bi Покажи пълното описание...

Inclusion Criteria: * Informed consent obtained before any study-related activities * A diagnosis of CD, based on clinical, radiologic, endoscopic, or histological evidence. * Men and women ≥18 years of age * Required surgical intervention consisting in an ileocecal resection Exclusion Criteria: * Previous history of dysplasia or cancer in the ileum or colon * Unwillingness or inability to follow the procedures outlined in the protocol * Pregnant women