BACKGROUND AND AIMS:Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), remain heterogeneous disorders with variable response to biologics. Post-operative recurrence in CD is common despite surgery and prophylactic biotherapies. Understanding the inflammatory mediators associated with recurrence and treatment response could pave the way for personalized strategies. METHODS:We analyzed serum inflammatory protein signatures using proteomics in two prospective cohorts. The REMIND cohort included post-operative CD patients undergoing ileocecal resection with endoscopic assessment at 6 months (M6). Serum samples were collected at surgery and 6 months later. The ELYP cohort consisted of active IBD patients starting new biotherapies (anti-tumor necrosis factor [anti-TNF], ustekinumab, or vedolizumab). Serum samples were collected pre- and post-treatment (Weeks 14 and 52). RESULTS:In the REMIND cohort, proteomic analysis revealed elevated levels of IFN-γ, CXCL9, and MMP-10 in patients with recurrence, with concentrations associated with recurrence severity. Preoperative MMP-10 levels predicted severe recurrence (AUC = 0.70). Under biotherapies, treatment-specific proteins were associated with recurrence: CXCL9 for anti-TNF and OSM/TGFα modules for ustekinumab. In the ELYP cohort, IFN-γ and CXCL9 were significantly elevated in CD compared to UC and associated with disease activity. Early response to anti-TNF treatment (Week 14) was associated with reductions in CXCL9, MMP-10, and OSM, while deep remission (Week 52) correlated with decreases in CXCL9 and OSM. CONCLUSION:Our findings reveal inflammatory blood proteomic signatures associated with post-operative recurrence and biologic treatment failure in IBD. Several key biomarkers were identified. These results support the rationale for personalized approaches, including combination therapies targeting multiple pathways.ClincialTrials.gov number, NCT02693340 and NCT02693340.

BACKGROUND:Hypersensitivity reactions (HSR) to the administration of infliximab (IFX) in Inflammatory Bowel Diseases (IBD) patients are not rare and usually lead to drug discontinuation. We report data on safety and effectiveness of desensitization to IFX in patients with previous HSR. METHODS:We conducted a retrospective monocentric observational study. Patients for whom a desensitization protocol to IFX was realized after a previous HSR were included. Anti-drug antibodies (ADA) and IFX trough levels at both inclusion and six months after desensitization were collected. Clinical outcomes, including recurrence of HSR were evaluated. RESULTS:From 2005 to 2020, 27 patients (Crohn's Disease: 26 (96%) were included). Desensitization after HSR was performed after a median time of 10.4 months (2.9-33.1). Nineteen (70%) patients received immunosuppressants at time of desensitization. Eight (30%) patients presented HSR at first (n = 2), second (n = 4) or third (n = 2) IFX perfusion after desensitization. None led to intensive care unit transfer or death. Thirteen (48%) had clinical response at 6 months and 8 (29%) were still under IFX treatment two years after desensitization. IFX trough levels and ADA were available for 14 patients at time of desensitization. Most patients (12 out of 14) had ADA at a high level. At 6 months, among the 7 patients with long term response to IFX, 4 presented a decrease of ADA titers and 2 had a significant trough level of IFX. CONCLUSION:IFX desensitization in patients with IBD is a safe therapeutic alternative and represents a potential option for patients refractory to multiple biologics.What is already known? Hypersensitivity reactions to the administration of infliximab is frequent. Occurrence of hypersensitivity reaction, either immediate or delayed, usually leads to permanent drug discontinuation.What is new here? Infliximab desensitization is well tolerated with no hypersensitivity reaction recurrence in 70% of patients. Clinical success at 6 months was of 48% and around a third of patients remained under infliximab therapy two years after desensitization. Antidrug antibodies decreased and infliximab trough levels increased in these patients showing the impact of desensitization on immunogenicity.How can this study help patient care? Infliximab desensitization represents a potential option for patients refractory to multiple biologics who presented hypersensitivity reaction to the drug.

Background and Aims Inflammatory Bowel Disease (IBD) is known to impact patients' sexual lives. The aim of this study is to create and validate a sexual quality of life (QoL) designed for youth with IBD.Methods This study was conducted in 2 phases: development of the score and validation of the items. A multidisciplinary team created a score called BLOOMI, based on 2 validated scores: the International Index of Erectile Function (IIEF) and the Sexual Function Questionnaire 28 (SFQ28). It was validated through a French multicentric cross-sectional study among patients aged 15-25 years with IBD by comparison with IIEF and SFQ28 gold standard scores.Results BLOOMI is a sexual QoL designed with 10 items and formatted as a disk. The score was validated through the participation of 104 patients with a median age of 23.2 years. BLOOMI was well correlated with both gold standards and had a strong internal consistency. In total, 19.1% of IIEF-responders have erectile dysfunction and median scores for the SFQ domains Desire, Arousal sensation and cognition, and orgasm are below the threshold for the absence of sexual dysfunction. Fatigue, abdominal pain, body image concerns, or fear of anal leakages are correlated to a poorer sexual QoL.Conclusions The BLOOMI score is a newly validated score to assess the sexual QoL in 15-25 years with IBD. This tool may improve the screening for sexual challenges encountered by youths with IBD and may support future research into the impact of IBD on young patients' lives.

Lympho-epithelial interactions between intestinal T resident memory cells (Trm) and the epithelium have been associated with inflammatory bowel disease (IBD) activity. We developed ex vivo autologous organoid-mucosal T cell cocultures to functionally assess lymphoepithelial interactions in Crohn's Disease (CD) patients compared to controls. We demonstrate the direct epithelial cell death induced by autologous mucosal T cells in CD patients but not in controls. These findings were positively correlated with T cell infiltration of the organoids. This potential was inhibited by limiting lympho-epithelial interactions through CD103 and NKG2D blocking antibodies. These data directly demonstrate for the first time the direct deleterious effect of mucosal T cells on the epithelium of CD patients. Such ex-vivo models are promising techniques to unravel the pathophysiology of these diseases and the potential mode of action of current and future therapies.

BACKGROUND:Hydrocortisone premedication reduces the risk of antibodies to infliximab [ATIs] formation in patients receiving infliximab [IFX] therapy for inflammatory bowel disease [IBD]. AIM:We aimed to determine the safety of hydrocortisone premedication withdrawal in IBD patients with sustained clinical response on maintenance therapy with IFX. METHODS:We performed an observational prospective pharmacoclinical study in a tertiary referral centre, including all consecutive IBD outpatients with no previous IFX infusion reaction and in clinical remission on maintenance IFX [alone or in combination therapy] for at least 6 months. This cohort was followed for 1 year after discontinuation of hydrocortisone premedication. RESULTS:Among the 268 IBD outpatients, 95 patients met the inclusion criteria [mean age 38 years; 64% male; 80% Crohn's disease; 45% combination therapy]. The median IFX duration was 5 years [0.54-14] with a mean infused dose of 533 mg [200-1000] and a mean interval duration of 7.9 weeks [4-10]. None of the patients developed permanent ATIs or infusion-related reaction at 1 year. Four patients developed transient ATIs without loss of clinical response. There was no significant variation of infliximab serum trough levels [5.5 µg/mL vs 5.9 µg/mL] measured at the time of the three IFX infusions before and after hydrocortisone withdrawal. Loss of response rate to IFX was 18% at 1 year. CONCLUSIONS:Hydrocortisone discontinuation is safe in IBD patients with sustained clinical remission on maintenance therapy with IFX. Our data suggest that routine premedication with hydrocortisone is unnecessary in patients in prolonged remission under IFX maintenance therapy.

Background and Aims Different types of histologic lesions at the ileal margin, detected by histology, have been associated with increased rates of recurrence after ileocaecal surgery in patients with Crohn's disease (CD). We aimed to characterize histologic features of the ileal margin and to evaluate their association with disease recurrence. Methods We collected histologic data from 211 patients with ileal or ileocolonic CD who underwent ileocolonic resections at hospitals in France from September 2010 through December 2016. Ileal margins were analyzed. Early endoscopic recurrence was defined by a Rutgeerts score of i2 or more, 6 months after surgery. We also collected data from 10 adults with healthy ileum who underwent ileocecal resection for colonic tumors (controls). Clinical relapse was defined by CD-related symptoms confirmed by imaging, endoscopy, therapy intensification, CD-related complication, or subsequent surgery. Results Six months after surgery, 49% of patients had endoscopic recurrence; 5 years after surgery, 57% of patients had clinical relapse. Ileal margins were macroscopically affected in 20.9% of patients. CD transmural lesions at the margin (defined by mucosal ulceration or cryptitis, submucosal fibrosis and lymphoplasmacytic infiltrate of the subserosa) were observed in 13.6% of patients. Endoscopic recurrence was observed in 75% of patients with CD transmural lesions vs 46% of patients without (P =.005). In multivariate analysis, CD transmural lesions at the margin were independently associated with early endoscopic recurrence (OR, 3.83; 95% CI, 1.47-11.05; P =.008) and clinical recurrence (OR 2.04; 95% CI, 1.09-3.99; P =.026). Conclusion In patients with CD, transmural lesions at the ileal margin were associated with an increased risk of post-operative recurrence. Histologic features of the ileal margin should be included in making decisions about post-operative therapy.

Objectives The determinants of refractory ascites have not been fully characterized. The aims of this study were to assess liver histopathological alterations associated with refractory ascites and their relationship with comorbidities. Methods Consecutive patients with cirrhosis who underwent liver transplantation were retrospectively included. Patients' characteristics at the time of listing were analysed. The native livers were reviewed and lesions associated with refractory ascites were examined. Results Out of the 89 patients included, 30 had refractory ascites and 59 did not (including 35 without ascites and 24 with diuretic-sensitive ascites). Patients with and without refractory ascites had a similar amount of fibrous tissue and features of fatty liver disease. By contrast, microvascular changes, namely sinusoidal dilatation (P < 0.001), diffuse perisinusoidal fibrosis (P = 0.001), hepatic venous thromboses (P = 0.004) and vascular proliferation (P = 0.01) were more frequently observed in the livers of patients with refractory ascites. Diabetes (57% vs. 31%, P = 0.02) and alcohol as a causal factor for cirrhosis (80% vs. 42%, P = 0.001) were more frequent in patients with refractory ascites than in those without. By multivariate analysis, refractory ascites was independently associated with diabetes mellitus [odds ratio (OR) (95% confidence interval, CI) 6.15 (1.47-25.71); P = 0.01], alcohol as a causal factor for cirrhosis [OR (95% CI) 4.63 (1.07-20.02); P = 0.04], higher Model For End Stage Liver Diseases [OR (95% CI) 1.21 (1.05-1.38); P = 0.008] and lower serum sodium [OR (95% CI) 0.87 (0.78-0.98); P = 0.03]. Conclusion Liver microcirculatory changes are associated with refractory ascites. Diabetes and alcohol may explain refractory ascites by causing microangiopathy. Copyright (C) 2020 Wolters Kluwer Health, Inc. All rights reserved.

T cell clonal expansions are present in the inflamed mucosa of patients with Crohn’s disease (CD) and may be implicated in postoperative recurrence after ileocolonic resection.MethodsT cell receptor (TCR) analysis was performed in 57 patients included in a prospective multicentre cohort. Endoscopic recurrence was defined by a Rutgeerts score >i0. DNA and mRNA were extracted from biopsies collected from the surgical specimen and endoscopy, and analysed by high throughput sequencing and microarray, respectively.ResultsTCR repertoire in the mucosa of patients with CD displayed diverse clonal expansions. Active smokers at time of surgery had a significantly increased proportion of clonal expansions as compared with non-smokers (25.9%vs17.9%, p=0.02). The percentage of high frequency clones in the surgical specimen was significantly higher in patients with recurrence and correlated with postoperative endoscopic recurrence (area under the curve (AUC) 0.69, 95% CI 0.54 to 0.83). All patients with clonality above 26.8% (18/57) had an endoscopic recurrence. These patients with a high clonality were more frequently smokers than patients with a low clonality (61% vs 23%, p=0.005). The persistence of a similar TCR repertoire at postoperative endoscopy was associated with smoking and disease recurrence. Patients with high clonality showed increased expression of genes associated with CD8 T cells and reduced expression of inflammation-related genes. Expanded clones were found predominantly in the CD8 T cell compartment.ConclusionClonal T cell expansions are implicated in postoperative endoscopic recurrence. CD patients with increased proportion of clonal T cell expansions in the ileal mucosa represent a subgroup associated with smoking and where pathogenesis appears as T cell driven.Trial registration numberNCT03458195.

Background: Infliximab (IFX) is effective in maintenance therapy for Crohn's disease (CD) and ulcerative colitis (UC). IFX efficacy may be limited by immunogenicity. It was previously shown that intravenous hydrocortisone premedication reduces IFX antibodies (ATI) formation [1]. This premedication is still now commonly used although its benefit is unclear. The aim of our study was to determine short-term impact of hydrocortisone withdrawal on ATI formation and IFX pharmacokinetic in a cohort of patients treated with IFX. Methods: Patients were included between February and April 2016. Inclusion criteria were: – diagnosis of CD or UC; – IFX treatment with a stable dose for at least 6 months. Exclusion criteria were: – modification in IFX and/or immunosuppressant dosage; – pregnancy. Hydrocortisone premedication was withdrawn in all patients except during induction phase or if patients had a previous IFX-related infusion reaction. Trough levels and ATIs were measured at each infusion on a one year period (during the 3 infusions preceding and the 3 infusions following hydrocortisone withdrawal). Results: Hydrocortisone premedication was stopped in 246 patients. One hundred and nine patients were included in the study (median age 36 years-old; 62% men; CD: n=82, UC: n=17). Mean duration of the disease was 13.7 years (1–42). Mean duration of IFX treatment was 5 years. IFX was used in combotherapy in 49 patients (thiopurines: n=39, methotrexate: n=10; mean duration of combotherapy 2 years). IFX treatment was modified after hydrocortisone withdrawal in 14 patients (dose diminution: n=8, optimization: n=5, stop for failure: n=1). Pharmacokinetic analysis was performed in 95 patients who had a stable dose. None of the patients developed permanent ATI, 4 patients had transient ATI and high trough level (>3mcg/ml). Mean IFX trough level before hydrocortisone withdrawal was 5.5 mcg/ml (respectively 4.9, 6.9, 5.1, 5.3 at T-3, T-2, T-1 and T0) and 5.9 mcg/ml after (5.6, 6.0, 6.2 at T+1, T+2, T+3), (NS). There was no significant variation of IFX trough levels, even in patients under monotherapy. Seven patients had symptoms after hydrocortisone withdrawal, without trough level variation and didn't change their treatment. There was no significant variation of CRP (2.55 mg/L versus 2.14 mg/L). None of the patients had IFX related infusion reaction. Conclusions: In our study, performed in patients on stable IFX maintenance, hydrocortisone discontinuation had no impact on IFX trough levels and was not associated with ATI formation or infusion reactions. References: [1] Farrell, (2003), Intravenous hydrocortisone premedication reduces antibodies to infliximab in Crohn's disease: a randomized controlled trial.

Systemic steroids, in association or not with cyclosporin, are indicated for the treatment of large or widespread Pyoderma gangrenosum (PG). We report the case of a 27-year-old woman with a 15-year history of severe Crohn's disease, who developed a severe and disseminated PG, refractory to multiple lines of treatment. Infliximab and adalimumab were contraindicated, either because of allergy or of ineffectiveness on Crohn's disease. The addition of certolizumab pegol to the baseline treatment, associating systemic steroids and tacrolimus, finally allowed the complete healing of PG. Oral prednisone was stopped and tacrolimus was decreased, without any cutaneous or digestive relapse. Certolizumab pegol could be an alternative therapy in the treatment of PG in case of intolerance or ineffectiveness of the other anti-tumor necrosis factor (anti-TNF) therapies.

AIM to describe the characteristics of incident cases of tuberculosis [TB] despite negative TB screening tests, in patients with inflammatory bowel disease [IBD] undergoing anti-TNF treatment, and to identify the risk factors involved. METHODS A retrospective descriptive study was conducted at GETAID centers on all IBD patients undergoing anti-TNF treatment who developed TB even though their initial screening test results were negative. The following data were collected using a standardized anonymous questionnaire: IBD, and TB characteristics and evolution, initial screening methods and results, and time before anti-TNF treatment was restarted. RESULTS A total of 44 IBD patients [including 23 men; median age 37 years] were identified at 20 French and Swiss centers at which TB screening was performed [before starting anti-TNF treatment] based on Tuberculin Skin Tests [n = 25], Interferon Gamma Release Assays [n = 12], or both [n = 7]. The median interval from the start of anti-TNF treatment to TB diagnosis was 14.5 months (interquartile range [IQR] 25-75: 4.9-43.3). Pulmonary TB involvement was observed in 25 [57%] patients, and 40 [91%] had at least one extrapulmonary location. One TB patient died as the result of cardiac tamponade. Mycobacterium tuberculosis exposure was thought to be a possible cause of TB in 14 cases [32%]: 7 patients [including 6 health care workers] were exposed to occupational risks, and 7 had travelled to endemic countries. Biotherapy was restarted on 27 patients after a median period of 11.2 months [IQR 25-75: 4.4-15.2] after TB diagnosis without any recurrence of the infection. CONCLUSION Tuberculosis can occur in IBD patients undergoing anti-TNF treatment, even if their initial screening results were negative. In the present population, TB was mostly extrapulmonary and disseminated. TB screening tests should be repeated on people exposed to occupational risks and/or travelers to endemic countries. Restarting anti-TNF treatment seems to be safe.

The introduction of anti-TNF monoclonal antibodies to the therapeutic arsenal has represented a major advance in the management of Crohn's disease (CD). Anti-TNF agents are able to induce and maintain remission of the disease over time. These treatments also have the ability to close fistulae, heal mucosal lesions, and reduce rates of hospitalizations and surgeries. Such properties have been demonstrated in randomized clinical trials and have been confirmed in patient cohorts. Anti-TNF monoclonal antibodies represent the most effective agents currently available for the treatment of CD. Three anti-TNF monoclonal antibodies have demonstrated efficacies for the treatment of this disease: infliximab, adalimumab and certolizumab pegol. They are classically administered following a step-up approach to patients with refractory disease who are unresponsive to conventional therapies or are steroid-dependent. They may be used earlier in the disease course to treat patients presenting with aggressive disease or features predictive of poor prognosis. Indeed, several studies have suggested that early intervention with combination therapy may modify the long-term course of CD. The higher efficacies of these therapies compared to those of classical treatments have incited clinicians to have more ambitious objectives, such as endoscopic healing. In this chapter, we describe the major randomized controlled trials that have demonstrated the efficacies of infliximab, adalimumab and certolizumab pegol in the treatment of luminal CD, and that, together with data on safety, have defined their drug labeling. We also summarize the current international guidelines and discuss their usage in clinical practice. (C) 2015 S. Karger AG, Basel

Upper gastrointestinal (GI) tract involvement in adult Crohn's disease (CD) is rare and severe complications unusual. Stenosis has been reported, but gastroduodenal fistulae are seldom detected during surgery and most of the fistulae are cologastric or ileogastric. In complicated gastroduodenal CD, medical treatments are often effective and surgery is only considered in exceptional cases. We here report the unusual case of a 23-year-old patient with upper GI CD presenting a hyperalgic giant ulcer of the bulb fistulized in the pancreatic gland. The failure of steroids and two lines of combined treatment led us to a salvage surgical option. Abdominal exploration showed a plate stomach with an inflammatory bulboduodenal block. Cephalic duodenopancreatectomy and cholecystectomy were performed; histological analysis reported large fissuring pylorus ulceration with micro abscesses reaching the pancreas and the presence of non-caseating granulomas. Six months after the surgery, the patient had stopped antalgic treatment and did not have residual abdominal pain. He had gained 11 kg in weight and had no diarrhea with pancreatic enzymes. To our knowledge, we report the first case of an upper GI and fistulizing CD patient heavily treated with steroids and combined immunosuppressant agents requiring salvage cephalic duodenopancreatectomy.

BACKGROUND:After ileocolic resection in Crohn's disease, studies concerning the influence of the laparoscopic or open approach on clinical and endoscopic recurrences are scarce.PATIENTS AND METHODS:In a prospective database, we identified all patients operated on between 2004 and 2012 for primary ileocolic resection in Crohn's disease, with at least 6 months of follow-up. The rates of endoscopic recurrence during the first postoperative year and the clinical recurrence at any time during follow-up were measured and compared after the laparoscopic or open approach.RESULTS:Sixty-two patients (mean±standard deviation age, 33.5±12.7 years; 35 females) were operated on through laparoscopy (n=28) or laparotomy (n=34). Medical treatment, evolution and phenotype of disease, and postoperative course were comparable in both groups. Mean±standard deviation follow-up was 3.5±1.9 years. Ileocolonoscopy was available in 46 (74.2%) patients. Normal endoscopy or minor recurrence (i0 or i1 grade) was significantly more frequent after laparoscopy (14/24 [58.3%]) versus laparotomy (5/22 [22.7%]) (P=.019). Clinical recurrence was comparable at 1 year (P=.116) and at the end of follow-up (P=.799) after laparoscopy (28.6% and 50%, respectively) or laparotomy (11.8% and 55.9%, respectively).CONCLUSIONS:After resection, normal or minor endoscopic lesions (i0 or i1 grade) were more frequent after laparoscopy than after laparotomy. However, clinical recurrence was similar after both techniques.

Background: After intestinal resection for Crohn's disease, the severity of endoscopic recurrence in the first year following surgery is predictive of clinical outcome. Aim of the study was to assess the impact on clinical recurrence of tailored therapy based on endoscopic findings in the first year following surgery for Crohn's disease.Methods: All patients who underwent an intestinal resection for Crohn's disease between 1995 and 2005 at Saint-Louis Hospital were retrospectively included. Time-to-clinical recurrence was compared in two groups: patients who had systematic ileocolonoscopy 6-12 months after intestinal surgery with tailored treatment according to the severity of endoscopic lesions (group C) and patients without systematic endoscopic evaluation (group NC).Results: 132 patients (group C = 90, group NC = 42) were included. Probabilities of clinical recurrence were significantly lower in group C (21% and 26% at 3 and 5 years, respectively) compared with group NC (31% and 52% at 3 and 5 years respectively, p = 0.01).Conclusion: Tailored treatment according to endoscopic assessment after ileocolonic resection is significantly associated with reduced clinical recurrence rate. c 2014 Editrice Gastroenterologica Italiana S. r. l. Published by Elsevier Ltd. All rights reserved.

BACKGROUND:Infliximab is effective for the treatment of refractory inflammatory bowel disease (IBD). Nevertheless, up to 40% of patients lose response to infliximab over time. The aim was to assess the clinical value of measuring infliximab trough levels and antibodies to infliximab (ATI) concentrations in IBD patients who lost response to infliximab therapy.METHODS:We retrospectively studied records of IBD patients who lost response to infliximab therapy. We first assessed clinical responses of different therapeutic strategies that were applied when patients lost response to infliximab and then we looked at the correlation between clinical response and infliximab trough levels and ATI concentrations.RESULTS:Seventy-six IBD patients were included. 31/76 patients (41%) continued infliximab therapy without any modification, 39 patients (51%) had an intensification of infliximab therapy, five patients (7%) had switched to adalimumab therapy, and one patient (1%) underwent surgery. Clinical response was observed in 27 patients (69%) with an intensification of infliximab therapy. There was no significant difference in mean infliximab trough level at inclusion in patients who responded to intensification of infliximab therapy (3.3 ± 4.1 μg/mL) as compared with patients who did not respond (2.3 ± 2.2 μg/mL, P = 0.85). In all, 16/76 patients (22.4%) presented detectable ATI in the serum. Ten ATI-positive patients had an intensification of infliximab therapy and six (60%) demonstrated a clinical response. After intensification of infliximab therapy the ATI concentration decreased in five patients.CONCLUSIONS:In patients with IBD who lose response to infliximab, clinical improvement may occur upon intensification of infliximab therapy, irrespective of infliximab serum concentration or presence of ATI.

Background: Total proctocolectomy with definitive ileostomy is the ultimate treatment for refractory colonic Crohn's disease (CD). Aim of the study was to report the outcome of Crohn's disease patients after total proctocolectomy with definitive ileostomy.Patients and methods: Between 1990 and 2005,55 patients underwent total proctocolectomy with definitive ileostomy for Crohn's disease in our institution. None of them received preventive post-operative treatment. We studied clinical recurrence, need for immunosuppressants (IS), anti-TNF therapy and re-operation in this retrospective cohort.Results: Median follow-up was 5.4 years. Probabilities of clinical Crohn's disease recurrence were 4%, 27% and 39% at 1,5 and 8 years, respectively. In multivariate analysis, clinical recurrence rate was significantly higher for patients with penetrating disease behaviour (RR 1.7 IC95% [1.5-19], p = 0.05) and absence of perianal disease (RR = 1.6, IC95% [1.4-10]: p = 0.01). Clinical recurrences were located in terminal ileum in all cases and treated medically in 9 of 16 patients including IS or anti TNF agents in 7 cases. Probabilities of treatment with immunosuppressants or anti-TNF therapy were 4%, 15% and 15% at 1, 5 and 8 years, respectively. Nearly one third of the patients (29%) underwent surgery for mechanical complications (N = 11) and/or CD recurrence (N = 7). Probabilities of reoperation for Crohn's disease recurrence were 0%, 10% and 18% at 1,5 and 8 years, respectively.Conclusion: Recurrence after total proctocolectomy with definitive ileostomy for Crohn's disease is not uncommon, and in our series often required immunosuppressants or surgical procedure. (C) 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.