Vedolizumab for perianal Crohn's disease: a multicentre cohort study in 151 patients.

BACKGROUND: The management of Crohn's disease patients with perianal lesions and anti-TNF failure is challenging. AIMS: To assess the effectiveness of vedolizumab in perianal Crohn's disease and the predictors of success in a real-life cohort. METHODS: We conducted a nationwide multicentre cohort study in patients with perianal Crohn's disease who received vedolizumab. In patients with active perianal Crohn's disease, the success of vedolizumab was defined by clinical success (no draining fistula at clinical examination and no anal ulcers for primary lesions) at 6 months without medical or surgical treatment for perianal Crohn's disease. Logistic regression analyses were performed to identify predictors of success. In patients with inactive perianal Crohn's disease, recurrence was defined by the occurrence of lesions and/or the need for medical or surgical treatments. RESULTS: One hundred and fifty-one patients were included. Among them 102 patients had active perianal disease, 33 (32.4%) males, mean age 39.8 years, mean Crohn's disease duration 14.6 years; 101 (99%) had received at least one anti-TNF. The median follow-up time was 52 weeks. Sixty-eight per cent of patients discontinued therapy after a median time of 33 weeks. Vedolizumab success was reached in 23/102 (22.5%). Among patients with setons at initiation, 9/61(15%) had a successful removal. In multivariable analysis, factors associated with success were the number of prior biologic agents (≥3, odds ratio, OR: 0.20, 95% CI 0.04-0.98) and no antibiotics at initiation (OR: 4.76, 95% CI 1.25-18.19). In 49 patients with inactive perianal Crohn's disease, perianal disease recurred in 15/49 (30.6%), 11/49 (22.4%) needed dedicated treatments. Median time to recurrence was 22 weeks. CONCLUSIONS: We identified a low rate of success of vedolizumab in patients with active perianal Crohn's disease, and nearly one third of patients with inactive perianal Crohn's disease had perianal recurrence. Further evaluation is warranted in prospective studies.

Deep remission on magnetic resonance imaging impacts outcomes of perianal fistulizing Crohn's disease.

BACKGROUND: The long-term management of perianal Crohn's disease for patients on anti-TNF-α therapy remains challenging. AIM: To evaluate the long-term course and complications of patients with perianal fistulas treated with anti-TNF-α based on their clinical remission and healing on MRI. METHODS: Patients were evaluated clinically and by MRI. Deep remission was defined as clinical remission associated with the absence of contrast enhancement and T2 hyperintensity on MRI. Flare-free survival, surgery and hospitalizations were compared based on the presence or not of deep remission. RESULTS: Forty-eight consecutive patients were included with a median follow-up of 62 months after anti-TNF-α first administration. Deep remission was observed in 16 patients (33.4%). For patients in deep remission, the median time to any perianal event was 116 months (95-130) versus 42 months (8-72) in patients with pathological MRI (p < 0.001). Sixteen patients (50%) with pathological MRI had perianal surgery versus 2 (12.5%) in the deep remission group (p < 0.05). The mean duration of cumulative hospital stays was 0.75 ±â€¯0.52 days in the deep remission group versus 19.7 ±â€¯7.4 in the pathological group (p < 0.05). CONCLUSIONS: Higher flare-free survival and lower rates of surgery and hospitalization were found in patients achieving deep remission.

Impact of Extra-Intestinal Manifestations at Diagnosis on Disease Outcome in Pediatric- and Elderly-Onset Crohn's Disease: A French Population-Based Study.

Background: Extraintestinal manifestations (EIM) have been associated with more severe course of inflammatory bowel disease. The aim was to study the frequency of EIM in pediatric- and elderly-onset Crohn's disease (CD) and the factors associated with EIM and their impact on long-term disease outcome. Methods: Pediatric- (age at diagnosis younger than 17 years) and elderly-onset CD patients (age at diagnosis 60 years or older) from a prospective population-based registry (EPIMAD) were recruited. Data on EIM and clinical factors at diagnosis and at maximal follow-up were collected. Results: We included 535 pediatric- and 370 elderly-onset patients (median age 14.5 and 69.9 years; median follow-up 11.1 and 5.9 years). Extraintestinal manifestations presented in 23.5% of childhood-onset and 4.9% of elderly-onset individuals at diagnosis, while in 29.8% and 5.9% of patients, EIM developed newly during the follow-up (hazard ration [HR] 4.4, 95% CI, 2.7-7.0, P < 0.001). The most frequently involved organ in both age cohorts, either at diagnosis or during disease course, were joints (pediatric: 11.2% and 22.6%; elderly: 3.2% and 3.5%, respectively) followed by skin (pediatric: 15.9% and 13.6%; elderly: 2.7% and 2.7%, respectively). Extraintestinal manifestations at diagnosis were associated with increased risk for corticosteroids (HR 1.42, 95% CI, 1.14-1.78 and HR 3.38, 95% CI, 1.88-6.08) and immunosuppressive therapy (HR 1.30, 95% CI, 1.02-1.65 and HR 4.24, 95% CI, 1.91-9.42), in both age populations. Conclusions: Extraintestinal manifestations occurred at lower frequency in elderly-onset compared with pediatric-onset patients. In both age populations, presence of EIM at diagnosis independently increased the need for corticosteroid and immunosuppressive treatment.

Impact of age at diagnosis on natural history of patients with elderly-onset ulcerative colitis: A French population-based study.

BACKGROUND: Recent population-based study of elderly-onset Crohn's disease patients reported age-related differences in disease phenotype and outcome. AIMS: The aim was to assess the impact of age at diagnosis on natural history of elderly-onset ulcerative colitis patients with emphasis on disease presentation, phenotype and treatment. METHODS: Elderly-onset patients with ulcerative colitis (≥60 years at diagnosis) registered in a French population-based Registry EPIMAD (1988-2006) were included. Demographic and clinical data at diagnosis and at maximal follow-up were collected using predefined questionnaire. RESULTS: Four-hundred and sixty-five elderly-onset ulcerative colitis patients were included (median follow-up 6.2 years); 276 (59%) were <70 and 189 (41%) ≥70 years at diagnosis. Patients aged <70 years presented with more rectal bleeding (86% vs. 79%, p = .06) and abdominal pain (44% vs. 34%, p = .04) while those ≥70 years had higher rate of left-sided colitis (62% vs. 49%; p = .02). Cumulative exposure to 5-ASA, corticosteroids and immunosuppressants was similar between the groups as well as surgery rate. However, patients <70 years were significantly more steroid-resistant than older individuals (12% vs. 3%, p < .05) while no significant difference in steroid-dependency was observed. CONCLUSION: Patients with elderly-onset ulcerative colitis differed in presentation, disease phenotype and response to medication with respect to age at diagnosis.

Dramatic Increase in Incidence of Ulcerative Colitis and Crohn's Disease (1988-2011): A Population-Based Study of French Adolescents.

OBJECTIVES: Few data are available to describe the changes in incidence of pediatric-onset inflammatory bowel disease (IBD). The aim of this study was to describe changes in incidence and phenotypic presentation of pediatric-onset IBD in northern France during a 24-year period. METHODS: Pediatric-onset IBD (<17 years) was issued from a population-based IBD study in France between 1988 and 2011. Age groups and digestive location were defined according to the Paris classification. RESULTS: 1,350 incident cases were recorded (8.3% of all IBD) including 990 Crohn's disease (CD), 326 ulcerative colitis (UC) and 34 IBD unclassified (IBDU). Median age at diagnosis was similar in CD (14.4 years (Q1=11.8-Q3=16.0)) and UC (14.0 years (11.0-16.0)) and did not change over time. There were significantly more males with CD (females/males=0.82) than UC (females/males=1.25) (P=0.0042). Median time between onset of symptoms and IBD diagnosis was consistently 3 months (1-6). Mean incidence was 4.4/105 for IBD overall (3.2 for CD, 1.1 for UC and 0.1 for IBDU). From 1988-1990 to 2009-2011, a dramatic increase in incidences of both CD and UC were observed in adolescents (10-16 years): for CD from 4.2 to 9.5/105 (+126%; P<0.001) and for UC, from 1.6 to 4.1/105 (+156%; P<0.001). No modification in age or location at diagnosis was observed in either CD or UC. CONCLUSIONS: In this population-based study, CD and UC incidences increased dramatically in adolescents across a 24-year span, suggesting that one or more strong environmental factors may predispose this population to IBD.

Extra-intestinal Manifestations at Diagnosis in Paediatric- and Elderly-onset Ulcerative Colitis are Associated With a More Severe Disease Outcome: A Population-based Study.

BACKGROUND AND AIMS: Data on extra-intestinal manifestations [EIM] and their impact on the disease course of ulcerative colitis [UC] in population-based cohorts are scarce, particularly in paediatric- and elderly-onset UC patients. The aims of this population-based study were to assess: 1] the occurrence of EIM in paediatric- and elderly-onset UC; 2] the factors associated with EIM; and 3] their impact on long-term disease outcome. METHODS: Paediatric-onset [< 17 years at diagnosis] and elderly-onset UC patients [> 60 years at diagnosis] from a French prospective population-based registry [EPIMAD] were included. Data on EIM and other clinical factors at diagnosis and at maximal follow-up were collected. RESULTS: In all, 158 paediatric- and 470 elderly-onset patients were included [median age at diagnosis 14.5 and 68.8 years, median follow-up 11.2 and 6.2 years, respectively]. EIM occurred in 8.9% of childhood- and 3% of elderly-onset patients at diagnosis and in 16.7% and 2.2% of individuals during follow-up [p < 0.01], respectively. The most frequent EIM was joint involvement [15.8% of paediatric onset and 2.6% of elderly-onset]. Presence of EIM at diagnosis was associated with more severe disease course [need for immunosuppressants or biologic therapy or colectomy] in both paediatric- and elderly-onset UC (hazard ratio [HR] = 2.0, 95% confidence interval [CI]: 1.0-4.2; and HR = 2.8, 0.9-7.9, respectively). Extensive colitis was another independent risk factor in both age groups. CONCLUSIONS: Elderly-onset UC patients had lower risk of EIM either at diagnosis or during follow-up than paediatric-onset individuals. EIM at diagnosis predicted more severe disease outcome, including need for immunosuppressive or biologic therapy or surgery, in both paediatric- and elderly-onset UC.

Magnetic resonance imaging may predict deep remission in patients with perianal fistulizing Crohn's disease.

AIM: To evaluate the imaging course of Crohn's disease (CD) patients with perianal fistulas on long-term maintenance anti-tumor necrosis factor (TNF)-α therapy and identify predictors of deep remission. METHODS: All patients with perianal CD treated with anti-TNF-α therapy at our tertiary care center were evaluated by magnetic resonance imaging (MRI) and clinical assessment. Two MR examinations were performed: at initiation of anti-TNF-α treatment and then at least 2 years after. Clinical assessment (remission, response and non-response) was based on Present's criteria. Rectoscopic patterns, MRI Van Assche score, and MRI fistula activity signs (T2 signal and contrast enhancement) were collected for the two MR examinations. Fistula healing was defined as the absence of T2 hyperintensity and contrast enhancement on MRI. Deep remission was defined as the association of both clinical remission, absence of anal canal ulcers and healing on MRI. Characteristics and imaging patterns of patients with and without deep remission were compared by univariate and multivariate analyses. RESULTS: Forty-nine consecutive patients (31 females and 18 males) were included. They ranged in age from 14-70 years (mean, 33 years). MRI and clinical assessment were performed after a mean period of exposure to anti-TNF-α therapy of 40 ± 3.7 mo. Clinical remission, response and non-response were observed in 53.1%, 20.4%, and 26.5% of patients, respectively. Deep remission was observed in 32.7% of patients. Among the 26 patients in clinical remission, 10 had persisting inflammation of fistulas on MRI (T2 hyperintensity, n = 7; contrast enhancement, n = 10). Univariate analysis showed that deep remission was associated with the absence of rectal involvement and the absence of switch of anti-TNF-α treatment or surgery requirement. Multivariate analysis demonstrated that only the absence of rectal involvement (OR = 4.6; 95%CI: 1.03-20.5) was associated with deep remission. CONCLUSION: Deep remission is achieved in approximately one third of patients on maintenance anti-TNF-α therapy. Absence of rectal involvement is predictive of deep remission.

Pregnancy is possible on long-term home parenteral nutrition in patients with chronic intestinal failure: Results of a long term retrospective observational study.

BACKGROUND & AIMS: Home parenteral nutrition (HPN) improves survival and quality of life in patients with chronic intestinal failure (IF). Few cases of pregnancy on HPN have been published. The aim of this study was to report pregnancy cases on long-term HPN in benign IF. METHODS: This retrospective study included all pregnant patients on HPN from 4 HPN referral centers. Data on demographics, ongoing pathology, HPN type, maternal and newborn complications were collected. RESULTS: From 1984 to 2014, 21 pregnancies occurred in 15 patients (short bowel syndrome (n = 11), motility disorders (n = 3), mucosal disease (n = 1)) of whom 14 occurred after 2010. Median follow-up was 12 years. Median HPN duration before pregnancy was 8 years. HPN was adapted monthly during pregnancy, with close monitoring and supplementations. Energy intake was regularly increased and median maternal weight gain was 10 kg. Median age at the first pregnancy was 27 years. In 55% of cases, the newborn was preterm. Maternal complications occurred in 67% of cases (mainly due to underlying disease or HPN complications). There were 3 post-partum hemorrhages and 6 hypotrophic newborns. Eighteen infants were healthy and 2 chronic intestinal pseudo-obstruction (CIPO) were suspected. CONCLUSION: Our series, the largest reported to date, shows that pregnancy is possible in HPN patients but the complication rate is high. A specific support is necessary, particularly in CIPO patients. As pregnancies have increased over the last 15 years, physicians practicing in HPN referral centers should be aware of the need for implementing a specific multidisciplinary monitoring in HPN patients considering pregnancy.

Copy number variations in DCC/18q and ERBB2/17q are associated with disease-free survival in microsatellite stable colon cancer.

We conducted a prospective study to assess the prognostic impact of selected copy number variations (CNVs) in Stage II-III microsatellite stable (MSS) colon cancer. A total of 401 patients were included from 01/2004 to 01/2009. The CNVs in 8 selected target genes, DCC/18q, EGFR/7p, TP53/17p, BLK/8p, MYC/8q, APC/5q, ERBB2/17q and STK6/20q, were detected using a quantitative multiplex polymerase chain reaction of short fluorescent fragment (QMPSF) method. The primary end-point was the impact of the CNVs on the 4-year disease-free survival (DFS). The recurrence rate at 4 years was 20.9%, corresponding to 14% Stage II patients versus 31% Stage III patients (p < 0.0001). The 4-year DFS was significantly decreased in patients with a loss at DCC/18q (p = 0.012) and a gain at ERBB2/17q (p = 0.041). The multivariate analysis demonstrated that Stage III, a loss at DCC/18q and a gain at ERBB2/17q were independent factors associated with DFS. A combination of DCC/18q and ERBB2/17q was also associated with relapse, with the hazard ratio increasing from 1 to 2.4 (95% confidence interval (CI), 1.5-4.1) and 3.1 (95% CI, 1.2-8.4) in the presence of 0, 1 or 2 alterations, respectively (p = 0.0013). CNVs in DCC/18q and ERBB2/17q are significantly associated with DFS in Stage II-III MSS colon cancer.

Natural History of Crohn's Disease in Elderly Patients Diagnosed Over the Age of 70 Years: A Population-Based Study.

INTRODUCTION: Elderly onset (>60 yrs at diagnosis) Crohn's disease (CD) seems to be associated with a better outcome than when diagnosed earlier in life. The aim of this study was to compare the natural history of patients with CD older than 70 years at diagnosis with that of elderly patients diagnosed between 60 and 70 years in the EPIMAD population-based registry. METHODS: Three hundred seventy patients with elderly onset CD diagnosed between January 1988 and December 2006 were identified. Among them, 188 (63%) were older than 70 years at diagnosis (≥70 yrs). Clinical presentation, disease location, and behavior at diagnosis and also natural history, surgery needs, and drug exposure were recorded, with a median follow-up of 4.5 years (1.1; 8.3) in CD diagnosed after 70 years and of 7.8 years (3.3; 12.1) in CD diagnosed between 60 and 70 years, respectively. RESULTS: CD incidence in elderly patients diagnosed ≥70 years was 2.3/100,000 inhabitants, compared with 2.6/100,000 in elderly patients diagnosed below the age of 70 (60-69 yrs). The proportion of males was lower in patients ≥70 years than in patients aged 60 to 69 (31% versus 45%, P = 0.006). Clinical presentation at diagnosis was similar in both groups. Pure colonic location (L2) was more frequent among patients >70 years both at diagnosis (73% versus 57%, P = 0.004) and maximal follow-up (70% versus 47%, P < 0.0001). Disease extension (from L1 or L2 to L3) was not significantly different among patients >70 years and patients aged 60 to 69 years (hazard ratio [HR] = 2.0 [0.9; 4.5] for 60 to 69 yrs, P = 0.09). The most frequent behavior in the 2 groups was inflammatory, both at diagnosis (75% versus 80%, P = 0.43) and at maximal follow-up (69% versus 70%, P = 0.55). There was no significant difference in patients >70 years compared with patients aged 60 to 69 years regarding treatment with 5-aminosalicylic acid (P = 0.72), oral corticosteroids (P = 0.83), and anti-tumor necrosis factor therapies (P = 0.37). However, the use of immunosuppressants was significantly less frequent in patients >70 years (HR = 2.1 [1.3; 3.5] for 60 to 69 yrs, P = 0.003). Risk of surgery was similar in both groups (P = 0.72). Extraintestinal manifestations at diagnosis were significantly associated with an evolution to complicated behavior (HR = 2.7 [1.0; 7.0], P = 0.045), immunosuppressant treatment (HR = 2.9 [1.4; 6.0], P = 0.006), and corticosteroid use (HR = 3.3 [1.8; 6.1], P < 0.0001). CONCLUSIONS: The natural history of CD in elderly patients diagnosed over the age of 70 is mild with low disease extension and complicated behavior. This needs to be taken into account when establishing therapeutic strategies.

Postoperative Complications in Pediatric Inflammatory Bowel Disease: A Population-based Study.

BACKGROUND: We describe, in a population-based cohort, the incidence of and factors associated with postoperative complications (POCs) in pediatric-onset inflammatory bowel disease. METHODS: Using the pediatric population-based EPIMAD Cohort (1988-2004), among 692 incident inflammatory bowel disease cases, 128 patients with Crohn's disease (CD) and 25 with ulcerative colitis (UC) (22%) had undergone at least 1 major abdominal surgery at a median age of 16 years [interquartile range, Q1-Q3 = 14-17]. Factors associated with POC were assessed using Cox models. RESULTS: After a median postoperative follow-up of 8 years (3-12), 76 (49.7%) patients had experienced at least 1 POC with a total of 113 complications. The frequency of severe POC (grade >2) was similar in CD and UC (28% of all complications versus 27%, P = 0.95). A total of 64 early POCs (within 30 d of surgery) were observed in 47 patients (31%), with 33 being infectious and 31 noninfectious, higher in UC than in CD (25% of patients with CD versus 60% of patients with UC, P < 0.001). Forty-nine late POCs (≥30 d) were observed in 37 patients (24%). The occurrence of late POC was similar in UC and CD. The cumulative probability of POC was 31% (95% confidence interval, 24-39) at 1 month, 46% (38-54) at 1 year, and 48% (41-57) at 5 years. Multivariate analysis found that the UC type was the only factor associated with early POC (hazard ratio = 2.9; 95% confidence interval, 1.6-5.4). CONCLUSIONS: One-half of the children with inflammatory bowel disease had experienced at least 1 POC. Only UC relative to CD was significantly associated with an increased risk of early POC.

Pathophysiological approach to bowel dysfunction after segmental colorectal resection for deep endometriosis infiltrating the rectum: a preliminary study.

BACKGROUND: Colorectal segmental resection is performed worldwide in a majority of women presenting with symptomatic deep endometriosis infiltrating the rectum. The aim of the present study was to investigate the pathophysiological mechanisms involved in post-operative digestive dysfunction. METHODS: We selected patients managed by colorectal resection for rectal endometriosis, who had developed post-operative severe constipation and whose follow up was superior to 24 months. To assess the mechanisms involved in the pathogenesis of this complaint, we performed a step-by-step work up including: low digestive tract endoscopy, colonic transit time measurement and when appropriate anorectal manometry, electromyography and defecographic evaluation. RESULTS: Five out of 25 (20%) patients, whose age ranged from 27 to 41 years, were investigated for severe post-operative terminal constipation. Four different mechanisms responsible for terminal constipation were identified: tight stenosis of the colorectal anastomosis, post-operative neurological sequelae, colonic intussusception through the colorectal anastomosis and transit constipation that developed post surgery. CONCLUSIONS: Post-operative constipation is a frequent complaint in women managed by colorectal resection for rectal endometriosis. A multidisciplinary approach is mandatory as pathophysiologic mechanisms may vary and prove difficult to understand. The risk of post-operative bowel dysfunction following colorectal endometriosis must be taken into account whenever this technique is proposed in young women presenting with a benign disease such as deep endometriosis.