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.

Costs of Crohn's Disease According to Severity States in France: A Prospective Observational Study and Statistical Modeling over 10 Years.

BACKGROUND: To describe the medico-economic characteristics of Crohn's disease (CD), we implemented a multicenter study in France. METHODS: From 2004 to 2006, disease severity states, direct (hospital and extra hospital) and indirect costs were prospectively collected over 1 year in patients with CD naive from anti-tumor necrosis factor alpha (infliximab) at inclusion. Economic valorization was performed from the French Social Insurance perspective, and a statistical modeling over 10 years was performed. RESULTS: In 341 patients, the mean total costs of management were &OV0556;6024 per year (&OV0556;4675 for direct costs). As compared to patients in remission, costs were 4 to 6 times higher in patients in an active period and 19 times higher for patients requiring surgery (SURG). The most important expense items were medical and surgical hospitalizations (56% of total costs), including cost of infliximab (36% of hospitalization costs, i.e., 20% of total costs), indirect costs (22%), and drugs (11%). The statistical modeling over 10 years showed that most of the clinical course was spent in drug-responsive state (54%) with 26% of costs or in remission (32%) with 11% of costs; time spent in a SURG state was small (3.2%) but generated 48% of total costs. CONCLUSIONS: Before the introduction of self-injectable anti-tumor necrosis factor alpha, the most important expenses were supported by hospitalizations, explaining why the most costly states were for patients requiring SURG or dependent on inhospital administrated drugs. Projected data show that most time is spent in a stabilized state with appropriate treatments or in remission, and that costs associated with SURG are high.

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.

Natural history of elderly-onset inflammatory bowel disease: a population-based cohort study.

UNLABELLED: Data on the natural history of elderly-onset inflammatory bowel disease (IBD) are scarce. METHODS: In a French population-based cohort we identified 841 IBD patients >60 years of age at diagnosis from 1988 to 2006, including 367 Crohn's disease (CD) and 472 ulcerative colitis (UC). RESULTS: Median age at diagnosis was similar for CD (70 years (IQR: 65-76)) and UC (69 years (64-74)). Median follow-up was 6 years (2-11) for both diseases. At diagnosis, in CD, pure colonic disease (65%) and inflammatory behaviour (78%) were the most frequent phenotype. At maximal follow-up digestive extension and complicated behaviour occurred in 8% and 9%, respectively. In UC, 29% of patients had proctitis, 45% left-sided and 26% extensive colitis without extension during follow-up in 84%. In CD cumulative probabilities of receiving corticosteroids (CSs), immunosuppressants (ISs) and anti tumor necrosis factor therapy were respectively 47%, 27% and 9% at 10 years. In UC cumulative probabilities of receiving CS and IS were 40% and 15%, respectively at 10 years. Cumulative probabilities of surgery at 1 year and 10 years were 18% and 32%, respectively in CD and 4% and 8%, respectively in UC. In CD complicated behaviour at diagnosis (HR: 2.6; 95% CI 1.5 to 4.6) was associated with an increased risk for surgery while CS was associated with a decreased risk (HR: 0.5; 0.3 to 0.8). In UC CS was associated with an increased risk (HR: 2.2; 1.1 to 4.6) for colectomy. CONCLUSIONS: Clinical course is mild in elderly-onset IBD patients. This information would need to be taken into account by physicians when therapeutic strategies are established.

Anaemia management in patients with inflammatory bowel disease: routine practice across nine European countries.

BACKGROUND AND OBJECTIVES: Anaemia and iron deficiency (ID) are common complications in inflammatory bowel disease (IBD). In patients undergoing iron therapy, intravenous iron supplementation is recommended in preference to oral therapy. This study evaluated routine practice in the management of IBD-associated anaemia and ID to verify implementation of international treatment guidelines. MATERIALS AND METHODS: Gastroenterologists from nine European countries (n=344) were surveyed about their last five IBD patients treated for anaemia (n=1404). Collected information included tests performed at anaemia diagnosis, haemoglobin (Hb) levels and iron status parameters, the anaemia treatment given and, if applicable, the iron administration route. RESULTS: Selection of diagnostic tests and treatment for IBD-associated anaemia varied considerably across Europe. Anaemia and iron status were mainly assessed by Hb (88%) and serum ferritin (75%). Transferrin saturation was only tested in 25% of patients. At diagnosis of anaemia, 56% presented with at least moderate anaemia (Hb<10 g/dl) and 15% with severe anaemia (Hb<8 g/dl). ID (ferritin<30 ng/ml) was detected in 76%. Almost all patients (92%) received iron supplementation; however, only 28% received intravenous iron and 67% oral iron. Management practice was similar in 2009 and 2011. CONCLUSION: In clinical practice, most IBD patients received oral iron even though this administration route may aggravate the disease, and despite international guidelines recommending intravenous administration as the preferred route. The high frequency of ID suggests insufficient monitoring of iron status in IBD patients. There is a need to increase awareness and implementation of international guidelines on iron supplementation in patients with IBD.

Mortality and cancer in pediatric-onset inflammatory bowel disease: a population-based study.

OBJECTIVES: Although the incidence of pediatric inflammatory bowel disease (IBD) continues to rise in Northern France, the risks of death and cancer in this population have not been characterized. METHODS: All patients <17 years, recorded in EPIMAD registry, and diagnosed between 1988 and 2004 with Crohn's disease (CD) or ulcerative colitis (UC) were included. The observed incidences of death and cancer were compared with those expected in the regional general population obtained by French Statistical Institute (INSEE) and the cancer Registry from Lille. Comparisons were performed using Fisher's exact test and were expressed using the standardized mortality ratios (SMRs) and standardized incidence ratios. RESULTS: A total of 698 patients (538 with CD and 160 with UC) were identified; 360 (52%) were men, the median age at IBD diagnosis was 14 years (12-16) and the median follow-up time was 11.5 years (7-15). During follow-up, the mortality rate was 0.84% (6/698) and did not differ from that in the reference population (SMR=1.4 (0.5-3.0); P=0.27). After a median follow-up of 15 years (10-17), 1.3% of patients (9/698) had a cancer: colon (n=2), biliary tract (cholangiocarcinoma; n=1), uterine cervix (n=1), prepuce (n=1), skin (basal cell carcinoma (n=2), hematological (acute leukemia; n=1), and small bowel carcinoid (n=1). There was a significantly increased risk of cancer regardless of gender and age (standardized incidence ratio=3.0 (1.3-5.9); P<0.02). Four out of nine patients who developed a cancer had received immunosuppressants or anti-tumor necrosis factor-α therapy (including combination therapy in three patients). CONCLUSIONS: In this large pediatric population-based IBD cohort, mortality did not differ from that of the general population but there was a significant threefold increased risk of neoplasia.

Long-term outcome after first intestinal resection in pediatric-onset Crohn's disease: a population-based study.

BACKGROUND: To describe long-term postoperative evolution of pediatric-onset Crohn's disease (CD) and identify predictors of outcome we studied a population-based cohort (1988-2004) of 404 patients (0-17 years), of which 130 underwent surgery. METHODS: Risks for a second resection and first need for immunosuppressors (IS) and/or biologics were estimated by survival analysis and Cox models used to determine predictors of outcome. Impact of time of first surgery on nutritional catch-up was studied using regression. RESULTS: In all, 130 patients (70 females) with a median age at diagnosis of 14.2 years (interquartile range: 12-16) were followed for 13 years (9.4-16.6). Probability of a second resection was 8%, 17%, and 29% at 2, 5, and 10 years, respectively. In multivariate analysis, age <14, stenosing (B2) and penetrating (B3) behaviors and upper gastrointestinal location (L4) at diagnosis were associated with an increased risk of second resection. Probability of receiving IS or biologics was 18%, 34%, and 47% at 2, 5, and 10 years, respectively. In multivariate analysis, L4 was a risk factor for requiring IS or biologics, while surgery within 3 years after CD diagnosis was protective. Catch-up in height and weight was better in patients who underwent surgery within 3 years after CD diagnosis than those operated on later. CONCLUSIONS: In this pediatric-onset CD study, mostly performed in a prebiologic era, a first surgery performed within 3 years after CD diagnosis was associated with a reduced need for IS and biologics and a better catch-up in height and weight compared to later surgery.

An enteral leucine supply modulates human duodenal mucosal proteome and decreases the expression of enzymes involved in fatty acid beta-oxidation.

Leucine is well known to regulate protein metabolism in muscle. We recently reported that enteral leucine infusion decreased proteasome activity in human duodenal mucosa and enhanced intestinal cell proliferation, but its effects on gut proteome remain unknown. Therefore, we aimed to assess the effects of an enteral leucine infusion on the whole proteome of duodenal mucosa. In this work, 5 healthy volunteers received for 5h, on 2 occasions and in random order, an enteral supply of maltodextrins (0.25 g kg(-1) h(-1)) or maltodextrins supplemented with leucine (0.035 g kg(-1) h(-1)). At the end of infusion, endoscopic duodenal biopsy samples were collected and analyzed by 2D-PAGE. Eleven protein spots were differentially and significantly (P<0.05) expressed in response to the leucine-supplemented maltodextrins compared with maltodextrins alone. Forty percent of identified proteins by mass spectrometry were located in mitochondria. Four proteins were involved in lipid metabolism: HADHA, ACADVL and CPT2 expressions were reduced, whereas FABP1 expression was increased. In addition, the expression of DHA kinase involved in glycerol metabolism was also downregulated. Finally, leucine supplementation altered the duodenal mucosal proteome by regulating the expression of several enzymes mainly involved in lipid metabolism. These results suggest that leucine supplementation may slowdown fatty acid beta-oxidation in human duodenal mucosa.

Inflammatory pseudotumor of the cerebellum in a patient with Crohn's disease.

BACKGROUND: Inflammatory pseudotumors are ubiquitous lesions characterized by a polymorphous inflammatory infiltrate containing plasma cells and lymphocytes. In the central nervous system, this pathological condition is rare and the association with Crohn's disease has never been described. CASE DESCRIPTION: A 31-year-old woman with a history of Crohn's disease was referred to our department for progressive headaches and nausea. Neurological examination was normal. Magnetic resonance imaging showed an irregular heterogeneous enhanced mass infiltrating the left cerebellar hemisphere. Total resection was performed and pathological examination led to the conclusion of an inflammatory pseudotumor. CONCLUSION: To our knowledge, this case is the first describing an intra-cerebral inflammatory pseudotumor associated with an inflammatory bowel disease. The diagnosis of an extradigestive location of Crohn's disease was excluded by pathological examination. Although the precise cause of this association remains unknown, it could be hypothesized that the intra-cranial lesion could be the result of the immunosuppressive therapy given for Crohn's disease, or, more likely, could be a part of a systemic dysimmune process.

Clinical predictors at diagnosis of disabling pediatric Crohn's disease.

BACKGROUND: Identification of children with Crohn's disease (CD) at high risk of disabling disease would be invaluable in guiding initial therapy. Our study aimed to identify predictors at diagnosis of a subsequent disabling course in a population-based cohort of patients with pediatric-onset CD. METHODS: Among 537 patients with pediatric CD diagnosed at <17 years of age, 309 (57%) with 5-year follow-up were included. Clinical and demographic factors associated with subsequent disabling CD were studied. Three definitions of disabling CD were used: Saint-Antoine and Liège Hospitals' definitions and a new pediatric definition based on the presence at maximal follow-up of: 1) growth delay defined by body mass index (BMI), weight or height lower than -2 SD Z score; and 2) at least one intestinal resection or two anal interventions. Predictors were determined using multivariate analyses and their accuracy using the kappa method considering a relevant value ≥ 0.6. RESULTS: According to the Saint-Antoine definition, the rate of disabling CD was 77% and predictors were complicated behavior and L1 location. According to the Liège definition, the rate was 37% and predictors included behavior, upper gastrointestinal disease, and extraintestinal manifestations. According to the pediatric definition, the rate of disabling CD was 15%, and predictors included complicated behavior, age <14, and growth delay at diagnosis. Kappa values for each combination of predictors were, respectively, 0.2, 0.3, and 0.2 and were nonrelevant. CONCLUSIONS: Clinical parameters at diagnosis are insufficient to predict a disabling course of pediatric CD. More complex models including serological and genetic biomarkers should be tested.

Excess primary intestinal lymphoproliferative disorders in patients with inflammatory bowel disease.

BACKGROUND: It remains to be shown whether inflammatory bowel disease (IBD) is associated with an increased risk of primary intestinal lymphoproliferative disorders (PILD). We assessed this risk in the CESAME French nationwide prospective observational cohort. METHODS: In all, 680 gastroenterologists enrolled 19,486 patients with IBD (Crohn's disease in 60.3%) from May 2004 to June 2005. Follow-up ended on 31 December 2007. Available biopsy samples and surgical specimens from patients with PILD (n = 14) were centralized for review. The reference incidence of PILD in the general population was obtained from the Côte d'Or registry and was used as a comparator to assess the standardized incidence ratio (SIR). The influence of thiopurine exposure was explored in a nested case-control study. RESULTS: In the CESAME population the crude incidence of PILD was 0.12/1000 patient-years, with a corresponding SIR of 17.51 (95% confidence interval [CI], 6.43-38.11; P < 0.0001). The risk was highest in patients exposed to thiopurines (SIR 49.52, 95% CI 13.49-126.8; P < 0.0001), while it did not reach statistical significance in patients naïve to thiopurines (SIR 4.83, 95% CI, 0.12-26.91; P = 0.37). The odds ratio associated with ongoing thiopurine exposure (vs. naïve) was 2.97 (95% CI, 0.30-infinity; P = 0.38). All 14 cases of PILD were non-Hodgkin's B-cell LD, 78.6% occurred in males, 85.7% arose in IBD lesions, and 45.5% were Epstein-Barr virus-positive. Eleven cases occurred in patients with Crohn's disease. Mean (SD) age at PILD diagnosis was 55.1 (5.6) years and the median time since IBD onset was 8.0 years (interquartile range, 3.0-15.8). CONCLUSIONS: Patients with IBD have an increased risk of developing PILD.

Effects of an enteral glucose supply on protein synthesis, proteolytic pathways, and proteome in human duodenal mucosa.

BACKGROUND: Previous studies have shown that the glucose supply reduces postoperative insulin resistance and improves patient outcomes. However, the effects of luminal glucose on intestinal mucosal proteins remain unknown. OBJECTIVE: We aimed to assess the effects of an enteral glucose supply on protein synthesis, proteolytic pathways, and proteome in human duodenal mucosa. DESIGN: Twenty healthy volunteers received a 5-h enteral infusion of either saline or glucose (0.12 g · kg(-1) · h(-1)). Simultaneously, a continuous intravenous infusion of l-[1-(13)C]leucine (12 µmol · kg(-1) · h(-1)) was maintained until endoscopy. The duodenal mucosal protein fractional synthesis rate (FSR) was calculated from leucine enrichments assessed in protein and free amino acid pools by gas chromatography-mass spectrometry. Cathepsin D, calpains, and chymotrypsin-like proteasome mucosal activities were evaluated by using specific fluorogenic substrates. A 2-dimensional PAGE-based comparative proteomics analysis was also performed on additional duodenal mucosal biopsy samples to identify differentially expressed proteins. RESULTS: Duodenal mucosal protein FSR and protease activities were not affected by glucose infusion relative to saline. Nevertheless, the comparative proteomics analysis indicated that 10 protein spots were significantly differentially expressed (ie, at least ±1.5-fold modulated; Student's t test, P < 0.05) in response to the glucose infusion relative to saline. Of the 8 proteins identified by mass spectrometry, α-enolase, cytoplasmic aconitate hydratase, and glutathione S-transferase ω-1 were upregulated, whereas epoxide hydrolase 2 was downregulated. CONCLUSION: Enteral glucose supply affected neither duodenal mucosal protein FSR nor activities of mucosal proteases but altered the duodenal mucosal proteome by modulating the expression of several enzymes involved mainly in carbohydrate and xenobiotic metabolism. This trial is registered at clinicaltrials.gov as NCT00213551.

Long-term outcome of treatment with infliximab in pediatric-onset Crohn's disease: a population-based study.

BACKGROUND: We examined short- and long-term benefits and safety of infliximab (IFX) in a population-based cohort of Crohn's disease (CD) patients <17 years old at diagnosis. METHODS: The following parameters were assessed: short- and long-term efficacy of IFX, impact of drug efficacy, and mode of administration on rate of resection surgery, growth and nutritional catch-up, and adverse events (AEs). RESULTS: In all, 120 patients (69 female) required IFX with a median duration of 32 months (Q1 = 8-Q3 = 60). Median age at diagnosis was 14.5 years (12-16) and median interval between diagnosis and IFX initiation was 41 months (22-78). Median follow-up since CD diagnosis was 111 months (75-161). Fifty patients (42%) received episodic and 70 (58%) maintenance therapy. Sixty-five (54%) patients were in the "IFX efficacy" group: 38 (32%) still receiving IFX at the last visit and 27 (22%) stopping IFX while in remission. The "IFX failure" group included 55 (46%) patients: 17 (14%) who stopped IFX due to AEs and 38 (32%) nonresponders. The risk of surgery was reduced (P = 0.009) in the "IFX efficacy" group and lower (P = 0.03) in patients with scheduled versus episodic therapy. Patients in the "IFX efficacy" group had significant catch-up growth (P = 0.04), while those in the "IFX failure" group did not. Twenty-four patients presented AEs leading to cessation of IFX in 17 of them. CONCLUSIONS: In this population-based cohort of pediatric-onset CD, IFX treatment was effective in more than half of patients during a median follow-up of 32 months. Long-term IFX responders had a lower rate of surgery and improved catch-up in growth, especially when receiving scheduled IFX therapy.

Pregnancy outcome in patients with inflammatory bowel disease treated with thiopurines: cohort from the CESAME Study.

BACKGROUND AND AIMS: Few studies have been conducted addressing the safety of thiopurine treatment in pregnant women with inflammatory bowel disease (IBD). The aim of this study was to evaluate the pregnancy outcome of women with IBD who have been exposed to thiopurines. METHODS: 215 pregnancies in 204 women were registered and documented in the CESAME cohort between May 2004 and October 2007. Physicians documented the following information from the women: last menstrual date, delivery term, details of pregnancy outcome, prematurity, birth weight and height, congenital abnormalities, medication history during each trimester, smoking history and alcohol ingestion. Data were compared between three groups: women exposed to thiopurines (group A), women receiving a drug other than thiopurines (group B) and women not receiving any medication (group C). RESULTS: Mean age at pregnancy was 28.3 years. 75.7% of the women had Crohn's disease and 21.8% had ulcerative colitis, with a mean disease duration of 6.8 years at inclusion. Of the 215 pregnancies, there were 138 births (142 newborns), and the mean birth weight was 3135 g. There were 86 pregnancies in group A, 84 in group B and 45 in group C. Interrupted pregnancies occurred in 36% of patients enrolled in group A, 33% of patients enrolled in group B, and 40% of patients enrolled in group C; congenital abnormalities arose in 3.6% of group A cases and 7.1% of group B cases. No significant differences were found between the three groups in overall pregnancy outcome. CONCLUSIONS: The results obtained from this cohort indicate that thiopurine use during pregnancy is not associated with increased risks, including congenital abnormalities.

Nutritional status and growth in pediatric Crohn's disease: a population-based study.

OBJECTIVES: Growth retardation and malnutrition are major features of pediatric Crohn's disease (CD). We examined nutritional and growth parameters from diagnosis to maximal follow-up in a population-based pediatric cohort, and we determined predictive factors. METHODS: A total of 261 patients (156 boys, 105 girls) with onset of CD before the age of 17 were identified from 1988 to 2004 through the EPIMAD registry (Registre des Maladies Inflammatoires Chroniques de l'Intestin) in northern France. Median age at diagnosis was 13 years (11.2-15.4) and median follow-up was 73 months (46-114). Z-scores of height/age, weight/age, and body mass index (BMI)/age were determined. Multivariate stepwise regression analysis identified predictive factors for malnutrition and growth retardation at maximal follow-up. RESULTS: At diagnosis, 25 children (9.5%) showed height less than -2 s.d., 70 (27%) weight less than -2 s.d., and 84 (32%) BMI less than -2 s.d. At maximal follow-up, growth retardation was present in 18 children (6.9%), whereas 40 (15%) had malnutrition. Nutritional status was more severely impaired in children with stricturing disease. Growth and nutritional retardation at diagnosis, young age, male gender, and extraintestinal manifestations at diagnosis were indicators of poor prognosis. A significant compensation was observed for weight and BMI in both genders and for height in girls. No treatment was associated with height, weight, or BMI at maximal follow-up. CONCLUSIONS: In our pediatric population-based study, growth retardation and severe malnutrition were still present at maximal follow-up in 6.9 and 15% of CD children, respectively. Young boys with substantial inflammatory manifestations of CD have a higher risk of subsequent growth failure, especially when growth retardation is present at diagnosis.

Mapping of inflammatory bowel disease in northern France: spatial variations and relation to affluence.

BACKGROUND: Geographic variations in the incidence of inflammatory bowel disease (IBD) may reflect variations in the distribution of environmental etiologic factors. We assessed spatial variation in the incidence of IBD in northern France and analyzed its association with a deprivation index. METHODS: All cases of IBD included in the EPIMAD registry between 1990 and 2003 were extracted. The standardized incidence ratio (SIR) was calculated for each canton in the region. The association between incidence and deprivation was assessed using the Townsend deprivation index. RESULTS: The mean annual incidence rates of Crohn's disease (CD) and ulcerative colitis (UC) were 6.2 x 10(-5) and 3.8 x 10(-5), respectively. The mean cumulative numbers of cases by canton were 18.4 (1-183) for CD and 11.3 (0-148) for UC. For both CD and UC, mapping depicted spatial heterogeneity in the SIR with spatial autocorrelation. A high relative risk (RR) of CD was observed in mainly rural and periurban cantons of the region. For UC, a high RR was found in cantons of the south and the center of Pas-de-Calais. No significant correlation was observed between spatial variations in IBD and deprivation. CONCLUSIONS: The incidence of IBD is associated with spatial heterogeneity in northern France. The noteworthy predominance of CD in agricultural areas warrants further investigations.

Jaundice revealing a k light chain myeloma because of liver light chain deposits.

We report the case of a 77-year-old man referred for jaundice and diagnosed with intrahepatic light chain deposit as primary manifestation of a kappa light chain multiple myeloma. Jaundice is a very rare way of presentation for myeloma. In our observation, diagnosis was made by liver biopsy, which found light chain deposits infiltrating perisinusoidal spaces. We discuss jaundice's possible mechanisms in myeloma.

The natural history of pediatric ulcerative colitis: a population-based cohort study.

OBJECTIVES: The natural history of ulcerative colitis (UC) has been poorly described in children. METHODS: In a geographically derived incidence cohort diagnosed from 1988 to 2002, we identified 113 UC patients (age 0-17 years at diagnosis) with a follow-up of at least 2 years. The cumulative risk of colectomy was estimated by the Kaplan-Meier method. Risk factors for disease extension were assessed with logistic regression models, and risk factors for colectomy with Cox hazards proportional models. RESULTS: Median follow-up time was 77 months (46-125). At diagnosis, 28% of patients had proctitis, 35% left-sided colitis, and 37% extensive colitis. Disease course was characterized by disease extension in 49% of patients. A delay in diagnosis of more than 6 months and a family history of inflammatory bowel disease were associated with an increased risk of disease extension, with odds ratios of 5.0 (1.2-21.5) and 11.8 (1.3-111.3), respectively. The cumulative rate of colectomy was 8% at 1 year, 15% at 3 years, and 20% at 5 years. The presence of extra-intestinal manifestations (EIMS) at diagnosis was associated with an increased risk of colectomy (hazard ratio (HR)=3.5 (1.2-10.5)). Among the patients with limited disease at diagnosis, the risk of colectomy was higher in those who experienced disease extension than in those who did not (HR=13.3 1.7-101.7). CONCLUSIONS: Pediatric UC was characterized by widespread localization at diagnosis and a high rate of disease extension. Twenty percent of children had their colon removed after 5 years. The colectomy rate was influenced by disease extension and was associated with the presence of EIMS at diagnosis.

Predicting factors of fistula healing and clinical remission after infliximab-based combined therapy for perianal fistulizing Crohn's disease.

UNLABELLED: Perianal fistulizing Crohn's disease (PFCD) treatment is based on fistula drainage, antibiotics, immunosuppressant (IS) drugs, and infliximab. Our aim was to study the effectiveness of combination therapy on PFCD and to search for clinical or imaging features associated with the initial complete clinical response and its stability overtime. PATIENTS AND METHODS: All patients with PFCD treated in our tertiary center between 2000 and 2005 by infliximab in combination with seton placement and/or IS and evaluated by MRI before treatment were included in the study. Basal clinical and MRI characteristics were recorded. Response to treatment was evaluated after the infliximab induction regiment and at the end of the follow-up. RESULTS: Twenty-six patients were included and followed-up for an average 4.9 years. A complex fistula was present in 69% (18/26 patients) of cases and eight (8/26 patients) had an ano-vaginal fistula. After infliximab induction therapy, 13 patients (50%) achieved a complete clinical response. The initial clinical response was significantly associated with the absence of both, active intestinal disease (54% vs. 8%, P = 0.03) and active proctitis (77% vs. 23%, P = 0.01). No initial MRI characteristics were linked to the initial response. In multivariate analysis, only the presence of active proctitis was associated with the lack of response (P = 0.047). At the end of the follow-up, 42% of the patients remained in clinical remission. No clinical characteristics were associated to sustained response when among long-standing responders two exhibited a normal post-treatment MRI. CONCLUSION: An initial complete response of PFCD was observed in half of the patients after combined therapy including infliximab that decreased to 42% later on. Complete healing of fistulas on MRI was possible but unusual. The initial response seemed related to the absence of active intestinal disease, especially in the rectum, when the long-term response could not be predicted by the basal characteristics of patients.

Azathioprine withdrawal in patients with Crohn's disease maintained on prolonged remission: a high risk of relapse.

BACKGROUND & AIMS: Azathioprine (AZA) withdrawal in Crohn's disease after long-term remission under treatment is controversial. In a Groupe d'Etude Thérapeutique des Affections Inflammatoires du tube Digestif randomized, double-blind, placebo-controlled trial, the hypothesis that AZA withdrawal was not inferior to AZA continuation in patients in prolonged clinical remission could not be shown. METHODS: A cohort of 66 patients in prolonged remission while being treated with AZA who stopped AZA, during or at the end of the randomized controlled trial, underwent long-term follow-up evaluation. The primary end point was clinical relapse. Prognostic factors of relapse were looked for through a proportional hazards model. RESULTS: Median durations of AZA therapy and of clinical remission were 68.4 months (interquartile range, 52.8-85.2 mo) and 63.6 months (interquartile range, 48.0-55.7 mo), respectively. The median follow-up time after AZA interruption was 54.5 months; 32 of 66 patients had a relapse. The cumulative probabilities +/- SE of relapse at 1, 3, and 5 years were 14.0% +/- 4.3%, 52.8% +/- 7.1%, and 62.7% +/- 7.2%, respectively. C-reactive protein concentration of 20 mg/L or greater (risk, 58.6; 95% confidence interval, 7.5-457; P = .002), hemoglobin level less than 12 g/dL (risk, 4.8; 95% confidence interval, 1.7-13.7; P = .04), and neutrophil count 4 x 10(9)/L or greater (risk, 3.2; 95% confidence interval, 1.6-6.3; P = .003) were associated independently with an increased risk of relapse. Among the 32 relapsing patients, 23 were retreated by AZA alone, all but 1 up to successful remission. CONCLUSIONS: Our results confirm that AZA withdrawal is associated with a high risk of relapse, whatever the duration of remission under this treatment. These data suggest that if AZA is well tolerated, it should not be interrupted.