Post-operative recurrence of Crohn's disease after definitive stoma: an underestimated risk.

INTRODUCTION: Crohn's disease (CD) is a progressive inflammatory disease affecting the entire gastrointestinal tract. The need for a definitive stoma (DS) is considered as the ultimate phase of damage. It is often believed that the risk of further disease progression is small when a DS has been performed. AIMS: The goals of the study were to establish the rate of CD recurrence above the DS and to identify predictive factors of CD recurrence at the time of DS. METHODS: We retrospectively reviewed all medical records of consecutive CD patients having undergone DS between 1973 and 2010. We collected clinical data at diagnosis, CD phenotype, treatment, and surgery after DS and mortality. Stoma was considered as definitive when restoration of continuity was not possible due to proctectomy, rectitis, anoperineal lesions (APL), or fecal incontinence. Clinical recurrence (CR) was defined as the need for re-introduction or intensification of medical therapy, and surgical recurrence (SR) was defined as a need for a new intestinal resection. RESULTS: Eighty-three patients (20 males, 63 females) with a median age of 34 years at CD diagnosis were included. The median time between diagnosis and DS was 9 years. The median follow-up after DS was 10 years. Thirty-five patients (42%) presented a CR after a median time of 28 months (2-211) and 32 patients (38%) presented a SR after a median time of 29 months (4-212). In a multivariate analysis, APL (HR = 5.1 (1.2-21.1), p = 0.03) and colostomy at time of DS (HR = 3.8 (1.9-7.3), p = 0.0001) were associated factors with the CR. CONCLUSION: After DS for CD, the risk of clinical recurrence was high and synonymous with surgical recurrence, especially for patients with APL and colostomy.

Vaccination and Risk for Developing Inflammatory Bowel Disease: A Meta-Analysis of Case-Control and Cohort Studies.

BACKGROUND & AIMS: Environmental factors may play a key role in the pathogenesis of inflammatory bowel disease (IBD). Whether vaccination is associated causally with IBD is controversial. We performed a meta-analysis of case-control and cohort studies on the association between vaccination and the risk for IBD. METHODS: Studies and abstracts investigating the relationship between vaccination and subsequent risk for developing IBD were reviewed. Childhood or adult immunizations with any vaccine type, at any dose, and with any vaccine schedule were used as inclusion criteria. RESULTS: Eleven studies were included in the systematic review and meta-analysis: 8 case-control studies and 3 cohort studies. Studied vaccines were bacille Calmette-Guérin), vaccines against diphtheria, tetanus, smallpox, poliomyelitis, pertussis, H1N1, measles, rubella, mumps, and the combined measles, mumps, and rubella vaccine. Only a few details about vaccine type or route of administration were found in studies. Overall, there was no association between childhood immunization and risk for developing IBD: bacille Calmette-Guérin, relative risk (RR) of 1.04 (95% confidence interval [CI], 0.78-1.38), diphtheria, RR of 1.24 (95% CI, 0.80-1.94), tetanus, RR of 1.27 (95% CI, 0.77-2.08), smallpox, RR of 1.08 (95% CI, 0.70-1.67), poliomyelitis, RR of 1.79 (95% CI, 0.88-3.66), an measles containing vaccines, RR of 1.33 (95% CI, 0.31-5.80) in cohort studies, and RR of 0.85 (95% CI, 0.60-1.20) in case-control studies. Subgroup analysis for Crohn's disease (CD) and ulcerative colitis (UC) found an association between the poliomyelitis vaccine and risk for developing CD (RR, 2.28; 95% CI, 1.12-4.63) or UC (RR, 3.48; 95% CI, 1.2-9.71). The RR of developing IBD after H1N1 vaccination was 1.13 (95% CI, 0.97-1.32). CONCLUSIONS: Results of this meta-analysis show no evidence supporting an association between childhood immunization or H1N1 vaccination in adults and risk of developing IBD. The association between the poliomyelitis vaccine and the risk for CD or UC should be analyzed with caution because of study heterogeneity.

Eosinophilic enteritis.

BACKGROUND: Eosinophilic enteritis, also known as eosinophilic gastroenteritis, is a rare primary eosinophilic gastrointestinal disorder (EGID) of unknown etiology characterized by the presence of an intense eosinophilic infiltrate on histopathology of the intestinal mucosa. KEY MESSAGES: The etiology of eosinophilic enteritis remains obscure. There is growing evidence to support the role of aeroallergens and food allergens in the pathogenesis of this disorder as children and adults with EGIDs often have positive skin testing for food allergens and a familial history of allergic diseases. Moreover, significant progress has been made in elucidating that EGIDs involve mechanisms that fall between pure IgE-mediated and delayed Th2 type responses. Preclinical studies have identified a contributory role for the cytokine IL-5 and eotaxin chemokines, providing a rationale for specific disease therapy. Eosinophilic enteritis causes a wide array of gastrointestinal symptoms such as abdominal pain, diarrhea, nausea, vomiting, bloating or ascites, and its diagnosis requires a high degree of clinical likelihood given the nonspecific presentation and physical examination findings. The Klein classification arbitrarily divided patients with eosinophilic enteritis into those with predominantly mucosal, muscle layer or subserosal disease relying on the concept that clinical presentation is dependent on the predominant involved layer of the gastrointestinal tract. Main therapeutic options are represented by oral corticosteroids for a short period with good efficacy. Antihistaminic drugs and sodium cromoglycate have also been used to treat patients with eosinophilic enteritis. CONCLUSION: Eosinophilic enteritis is generally considered as a benign disease with no relapse, but half of the patients may present a more complex natural history characterized by unpredictable relapses and a chronic course.

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.

Glugacon-like peptide-2: broad receptor expression, limited therapeutic effect on intestinal inflammation and novel role in liver regeneration.

The glucagon-like peptide 2 (GLP-2) is an intestinotrophic hormone with growth promoting and anti-inflammatory actions. However, the full biological functions of GLP-2 and the localization of its receptor (GLP-2R) remain controversial. Among cell lines tested, the expression of GLP-2R transcript was detected in human colonic myofibroblasts (CCD-18Co) and in primary culture of rat enteric nervous system but not in intestinal epithelial cell lines, lymphocytes, monocytes, or endothelial cells. Surprisingly, GLP-2R was expressed in murine (GLUTag), but not human (NCI-H716) enteroendocrine cells. The screening of GLP-2R mRNA in mice organs revealed an increasing gradient of GLP-2R toward the distal gut. An unexpected expression was detected in the mesenteric fat, mesenteric lymph nodes, bladder, spleen, and liver, particularly in hepatocytes. In two mice models of trinitrobenzene sulfonic acid (TNBS)- and dextran sulfate sodium (DSS)-induced colitis, the colonic expression of GLP-2R mRNA was decreased by 60% compared with control mice. Also, GLP-2R mRNA was significantly downregulated in intestinal tissues of inflammatory bowel disease patients. Therapeutically, GLP-2 showed a weak restorative effect on intestinal inflammation during TNBS-induced colitis as assessed by macroscopic score and inflammatory markers. Finally, GLP-2 treatment accelerated mouse liver regeneration following partial hepatectomy as assessed by histological and molecular analyses. In conclusion, the limited therapeutic effect of GLP-2 on colonic inflammation dampens its utility in the management of severe inflammatory intestinal disorders. However, the role of GLP-2 in liver regeneration is a novelty that might introduce GLP-2 into the management of liver diseases and emphasizes on the importance of elucidating other extraintestinal functions of GLP-2.

The 5-aminosalicylic acid antineoplastic effect in the intestine is mediated by PPARγ.

Epidemiological evidences suggested that 5-aminosalicylic acid (5-ASA) therapy may prevent the development of colorectal cancer in inflammatory bowel disease patients. Our aim is to investigate whether peroxisome proliferator-activated receptor-γ (PPARγ) mediates the antineoplastic effects of 5-ASA. HT-29 and Caco-2 cells were treated by 5-ASA, rosiglitazone (PPARγ ligand) or etoposide (anticarcinogenic drug). Epithelial cell growth, proliferation and apoptosis were assessed by cell count, Ki-67 staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, respectively. The antineoplastic effect of 5-ASA was evaluated in a xenograft tumor model in SCID mice and in azoxymethane (AOM)-induced colon carcinogenesis in A/JOlaHsd mice. The role of PPARγ was examined by administration of PPARγ antagonist, GW9662 and in PPAR knockdown cells. Compared with untreated cells, treatment of HT-29 cells by 5-ASA inhibited significantly cell growth and cell proliferation (respectively, 60% and 63%) and induced apoptosis in 75% of cells. These effects were abolished by co-treatment with GW9662 and blunted in PPAR knockdown cells. Contrarily to etoposide, similar inhibitory effects of GW9662 were obtained in HT-29 cells treated with rosiglitazone. In the xenograft model, GW9662 abolished the therapeutic effect of 5-ASA, which decreased tumor weight and volume by 80% in SCID mice compared with untreated mice. In A/JOlaHsd mice, 5-ASA suppressed colon carcinogenesis by decreasing the number of aberrant crypt foci (75%) and aberrant crypts (22%) induced by AOM treatment with an absence of 5-ASA response after GW9662 administration. In conclusion, 5-ASA exerts potent antineoplastic effects that are mediated through PPARγ. These data provide new rational for designing more effective and safe antineoplastic PPARγ ligands with topical effects.

Placental transfer of anti-tumor necrosis factor agents in pregnant patients with inflammatory bowel disease.

BACKGROUND & AIMS: Some women with inflammatory bowel disease require therapy with tumor necrosis factor (TNF) antagonists during pregnancy. It is not clear whether these drugs are transferred to the fetus via the placenta and then cleared, or whether structurally different TNF antagonists have different rates of transfer. METHODS: We studied 31 pregnant women with inflammatory bowel disease receiving infliximab (IFX, n = 11), adalimumab (ADA, n = 10), or certolizumab (CZP, n = 10). Serum concentrations of the drugs were measured at birth in the mother, infant, and in cord blood, and then monthly in the infant until the drugs were undetectable. Drug concentrations in the cord and the infant at birth were compared with those of the mother. RESULTS: Concentrations of IFX and ADA, but not CZP, were higher in infants at birth and their cords than in their mothers. The levels of CZP in infants and their cords were less than 2 µg/mL. The median level of IFX in the cord was 160% that of the mother, the median level of ADA in the cord was 153% that of the mother, and the median level of CZP in the cord was 3.9% that of the mother. IFX and ADA could be detected in the infants for as long as 6 months. No congenital anomalies or serious complications were reported. CONCLUSIONS: The TNF antagonists IFX and ADA are transferred across the placenta and can be detected in infants at birth; the drugs were detected in infants up to 6 months after birth. CZP has the lowest level of placental transfer, based on levels measured in cords and infants at birth, of the drugs tested.

Epidemiology and natural history of inflammatory bowel diseases.

In the West, the incidence and prevalence of inflammatory bowel diseases has increased in the past 50 years, up to 8-14/100,000 and 120-200/100,000 persons, respectively, for ulcerative colitis (UC) and 6-15/100,000 and 50-200/100,000 persons, respectively, for Crohn's disease (CD). Studies of migrant populations and populations of developing countries demonstrated a recent, slow increase in the incidence of UC, whereas that of CD remained low, but CD incidence eventually increased to the level of UC. CD and UC are incurable; they begin in young adulthood and continue throughout life. The anatomic evolution of CD has been determined from studies of postoperative recurrence; CD begins with aphthous ulcers that develop into strictures or fistulas. Lesions usually arise in a single digestive segment; this site tends to be stable over time. Strictures and fistulas are more frequent in patients with ileal disease, whereas Crohn's colitis remains uncomplicated for many years. Among patients with CD, intestinal surgery is required for as many as 80% and a permanent stoma required in more than 10%. In patients with UC, the lesions usually remain superficial and extend proximally; colectomy is required for 10%-30% of patients. Prognosis is difficult to determine. The mortality of patients with UC is not greater than that of the population, but patients with CD have greater mortality than the population. It has been proposed that only aggressive therapeutic approaches, based on treatment of early recurrent lesions in asymptomatic individuals, have a significant impact on progression of these chronic diseases.

Intestinal antiinflammatory effect of 5-aminosalicylic acid is dependent on peroxisome proliferator-activated receptor-gamma.

5-aminosalicylic acid (5-ASA) is an antiinflammatory drug widely used in the treatment of inflammatory bowel diseases. It is known to inhibit the production of cytokines and inflammatory mediators, but the mechanism underlying the intestinal effects of 5-ASA remains unknown. Based on the common activities of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligands and 5-ASA, we hypothesized that this nuclear receptor mediates 5-ASA therapeutic action. To test this possibility, colitis was induced in heterozygous PPAR-gamma(+/-) mice and their wild-type littermates, which were then treated with 5-ASA. 5-ASA treatment had a beneficial effect on colitis only in wild-type and not in heterozygous mice. In epithelial cells, 5-ASA increased PPAR-gamma expression, promoted its translocation from the cytoplasm to the nucleus, and induced a modification of its conformation permitting the recruitment of coactivators and the activation of a peroxisome-proliferator response element-driven gene. Validation of these results was obtained with organ cultures of human colonic biopsies. These data identify PPAR-gamma as a target of 5-ASA underlying antiinflammatory effects in the colon.

Natural history of eosinophilic gastroenteritis.

BACKGROUND & AIMS: Eosinophilic gastroenteritis (EGE) is a rare gastrointestinal disorder; little is known about its natural history. We determined the clinical features and long-term outcomes of patients with EGE. METHODS: We reviewed files from 43 patients diagnosed with EGE who were followed from January 1988 to April 2009. The diagnosis was made according to standard criteria after other eosinophilic gastrointestinal disorders were excluded. We analyzed data on initial clinical presentation and long-term outcomes. RESULTS: EGE was classified as mucosal, subserosal, or muscular in 44%, 39%, and 12% of cases, respectively. Disease location was mostly duodenal (62%), ileal (72%), or colonic (88%); it was less frequently esophageal (30%) or gastric (38%). Blood eosinophilia (numbers >500/mm(3)) was observed in 74% of cases. Spontaneous remission occurred in 40% of patients; the majority of treated patients (74%) received oral corticosteroids, which were effective in most cases. After a median follow-up period of 13 years (0.8-29 years), we identified 3 different courses of disease progression: 18 patients (42%; 9 with subserosal disease) had an initial flare of the disease without relapse, 16 (37%) had multiple flares that were separated by periods of full remission (recurring disease), and 9 (21%) had chronic disease. CONCLUSIONS: The clinical presentation of EGE is heterogeneous and varies in histologic pattern; about 40% of patients resolve the disease spontaneously, without relapse. Approximately 50% have a more complex disease, which is characterized by unpredictable relapses and a chronic course.

Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study.

BACKGROUND: Reports of an increased risk of lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease are controversial. We assessed this risk in a prospective observational cohort study. METHODS: 19,486 patients with inflammatory bowel disease, of whom 11,759 (60.3%) had Crohn's disease and 7727 (39.7%) had ulcerative colitis or unclassified inflammatory bowel disease, were enrolled in a nationwide French cohort by 680 gastroenterologists, who reported details of immunosuppressive therapy during the observation period, cases of cancer, and deaths. The risk of lymphoproliferative disorder was assessed according to thiopurine exposure. Median follow-up was 35 months (IQR 29-40). FINDINGS: At baseline, 5867 (30.1%) of patients were receiving, 2809 (14.4%) had discontinued, and 10,810 (55.5%) had never received thiopurines. 23 new cases of lymphoproliferative disorder were diagnosed, consisting of one case of Hodgkin's lymphoma and 22 cases of non-Hodgkin lymphoproliferative disorder. The incidence rates of lymphoproliferative disorder were 0.90 per 1000 (95% CI 0.50-1.49) patient-years in those receiving, 0.20/1000 (0.02-0.72) patient-years in those who had discontinued, and 0.26/1000 (0.10-0.57) patient-years in those who had never received thiopurines (p=0.0054). The multivariate-adjusted hazard ratio of lymphoproliferative disorder between patients receiving thiopurines and those who had never received the drugs was 5.28 (2.01-13.9, p=0.0007). Most cases associated with thiopurine exposure matched the pathological range of post-transplant disease. INTERPRETATION: Patients receiving thiopurines for inflammatory bowel disease have an increased risk of developing lymphoproliferative disorders. FUNDING: Programme Hospitalier de Recherche Clinique National (AOM05157), Association François Aupetit, Délégation Inter-régionale de la Recherche clinique Ile de France-Assistance Publique Hôpitaux de Paris (AP-HP), Ligue contre le Cancer, and Fonds de Recherche de la Société Nationale Française de Gastro-entérologie.

Severe skin lesions cause patients with inflammatory bowel disease to discontinue anti-tumor necrosis factor therapy.

BACKGROUND & AIMS: Psoriasiform and eczematiform lesions are associated with anti-tumor necrosis factor (TNF)-α therapies. We assessed clinical characteristics, risk factors, and outcomes of skin disease in patients with inflammatory bowel diseases that presented with psoriasiform and eczematiform lesions induced by anti-TNF-α agents. METHODS: We studied 85 patients (69 with Crohn's disease, 15 with ulcerative colitis, and 1 with indeterminate colitis; 62 women) with inflammatory skin lesions (62 psoriasiform and 23 eczematiform lesions). RESULTS: Twenty-four patients had a history of inflammatory skin lesions and 15 had a familial history of inflammatory skin disease. Locations of eczematiform lesions varied whereas scalp and flexural varieties were mostly psoriasiform. Skin lesions emerged but inflammatory bowel disease was quiescent in 69 patients following treatment with any type of anti-TNF-α agent (60 with infliximab, 20 with adalimumab, and 5 with certolizumab). Topical therapy resulted in partial or total remission in 41 patients. Patients with psoriasiform lesions that were resistant to topical therapy and that changed anti-TNF-α therapies once or twice developed recurring lesions. Overall, uncontrolled skin lesions caused 29 patients to stop taking TNF-α inhibitors. CONCLUSIONS: Inflammatory skin lesions following therapy with TNF-α inhibitors occurred most frequently among women and patients with a personal or familial history of inflammatory skin disease; lesions did not correlate with intestinal disease activity. Recurring and intense skin lesions caused 34% of patients in this study to discontinue use of anti-TNF-α agents.

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.

Natural history of pediatric Crohn's disease: a population-based cohort study.

BACKGROUND & AIMS: The natural history of pediatric Crohn's disease and risk factors necessitating surgery have not been thoroughly described. METHODS: In a geographically derived incidence cohort diagnosed from 1988 to 2002, we identified 404 Crohn's disease patients (ages, 0-17 years at diagnosis) with a follow-up time >or=2 years. RESULTS: Median follow-up time was 84 months (range, 52-124 months). The most frequent disease location at diagnosis was the terminal ileum/colon (63%). Follow-up was characterized by disease extension in 31% of children. Complicated behavior was observed in 29% of children at diagnosis and 59% at follow-up. Kaplan-Meier survival estimates of the cumulative incidence of surgery were 20% at 3 years and 34% at 5 years from diagnosis. Multivariate Cox models showed that both structuring behavior at diagnosis (hazard ratio [HR], 2.54; 95% confidence interval [CI]: 1.58-4.01) and treatment with corticosteroids (HR, 2.98; 95% CI: 1.64-5.41) were associated with increased risk for surgery, whereas treatment with azathioprine (HR, 0.51; 95% CI: 0.33-0.78) was associated with decreased risk. Azathioprine was introduced earlier in the course of disease in patients not undergoing surgery than in patients requiring surgery. CONCLUSIONS: Pediatric Crohn's disease was characterized by frequent occurrence, with time, of a severe phenotype with extensive, complicated disease. Immunosuppressive therapy may improve the natural history of this disease and decrease the need for performing surgery.

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.

Mesalamine foam enema versus mesalamine liquid enema in active left-sided ulcerative colitis.

AIM: To determine in a noninferiority study whether mesalamine foam is as effective as mesalamine liquid enema for inducing clinical remission in patients with active left-sided ulcerative colitis (UC). METHODS: In a multicenter investigator-blind trial, 375 patients with mild-to-moderate UC were randomized to receive mesalamine foam 1 g/80 mL/day or mesalamine liquid enema 1 g/100 mL/day for 4 wk (W). Inclusion criteria were: disease extension at least 5 cm from anorectal junction and not above splenic flexure and Clinical Activity Index (CAI) 1-4 > or = 4. Primary end point was clinical remission at W4 defined as a CAI 1-4 < or = 2. Noninferiority of the foam to liquid enema was declared if the lower limit of the 97.5% unilateral confidence interval (97.5% CI) of the difference in remission rates between foam and liquid enema groups was greater than -15% . RESULTS: Remission rates at W4 in foam versus liquid were 68.3%versus 73.6% in per protocol (PP) population (lower limit of 97.5% CI -15.1%) and 66.7%versus 70.5% in intention-to-treat (ITT) population (97.5% CI -13.4%). Remission rates at W2 were 48.1 %versus 50.6% in ITT (97.5% CI -12.8%) and 49.1%versus 52.1% in PP (97.5% CI -13.8%) in foam versus liquid, respectively. Both treatments were well tolerated. CONCLUSIONS: A 4-wk treatment of 1 g mesalamine foam induced a clinical remission in 68% patients versus 73% with 1 g mesalamine liquid enema. Although the noninferiority of mesalamine foam could not be strictly demonstrated at W4 in the PP analysis, it was achieved in the ITT population and at W2 in both populations. Mesalamine foam represents a therapeutic alternative to mesalamine liquid enema in patients with mild-to-moderate active proctitis and proctosigmoiditis.

[Epidemiology and risk factors of inflammatory bowel diseases]. / Epidémiologie et facteurs de risque des maladies inflammatoires chroniques de l'intestin.

Inflammatory bowel diseases (IBD) are a public health problem in industrialized countries, where 1 in 1000 people are affected Most patients are young adults. The incidence of IBD has increased considerably in western countries since the second world war but is beginning to level off. On the other hand, the incidence is still rising in low-incidence areas such as Eastern Europe, Asia and developing countries. Differences in incidence rates across age, time, and geographic areas suggest that environmental factors are involved in IBD, but only cigarette smoking and appendectomy have consistently been identified as risk factors. An important role of genetic factors in IBD was first suggested by epidemiological studies showing familial aggregation of IBD and by twin studies. In 2001, the first CD susceptibility gene, NOD2/CARD15 on chromosome 16, was characterized. Other susceptibility genes have since been located. Their identification should help to understand the complex interaction between the environment and the intestinal immune system.

Previous Exposure to Multiple Anti-TNF Is Associated with Decreased Efficiency in Preventing Postoperative Crohn's Disease Recurrence.

BACKGROUND AND AIMS: Infliximab and adalimumab are increasingly used to prevent postoperative recurrence in Crohn's disease patients. The impact of previous exposure to one or more anti-tumour necrosis factor [TNF] agents before surgery on the efficacy of anti-TNF therapy on postoperative recurrence is unknown. METHODS: We performed a retrospective analysis of Crohn's disease patients who underwent surgical bowel resection with anastomosis and prophylactic treatment with anti-TNF therapy between January 2005 and June 2013. RESULTS: A total of 57 consecutive Crohn's disease patients with bowel resection and anastomosis followed by prophylactic treatment with anti-TNF were included; 21 [37%] and 24 [42%] patients had a previous exposure to one and more than one anti-TNF agents, respectively; 39 patients [68%] had a surveillance colonoscopy. Cumulative rates of postoperative endoscopic recurrence at 2 years were 45.5% [26.6-69.6%] in patients exposed to two or more anti-TNFα as compared with 29.1% [11.5-48.1%] in patients exposed to one or to zero anti-TNFα before surgery [p = 0.07]. Cumulative rates of clinical recurrence at 1 year were 21.6% [9.6-44.4%] in patients exposed to two or more anti-TNFα as compared with 6.9% [1.8-25.1%] in patients exposed to zero or one anti-TNFα before surgery [p = 0.02]. Multivariable analysis identified smoking and previous exposure to two or more anti-TNFα as risk factors for Crohn's disease clinical or endoscopic postoperative recurrence (hazard ratio [HR] = 3.17; 95% confidence interval [CI]: 1.3-7.8, p = 0.01 and HR = 4.2; 95% CI: 1.8-10.2, p = 0.001, respectively). CONCLUSIONS: Previous exposure to two or more anti-TNF agents was associated with a higher risk of postoperative recurrence in Crohn's disease patients.

Colectomy with ileorectal anastomosis preserves female fertility in ulcerative colitis.

OBJECTIVES: Restorative proctocolectomy with ileoanal anastomosis (IPAA) is the surgical standard for patients with ulcerative colitis (UC). Significant reduction in female fertility and fecundity after IPAA has been shown in recent studies. In selected cases, colectomy with ileorectal anastomosis (IRA) is another surgical option. The aim of this study was to evaluate fertility in women with UC who underwent IRA. PATIENTS AND METHODS: This study included all women with UC who underwent IRA between 1962 and 1999 and who were 40 years old or younger at the time of surgery, and older than 18 years of age at the time of the interview. Data were collected using a structured telephone interview concerning reproductive behavior and waiting times to pregnancy. RESULTS: Among 40 eligible patients, 37 whose mean age at IRA was 28 years (range 11-39) answered the questionnaire. Twenty-two were unmarried, not wishful of pregnancy and/or already had children. Among 15 females wishing children after IRA, 10 (66%) became pregnant: one had therapeutic abortion, two had a miscarriage, four had 1 child, two had 2 children and one had 4 children. Five patients were sterile after IRA. CONCLUSION: These preliminary results suggest that IRA for UC preserves female fertility. If confirmed in other series this information should be provided to young women with UC before deciding surgical option.