The molecular landscape of colitis-associated carcinogenesis

In spite of the well-established histopathological phenotyping of IBD-associated preneoplastic and neoplastic lesions, their molecular landscape remains to be fully elucidated. Several studies have pinpointed the initiating role of longstanding/relapsing inflammatory insult on the intestinal mucosa, with the activation of different pro-inflammatory cytokines (TNF-\u3b1, IL-6, IL-10, IFN-\u3b3), chemokines and metabolites of arachidonic acid resulting in the activation of key transcription factors such as NF-\u3baB. Longstanding inflammation may also modify the intestinal microbiota, prompting the overgrowth of genotoxic microorganisms, which may act as further cancer promoters. Most of the molecular dysregulation occurring in sporadic colorectal carcinogenesis is documented in colitis-associated adenocarcinoma too, but marked differences have been established in both their timing and prevalence. Unlike sporadic cancers, TP53 alterations occur early in IBD-related carcinogenesis, while APC dysregulation emerges mainly in the most advanced stages of the oncogenic cascade. From the therapeutic standpoint, colitis-associated cancers are associated with a lower prevalence of KRAS mutations than the sporadic variant. Epigenetic changes, including DNA methylation, histone modifications, chromatin remodeling, and non-coding RNAs, are significantly involved in colitis-associated cancer development and progression. The focus now is on identifying diagnostic and prognostic biomarkers, with a view to ultimately designing patient-tailored therapie

Exercise and inflammatory bowel disease : immunological aspects

Effet de l'activité physique d'intensité modérée chez des sujets atteints d'affections intestinales inflammatoires : rectocolite hémorragique et maladie de Crohn. Effets sur les symptômes, sur le temps de transit intestinal, sur la perméabilité des parois intestinales. Effets immunitaires de l'exercice, effets sur l'activation de la fonction neutrophile, rôle dans la prévention des maladies de l'intestin d'après l'étude des données épidémiologiques, incidences sur l'état de santé et la qualité de vie des malades entre les crises inflammatoires ou après des interventions chirurgicales de résection d'une partie de l'intestin

Primary sclerosing cholangitis associated with inflammatory bowel disease: an observational study in a Southern Europe population focusing on new therapeutic options

BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease with a strong association with inflammatory bowel disease (IBD). Medical treatment for PSC is still disappointing, whereas immunomodulators and biologics have been proven to be effective in IBD. AIMS: This study aimed to analyze (i) the natural history of patients with PSC with or without IBD and (ii) the long-term efficacy of biologics in patients with PSC and concomitant IBD or rheumatological disorders. PATIENTS AND METHODS: This study included 92 consecutive PSC patients, 50 (54.3%) men and 42 (45.7%) women, with a mean age of 32.0\ub114.3 years at diagnosis and a mean follow-up duration of 103.8\ub186 months. Forty-nine (53.3%) patients had associated IBD (38 ulcerative colitis, 10 Crohn's disease, one indeterminate colitis). RESULTS: No significant differences were found between PSC patients with and without associated IBD in terms of liver transplantation, cancer, and death rates. Cholangiocarcinoma was only identified among patients with PSC alone, whereas other cancers (hepatocellular carcinoma, colorectal, and gallbladder cancer) were found only in the group with associated IBD. Five PSC patients were treated with biologic agents: three with adalimumab and one with infliximab for IBD or for rheumatoid arthritis, and one patient with rituximab for rheumatoid arthritis. Adalimumab decreased alkaline phosphatase in two of three patients after 6 and 12 months, infliximab reduced \u3b3-glutamyltransferase after 6 and 12 months, but liver function tests tended to deteriorate thereafter. Cholangiography changes remained stable in all patients. CONCLUSION: Biologic agents may improve liver function tests in PSC patients, but may be associated with adverse events including deterioration of liver function

Rectal Administration of Lactobacillus casei DG Modifies Flora Composition and Toll-Like Receptor Expression in Colonic Mucosa of Patients with Mild Ulcerative Colitis.

BACKGROUND: An imbalance in gut microbiota seems to contribute to the development of chronic inflammatory disorders of the gastrointestinal tract, such as ulcerative colitis (UC). Although it has been suggested that probiotic supplementation is an effective approach to colitis, its effects on intestinal flora and on mucosal cytokine balance have never been explored. AIM: To evaluate the effect of Lactobacillus casei (L. casei) DG, a probiotic strain, on colonic-associated microbiota, mucosal cytokine balance, and toll-like receptor (TLR) expression. METHODS: Twenty-six patients with mild left-sided UC were randomly allocated to one of three groups for an 8-week treatment period: the first group of 7 patients received oral 5-aminosalicylic acid (5-ASA) alone, the second group of 8 patients received oral 5-ASA plus oral L. casei DG, and the third group of 11 patients received oral 5-ASA and rectal L. casei DG. Biopsies were collected from the sigmoid region to culture mucosal-associated microbes and to assess cytokine and TLR messenger RNA (mRNA) levels by quantitative real-time polymerase chain reaction (RT-PCR). RESULTS: 5-ASA alone or together with oral L. casei DG failed to affect colonic flora and TLR expression in a significant manner, but when coupled with rectally administered L. casei DG, it modified colonic microbiota by increasing Lactobacillus spp. and reducing Enterobacteriaceae. It also significantly reduced TLR-4 and interleukin (IL)-1\u3b2 mRNA levels and significantly increased mucosal IL-10. CONCLUSIONS: Manipulation of mucosal microbiota by L. casei DG and its effects on the mucosal immune system seem to be required to mediate the beneficial activities of probiotics in UC patients

Gastrointestinal telangiectasia: a study by EGD, colonoscopy, and capsule endoscopy in 75 patients

BACKGROUND: The distribution of lesions in the gastrointestinal tract in patients with sporadic telangiectasia is at present unknown. PATIENTS AND METHODS: 75 patients with sporadic telangiectasia underwent esophagogastroduodenoscopy (EGD), capsule endoscopy, and colonoscopy. Endoscopic diagnosis of telangiectasia and gastrointestinal bleeding were required for enrollment in the study. Hemorrhagic diathesis, co-morbidity, number of blood transfusions, and subsequent management were also noted. RESULTS: 35 of the patients presented with gastroduodenal vascular lesions, 51 with small-bowel lesions, and 28 with colonic lesions. 67 % of patients in whom EGD found telangiectasia also presented small-bowel vascular lesions at capsule endoscopy and 43 % colonic lesions at colonoscopy. 54 % percent of patients with positive colonoscopy also presented gastroduodenal lesions and 48 % small-bowel lesions. Patients with known duodenal lesions were more likely to have small-bowel lesions at capsule endoscopy (odds ratio [OR] 10.19, 95 % CI 2.1 - 49.33, P = 0.003). Patients with associated diseases, such as liver cirrhosis, chronic renal failure, or heart valvulopathy, presented more severe disease requiring blood transfusions (OR 6.37, 95 % CI 1.39 - 29.2, P = 0.015). The number of blood transfusions correlated with the number of sites affected ( R = 0.35, P = 0.002). The detection of new lesions at capsule endoscopy allowed new treatment in 46 % of patients. Mean follow-up was 18 months. CONCLUSIONS: Sporadic telangiectasia is a multifocal disease potentially involving the whole digestive tract. Patients with duodenal telangiectasia show a higher risk of jejunal or ileal lesions. Capsule endoscopy is a useful diagnostic tool for the detection of such small-bowel vascular lesions, indicating a more specific prognosis and treatment strategy