Colorectal cancers are believed to arise predominantly from adenomas. Although these precancerous lesions have been subjected to extensive clinical, pathologic, and molecular analyses, little is currently known about the global gene expression changes accompanying their formation. To characterize the molecular processes underlying the transformation of normal colonic epithelium, we compared the transcriptomes of 32 prospectively collected adenomas with those of normal mucosa from the same individuals. Important differences emerged not only between the expression profiles of normal and adenomatous tissues but also between those of small and large adenomas. A key feature of the transformation process was the remodeling of the Wnt pathway reflected in patent overexpression and underexpression of 78 known components of this signaling cascade. The expression of 19 Wnt targets was closely correlated with clear up-regulation of KIAA1199, whose function is currently unknown. In normal mucosa, KIAA1199 expression was confined to cells in the lower portion of intestinal crypts, where Wnt signaling is physiologically active, but it was markedly increased in all adenomas, where it was expressed in most of the epithelial cells, and in colon cancer cell lines, it was markedly reduced by inactivation of the B-catenin/T-cell factor(s) transcription complex, the pivotal mediator of Wnt signaling. Our transcriptomic profiles of normal colonic mucosa and colorectal adenomas shed new light on the early stages of colorectal tumorigenesis and identified KIAA1199 as a novel target of the Wnt signaling pathway and a putative marker of colorectal adenomatous transformation.

Background: A validated endoscopic classification of diverticular disease (DD) of the colon is lacking at present. Our aim was to develop a simple endoscopic score of DD: the Diverticular Inflammation and Complication Assessment (DICA) score. Methods: The DICA score for DD resulted in the sum of the scores for the extension of diverticulosis, the number of diverticula per region, the presence and type of inflammation, and the presence and type of complications: DICA 1 (≤3), DICA 2 (4-7) and DICA 3 (>7). A comparison with abdominal pain and inflammatory marker expression was also performed. A total of 50 videos of DD patients were reassessed in order to investigate the predictive role of DICA on the outcome of the disease. Results: Overall agreement in using DICA was 0.847 (95% confidence interval, CI, 0.812-0.893): 0.878 (95% CI 0.832-0.895) for DICA 1, 0.765 (95% CI 0.735-0.786) for DICA 2 and 0.891 (95% CI 0.845-0.7923) for DICA 3. Intra-observer agreement (kappa) was 0.91 (95% CI 0.886-0.947). A significant correlation was found between the DICA score and C-reactive protein values (p = 0.0001), as well as between the median pain score and the DICA score (p = 0.0001). With respect to the 50 patients retrospectively reassessed, occurrence/recurrence of disease complications was recorded in 29 patients (58%): 10 (34.5%) were classified as DICA 1 and 19 (65.5%) as DICA 2 (p = 0.036). Conclusions: The DICA score is a simple, reproducible, validated and easy-to-use endoscopic scoring system for DD of the colon.

Background & Aims: Golimumab (GOL) has been recently approved in Italy for the treatment of ulcerative colitis (UC) unresponsive to standard treatments. Our aims were to assess the real-life efficacy and safety of GOL in managing UC outpatients in Italian primary Inflammatory Bowel Diseases (IBD) centres.Methods: Consecutive UC outpatients with at least 3-months follow-up were enrolled. Primary end-point was the induction and maintenance of remission in UC, defined as Mayo score ≤2, at 6-month follow-up.Results: Ninety-three patients were enrolled. At 6-month follow-up, remission was obtained in 34 (36.5%) patients. Shorter duration of disease was the only significant predictive factor of remission. Clinical response was achieved in 60 (64.5%) patients, while mucosal healing (MH) was obtained in 18 (19.3%) patients. Sixteen (47.0%) patients under remission were still under therapy with steroids. C-reactive protein and fecal calprotectin significantly dropped during the follow-up (p<0.001 for both proteins). Adverse events occurred in 4 (4.3%) patients and 3 of them stopped treatment. Colectomy was performed in only one patient (1.1%).Conclusions: Golimumab seems to be safe and effective in inducing and maintaining remission in real life UC outpatients.Abbreviations: ADA: Adalimumab; CRP: C-reactive Protein; GOL: Golimumab; FC: Fecal calprotectin; IBD: Inflammatory Bowel Diseases; IFX: Infliximab; IQR: Interquartile range; MH: Mucosal Healing; SC: Subcutaneously; TBC: Tuberculosis; TNFα: Tumor necrosis factor α; UC: Ulcerative Colitis.    

DICA classification is a valid parameter to predict the risk of diverticulitis occurrence/recurrence in patients suffering from diverticular disease of the colon.

Background Infliximab and adalimumab are widely used for the treatment of Crohn’s disease and ulcerative colitis. Aim To compare the long-term efficacy and safety of infliximab and adalimumab in a large cohort of Crohn’s disease and ulcerative colitis patients reflecting real-life clinical practice. Methods Seven hundred twelve patients were retrospectively reviewed, 410 with Crohn’s disease (268 treated with adalimumab and 142 with infliximab; median follow-up 60 months, range, 36–72) and 302 with ulcerative colitis (118 treated with adalimumab and 184 with infliximab; median follow-up 48 months, range, 36–84). Results In Crohn’s disease, clinical remission was maintained in 75.0% of adalimumab vs. in 72.5% of infliximab patients (P = 0.699); mucosal healing and steroid-free remission were maintained in 49.5% of adalimumab vs. 63.9% of infliximab patients (P = 0.077) and in 77.7% of adalimumab vs. 77.3% in infliximab group (P = 0.957), respectively. In ulcerative colitis, clinical remission was maintained in 50.0% of adalimumab vs. 65.8% of infliximab patients (P < 0.000); mucosal healing and steroid-free remission were maintained in 80.6% of adalimumab vs. 77.0% of infliximab patients (P = 0.494) and in 90.2% of adalimumab vs. 87.5% of infliximab patients (P = 0.662), respectively. At the multivariate analysis, ileocolonic location and simple endoscopic score for Crohn’s disease >10 were predictors of failure in Crohn’s disease; treatment with adalimumab, BMI ≥30 and Mayo score >10 were predictors of failure in ulcerative colitis. infliximab was more likely to cause adverse events than adalimumab (16.6 vs. 6.2%, P < 0.000). Conclusion Both adalimumab and infliximab are effective in long-term outpatients management of inflammatory bowel diseases. Adalimumab had a lower rate of adverse events.