Can supplementation of phytoestrogens/insoluble fibers help the management of duodenal polyps in familial adenomatous polyposis?

Familial adenomatous polyposis (FAP) is an autosomal dominant inherited disorder, and prophylactic colectomy has been shown to decrease the incidence of colorectal cancer (CRC). Duodenal cancer and desmoids are now the leading causes of death in FAP. We evaluate whether 3 months of oral supplementation with a patented blend of phytoestrogens and indigestible insoluble fibers (ADI) help the management of FAP patients with ileal pouch-anal anastomosis (IPAA). In a prospective open label study, we enrolled 15 FAP patients with IPAA and duodenal polyps who underwent upper gastrointestinal endoscopy at baseline and after 3 months of treatment. The primary endpoint was the change in gene expression in polyp mucosa, whereas the secondary endpoint was the reduction in polyp number and size. After 3 months of ADI treatment, all patients showed a reduction in the number and size of duodenal polyps (P = 0.021). Analysis of the expression of CRC promoting/inhibiting genes in duodenal polyps biopsies demonstrated that different CRC-promoting genes (PCNA, MUC1 and COX-2) were significantly downregulated, whereas CRC-inhibiting genes (ER-ß and MUC2) were significantly upregulated after ADI treatment. In conclusion, ADI proved to be safe and effective, and its long-term effects on FAP patients need further investigation. Judging from the results we observed on COX-2 and miR-101 expression, the short-term effects of ADI treatment could be comparable with those obtained using COX-2 inhibitors, with the advantage of being much more tolerable in chronic therapies and void of adverse events.

The safety of beclomethasone dipropionate in the treatment of ulcerative colitis.

INTRODUCTION: Beclomethasone dipropionate (BDP) is a second-generation corticosteroid that uses novel drug technologies to ensure colonic targeting and potentially reducing systemic corticosteroid concentrations. It is approved for treatment of patients with mild-to-moderate ulcerative colitis (UC) who do not respond to mesalazine. The gut-selective mechanism of action has the potential to improve the safety profile of BDP compared with other conventional corticosteroids. Areas covered: We reviewed the mechanism of action, efficacy, and safety of BDP in the treatment of UC. The positioning of BDP in management algorithms is also discussed. Expert opinion: The highly selective mechanism of action of BDP restricts the steroid-related side effects. BDP is efficacious in the treatment of active UC. Topical formulation is the first choice in distal UC, while oral formulation is used in patients with an extensive involvement of the colon. The rates of adverse events (AE), serious AEs, and steroid-related side-effects are similar to placebo and mesalamine and slightly inferior to traditional corticosteroids.

Sporadic small bowel tumors detected by capsule endoscopy in patients with occult gastrointestinal bleeding.

Intestinal tumors represent less than 6% of digestive tumors, and, because of the limitations of intestinal investigations, these tumors are difficult to diagnose. In this context, capsule endoscopy has proven effective, especially in patients with obscure digestive bleeding. In a large series of patients undergoing capsule endoscopy, small bowel tumors are found in 2.4-8.9% of cases. The aim of this retrospective, single-center study, based on prospective database, is to evaluate the frequency of small bowel tumors detected by capsule endoscopy in patients with occult gastrointestinal bleeding. During 2004-2014, 849 consecutive patients underwent CE at our Department for occult gastrointestinal bleeding. Following capsule endoscopy, the medical records of the study population were reviewed. Results of double-balloon enteroscopy or surgery performed after capsule endoscopy were retrieved. Capsule endoscopy identified 55 small bowel tumors (6.5%), of which 28 malignancies (51%) and 27 benign neoplasms (49%) underwent surgery or endoscopic treatment. Malignancies included adenocarcinoma (18.7%), gastrointestinal stromal tumors (GIST) (12%) and lymphoma (6.7%). Benign neoplasms included dysplastic adenomatous polyps (36%) and hyperplastic polyps (25.3%). Non-neoplastic masses included one inflammatory polyp. Capsule retention occurred in four patients (5.3%) and the retained capsule was retrieved during surgery. In our experience neoplasms of small bowel are found in 6.5% of patients with occult gastrointestinal bleeding. Of these malignancies, small bowel neoplasms are found in 3.3% of cases. Capsule endoscopy is an effective and sensitive diagnostic tool, and plays an important role in the algorithm for the diagnostic workup of suspected small bowel tumors.

The role of Budesonide-MMX in active ulcerative colitis.

Traditional corticosteroids represent a well-established and effective treatment for active ulcerative colitis (UC). However, the severity of their systemic side effects, led in recent years to look for new steroid molecules that could reduce them, maximizing the anti-inflammatory activity. Budesonide has been one of the most studied steroid compounds and it has been approved for the treatment of mild to moderate active Crohn's disease (CD). In order to extend the release until the distally located inflammation, budesonide has been coupled with a controlled delivery system, called Multi-Matrix system (MMX), already successfully tested with oral mesalazine for the treatment of distal UC. After in vitro and in vivo models, the efficacy of Budesonide-MMX has been investigated in active UC with a first small phase II study, and partially encouraging results. This article will review the evidences on the use of budesonide in inflammatory bowel diseases and will discuss the role of Budesonide-MMX in active UC nowadays.

Oral beclomethasone dipropionate in chronic refractory pouchitis.

BACKGROUND: Pouchitis is the major long-term complication after ileal-pouch anal-anastomosis for ulcerative colitis. Ten to 15% of patients develop chronic pouchitis, either treatment responsive or treatment refractory. AIM: To evaluate the efficacy of oral beclomethasone dipropionate in inducing remission and improving quality of life in patients with chronic refractory pouchitis. METHODS: Ten consecutive patients with active pouchitis, not responding to 1-month antibiotic treatment, were treated with beclomethasone dipropionate 10 mg/day for 8 weeks. Clinical, endoscopic and histological evaluations were undertaken before and after treatment, according to the Pouchitis Disease Activity Index (PDAI). Remission was defined as a combination of PDAI clinical score of ≤2, endoscopic score of ≤1 and a total PDAI score of ≤4. The quality of life was assessed with the Inflammatory Bowel Disease Questionnaire (IBDQ). RESULTS: Eight of 10 patients (80%) achieved remission. The median total PDAI scores before and after therapy were, respectively, 12 (range 8-14) and 3 (range 2-9) (P<0.001). The median IBDQ score also significantly improved from 120 (range 77-175) to 175 (range 85-220) (p<0.001). CONCLUSION: Eight-week treatment with oral beclomethasone dipropionate appears effective in inducing remission in patients with active pouchitis refractory to antibiotic treatment.

Eviendep® reduces number and size of duodenal polyps in familial adenomatous polyposis patients with ileal pouch-anal anastomosis.

AIM: To evaluate if 3 mo oral supplementation with Eviendep® was able to reduce the number of duodenal polyps in familial adenomatous polyposis (FAP) patients with ileal pouch-anal anastomosis (IPAA). METHODS: Eleven FAP patients with IPAA and duodenal polyps were enrolled. They underwent upper gastrointestinal (GI) endoscopy at the baseline and after 3 mo of treatment. Each patient received 5 mg Eviendep twice a day, at breakfast and dinner time, for 3 mo. Two endoscopists evaluated in a blinded manner the number and size of duodenal polyps. Upper GI endoscopies with biopsies were performed at the baseline (T0) with the assessment of the Spigelman score. Polyps > 10 mm were removed during endoscopy and at the end of the procedure a new Spigelman score was determined (T1). The procedure was repeated 3 mo after the baseline (T2). Four photograms were examined for each patient, at T1 and T2. The examined area was divided into 3 segments: duodenal bulb, second and third portion duodenum. Biopsy specimens were taken from all polyps > 10 mm and from all suspicious ones, defined by the presence of a central depression, irregular surface, or irregular vascular pattern. Histology was classified according to the updated Vienna criteria. RESULTS: At baseline the mean number of duodenal detected polyps was 27.7 and mean sizes were 15.8 mm; the mean Spigelman score was 7.1. After polypectomy the mean number of duodenal detected polyps was 25.7 and mean sizes were 7.6 mm; the mean Spigelman score was 6.4. After 3 mo of Eviendep bid, all patients showed a reduction of number and size of duodenal polyps. The mean number of duodenal polyps was 8 (P = 0.021) and mean size was 4.4 mm; the mean Spigelman score was 6.6. Interrater agreement was measured. Lesions > 1 cm found a very good degree of concordance (kappa 0.851) and a good concordance was as well encountered for smaller lesions (kappa 0.641). CONCLUSION: Our study demonstrated that short-term (90 d) supplementation with Eviendep® in FAP patients with IPAA and with recurrent adenomas in the duodenal mucosa, resulted effective in reducing polyps number of 32% and size of 51%.

The role of antibiotics and probiotics in pouchitis.

Pouchitis is a non-specific inflammation of the ileal reservoir and the most common complication of proctocolectomy with ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis. Its frequency is related to the duration of the follow up, occurring in up to 50% of patients 10 years after IPAA in large series from major referral centers. Treatment of pouchitis is largely empirical and only small placebo-controlled trials have been conducted. The rationale for using probiotics and antibiotics in pouchitis is based on convincing evidence that implicates intestinal bacteria in the pathogenesis of this disease. Probiotics are living organisms, which, upon ingestion in certain numbers, exert health benefits beyond inherent basic nutrition. VSL#3, a highly concentrated cocktail of probiotics has been shown to be effective in the prevention of pouchitis onset and relapses. Antibiotics are the mainstay of treatment of pouchitis, and metronidazole and ciprofloxacin are the most common initial approaches, often with a rapid response. The use of antibiotics in pouchitis is largely justified although proper controlled trials have not been conducted.

Intestinal epithelial cells in inflammatory bowel diseases.

The pathogenesis of inflammatory bowel diseases (IBDs) seems to involve a primary defect in one or more of the elements responsible for the maintenance of intestinal homeostasis and oral tolerance. The most important element is represented by the intestinal barrier, a complex system formed mostly by intestinal epithelial cells (IECs). IECs have an active role in producing mucus and regulating its composition; they provide a physical barrier capable of controlling antigen traffic through the intestinal mucosa. At the same time, they are able to play the role of non-professional antigen presenting cells, by processing and presenting antigens directly to the cells of the intestinal immune system. On the other hand, immune cells regulate epithelial growth and differentiation, producing a continuous bi-directional cross-talk within the barrier. Several alterations of the barrier function have been identified in IBD, starting from mucus features up to its components, from epithelial junctions up to the Toll-like receptors, and altered immune responses. It remains to be understood whether these defects are primary causes of epithelial damage or secondary effects. We review the possible role of the epithelial barrier and particularly describe the role of IECs in the pathogenesis of IBD.