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Aliment Pharmacol Ther 2010; 32: 603–611 Background Cannabinoid (CB) receptors have been located in brain areas involved in the triggering of TLESRs as well as in the nodose ganglion from which vagal afferents emanate. The distribution of CB1 receptors has been investigated in the human gastrointestinal mucosa, as expression of inflammatory process. Aim To evaluate the CB1 expression in oesophageal mucosa. Methods A total of 87 consecutive subjects were enrolled: 10 controls, 39 NERD and 38 erosive oesophagitis. Eight specimens were taken from macroscopically normal mucosa. Five were processed by haematoxylin–eosin, MIB1/CB1 evaluation and three for the RNA and proteins extraction. Results The mean MIB1-LI value was 31% and 22% in NERD and ERD patients, respectively, compared to 68% in the healthy subjects. Mean CB1mRNA/GUSB mRNA value of the controls was 0.66, while in GERD patients, it was 0.28. In NERD and ERD, the mean values of CB1/GUSB were 0.38 and 0.17, respectively, with highly significant differences between the NERD vs. ERD groups. Semi-quantitative analysis of CB1 expression, performed with WB, shows in NERD patients a higher CB1 receptor expression than ERD patients. Conclusions With this study, we showed for the first time the presence of CB1 receptors in the human oesophageal epithelium. [ABSTRACT FROM AUTHOR]

Background 5-ASA-MMX® (1.2 g/tablet) is a 5-aminosalicylic acid formulation, designed for once-daily dosing in the treatment of ulcerative colitis. Aim To evaluate the efficacy and safety of 5-ASA-MMX (2.4 g/day, once daily), compared with Asacol® (2.4 g/day, twice daily) in the maintenance of left-sided UC, through a double-blind, double-dummy, parallel-group, randomized, comparator study. Methods In all, 331 patients with UC were randomized to receive either 5-ASA-MMX 2.4 g/day, once daily, or Asacol 2.4 g/day, twice daily, for 12 months. All patients were in remission for ≥1 month prior to the trial, with ≥1 documented relapse in the previous year. The co-primary endpoints of this study were the proportion of patients in clinical, and clinical and endoscopic remission following 12 months’ treatment. Results In the intent-to-treat population, excluding those with major protocol deviations, 68.0 and 65.9% patients in the 5-ASA-MMX and Asacol groups, respectively, were in clinical remission ( P = 0.69), and 60.9 and 61.7% of patients, respectively, were in clinical and endoscopic remission ( P = 0.89). Diary card data revealed statistically significant treatment differences favouring 5-ASA-MMX. Both treatments were similarly tolerated. Conclusions Once-daily 5-ASA-MMX is similarly effective with a comparable safety profile to Asacol administered twice daily, for the maintenance treatment of ulcerative colitis. [ABSTRACT FROM AUTHOR]

Background Pouchitis is a common long-term complication after ileal pouch anal anastomosis for ulcerative colitis. Chronic refractory pouchitis is a treatment-resistant condition that affects 5–15% of patients. Aim To test the hypothesis of a small bowel involvement using wireless capsule endoscopy. Material and methods This is a single-blind, prospective, cohort study. Twenty-four patients: 16 were patients with chronic refractory pouchitis and eight, with a macroscopically and histologically normal ileal pouch, were considered as control subjects. Diagnosis of pouchitis was confirmed using the pouchitis disease activity index. All subjects were submitted to wireless capsule endoscopy procedure. Within 2 weeks before wireless capsule endoscopy, patients underwent a pouch endoscopy and a small bowel follow-through. Re-examination of the colonic surgical and histological specimens was also performed. Results One patient with chronic pouchitis was excluded because of incomplete bowel cleaning. At small bowel follow-through of 16 patients, two subjects (13%) showed only a focal ectasia of the middle ileum and a substenosis of the pouch. At wireless capsule endoscopy all the 15 evaluable patients with chronic pouchitis (100%) showed diffuse lesions from duodenum to ileum consisting of aphthae, erosions, erythema, atrophy, cobblestone, deep/fissural ulcers. Conclusions This enteropathy needs further research, and wireless capsule endoscopy could be useful to show involvement of small bowel in patients with chronic pouchitis. [ABSTRACT FROM AUTHOR]

Background Pouchitis is the major long-term complication after ileal-pouch nal anastomosis for ulcerative colitis. Ten to 15% of patients develop a chronic pouchitis, either treatment responsive or treatment refractory. Aim To evaluate the efficacy of oral budesonide in inducing remission and improving quality of life in patients with chronic refractory pouchitis. Methods Twenty consecutive patients with active pouchitis, not responding after 1 month of antibiotic treatment were treated with budesonide controlled ileal release 9 mg/day for 8 weeks. Symptomatic, endoscopic and histological evaluations were undertaken before and after treatment according to Pouchitis Disease Activity Index. Remission was defined as a combination of Pouchitis Disease Activity Index clinical score of ≤2, endoscopic score of ≤1 and total Pouchitis Disease Activity Index score of ≤4. The quality of life was assessed with the Inflammatory Bowel Disease Questionnaire. Results Fifteen of 20 patients (75%) achieved remission. The median total Pouchitis Disease Activity Index scores before and after therapy were, respectively, 14 (range 9–16) and 3 (range 2–10) ( P < 0.001). The median Inflammatory Bowel Disease Questionnaire score also significantly improved from 105 (range 77–175) to 180 (range 85–220) ( P < 0.001). Conclusion Eight-week treatment with oral budesonide appears effective in inducing remission in patients with active pouchitis refractory to antibiotic treatment in this open-label study. [ABSTRACT FROM AUTHOR]

Abstract: Background: Topical beclomethasone diproprionate has shown efficacy in ulcerative colitis. Aim: To assess, in a multicenter, randomized, double-blind study, the tolerability and safety of topical beclomethasone diproprionate (3mg) enema and foam versus mesalazine (2g) enema and foam in mild–moderate distal ulcerative colitis. Patients: In 15 referral gastrointestinal units, 99 patients with distal ulcerative colitis were enrolled. This number was lower than planned according to the statistical analysis, due to a low recruitment rate. Methods: Patients were randomly assigned to random preparations (beclomethasone diproprionate enema, beclomethasone diproprionate foam, mesalazine enema, mesalazine foam) once nightly for 8 weeks, with clinical and endoscopical assessment (Disease Activity Index score) at baseline (T0), 4 (T4) and 8 weeks (T8). Results were expressed as median and range (95% confidence interval). The efficacy was assessed by comparing the Disease Activity Index value at T4 and T8 by using the Student''s t-test or the Wilcoxon–Mann–Whitney test. Results: Efficacy was comparable in the beclomethasone diproprionate or mesalazine groups at both T4 and T8 (response at T4: beclomethasone diproprionate 78% [95% confidence interval 0.6–0.8] versus mesalazine 79% [95% confidence interval 0.6–0.8]; T8: beclomethasone diproprionate 84% [95% confidence interval 0.7–0.9] versus mesalazine 90% [95% confidence interval 0.7–1.0]; p =n.s.; remission at T4: beclomethasone diproprionate 24% [95% confidence interval 0.1–0.3] versus mesalazine 28% [95% confidence interval 0.1–0.3]; remission at T8: beclomethasone diproprionate 36% [95% confidence interval 0.2–0.5] versus mesalazine 52% [95% confidence interval 0.3–0.6]; p =n.s.).The Disease Activity Index lowered at T4 and T8 versus T0 in the four groups (T4 versus T0: beclomethasone diproprionate foam Disease Activity Index 2 versus 6 p <0.0001; beclomethasone diproprionate enema 4 versus 6, mesalazine enema 3 versus 6, mesalazine foam 3.5 versus 7, p <0.001 for all three groups; T8 versus T0: p <0.01). The Disease Activity Index lowered at T8 versus T4 in the beclomethasone diproprionate enema and foam (Disease Activity Index: 2 versus 4 and 1 versus 4, respectively; p <0.05) and in the mesalazine enema (Disease Activity Index: 1.5, range 0–4 versus 3, range 0–12; p <0.01), but not in the mesalazine foam group (Disease Activity Index: 1, range 0–9 versus 3.5, range 0–8; p =n.s.). The safety profile was favourable for all groups. Conclusions: Beclomethasone diproprionate and mesalazine enema and foam show a comparable tolerability and efficacy in mild active distal ulcerative colitis. [Copyright &y& Elsevier]

About two-thirds of patients with ulcerative colitis have an inflammatory involvement distal to the splenic flexure and therefore may be effectively treated with topical treatment. This allows the delivery of the active drug directly to the site of inflammation, limiting the systemic absorption and the potential side effects. Topical aminosalicylate therapy is the most effective approach, provided that the formulation reaches the upper extent of the disease. Suppositories should be considered the treatment of choice for proctitis and distal sigmoiditis. A 1 g Pentasa-suppository once daily induces a quicker clinical and endoscopic remission and was better tolerated than a 500-mg suppository twice daily. Enemas, foams and gel, thanks to their proximal spread, should be the treatment of choice for proctosigmoiditis and left-sided colitis. Oral aminosalicylates are less effective than topical therapies for patients with active disease; however, a combination of oral and topical aminosalicylates can be successfully tried in refractory patients. Topical aminosalicylates also play an important role in the maintenance of remission, and the combination of oral plus rectal 5-aminosalicylate is superior to the single agent. Patients who prefer not to continue on long-term rectal therapy can be treated with oral aminosalicylates. [ABSTRACT FROM AUTHOR]

Background Percutaneous abscess drainage (PAD) is the current therapy for abdominal or pelvic collections. PAD has poorer curative rate for abscesses in Crohn's disease (CD), commonly complicated by wide fistulas and multiloculations. Methods We retrospectively evaluated abscess cure rate, complications and final outcome in 87 CD patients, 70 with spontaneous and 17 with postoperative pelvic abscesses, all treated with CT-guided PAD during the last 7 years. Results A 77% primary success rate and an 84.3% secondary success rate were obtained without major complications. The higher success rate for PAD was for postoperative (88.2%) rather than spontaneous abscesses (74.2%). Seventy-two percent of treated patients did not develop recurrent abscesses and underwent elective surgery up to 40 months later. Conclusions PAD in pelvic abscess complicating CD is an effective alternative to early surgery with satisfactory curative success rates. In unsuccessful cases, due to wide fistulas or postoperative anastomotic dehiscence, PAD helped in planning elective surgery, reducing surgical complications. [ABSTRACT FROM AUTHOR]

Background: The intestinal microbiota plays a critical role in the pathophysiology of pouchitis, a major complication after ileal pouch anal anastomosis in patients with ulcerative colitis. Recently, controlled trials have demonstrated that probiotics are effective in maintenance of remission in pouchitis patients. However, the mechanism by which therapy with probiotics works remains elusive. This study explores the role of the bacterial and fungal flora in a controlled trial for maintenance of remission in pouchitis patients with the probiotic VSL#3 compound. Methods: The mucosa associated pouch microbiota was investigated before and after therapy with VSL#3 by analysis of endoscopic biopsies using ribosomal DNA/RNA based community fingerprint analysis, clone libraries, real time polymerase chain reaction (PCR), and fluorescence in situ hybridisation. Patients were recruited from a placebo controlled remission maintenance trial with VSL#3. Results: Patients who developed pouchitis while treated with placebo had low bacterial and high fungal diversity. Bacterial diversity was increased and fungal diversity was reduced in patients in remission maintained with VSL#3 (p = 0.001). Real time PCR experiments demonstrated that VSL#3 increased the total number of bacterial cells (p=0.002) and modified the spectrum of bacteria towards anaerobic species. Taxa specific clone libraries for Lactobacilli and Bifidobacteria showed that the richness and spectrum of these bacteria were altered under probiotic therapy. Conclusions: Probiotic therapy with VSL#3 increases the total number of intestinal bacterial cells as well as the richness and diversity of the bacterial microbiota, especially the anaerobic flora. The diversity of the fungal flora is repressed. Restoration of the integrity of a "protective" intestinal mucosa related microbiota could therefore be a potential mechanism of probiotic bacteria in inflammatory barrier diseases of the lower gastrointestinal tract. [ABSTRACT FROM AUTHOR]

Background Clinicians often employ antibiotics in Crohn's disease. Rifaximin is active against bacteria frequently found in the intestinal mucosa of Crohn's disease patients. Aim To evaluate the difference in efficacy between once and twice/daily oral administration of rifaximin and placebo in the treatment of active Crohn's disease. Methods We enrolled 83 patients with mild-to-moderate Crohn's disease and randomized to three treatments for 12 weeks: Group A (rifaximin 800 mg o.d. + placebo), Group B (rifaximin 800 mg b.d.) and Group C (placebo b.d.). Results Clinical remission was achieved by 52% of Group B, 32% (A) and 33% (C). Clinical response was seen in 67% (B), 48% (A) and 41% (C), without reaching a statistically significant difference. Treatment failures were: 4% (B), 12% (A) and 33% (C), ( P = 0.010). Remission and response rates of rifaximin 800 mg b.d. were significantly higher than those of placebo and rifaximin 800 mg o.d. in patients with elevated C reactive protein values ( P < 0.05). Conclusions Rifaximin 800 mg b.d. was superior to placebo in inducing clinical remission of active Crohn's disease. Although this difference was not statistically significant, the number of the failures in the placebo group was significantly higher than those who received rifaximin 800 mg b.d. [ABSTRACT FROM AUTHOR]

PURPOSE: Perianal disease is a serious complication of Crohn' s disease and its surgical management is still controversial. It has been suggested that the local injection of inflixinlab has resulted in some potential benefit. This pilot study analyzed the feasibility and safety of such therapy in selected patients with severe perianal Crohn's disease. METHODS: The study included 15 patients with complex perianal Crohn's disease in which sepsis was not controllable using surgical and medical therapy. Among them, four had previously undergone intravenous infusion of influx- imab with no significant response, nine had contraindications for intravenous infusion, and two had associated stenosing ileitis and severe coloproctitis. The injection of 15 to 21 mg of inflixiniab, associated with surgical treatment, was performed at the internal and external orifices and along the fistula tract. Efficacy was measured by a complete morphologic evaluation using a personal score. RESULTS: No major adverse effects were reported. Ten of 15 patients healed after 3 to 12 infusions. CONCLUSIONS: Local injection of inflixiniab adjacent to the fistula tract of perianal Crohn's disease is safe and may help in fistula healing. A controlled, randomized trial is required to prove the value. [ABSTRACT FROM AUTHOR]

Background: ‘Probiotic’ bacteria are effective in treating some inflammatory bowel diseases. However which bacteria confer benefit and mechanisms of action remain poorly defined. Dendritic cells, which are pivotal in early bacterial recognition, tolerance induction, and shaping of T cell responses, may be central in mediating the effects of these bacteria. Aims: To assess effects of different probiotic bacteria on dendritic cell function. Methods: Human intestinal lamina propria mononuclear cells, whole blood, or an enriched blood dendritic cell population were cultured with cell wall components of the eight bacterial strains in the probiotic preparation VSL#3 (four lactobacilli, three bifidobacteria, and one streptococcal strains). Dendritic cells were identified and changes in dendritic cell maturation/costimulatory markers and cytokine production in response to probiotic bacteria were analysed by multicolour flow cytometry, in addition to subsequent effects on T cell polarisation. Results: VSL#3 was a potent inducer of IL-10 by dendritic cells from blood and intestinal tissue, and inhibited generation of Th1 cells. Individual strains within VSL#3 displayed distinct immunomodulatory effects on dendritic cells; the most marked anti-inflammatory effects were produced by bifidobacteria strains which upregulated IL-10 production by dendritic cells, decreased expression of the costimulatory molecule CD80, and decreased interferon-c production by T cells. VSL#3 diminished proinflammatory effects of LPS by decreasing LPS induced production of IL-12 while maintaining IL-10 production. Conclusions: Probiotic bacteria differ in their immunomodulatory activity and influence polarisation of immune responses at the earliest stage of antigen presentation by dendritic cells. [ABSTRACT FROM AUTHOR]