A. Calafiore

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 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 Crohns 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.

Four cases of carcinoid tumour in Crohn's disease: coincidence or correlation?

Dear Editor:Inflammatoryboweldiseasesareassociatedwithanincreasedrisk of large and small bowel cancers.The association between Crohn’s disease and adenocarci-noma of the small intestine has been established, but therelation between Crohn’s and carcinoid tumours remains un-certain, although the diagnosis of carcinoid tumours has sig-nificantly increased in the last years.We describe four cases of carcinoid tumour diagnosed inpatients with Crohn’s disease followed at our IBD outpa-tients’ clinic.First case A 46-year-old male non-smoker presented with26 years history of ileocolonic Crohn ’s disease and psoriasis.The patient underwent several surgeries over these years, endingup with colectomy with ileal–rectal anastomosis. After that, thedisease has been poorly controlled by the therapy (mesalazine),andseveralsteroidscourseswereneeded.In2011,anabdominalCT scan showed a pre-anastomotic Crohn ’s disease relapse andan unexpected expansive mass in the left kidney. The patientunderwent resection of the anastomosis and left nephrectomy.Post-operative histology showed active ileal and rectal Crohn ’sdisease and papillary renal can cer type 1, with Fuhrman nucleargradeof2andnopyeluminfiltration.Noadjuvantchemotherapytreatment was set. Few months after, he presented a Crohn’srelapse,withtwentybowelmovementsperdaywithurgencyandsevere weight loss. He also repor ted unusual skin rushes aftersomekindoffoodconsumption, whichwereself-solving.Bloodtests were normal, except for a mild creatinine rise. The endos-copy revealed normal ileal mucosa with a small polyp, whichwas removed, regular anastomo sis and rectal erosions. Polyp ’shistology pointed out muscularis propria infiltrating cells withdiffuse positivity for neuroe ndocrine markers, includingchromograninAandCD56andlownuclearproliferationmarkerKi-67(<2%).Immunohistochemist rystainingforsomatostatin2receptor (SSTR2A) was positive. These findings resulted in thediagnosis of well-differentiated neuroendocrine tumour (NET)-G1 (G1 category according to the WHO 2010).An abdominal CT scan showed no signs of renal tumourlocal recurrence but thickened anastomotic wall andoedematous mesenteric fat. The SPECTscan with a somato-statin receptor marker as contrast agent pointed out a roundarea on the anterior abdominal wall, lymph node like.A second endoscopy detected severe endoscopic Crohn’srelapse associated with another polyp, which was positivefor a new carcinoid recurrence (NET-G1). The patientunderwent proctectomy with ileal stoma.Second case A 45-year-old male smoker presented with12 years history of ileocolonic Crohn’s disease and vitiligo.Crohn’s diagnosis was made after an emergency rightemicolectomy due to peritonitis. In 2011, he started to expe-rience obstructive symptoms with low response to steroids.The enteric MRI detected two stenotic segments of the pre-anastomotic ileum and a voluminous solid lesion (O70×40×70 mm) in the retroperitoneum, adjacent to thepancreatic head, duodenum and inferior caval vein. Histologyof CT-guided biopsy revealed a well-differentiated NET-G1.The patient was referred to the surgeon and underwent apancreatic duodenectomy (Whipple procedure) and resectionof the previous ileal colonic anastomosis. Post-operative his-tology pointed out an infiltrating neoplasia of the duodenumwall, next to the duodenal papilla. The pancreas was cancerfree as well as the surgical resection borders; two peri-duodenal lymph nodes were infiltrated. Neoplastic cells werediffusely positive for the neuroendocrine marker synap-tophysin and for the nuclear proliferation marker Ki-67(1 %). Immunohistochemistry staining for SSTR2A was

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-β 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.

P393 Combination of surgical therapy and local injections of adalimumab in treatment of complex perianal Crohn's disease

In the emergency subgroup (3 patients), mean LoHS was 27.66 days (range: 15 47 days). Two patients were on steroid treatment at time of surgery and one encountered postoperative complications. Conclusions: LoHS and incidence of postoperative complications are significantly raised in those patients undergoing emergency procedures for UC. Multiple drug therapy and the use of a biological agent or steroids at time of surgery do not appear to affect LoHS significantly in this small sample. More extensive data is needed to identify potentially modifiable presurgical factors influencing LoHS and a larger data set would increase reliability of results.

Medical Treatment of Ulcerative Colitis: Does Traditional Therapy Still Have a Role?

Ulcerative colitis (UC) is a chronic inflammatory disease which involves the colonic mucosa continuously starting from the rectum and progressively involving the entire colon. Its etiology is still unknown, although numerous studies have clarified the inflammatory mechanisms involved in the pathogenesis, allowing the development of new targeted drugs. Correct medical treatment requires the evaluation of disease extension, activity and behavior [1]. The Montreal classification allows extent to be defined into three subgroups: proctitis (when the inflammation is limited to the rectum), left-sided colitis (distal to the splenic flexure), and extensive or pancolitis (proximal to the splenic flexure) [2]. Drug formulation is chosen based on the disease extent: suppositories for proctitis, enemas for left-sided colitis and tablets for extensive colitis. Furthermore, patients with extensive colitis have a higher risk of colectomy or of developing colorectal...

The safety of beclomethasone dipropionate in the treatment of ulcerative colitis

ABSTRACT 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.

Probiotics, Prebiotics, and Antibiotics in IBD

The rationale for using probiotics, prebiotics, and antibiotics in IBD is based on convincing evidence that implicates intestinal bacteria in the pathogenesis of the disease.

P395 Re-induction regimen in Crohn's disease adalimumab failure or disease relapse after a first adalimumab course. A single centre experience

Background: Adalimumab (ADA) is a fully human monoclonal antibody targeting TNF-alfa with proven efficacy in the treatment of Crohn’s disease (CD). We evaluate the efficacy of a second new ADA induction regimen. Methods: Forty-six CD patients were treated with a second ADA induction regimen (40 patients with 160/80mg, 6 with 80/40mg) and maintenance with 40mg every other week (22 patients) or weekly (24 patients). Patients were divided into 3 groups: moderate CD relapses [Harvey Bradshaw score (HBI) >8] during ADA maintenance treatment after an initial response were defined as ‘secondary non responders’ (SNR), failures at week 12 of the first induction regimen as ‘primary non responders’ (PNR) and CD recurrences [HBI score >5] within 6 months after the first successful ADA course as ‘early relapses’ (ER). Three of them received azathioprine (AZA) plus ADA. Clinical response or remission were evaluated at week 12 [remission: HBI <4; response: 3-point reduction in the HBI vs baseline]. Results: Of 149 CD patients treated with ADA and followed prospectively, 46 patients [M/F: 24/22; mean age 31.7 years (18 63 years); median disease duration 7 years (0.3 18 years); disease location: 7 ileal, 23 ileo-colonic, 16 colonic; mean HBI at the baseline 11.9 (6 38)] were enrolled. Eighteen patients were SNR (mean first ADA treatment duration: 50 weeks), 14 were PNR (mean first ADA treatment duration:14 weeks) and 14 had an ER (mean first ADA treatment duration:77 weeks). Considering the overall group of patients, at week 12 remission was observed in 24 patients (52.2%), 10 patients (21.7%) had partial response, while 12 patients (26.1%) had no improvement. In the subgroup of SNR, 5 patients (27.8%) regained remission, 5 regained (27.8%) response, while 8 (44.4%) had no response. Seven patients (50.0%) out of the 14 PNR gained remission, 3 patients (21.4%) had a partial response and 4 patients (28.6%) had no response to the second ADA course. The 3 patients treated with ADA plus AZA achieved complete remission around week 24. All of the 14 ER patients responded to the second ADA course: 12 (85.7%) showed new complete remission, 2 patients (14.3%) had partial response. Conclusions: ADA re-induction regimen seems to be effective in patients who lost response during ADA maintenance treatment (SNR). Dose intensification with a new early induction regimen showed efficacy to gain response in PNR. A new induction regimen with ADA seems to be extremely effective to regain remission in patients with ER and previous ADA-response.