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Development of Fistulae in Ileo-Anal Pouch does not Necessarily Indicate Crohn's Disease: Response

SUMMARY Background: Some evidence indicates that short-chain fatty acid (SCFA) enemas are effective in the treatment of distal ulcerative colitis. Methods: In a randomized, double-blind, placebo-controlled study, we tested the efficacy of a 6-week course of topical SCFA (100 mL, twice daily enemas of sodium acetate 80 mmol/L, sodium propionate 30 mmol/L and sodium butyrate 40 mmol/L) in 40 patients with mild to moderate distal colitis. Clinical, endoscopic and histological data were collected at the beginning and end of the study. Results: Fourteen patients on SCFA improved (overall score 11.3 ± 2.0 vs. 7.4 ± 3.5) as compared to five in the placebo group (overall score 10.0 ± 1.9 vs. 8.9 ± 2.5). In the SCFA-treated group all parameters significantly improved except the number of bowel motions, whereas no significant changes were recorded in the control group. A statistically significant difference between the two treatment regimens, however, was observed only for intestinal bleeding (P < 0.05), urgency (P < 0.02) and the patient self-evaluation score (P < 0.05). This was probably due to the random inclusion of more patients with moderate disease into the SCFA-treated group, thus causing pre-trial differences between the two groups. Conclusion: the present study confirms that irrigation with SCFA enemas is effective in distal colitis, and may represent an alternative therapeutic tool in the treatment of the disease.

The purpose of this work was to set up an in vitro model for the study of normal and pathological functions of the colonic epithelium. We have isolated colonic crypts by mild proteolytic digestion and mechanical dissociation of human biopsy material obtained during colonoscopy. The crypts, free of connective tissue, when placed in culture rapidly attached to the substrate and formed colonies containing over 95% of epithelial cells. Histochemical and ultrastructural characterization of the colonies showed the presence of both absorptive and secretory cells, exhibiting a high degree of differentiation. Proliferative activity occurred mostly during the first 24 h and progressively declined thereafter. The cells survived and maintained differentiated characteristics for at least three days in culture. This method can be used to study normal functions of the colonic epithelium. It may also be employed to investigate both noxious and protective factors in pathological conditions such as inflammatory bowel disease and colorectal neoplasia.

Purpose: Basiliximab (BSX) is a chimeric monoclonal antibody that binds with high affinity to CD25, thereby inhibiting IL-2 binding, and IL-2 mediated proliferation of lymphocytes. Evidence suggests that IL-2 plays a role in the development of steroid-resistant T lymphocytes, and an open label study of BSX in steroid-resistant ulcerative colitis (UC) suggested benefits in reduced disease activity and steroid dose. We sought to determine the efficacy and safety of BSX in steroid-refractory UC. Methods: Adults with moderate to severe (Mayo score ≥6 and endoscopic subscore ≥2) UC extending above the rectum despite at least 14 days of oral prednisone (PRED) 40 to 50 mg/d prior to study entry. Concomitant 5ASA, 6MP/AZA were permitted with stable doses. Subjects with systemic features of toxicity, or who had received infliximab or cyclosporine within 3 months, or IV steroids or rectally administered medications within 2 weeks, were excluded. The first 135 subjects were randomized 1:1:1 to blinded BSX 40 mg, 20 mg, or placebo (PBO) IV at weeks 0, 2, 4. An additional 14 subjects were randomized to BSX 40 mg or placebo groups after the first 135 subjects were enrolled. All subjects received PRED 30 mg/d po from day 0 to week 2, then tapered by 5 mg weekly to 20 mg/d, and maintained this dose till week 8. The primary analysis was a comparison of the rate of clinical remission (Mayo score ≤2, no subscore >1) in the BSX 40 mg group compared to PBO at week 8. Secondary analyses compared BSX 20 mg to PBO at week 8, and clinical response (decrease in Mayo score by ≥3) for both groups to PBO at week 8 using Cochran-Mantel-Haenzel test stratified by Mayo Score (≤10, >10), use of 6MP/AZA, and geographic region of study site. Subjects were followed until week 12 for safety. The study had 80% power to detect a difference of 21% assuming PBO clinical remission rate of 19% with a 2-sided alpha of 0.1. Results: A total of 149 subjects were randomized and received at least 1 dose of study drug. Results are shown in the table below. Six subjects (2 in each group) had serious adverse events, including 1 patient assigned to BSX 20 mg who died with disseminated tuberculosis and previously undiagnosed HIV. Forty-five percent of subjects who received BSX developed neutralizing anti-BSX antibodies. Conclusions: Basiliximab was not effective for steroid sensitization and induction of remission in outpatients with steroid-resistant moderate-to-severe UC.

Background and Aim: Seasonal variations have been shown to predispose to the development of a number of different diseases. Seasonal clustering of birth dates could support the hypothesis that exposure to seasonally varying environmental risk factors before or shortly after birth could partly responsible for the disease occurrence. A seasonal variation in birth dates among IBD patients was found by a number of studies but not confirmed by other. Aim of the present study was to evaluate whether an association exists among month and season of birth and the occurrence of CD. Patients and Method: A population of 340 consecutive CD patients (male: 193, 56.77%; female: 147, 43.23%; medium age: 51.2 years, range 20 91 years), followed up at our two GI Units from 1985 to 2006 was retrospectively considered. To test whether there was heterogeneity between the different months and seasons (that is, to test whether any significant departure from a uniform distribution had occurred) we used a c2 test and odds ratio (OR) with 95% confidence intervals (CI), taking into account the differences in the number of days in the months.

P221 Lack of association of previously identified disease loci 10q12, 11p15, and 20q13 in IBD A. Latiano1 *, E. Colombo1, O. Palmieri1, M.R. Valvano1, T. Latiano1, G. Corritore1, R. D’Inca2, M. Vecchi3, R. Caprilli4, S. Ardizzone5, S. Nobile6, D. De Venuto7, C. Sferlazzas8, A. Staiano9, V. Lodde10, G. Iacono11, C. Bascietto12, B. Papadatou13, A. Marseglia14, M. Castro13, S. Cucchiara12, V. Annese1. 1Unit of Gastroenterology, San Giovanni Rotondo, Italy, 2Unit of Gastroenterology, Padova, Italy, 3Unit of Gastroenterology, San Donato Milanese, Milano, Italy, 4Unit of Gastroenterology, “La Sapienza”, Roma, Italy, 5Unit of Gastroenterology, “Sacco”, Milano, Italy, 6Unit of Pediatrics of SIGENP (Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition), Ancona, Italy, 7SIGENP, Bari, Italy, 8SIGENP, Messina, Italy, 9SIGENP, Napoli, Italy, 10SIGENP, Padova, Italy, 11SIGENP, Palermo, Italy, 12SIGENP, “La Sapienza”, Roma, Italy, 13SIGENP, “Bambino Gesu”, Roma, Italy, 14SIGENP, San Giovanni Rotondo, Italy

P240 Association between non-synonymous variant in the MST1 gene and IBD in Italian population A. Latiano1 *, O. Palmieri1, M.R. Valvano1, R. D’Incaa2, T. Latiano1, G. Corritore1, E. Colombo1, M. Vecchi3, G. Riegler4, A. Ferraris5, G. de Angelis6, G. Lombardi7, C. Romano8, O. Borrelli9, P. Lionetti10, A. Barabino11, M. Pastore12, M. Castro13, S. Cucchiara9, V. Annese1. 1Unit of Gastroenterology, San Giovanni Rotondo, Italy, 2Unit of Gastroenterology, Padova, Italy, 3Unit of Gastroenterology, San Donato Milanese, Milano, Italy, 4Unit of Gastroenterology, Napoli, Italy, 5CSS, Mendel Institute, Roma, Italy, 6Units of Pediatrics of SIGENP (Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition), Parma, Italy, 7SIGENP, Pescara, Italy, 8SIGENP, Reggio Calabria, Italy, 9SIGENP, “La Sapienza”, Roma, Italy, 10SIGENP, Firenze, Italy, 11SIGENP, Genova, Italy, 12SIGENP, San Giovanni Rotondo, Italy, 13SIGENP, “Bambino Gesu”, Roma, Italy

AIM: To evaluate the possible differences in morphology and immunohistochemical expression of CD3, transforming growth factor β1(TGF-β1), Smad7, α-smooth muscle actin (α-Sma), and collagen types I-VII of small and large intestine in Smad3 null and wild-type mice. METHODS: Ten null and ten wild-type adult mice were sacrifi ced at 4 mo of age and the organs (esophagus, small and large bowel, ureters) were collected for histology(hematoxylin and eosin, Masson thrichrome, silver staining), morphometry and immunohistochemistry analysis. TGF-β1 levels of intestinal tissue homogenates were assessed by ELISA. RESULTS: No macroscopic intestinal lesions were detected both in null and wild-type mice. Histological and morphometric evaluation revealed a signifi cant reduction in muscle layer thickness of small and large intestine in null mice as compared to wild-type mice. Immunohistochemistry evaluation showed a signifi cant increase of CD3+T cell, TGF-β1 and Smad7 staining in the small and large intestine mucosa of Smad3 null mice as compared to wild-type mice. α-Sma and collagen I-VII staining of small and large intestine did not differ between the two groups of mice. TGF-β1 levels of colonic tissue homogenates were signifi cantly higher in null mice than in wildtype mice. In preliminary experiments a signifi cant reduction of TNBS-induced intestinal fi brosis was observed in null mice as compared to wild-type mice. CONCLUSION: Smad3 null mice are a useful model to investigate the in vivo role of the TGF-β/Smad signalling pathway in intestinal infl ammation and fi brosis.

Antiendomysial antibodies (EMA) are today considered the most sensitive and specific serological marker of celiac disease (CD). The aim of the present study was to assess the occurrence of EMA of IgG isotype in EMA IgA negative children with clinical suspicion of malabsorption and their relationship with CD. Serum EMA IgG1 determination was performed on 30 EMA IgA negative children with clinical suspicion of CD. Total serum IgA levels were further investigated. Sixty children with gastroenterological diseases other than CD were used as control disease patients and 63 healthy children were evaluated as the control group. Eighteen out of 30 children in the study showed EMA IgG1 positivity in sera and a villous height/crypt depth ratio