A. Viscido

Infliximab in severe ulcerative colitis: short-term results of different infusion regimens and long-term follow-up.

Severe ulcerative colitis is a life‐threatening disorder, despite i.v. glucocorticoids treatment. Infliximab has been proposed as a safe rescue therapy.

A new oral delivery system for 5-ASA: Preliminary clinical findings for MMx

Background: Multi‐matrix (MMx), a new delivery system for mesalazine, seems to release 5‐aminosalicyclic acid (5‐ASA) preferentially in the sigmoid colon. This study had 2 objectives: (1) to evaluate the therapeutic response to MMx in patients with active left‐sided disease and (2) to gain additional insights as to how the therapy would compare with topical 5‐ASA. Methods: Patients received either 1.2 g of 5‐ASA MMx three times per day plus placebo enema or 4 g of 5‐ASA enema plus placebo tablets for 8 weeks. The primary endpoint was clinical remission (clinical activity index ≤4) at 8 weeks. Secondary endpoints were endoscopic and histologic remissions. Results: Seventy‐nine patients were enrolled. Clinical remission rates at 4 and 8 weeks were 57.5% and 60.0% for patients treated with MMx and 68.4% and 50.0% for patients randomized to 5‐ASA enemas, respectively (95% confidence interval for the difference at 8 weeks, −12 to +32). Endoscopic remission was achieved by 45.0% of patients on 5‐ASA MMx and by 36.8% of those on enema, whereas 15.0% and 8% of patients, respectively, showed histologic remission. Compliance was 97.0% for oral and 87.5% for topical therapy. In the enema group, compliance was 88.0% for the patients in remission and 65.5% for those with active disease. Conclusions: Preliminary studies suggest that similar rates for induction of remission can be expected from 5‐ASA enemas and MMx for patients with left‐sided ulcerative colitis.

Small intestine contrast ultrasonography: an alternative to radiology in the assessment of small bowel disease.

Background: Radiology and transabdominal ultrasonography (TUS) are used in the evaluation of the small bowel; however, the former technique is limited by radiation exposure, and the latter by its inability to visualize the entire small bowel. Aim: To evaluate the diagnostic accuracy of small intestine contrast ultrasonography (SICUS) to assess the presence, number, site, and extension of small bowel lesions. Subjects and Methods: TUS, SICUS, and small bowel follow‐through (SBFT) were performed in 148 consecutive patients (78 women; age range, 12 to 89 yr), 91 with undiagnosed conditions, and 57 with previously diagnosed Crohns disease (CD). Results: In the undiagnosed patients, the sensitivity and specificity of TUS and SICUS were 57% and 100%, and 94.3% and 98%, respectively. In the CD patients, the sensitivity of TUS and SICUS was 87.3% and 98%, respectively. In comparison with SBFT, the extension of lesions was correctly assessed with SICUS and greatly underestimated with TUS. The concordance index between SBFT and SICUS for the number and site of lesions was 1 and 1 (P < 0.001), respectively, in undiagnosed patients, and 0.81 and 0.83 (P < 0.001), respectively, in CD patients. Between SBFT and TUS, the concordance index was 0.28 and 0.27 (not significant), respectively, in undiagnosed patients, and 0.28 and 0.31 (not significant), respectively, in CD patients. Conclusions: The diagnostic accuracy of SICUS is comparable to that of a radiologic examination, and is superior to that of TUS in detecting the presence, number, extension, and sites of small bowel lesions. These findings support the use of noninvasive SICUS for an initial investigation when small bowel disease is suspected and in the follow‐up of CD patients.

Two mesalazine regimens in the prevention of the post-operative recurrence of Crohn's disease: a pragmatic, double-blind, randomized controlled trial

Background : The role of mesalazine in preventing the clinical recurrence of Crohns disease after surgery has been shown in a meta‐analysis of all published studies. No clear relationship, however, has been shown between dosage and response.

Infliximab in refractory pouchitis complicated by fistulae following ileo-anal pouch for ulcerative colitis.

Aim:  To determine the efficacy of infliximab in the treatment of chronic refractory pouchitis complicated by fistulae following ileal pouch‐anal anastomosis for ulcerative colitis.

Cytomegalovirus infection in inflammatory bowel disease patients undergoing anti-TNFα therapy

BACKGROUND Cytomegalovirus infection and disease is associated with poor prognosis and steroid refractoriness in inflammatory bowel disease patients. The unfavourable effect of steroids and immunosuppressive therapy on CMV infection is well known but few data are available concerning anti-TNFalpha therapy (Infliximab). Aim of the study was to evaluate the presence and severity of CMV infection and disease in Infliximab-treated IBD patients. PATIENTS AND METHODS The severity of active CMV infection and disease was assessed in 11 consecutive patients with ileocolonic/colonic disease and 4 patients with ulcerative colitis before and after a standard 3-infusion course of Infliximab. Active CMV infection was evaluated by serology and diagnosed by means of pp65-antigenemia (pp65 AG), and quantification of CMV DNA isolated from biopsy specimens of colonic tissue. CMV disease was assessed on haematoxylin/eosin-stained colonic biopsies and immunohistochemical stains. RESULTS Of the 11 patients, nine were CMV seropositive. As far as concerns CMV infection, only one patient had positive pp65 AG, before and after Infliximab. CMV DNA was detected in the colonic biopsies of three patients. In 2, CMV DNA persisted also after therapy with 410 and 1300 copies/microg of DNA, respectively, albeit with no evidence of worsening of the colonic disease. In the remaining patient, CMV DNA load became undetectable. Conventional histology and immunohistochemical stains were negative for CMV in all the patients, without evidence of CMV disease. CONCLUSIONS Active CMV infection did not progress to disease following Infliximab therapy. Although these preliminary observations require confirmation, the response to Infliximab therapy does not appear to be influenced by, or influence the course of, CMV infection/disease.

Anti-tissue transglutaminase antibodies in inflammatory bowel disease: new evidence

Abstract Anti-tissue transglutaminase, previously held to be identical to anti-endomysial antibodies in celiac sprue, has been reported in inflammatory bowel disease patients. To investigate these data further, we evaluated serum and intestinal anti-tissue transglutaminase in inflammatory bowel disease patients, with respect to the Crohn’s disease activity index and the integrated disease activity index. Study population comprised: 49 patients with Crohn’s disease and 29 patients with ulcerative colitis; 45 patients with celiac sprue and 85 autoimmune patients as disease controls; and 58 volunteers as healthy controls. Immunoglobulin A (IgA) anti-recombinant human tissue transglutaminase and anti-endomysial antibody detection in sera and fecal supernatants were performed. Adsorption of positive sera with recombinant human tissue transglutaminase were also performed. Marked increased anti-tissue transglutaminase concentrations were found in celiac sprue, while low-positive values were also found in Crohn’s disease and ulcerative colitis. Anti-endomysial antibodies were detectable only in celiac sprue. Antigen adsorption resulted in a significant reduction of the anti-tissue transglutaminase either in celiac sprue or inflammatory bowel disease sera. A significant correlation between anti-tissue transglutaminase and Crohn’s disease activity index or integrated disease activity index scores was found. Anti-tissue transglutaminase was also detectable in fecal supernatants from inflammatory bowel disease patients. Data highlight that both circulating and intestinal anti-tissue transglutaminases are detectable in inflammatory bowel disease, and that they are related to disease activity. These features underline that, in addition to anti-tissue transglutaminase, an anti-endomysial antibody test is necessary in the diagnostic work-up of celiac sprue, especially in patients with known inflammatory bowel disease.

GI distension in severe ulcerative colitis.

OBJECTIVES:In previous retrospective studies in patients with severe ulcerative colitis (UC), small bowel distension was found to characterize a subgroup of patients at higher risk for both toxic megacolon (TMC) and multiple organ dysfunction syndrome (MODS). In this study we prospectively evaluated the prevalence of GI distension and its relationship to clinical outcome in patients with severe UC.METHODS:Of 109 consecutive inpatients with acute UC (admitted to the GI Unit of the University of Rome during the period 1995–2000), 45 had severe colitis. Routine blood tests and acid-base balance and plain abdominal film evaluations were performed upon admission and repeated every 1–3 days. The gas content of the stomach and small and large intestines was evaluated on plain abdominal films. All patients were submitted to the standard Oxford intensive medical regimen; clinical improvement, occurrence of major complications, need for surgery, and mortality were evaluated. Statistical analysis was carried out using Students t, χ2, Fishers exact, Mann-Whitney, and Wilcoxon rank sum tests, when appropriate.RESULTS:Of 45 patients with severe UC, 24 (53%) had GI distension. Three of these 24 patients had TMC on admission (all underwent surgery and survived), 21 showed increased GI gas content (four developed TMC 1–4 days after the detection of GI distension and were operated on, two developed MODS and died, and eight did not improve but were submitted to surgery and survived). None of the 21 patients with normal GI gas content had complications; all survived (five did not improve and required surgery).CONCLUSIONS:In severe UC, persistent GI distension characterized a subgroup of patients with poor response to medical therapy and at higher risk for TMC and of need for surgery. The development of MODS was the most important predicting factor for fatal outcome.

MRI evaluation of Crohn's disease of the small and large bowel with the use of negative superparamagnetic oral contrast agents.

Crohn’s disease (CD) is a chronic inflammatory disorder of the bowel wall; it starts in the submucosal layer and progresses to the entire wall and beyond it, leading to a diffuse perivisceral inflammation, adhesions, fissures, fistulas, and abscesses. For this typical transmural and extramural course, most of its findings (wall thickening and enhancement, fibrofatty proliferation, phlegmons, abscesses, etc) can be directly detected and evaluated only with the use of cross-sectional imaging techniques rather with than barium studies [1–4]. In the past few years, the evaluation of CD with sectional imaging modalities such as ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) has significantly explanded the spectrum of information about the disease and changed its diagnostic workup. Radiologic barium studies such as small bowel followthrough and enteroclysis are projection techniques that focus on lumenal abnormalities. Thanks to their highspatial resolution, these modalities can image the inner profile of the wall and thus detect all the main mucosal changes of CD [5, 6]. Conversely, the effects of the changes produced by CD in the outer wall layers and contiguous tissues can be evaluated only indirectly by radiologic barium studies. Cross-sectional modalities have added a third spatial dimension, thus allowing visualization of the disease “outside of the lumen.” For many years, MRI, has been used mainly to assess anal and perianal CD abnormalities [7, 8]. In fact, the slow acquisition times of early MRI systems caused severe image degradation due to peristaltic and respiratory movements throughout the abdomen, except in the pelvis, thus limiting the evaluation of the small and large bowel. The recent technical improvements of MRI systems have greatly increased the diagnostic possibilities of abdominal MRI, particularly in the study of the intestinal wall. At present, fast acquisition techniques significantly reduce motion artifacts and provide excellent dynamic contrast-enhanced studies of the bowel wall. The simultaneous increase of spatial resolution achieved by phased array or the newer body coils has further improved the diagnostic accuracy of MRI in the evaluation of the bowel wall. The recent possibility of signal modulation, e.g., by selectively suppressing the fat signal, has led to unexpected results in body imaging. Further, positive and negative oral contrast agents are now commercially available. All these technical improvements have spontaneously expanded the application of MRI in inflammatory bowel diseases, and numerous recent studies have documented this increasing interest in the investigation of the full range of CD abnormalities with the newest MRI techniques [9–25]. Several techniques have been proposed for the assessment of CD and other inflammatory bowel diseases. One is based on the nasojejunal intubation, the so-called MR enteroclysis [9–13], which can be performed with positive or negative oral contrast agents. The goal of this technique is to obtain more detailed information on lumenal abnormalities by bowel distention, in a manner similar to conventional enteroclysis. Other techniques are based on the oral administration of contrast agents rather than on nasojejunal intubation. In general, these techniques try to optimize the cross-sectional multiplanar evaluation of CD based on the belief that the intrinsic transmural and extramural courses of the disease mainly require a direct evaluation of wall changes and perivisceral abnormalities rather than of lumenal abnormalities [14–25]. Many of the CD findings observed on axial and coronal MR images are similar to those described on CT, whereas others are completely new and inherent to MRI. Correspondence to: F. Maccioni Abdom Imaging 27:384–393 (2002) DOI: 10.1007/s00261-001-0119-3 Abdominal Imaging

Early versus late surgery for ileo-caecal Crohn’s disease

Background  Surgical resection is almost inevitable in Crohn’s disease. Surgery is usually performed for refractory or complicated disease: no studies appear to have been carried out, so far, to evaluate the potential benefits of performing surgery early in the course of the disease.