Acute and late toxicity of patients with inflammatory bowel disease undergoing irradiation for abdominal and pelvic neoplasms.

PURPOSE: Little data exists in the medical literature describing the response of patients with inflammatory bowel disease (IBD) to abdominal and pelvic irradiation. To clarify the use of this modality in this setting, this study assesses the short- and long-term tolerance of 28 patients with IBD to abdominal and pelvic irradiation. METHODS AND MATERIALS: From 1970 to 1999, 28 patients with IBD (10 patients-Crohn's disease, 18 patients-ulcerative colitis) were identified and underwent external beam abdominal or pelvic irradiation. Mean follow-up time after radiation therapy was 32 months. Patients were treated either by specialized techniques (16 patients) to minimize small and large bowel irradiation or by more conventional approaches (12 patients). Acute and late toxicity was scored. RESULTS: The overall incidence of severe toxicity was 46% (13/28 patients). Six of 28 patients (21%) experienced severe acute toxicity necessitating cessation of radiation therapy. Late toxicity requiring hospitalization or surgical intervention was observed in 8 of 28 patients (29%). One patient experienced both an acute as well as late toxicity. For patients undergoing radiation therapy by conventional approaches, the 5-year actuarial rate of late toxicity was 73%. This figure was 23% for patients treated by specialized techniques (p = 0.02). CONCLUSIONS: Because of the potentially severe toxicity experienced by patients with IBD undergoing abdominal and pelvic irradiation, judicious use of this modality must be employed. Definition of IBD location and activity as well as careful attention to irradiation technique may allow treatment of these patients with acceptable rates of morbidity.

Antineutrophil cytoplasmic antibodies (ANCAs) in patients with inflammatory bowel disease show no correlation with proteinase 3, lactoferrin, myeloperoxidase, elastase, cathepsin G and lysozyme: a Singapore study.

INTRODUCTION: The pathogenic importance of antineutrophil cytoplasmic antibodies (ANCAs) in inflammatory bowel disease (IBD) is unclear and target antigen localisation studies may lend insight to the specific pathogenic mechanisms of IBD. In this pilot study, we looked at occurrence of ANCA in Asian IBD patients. In ANCA-positive samples, we analysed for the presence of target antigens i.e. proteinase 3, lactoferrin, myeloperoxidase, elastase, cathepsin G and lysozyme. MATERIALS AND METHODS: This prospective study was carried out from July 1997 to February 1998. Sera were screened for ANCAs with indirect immunofluorescent test and tested with an enzyme immunoassay (ELISA) kit which provides a semi-quantitative assay for human IgG autoantibodies against 6 antigens: proteinase 3, lactoferrin, myeloperoxidase, elastase, cathepsin G and lysozyme. RESULTS: A total of 75 patients were studied: 50 with IBD and 25 controls with functional bowel disease. Ten had Crohn's disease (CD) and 40 had ulcerative colitis (UC). There was no racial predilection among the Chinese, Malays or Indians. In CD, 1 was positive for cytoplasmic ANCA (cANCA) and 2 for perinuclear ANCA (pANCA). In UC, 4 were positive for pANCA, 15 for atypical perinuclear ANCA (apANCA) and 1 for cANCA. In the CD and UC population, the proportion positive for ANCA was 30% and 50%, respectively. There was no ANCA detected among the controls. Of those ANCA-positive IBD patients (n:23), only 1 demonstrated anti-myeloperoxidase antibodies. No antibodies were detected against the other 5 antigens tested. CONCLUSIONS: This pilot Singapore study concludes that there is no significant ANCA association with proteinase 3, lactoferrin, myeloperoxidase, elastase, cathepsin G and lysozyme.

Endoscopic biopsy features and diagnostic challenges of adult Crohn's disease at initial presentation.

AIMS: Endoscopic biopsy diagnosis of Crohn's disease (CD) is problematic due to lack of specific microscopic features and patchy involvement. There is no documentation of the pattern and severity of microscopic features of CD at initial presentation in adults or children. We aimed to assess the initial mucosal biopsy features of CD in adults and to identify any specific features to confirm the diagnosis. METHODS: Thirty sets of initial, adult endoscopic biopsies suspected to be CD with subsequent resections, repeat biopsies with long-term follow-up, and/or other confirmatory laboratory results were analysed by three gastrointestinal pathologists, blinded for the final diagnosis for mucosal architectural changes, epithelial abnormalities, chronic and active inflammation and changes of muscularis mucosae and submucosa. There were 25 cases of CD and five cases of non-CD for comparison (3 tuberculosis and 2 right-sided diverticular disease and associated colitis). Cases confirmed as ulcerative colitis were excluded, as diagnostic challenges are already well established. RESULTS: The majority of initial biopsies (96%) of CD were abnormal with active chronic ileocolitis with a very high proportion (80%) showing the classic combination of abnormal mucosal architecture, epithelial abnormalities and active chronic inflammation. The most sensitive feature was lamina proprial chronic inflammation (sensitivity 92.7%). Sensitivity for other features was as follows: active inflammation 87.8%, basal plasmacytosis 82.1%, architectural changes 80.5% and epithelial abnormalities 70.7%. Abnormalities were found in 94% of ileal and 76% of colonic biopsies. No feature was specific as all tuberculosis and diverticular disease cases showed the classic combination. Granulomata were seen in 10 of 41 CD, in all five tuberculosis and in no diverticular disease biopsies. Small, tight, well defined granulomata characterised CD over large coalesced ganulomata of tuberculosis. Paneth cell and pseudopyloric metaplasia was seen only in CD (2/25). CONCLUSIONS: Initial endoscopic biopsies of adult CD are significantly abnormal and a majority shows active chronic ileocolitis. The features are sufficiently important to suspect CD at initial presentation in the appropriate clinical setting. Tuberculosis and diverticular disease associated colitis are two important mimics to consider in addition to ulcerative colitis.

Early experience with double balloon enteroscopy: a leap forward for the gastroenterologist.

INTRODUCTION: Double balloon enteroscopy (DBE) is a novel procedure that allows complete visualisation, biopsy and treatment of small intestinal disorders. We describe our early experience with the use of DBE, evaluating the indications, diagnostic rates and complications. A secondary aim of the study was to compare the findings from DBE with wireless capsule endoscopy (WCE). METHODS: Retrospective study of patients referred to the Department of Gastroenterology and Hepathology at the Singapore General Hospital for evaluation of suspected small bowel diseases between February 2005 and May 2006 was done. A total of 34 procedures were conducted on 30 patients. A standardised data collection form was used. RESULTS: DBE was carried out via the oral approach (19 patients), anal approach (eight patients), and both approaches (three patients). Mean age was 53 (range 16-79) years. 12 procedures (35.3 percent) had one endoscopist and 22 (64.7 percent) procedures had two. The overall diagnostic input from DBE was 73.3 percent (22 of 30 patients). A positive diagnosis was achieved in 19 patients: jejunal gastrointestinal stromal tumour (GIST) (one), jejunal sarcoma (one), jejunal adenocarcinoma (one), duodenal adenocarcinoma (one), malignant lymphangioma (one), eosinophilic enteritis (one), pseudomembranous ileitis (one), tuberculous ileitis (one), jejunitis/ileitis (seven), lymphangiectasia attributed to relapsed Non-Hodgkins lymphoma (one), combination of angiodysplastic lesions and apthous jejunal/ileal lesions (one), and focal villous atrophy (two). Small intestinal pathology was excluded in three patients with abnormal computed tomography (CT) findings. Endoscopy time for antegrade DBE was 46.1 (+/- 20.1) minutes and for retrograde DBE was 70.8 (+/- 11.0) minutes. The findings of WCE correlated with DBE findings in nine of 12 (75 percent) patients. Apart from the first three DBE procedures, all subsequent cases were performed without fluoroscopy. When stratified into antegrade and retrograde DBEs respectively, procedural duration, sedative use and diagnostic yield were comparable for one and two endoscopist DBEs. No complications were recorded. CONCLUSION: Our early experience with DBE shows it to be safe and effective in imaging the small intestine, and it may soon become a standard mode of investigation for the gastroenterologist.

Treatment of ulcerative colitis.

Advances in the treatment of ulcerative colitis have continued to focus on improved local delivery of existing agents, such as 5-aminosalicylate and corticosteroids, and on novel immunosuppressive agents. Although newer preparations of 5-aminosalicylate continue to provide incremental benefits in safety, tolerance, and efficacy, there is a growing understanding of the limits of benefit from increasing doses. Knowledge of the safety of these agents, particularly in regard to their use in pregnancy, continues to expand. Novel corticosteroids are used in much of the world for the treatment of ulcerative colitis, with the exception of the United States, with anticipated benefits in safety but little additional therapeutic benefit. Innovative use of oral emulsion preparations of cyclosporine has been reported in the treatment of ulcerative colitis and adds to the growing body of literature on the efficacy of cyclosporine in severe disease. Relatively limited experience with other immunosuppressive agents, such as tacrolimus, has been reported. The role of antibiotics in the treatment of ulcerative colitis has continued to present controversy.