Ulcerative Colitis: Ooi CJ

Ouyang Q, Tandon R, Goh KL, Ooi CJ, Ogata H, Fiocchi C. · Department of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China. · Curr Opin Gastroenterol. · Pubmed #15930979 No free full text.

Abstract: PURPOSE OF REVIEW: Inflammatory bowel disease has been traditionally considered rare in the Asian Pacific region, but recent evidence indicates that both Crohn disease and ulcerative colitis are becoming increasingly common among local populations. This review will validate this significant epidemiological and clinical observation using data published in the current Asian literature and information presented at the 2004 Asian Pacific Digestive Week in Beijing, China. RECENT FINDINGS: A progressive rise in the incidence and prevalence of inflammatory bowel disease is discernible is most Asian Pacific countries, more so for ulcerative colitis than Crohn disease. Some ethnic differences are notably evident, as Indians suffer more inflammatory bowel disease than Chinese or Malays. Age of onset and gender are similar to those of Western patients, as are the distribution and extent of disease which, however, tends to be clinically less severe than in European and North American patients. A family history is occasionally elicited, whereas smoking and appendectomy appear to have the same impact on inflammatory bowel disease as seen in the West. A remarkable difference is the absence of any association of Asian Crohn disease with NOD2/CARD15 mutations, as repeatedly observed in white and Jewish populations. Intestinal tuberculosis is still common in the Asian Pacific region, and poses major diagnostic and therapeutic hurdles, often delaying the diagnosis of true Crohn disease. SUMMARY: Investigation of inflammatory bowel disease in the Asian Pacific region offers the unprecedented opportunity to study the 'early stages' of the disease, and may provide new clues to its pathophysiology by identifying key environmental factors and distinct genetic make-ups.

Ooi CJ, Lim BL, Cheong WK, Ling AE, Ng HS. · Department of Gastroenterology, Singapore General Hospital, 1 Hospital Drive, Singapore 169608. · Ann Acad Med Singapore. · Pubmed #11269973 No free full text.

Abstract: 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.

Ooi CJ, Sands BE. · Center for the Study of Inflammatory Bowel Diseases, Gastrointestinal Unit, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts 02114, USA. · Curr Opin Gastroenterol. · Pubmed #17023961 No free full text.

Abstract: 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.

Ling KL, Ooi CJ, Luman W, Cheong WK, Choen FS, Ng HS. · Department of Gastroenterology, Singapore General Hospital, Outram Road, Singapore, Republic of Singapore. · J Clin Gastroenterol. · Pubmed #12172359 No free full text.

Abstract: BACKGROUND: Ulcerative colitis (UC) is rare in Asia. Singapore is an ethnically heterogeneous city-state with a population made up of Chinese (77%), Indians (7.5%), and Malays (14%). This study describes and compares the characteristics of Chinese, Malay, and Indian patients with UC. STUDY: Retrospective chart review was performed of 235 patients seen in the largest tertiary care hospital in Singapore between 1971 and June 2000. RESULTS: There were 169 (72%) Chinese, 24 (10%) Malays, and 42 (18%) Indians with UC. Male-to-female ratio was 1.8:1 (150:85). Most patients in all three races presented between the ages of 20 and 39 years. No bimodal peak in the age at presentation was seen. The median period from onset of symptoms to diagnosis was 1 month in all three races. More Malay (57%) and Indian (55%) patients had colitis extending proximal to splenic flexure at presentation compared with Chinese (32%) patients (p = 0.04). There were more Indian patients (29%) with severe disease at onset compared with Chinese (12%) and Malay (22%) patients (p = 0.035). Thirty-one percent of patients had only one episode of colitis, 12% were steroid dependent, and 4% were steroid refractory. Proctocolectomy was needed in 31 (18.3%) Chinese, 3 (12.5%) Malay, and 4 (9.5%) Indian patients. Extraintestinal manifestations were found in 6% of the Chinese, 12% of Malay patients, and 14% of Indian patients. The most common extraintestinal manifestation was arthritis, present in 6.4% of patients. CONCLUSION: There were more Indians with UC than expected in this population. Whereas Indian and Malay patients have more extensive and severe disease at presentation than Chinese patients, this does not predict for more refractory disease or a greater need for surgery.

Mizoguchi E, Mizoguchi A, Takedatsu H, Cario E, de Jong YP, Ooi CJ, Xavier RJ, Terhorst C, Podolsky DK, Bhan AK. · Center for the Study of Inflammatory Bowel Disease, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA. · Gastroenterology. · Pubmed #11781288 No free full text.

Abstract: BACKGROUND & AIMS: Tumor necrosis factor (TNF) induces multiple effects including cell proliferation and death by ligation with TNF receptor type II (TNFR2). We studied the role of TNFR2 in chronic inflammation-induced colonic epithelial alteration. METHODS: TNFR2 expression in colonic epithelial cells (CECs) was assessed by ribonuclease protection assay (RPA) and immunohistochemistry (IHC) in patients with inflammatory bowel disease (IBD) and murine colitis models. TNFR2 expression was also analyzed using COLO205 cells. The role of TNFR2 in colonic epithelial homeostasis was examined by generating interleukin 6-deficient TCR alpha KO (alpha IL-6DKO) or TNFR2-deficient TCR alpha (alpha TNFR2DKO) mice. RESULTS: TNFR2 expression was up-regulated in CEC in both human ulcerative colitis and Crohn's disease. In vitro studies showed that TNFR2 expression was up-regulated by a cooperative effect of key proinflammatory cytokines. By RPA, the increased expression of TNFR2 was detectable in TCR alpha KO mice with colitis compared with TCR alpha KO mice without colitis or wild-type mice. In alpha IL-6DKO mice, TNFR2 expression, proliferation, and nuclear factor kappa B activation of CECs were markedly reduced compared with TCR alpha KO mice. alpha TNFR2 mice also showed significantly less colonic epithelial proliferation compared with TCR alpha KO mice. CONCLUSIONS: Expression of TNFR2 is consistently increased on CECs in both murine colitis models as well as patients with IBD. TNFR2 may play an important role in colonic inflammation-associated alteration in the intestinal epithelium.

Willett CG, Ooi CJ, Zietman AL, Menon V, Goldberg S, Sands BE, Podolsky DK. · Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #10705022 No free full text.

Abstract: 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.