Appendectomy Protects Against the Development of Ulcerative Colitis but Does Not Affect Its Course Warwick S. Selby, M.B.B.S., M.D., F.R.A.C.P., Sean Griffin, M.B.B.S., F.R.A.C.P., Ned Abraham, M.B.B.S., F.R.A.C.S., and Michael J. Solomon, M.B., B.Ch., M.Sc., F.R.A.C.S. A. W. Morrow Gastroenterology and Liver Centre and Department of Colorectal Surgery, Royal Prince Alfred Hospital, Sydney; and Department of Medicine, The University of Sydney, Sydney, New South Wales, Australia OBJECTIVES: Appendectomy has been shown to protect against the development of ulcerative colitis. The objective of this study was to examine the effect of appendectomy on the clinical features and natural history of colitis. METHODS: A total of 259 consecutive adults patients with ulcerative colitis were studied. Of the patients, 20 had un- dergone appendectomy (12 before onset of colitis and eight after diagnosis). RESULTS: The frequency of appendectomy was significantly less than in a group of 280 controls, which comprised partners of the patients and a group from the community (OR = 0.25; 95% CI = 0.14 – 0.44). This was even more significant if only the 12 patients who underwent surgery before the onset of colitis were considered (OR = 0.15; 95% CI = 0.07– 0.28). Patients with prior appendectomy devel- oped symptoms of ulcerative colitis for the first time at a significantly later age than those without appendectomy (42.5  6.5 vs 32.1  0.8 yr; p  0.01) or those who had appendectomy after the onset of colitis (24.6  3.4 yr; p  0.05). Appendectomy did not influence disease extent, need for immunosuppressive treatment with azathioprine or 6-mercaptopurine (as a marker of resistant disease), or the likelihood of colectomy. Five patients in the appendectomy group had clinical evidence of primary sclerosing cholan- gitis (25%). This was more common than in those without appendectomy (8%; OR = 4.09; 95% CI = 1.04 –13.60). CONCLUSIONS: These results indicate that although appen- dectomy may delay onset of colitis, it does not influence its course. However, it is associated with the development of primary sclerosing cholangitis. Appendectomy is unlikely to be of benefit in established ulcerative colitis. (Am J Gas- troenterol 2002;97:2834 –2838. © 2002 by Am. Coll. of Gastroenterology) INTRODUCTION Studies into the influence of childhood factors on the de- velopment of inflammatory bowel disease were the first to show a negative association between ulcerative colitis and appendectomy (1–3). This has been confirmed by a number of reports from Europe, North America, and Australasia (4 –12). A recent, large Swedish follow-up study of more than 210,000 subjects who had undergone appendectomy before the age of 50 yr showed that the likelihood of subsequently developing ulcerative colitis was significantly reduced if the appendix had been removed for appendicitis or mesenteric adenitis before the age of 20 yr, but not if done later than this (13). The significance of the appendix in ulcerative colitis has been further demonstrated by the de- scription of appendiceal inflammation in a significant pro- portion of patients who do not have cecal involvement (14 –18). Appendectomy performed at 1 month of age has been shown to suppress the development of spontaneous colitis in a TCR- mutant mouse model (19). Okazaki et al. described a single patient who had sustained improvement in his colitis after appendectomy (20). These findings, in addition to the studies of ulcerative colitis described above, have led to the suggestion that appendectomy be considered as a possible treatment for patients with ulcerative colitis. The purpose of the current study was to confirm the negative association between appendectomy and ulcerative colitis and also to examine the clinical features and course of colitis in a cohort of patients in whom the appendix had been removed, either before or after the onset of colitis. MATERIALS AND METHODS Study Patients The study group compromised 259 adult patients with ul- cerative colitis from a single practice (W.S.S.) attached to a large university teaching hospital. The diagnosis had been confirmed in all subjects by conventional clinical, endo- scopic, and histological findings. Patients with indetermi- nate colitis were excluded. Data were collected prospec- tively and stored in a computerized database. Demographic details, age at onset of symptoms and at diagnosis, smoking history, and family history of inflammatory bowel disease were recorded, as were the extent of colonic involvement, previous and current medical therapy, and any extra-intes- tinal complications of ulcerative colitis (cutaneous, ocular, THE AMERICAN JOURNAL OF GASTROENTEROLOGY Vol. 97, No. 11, 2002 © 2002 by Am. Coll. of Gastroenterology ISSN 0002-9270/02/$22.00 Published by Elsevier Science Inc. PII S0002-9270(02)05466-7