The ACCURE-trial: the Effect of Appendectomy on the Clinical Course of Ulcerative Colitis, a Randomised International Multicenter Trial (NTR2883) and the ACCURE-UK Trial: a Randomised External Pilot Trial (ISRCTN56523019)

Background: Over the past 20 years evidence has accumulated confirming the immunomodulatory role of the appendix in ulcerative colitis (UC). This led to the idea that appendectomy might alter the clinical course of established UC. The objective of this body of research is to evaluate the short-term and medium-term efficacy of appendectomy to maintain remission in patients with UC, and to establish the acceptability and cost-effectiveness of the intervention compared to standard treatment.

Methods/design: These paired phase III multicenter prospective randomised studies will include patients over 18 years of age with an established diagnosis of ulcerative colitis and a disease relapse within 12 months prior to randomisation. Patients need to have been medically treated until complete clinical (Mayo score <3) and endoscopic (Mayo score 0 or 1) remission. Patients will then be randomised 1:1 to a control group (maintenance 5-ASA treatment, no appendectomy) or elective laparoscopic appendectomy plus maintenance treatment. The primary outcome measure is the one year cumulative UC relapse rate - defined both clinically and endoscopically as a total Mayo-score ≥5 with endoscopic subscore of 2 or 3. Secondary outcomes that will be assessed include the number of relapses per patient at 12 months, the time to first relapse, health related quality of life and treatment costs, and number of colectomies in each arm.

Discussion: The ACCURE and ACCURE-UK trials will provide evidence on the role and acceptability of appendectomy in the treatment of ulcerative colitis and the effects of appendectomy on the disease course.

Trial Registration: NTR2883 ; ISRCTN56523019.

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References

Panaccione R, Sandborn W . The appendix in ulcerative colitis: a not so innocent bystander. Gastroenterology. 1999; 117(1):272-3. DOI: 10.1016/s0016-5085(99)70581-0. View

Hawthorne A, Logan R, Hawkey C, Foster P, Axon A, Swarbrick E . Randomised controlled trial of azathioprine withdrawal in ulcerative colitis. BMJ. 1992; 305(6844):20-2. PMC: 1882467. DOI: 10.1136/bmj.305.6844.20. View

Groisman G, George J, Harpaz N . Ulcerative appendicitis in universal and nonuniversal ulcerative colitis. Mod Pathol. 1994; 7(3):322-5. View

Ross H, Steele S, Varma M, Dykes S, Cima R, Buie W . Practice parameters for the surgical treatment of ulcerative colitis. Dis Colon Rectum. 2013; 57(1):5-22. DOI: 10.1097/DCR.0000000000000030. View

Sauerland S, Jaschinski T, Neugebauer E . Laparoscopic versus open surgery for suspected appendicitis. Cochrane Database Syst Rev. 2010; (10):CD001546. DOI: 10.1002/14651858.CD001546.pub3. View

Hueting W, Buskens E, van der Tweel I, Gooszen H, van Laarhoven C . Results and complications after ileal pouch anal anastomosis: a meta-analysis of 43 observational studies comprising 9,317 patients. Dig Surg. 2005; 22(1-2):69-79. DOI: 10.1159/000085356. View

Gilat T, Hacohen D, Lilos P, Langman M . Childhood factors in ulcerative colitis and Crohn's disease. An international cooperative study. Scand J Gastroenterol. 1987; 22(8):1009-24. DOI: 10.3109/00365528708991950. View

Rutgeerts P, DHaens G, Hiele M, Geboes K, VANTRAPPEN G . Appendectomy protects against ulcerative colitis. Gastroenterology. 1994; 106(5):1251-3. DOI: 10.1016/0016-5085(94)90016-7. View

Radford-Smith G, Edwards J, Purdie D, Pandeya N, Watson M, Martin N . Protective role of appendicectomy on onset and severity of ulcerative colitis and Crohn's disease. Gut. 2002; 51(6):808-13. PMC: 1773455. DOI: 10.1136/gut.51.6.808. View

10.

DHaens G, Geboes K, Peeters M, Baert F, Ectors N, Rutgeerts P . Patchy cecal inflammation associated with distal ulcerative colitis: a prospective endoscopic study. Am J Gastroenterol. 1997; 92(8):1275-9. View

11.

Matsushita M, Uchida K, Okazaki K . Role of the appendix in the pathogenesis of ulcerative colitis. Inflammopharmacology. 2007; 15(4):154-7. DOI: 10.1007/s10787-007-1563-7. View

12.

Cosnes J, Carbonnel F, Beaugerie L, Blain A, Reijasse D, Gendre J . Effects of appendicectomy on the course of ulcerative colitis. Gut. 2002; 51(6):803-7. PMC: 1773481. DOI: 10.1136/gut.51.6.803. View

13.

Matsushita M, Takakuwa H, Matsubayashi Y, Nishio A, Ikehara S, Okazaki K . Appendix is a priming site in the development of ulcerative colitis. World J Gastroenterol. 2005; 11(31):4869-74. PMC: 4398739. DOI: 10.3748/wjg.v11.i31.4869. View

14.

Langholz E, Munkholm P, Davidsen M, Binder V . Course of ulcerative colitis: analysis of changes in disease activity over years. Gastroenterology. 1994; 107(1):3-11. DOI: 10.1016/0016-5085(94)90054-x. View

15.

Dolan P . Modeling valuations for EuroQol health states. Med Care. 1997; 35(11):1095-108. DOI: 10.1097/00005650-199711000-00002. View

16.

Shanahan F . Pathogenesis of ulcerative colitis. Lancet. 1993; 342(8868):407-11. DOI: 10.1016/0140-6736(93)92818-e. View

17.

Travis S, Stange E, Lemann M, Oresland T, Bemelman W, Chowers Y . European evidence-based Consensus on the management of ulcerative colitis: Current management. J Crohns Colitis. 2010; 2(1):24-62. DOI: 10.1016/j.crohns.2007.11.002. View

18.

Mombaerts P, Mizoguchi E, Grusby M, Glimcher L, Bhan A, Tonegawa S . Spontaneous development of inflammatory bowel disease in T cell receptor mutant mice. Cell. 1993; 75(2):274-82. DOI: 10.1016/0092-8674(93)80069-q. View

19.

Margenthaler J, Longo W, Virgo K, Johnson F, Oprian C, Henderson W . Risk factors for adverse outcomes after the surgical treatment of appendicitis in adults. Ann Surg. 2003; 238(1):59-66. PMC: 1422654. DOI: 10.1097/01.SLA.0000074961.50020.f8. View

20.

Ghosh S, Mitchell R . Impact of inflammatory bowel disease on quality of life: Results of the European Federation of Crohn's and Ulcerative Colitis Associations (EFCCA) patient survey. J Crohns Colitis. 2010; 1(1):10-20. DOI: 10.1016/j.crohns.2007.06.005. View