Ursodeoxycholic Acid Treatment in IBD-patients with Colorectal Dysplasia and/or DNA-aneuploidy: a Prospective, Double-blind, Randomized Controlled Pilot Study

• Published in: Anticancer research Vol. 24; no. 5B; pp. 3121 - 3127
• Main Authors: SJÖQVIST, Urban, TRIBUKAIT, Bernhard, ÖST, Ake, EINARSSON, Curt, OXELMARK, Lena, LÖFBERG, Robert
• Format: Journal Article
• Language: English
• Published: Attiki International Institute of Anticancer Research 01.09.2004
• Subjects: Adult; Aged; Aneuploidy; Biological and medical sciences; Cholagogues and Choleretics - therapeutic use; Chromosome aberrations; Colitis, Ulcerative - complications; Colitis, Ulcerative - drug therapy; Colitis, Ulcerative - genetics; Colorectal Neoplasms - etiology; Colorectal Neoplasms - genetics; Colorectal Neoplasms - prevention & control; Crohn Disease - complications; Crohn Disease - drug therapy; Crohn Disease - genetics; Double-Blind Method; Female; Genetic Predisposition to Disease; Humans; Male; Medical genetics; Medical sciences; Medicin och hälsovetenskap; Middle Aged; Pilot Projects; Precancerous Conditions - drug therapy; Precancerous Conditions - etiology; Precancerous Conditions - genetics; Tumors; Ursodeoxycholic Acid - therapeutic use; Chromosomal aberration; Human; Dysplasia; inflammatory bowel diseases; Digestive system; Aneuploidy; Crohn's disease; DNA-aneuploidy; Inflammatory disease; Ursodeoxycholic acid; Crohn disease; Randomization; Cancerology; Treatment; Bile acid; DNA; Rectum; Double blind study; Digestive diseases; Intestinal disease; Colon; Ulcerative colitis
• ISSN: 0250-7005; 1791-7530

Background & Aims: There is an increased risk of colorectal carcinoma (CRC) in patients with longstanding, extensive colonic inflammatory bowel disease (IBD). Primary sclerosing cholangitis, family history of CRC, mucosal dysplasia and DNA-aneuploidy are other risk factors. Recently, results from animal studies have shown that the bile acid ursodeoxycholic acid (UDCA) has a favourable impact on experimentally-induced CRC/neoplasia in rats. The aim of this proof of the concept study was to explore the possible preventive/reverting effects of UDCA in patients with colorectal IBD with existing findings of low grade dysplasia and/or DNA-aneuploidy. Patients and Methods: Nineteen patients (13 UC, 6 CD, median age 43 years) with long-standing, extensive IBD (median duration 21 years), with previous findings of low-grade dysplasia and/or DNA-aneuploidy, were randomized to receive either UDCA (500 mg b.i.d) (n=10) or placebo (n=9) in a controlled, double-blind, two-year study. Colonoscopy with multiple biopsies for histopathology and for DNA-flow cytometry was performed at the start and at six-month intervals during the study period. The primary outcome was the need for colectomy due to progression of dysplasia. Changes in dysplasia and DNA-aneuploidy scores were also assessed. Results: There were no significant differences in the overall composed score between the two groups, either at study start or during the study period. In the placebo group one patient had a progression of dysplasia into high-grade and one patient developed DALM with low-grade dysplasia; both had a colectomy. In contrast, no UDCA-treated patient had progression of dysplasia. Conclusion: UDCA may prevent further progression of manifest low-grade dysplasia in colorectal IBD. Prolonged treatment or an increased dose may be needed to fully exploit the chemopreventive properties of this compound.