Ursodeoxycholic acid treatment in IBD-patients with colorectal dysplasia and/or DNA-aneuploidy: a prospective, double-blind, randomized controlled pilot study.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Sjöqvist
Urban
U
Department of Medicine, Stockholm South Hospital, Karolinska Institutet, Stockholm, Sweden. urban.sjoqvist@sos.sll.se
Tribukait
Bernhard
B
Ost
Ake
A
Einarsson
Curt
C
Oxelmark
Lena
L
Löfberg
Robert
R
D000328:Adult; D000368:Aged; D000782:Aneuploidy; D002756:Cholagogues and Choleretics / Q000627:therapeutic use*; D003093:Colitis, Ulcerative / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D015179:Colorectal Neoplasms / Q000209:etiology / Q000235:genetics / Q000517:prevention & control*; D003424:Crohn Disease / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D004311:Double-Blind Method; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011230:Precancerous Conditions / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*
D002756:Cholagogues and Choleretics; D014580:Ursodeoxycholic Acid