Ursodiol Use Is Associated with Lower Prevalence of Colonic Neoplasia in Patients with Ulcerative Colitis and Primary Sclerosing Cholangitis

Tung, Bruce Y.; Emond, Mary J.; Haggitt, Rodger C.; Bronner, Mary P.; Kimmey, Michael B.; Kowdley, Kris V.; Brentnall, Teresa A.

doi:10.7326/0003-4819-134-2-200101160-00008

Cited by 420 publications

(247 citation statements)

References 37 publications

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“…The chemopreventive role for ursodeoxycholic acid (UDCA) therapy in PSC is well-supported by both experimental data and clinical studies [91,92] . In a post hoc analysis of a randomized clinical trial, three patients (10%) initially assigned to UDCA developed colorectal dysplasia or CRC compared to eight patients initially assigned to placebo (35%) [92] .…”

Section: Chemoprevention In Ibd-is It Possible?mentioning

confidence: 89%

Risk for colorectal cancer in ulcerative colitis: Changes, causes and management strategies

Lakatos¹,

Lakatos²

2008

WJG

357

245

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Since the first report of an inflammatory bowel disease (IBD) case associated with colorectal cancer (CRC) by Crohn and Rosenberg [1] , significant efforts have been made to elucidate this presumed association. Nowadays, the association between IBD and the increased risk for CRC is widely accepted. Although CRC, complicating ulcerative colitis and Crohn's disease, accounts only for 1%-2% of all cases of CRC in the general population, it is considered a serious complication of the disease and accounts for approximately 10%-15% of all deaths in IBD patients [2] . The age at diagnosis of CRC associated with IBD is 15-20 years earlier compared to sporadic cancers. In the meta-analysis by Eaden et al [3] , the average age at diagnosis was 43.2 years. Similarly, in a recent publication from Eastern Europe [4] , it was found to be 50.9 years, 10-15 years younger compared to sporadic CRC cases from the same area (62.2 years) [5] . According to US [6] and Canadian [7] publications, almost two-thirds of the affected patients were males, yet results are conflicting [4,8] . In addition, the frequency of multiple CRCs is higher than in patients with sporadic CRC [9] .The increased risk of CRC in UC is almost a universal finding [3,[10][11][12][13] , yet the extent of this risk varies considerably with differences in study design and geographic area. The initial reports were published by tertiary gastroenterology centers, thus the high risk detected might have been a consequence of referral bias and overinterpretation due to the high percentage of extensive and chronically active cases in these cohorts. Results of population-based studies are more reliable; however, several geographical and ethnic differences have been noted.The report of the meta-analysis by Eaden et al [3] in 2001 was one of several milestones in this subject. The incidence of UC-associated CRC was estimated based on 116 articles involving 54 478 patients in whom 1698 CRC cases were detected. This was a mixture of referral center-based, hospital-based, and population-based studies of variable methodological qualities and levels of detail. The reported incidence was higher in the US AbstractThe risk of colorectal cancer for any patient with ulcerative colitis is known to be elevated, and is estimated to be 2% after 10 years, 8% after 20 years and 18% after 30 years of disease. Risk factors for cancer include extent and duration of ulcerative colitis, primary sclerosing cholangitis, a family history of sporadic colorectal cancer, severity of histologic bowel inflammation, and in some studies, young age at onset of colitis. In this review, the authors discuss recent epidemiological trends and causes for the observed changes. Population-based studies published within the past 5 years suggest that this risk has decreased over time, despite the low frequency of colectomies. The crude annual incidence rate of colorectal cancer in ulcerative colitis ranges from approximately 0.06% to 0.16% with a relative risk of 1.0-2.75. The exact mechanism for this chang...

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Section: Chemoprevention In Ibd-is It Possible?mentioning

confidence: 89%

Risk for colorectal cancer in ulcerative colitis: Changes, causes and management strategies

Lakatos¹,

Lakatos²

2008

WJG

357

245

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“…8,9 Two retrospective studies showed that patients with PSC and UC, who were treated with UDCA to improve the liver function, have a significantly lower risk of colitis-associated cancer than the non-treated group. 10,11 Whether UDCA treatment has also a protective effect in patients with UC alone, in whom the treatment with UDCA is not a standard therapy, has not been investigated.The lack of data on this important subject is due to the very slow development of colitis-associated carcinomas and to the dysplasia-related preventive colectomy, which in most cases is performed prior to carcinoma development. This makes an animal model necessary for the investigation of the mechanism of action of UDCA in vivo.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Prevention of colitis‐associated carcinogenesis in a mouse model by diet supplementation with ursodeoxycholic acid

Loddenkemper

Keller

Hanski

et al. 2006

Intl Journal of Cancer

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Bile acids in the intestinal lumen contribute to the homeostatic regulation of proliferation and death of the colonic epithelial cells: Deoxycholic acid (DCA) appears to enhance and ursodeoxycholic acid (UDCA) to attenuate the process of chemically induced carcinogenesis. We studied the effects of UDCA on colitis-related colorectal carcinogenesis. Three groups of 25 mice were given 0.7% dextran sulphate in drinking water for 7 days and pure water for 10 days and were fed a standard diet containing double iron concentration. In 2 groups, the diet was supplemented with 0.2% cholic acid (CA), the precursor of DCA, or with 0.4% UDCA. After 15 cycles, the histology, the expression of MUC2, b-catenin, p27 and p16 and the fecal water concentration of DCA and UDCA were investigated. All animals showed colitis with similar severity and histologic as well as immunophenotypic alterations, resembling those of human colitis. Among the animals fed the nonsupplemented diet, 46% developed colorectal adenocarcinomas and 54% anal-rectal squamous cell carcinomas. The prevalence of dysplasia and carcinomas did not change significantly in the animals given CA. Among the mice fed with UDCA, none developed adenocarcinomas and 20% squamous carcinomas. Dysplastic lesions were found in 88%, 67% and 40% of each group, respectively. The prevalence of dysplasia as well as of carcinoma showed an inverse relationship to the UDCA concentration in the fecal water. These data indicate that UDCA suppresses colitis-associated carcinogenesis. This model is suitable for investigation of the mechanism of the anticarcinogenic effect of UDCA in vivo. ' 2005 Wiley-Liss, Inc.Key words: murine colitis; colon carcinogenesis; DSS colitis; ursodeoxycholic acid Ulcerative colitis (UC) in patients and in experimental animals is associated with a high risk of intraepithelial neoplasia and colonic carcinoma. The cumulative risk for colorectal cancer in a patient with UC is 2% at 10 years, 8% at 20 years and 18% at 30 years of disease duration. 1 Since the occurrence of dysplasia can be a strong indication for prophylactic proctocolectomy, 2 the inhibition or slowing down of the colitis-associated carcinogenesis would essentially reduce the number of necessary operations.Factors contributing to colon carcinogenesis are high epithelial proliferation rate in the inflamed region and the resulting increased accumulation of mutations as well as the disturbed regulation of cell death and proliferation. Intestinal bile acids contribute to the homeostatic regulation of proliferation and apoptosis of the colonic epithelium. Deoxycholic acid (DCA), whose fecal water concentration in patients with colitis is increased, 3 stimulates the proliferation of the colonic epithelial cells 4 and promotes colon carcinogenesis in an azoxymethane (AOM) rat model. 5 The addition of ursodeoxycholic acid (UDCA) to the diet decreases the prevalence of AOM-induced rat colonic tumors 6 as well as the prevalence of tumors in MIN mice. 7 These data indicate that DCA enhances the chemical colo...

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“…Ursodoxycholic acid was first used in UC patients, to treat effects of contaminant primary sclerosing cholangitis, and a relationship with decreased CRC was noted [76]. Follow-up studies have demonstrated mixed results [77][78][79], with some studies even noting an increase CRC risk in when high-doses of ursodoxycholic acid were employed [80].…”

Section: Prevention Of Crcmentioning

confidence: 99%

Colorectal Adenocarcinoma and Inflammatory Bowel Disease: An Update and Review

Karmali¹

2015

Surgery Curr Res

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Ursodiol Use Is Associated with Lower Prevalence of Colonic Neoplasia in Patients with Ulcerative Colitis and Primary Sclerosing Cholangitis

Abstract: Ursodiol use appears to be associated with a lower frequency of colonic dysplasia in patients with ulcerative colitis and primary sclerosing cholangitis. A randomized trial investigating the chemoprotective effect of ursodiol in patients with ulcerative colitis may be warranted.

Cited by 420 publications

References 37 publications

Risk for colorectal cancer in ulcerative colitis: Changes, causes and management strategies

Risk for colorectal cancer in ulcerative colitis: Changes, causes and management strategies

Prevention of colitis‐associated carcinogenesis in a mouse model by diet supplementation with ursodeoxycholic acid

Colorectal Adenocarcinoma and Inflammatory Bowel Disease: An Update and Review

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