Cholangiocarcinoma in patients with primary sclerosing cholangitis: A multicenter case-control study

Abstract

Patients with primary sclerosing cholangitis (PSC) have a significantly increased risk of developing cholangiocarcinoma (CCA). Risk factors for developing such a complication are not well defined. We conducted a multicenter, case-control study to determine the risk factors and possible predictors for CCA in patients with PSC. The demographic, clinical, and laboratory features of 26 PSC patients with CCA diagnosed over a 7-year period at eight academic centers were compared with 87 patients with PSC but no CCA (controls). There was no statistically significant difference in demographics, smoking, signs or symptoms or complications of PSC, indices of disease severity (Mayo Risk score or Child-Pugh score), frequency or duration or complications of inflammatory bowel disease (IBD), frequency of biliary surgery, or therapeutic endoscopy between the two groups. Alcohol consumption was significantly associated with CCA in patients with PSC (odds ratio: 2.95; 95% CI: 1.04-8.3). Serum carbohydrate antigen 19-9 (CA 19-9) was significantly higher in patients with CCA than those without (177 ؎ 89 and 61 ؎ 58 U/mL, respectively; P ‫؍‬ .002). A serum CA 19-9 level G 100 U/mL had 75% sensitivity and 80% specificity in identifying PSC patients with CCA. In conclusion, alcohol consumption was a risk factor for having CCA in PSC patients. The indices of severity of liver disease were not associated with CCA in patients with PSC. Serum CA 19-9 appeared to have good ability to discriminate PSC patients with and without CCA. (HEPATOLOGY 2000;31:7-11.)Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disorder that is characterized by multiple fibrotic strictures of the intra-and extrahepatic biliary tree. It is a progressive disorder in which approximately 50% of symptomatic patients eventually develop cirrhosis and liver failure. 1

Differential expression of cyclooxygenase-2 (COX-2) in human bile duct epithelial cells and bile duct neoplasm

“…36,37 Clinical and pathological evidence has suggested that inflammatory conditions involving the bile ducts predispose these ducts to the development of BDC, [39][40][41][42][43][44][45]72 however, the relationship between chronic inflammation and malignant transformation remains unclear. Recently, in many tumors, COX-2 overexpression has been suggested to play an important role in both carciogenesis and increased malignant potential.…”

“…Both were accompanied with various degree of inflammatory reaction, and PSC is considered to develop cholangiocarcionoma (IHBC), but not PBC. [39][40][41] Main morbid regions of the bile duct have been classically regarded as large and small ones, for PSC and PBC, respectively, 69 however, there are variant forms of these 2 cholestatic diseases. 70,71 Additionally, small bile ducts are frequently the target of inflammatory attacks in these cholestatic diseases.…”

“…The risk of developing hepatocellular carcinoma is low for patients with PBC, whereas IHBC (cholangiocarcinoma) is common in PSC. [39][40][41] Moreover, we have examined the direct effect of COX-2 specific inhibitors on proliferation of BDC and GBC cell lines in vitro. These observations may provide insight into the possible potent mechanism of bile duct carcinogenesis.…”

Dissecting the genetic susceptibility for cholangiocarcinoma in primary sclerosing cholangitis

“…[2][3][4] Interestingly, one-third to onehalf of those who develop CCA do so within the first year of being diagnosed with the cholestatic liver disease. 3,5 Furthermore, the risk of CCA does not correlate with the severity 6 or duration 2 of PSC. These interesting observations from retrospective studies imply that the development of CCA in PSC is likely subject to individual susceptibility.…”

“…For example, because the cholangiographic characteristics of extrahepatic CCA can imitate the stricturing lesions of PSC, the diagnosis of the former in these patients is difficult or at times impossible. Retrospective studies revealed risk factors associated with the development of CCA in PSC patients, including jaundice, 5 pruritus, 5 fatigue, 5 smoking, 4 alcohol, 6 variceal bleeding, 2 long history of inflammatory bowel disease, 5 and chronic ulcerative colitis with colon cancer/dysplasia. 8 However, these factors were not confirmed between the different studies.…”