Journal of Hepatology
Volume 36, Issue 3 , Pages 433-434, March 2002

Primary sclerosing cholangitis: neoplastic potential in bile ducts, colon and the pancreas?

  • Adolf Stiehl

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    • Corresponding Author InformationTel.: +49-6221-568-707; fax: +49-6221-565-687

Department of Medicine, University of Heidelberg, Medizinische Universitätsklinik, Bergheimertsr. 58, D-69115 Heidelberg, Germany

Accepted 2 January 2002.

See Article, pages 321–327

Article Outline

 

It is well established that patients with primary sclerosing cholangitis (PSC) have an increased risk of developing a cholangiocarcinoma [1], [2], [3]. If such patients have ulcerative colitis they probably have an even higher risk of developing a colonic carcinoma than those with colitis without PSC [4]. As we learn from the present article by Bergquist et al. [5], patients with PSC also have an increased risk of developing a pancreatic carcinoma.

The cumulative risk of developing a cholangiocarcinoma in various studies varies from 5% to over 20%. These differences are due to differences in patient selection and diagnostic procedures used to identify the bile duct carcinoma. In patients with endstage liver disease presenting at transplantation centers the incidence of such tumors usually is higher than in the average PSC population. In a study of 305 patients Broome et al. [3] previously already had shown that in patients who died or were transplanted overall 30% had a cholangiocarcinoma whereas in its incidence in all 305 patients was only 8%. In the extension of this previous study the authors now report on 604 Swedish patients with PSC which represents the largest population of PSC patients ever studied. The study can be considered the most representative study on the natural course of the disease ever published since: (a) the majority of Swedish patients having the disease have been included; and (b) only in 26% who died or were transplanted the liver had not been evaluated at autopsy or at liver transplantation. The incidence of hepatobiliary carcinomas in the present study was 13%. This figure is higher than in many previous studies which may be due to the very high rate of livers studied at liver transplantation or at autopsy. In view of the fact that the diagnosis of cholangiocarcinoma is sometimes very difficult to establish, reliable data can only be obtained in studies in which a high proportion of explanted livers are examined. In this respect the presented study may be considered unique since in most other countries such high autopsy rates are not achieved.

Many of the hepatobiliary carcinomas (37%) were diagnosed within 1 year after the first diagnosis of the disease. After the 1st year the annual incidence of hepatobiliary carcinomas was 1.5% per year. This seems to confirm an earlier study of the same group of authors [3] in which no difference in time from the first diagnosis of PSC until the diagnosis of cholangiocarcinoma between patients developing and not developing a cholangiocarcinoma was found. The data indicate that one has to be aware of a high incidence of bile duct carcinomas already in the 1st year after the diagnosis of PSC has been made. This is especially the case in older patients. Unfortunately up to now there is no good tool to detect these carcinomas early. Brush cytology of the bile duct [6] is hampered by the number of 40% false negative and 11% false positive results. The sensitivity and specificity of the tumor marker Ca 19-9 over 100 U/ml in detecting a cholangiocacinoma has been reported to be 75 and 80% [7]. In the hand of others, however, Ca 19-9 is no reliable marker of cholangiocarcinoma [8] and its value in detecting early carcinomas is unclear. Several reports suggest that PET allows the detection of cholangiocarcinoma with a relatively high sensitivity and specificity [9], [10] but these data need confirmation in larger trials. In view of the bad prognosis of cholangiocarcinoma, markers of early cholangiocarcinoma are urgently needed but up to now are not available. Liver transplantation at an very early stage might prevent the development of cholangiocarcinomas. However, the evaluation of the outcome of PSC patients after transplantation at centers where early transplantation is recommended indicates that after 8 years, 20–30% have died after transplantation [11]. This figure is similar to that of the present study in which 34% of PSC patients have died after transplantation during a median follow-up of 5.7 years. Prophylactic transplantation in order to prevent cholangiocarcinomas may therefore not be the answer. At present the hope is that the recent trend in studies using ursodeoxycholic acid for the treatment of PSC, suggesting that patients treated with this bile acid may develop fewer cholangiocarcinomas [12], [13], will be confirmed in the future.

In the study by Bergquist et al. [5] for the first time an 14-fold increased incidence of pancreatic carcinomas has been demonstrated. Surprisingly the risk is even higher than that of colonic carcinomas which was only 10-fold increased. The figure may be somewhat overestimated due to the overlap of pancreatic carcinomas in the head of the pancreas and bile duct carcinomas at the same location and the difficulties in differentiating one from the other. The large cohort and the long observation time of this study makes it likely that there is a true increased risk of PSC patients to have a pancreatic carcinoma. The underlying mechanism is not clear. An increased incidence of pancreatic duct alterations has been described earlier [14], [15] but the findings have not been confirmed by others [16]. From now on the increased incidence of pancreatic carcinomas in PSC has to be considered in the clinical work up of PSC patients. Unfortunately, pancreatic carcinomas similar to cholangiocarcinomas very often are only diagnosed in an advanced stage of the disease when curative resection is no more possible and as a consequence of this the 5 year survival is very poor.

Of the patients studied 79% had inflammatory bowel disease and of these, during the time of follow-up, 2.5% developed a colonic carcinoma which is ten times the expected incidence. The increased incidence of colonic carcinomas in patients with PSC and colitis is well established [4]. In contrast to bile duct and pancreatic carcinomas these colonic carcinomas can be detected at an early stage of the disease and may be treated with good success. Therefore the search for colonic adenomas and carcinomas by colonoscopy in regular time intervals appears mandatory.

The authors present the largest cohort of PSC patients ever studied presenting the majority of all Swedish PSC patients. The use of the complete National Swedish cancer registry with a follow-up of all patients decreases the risk of cancer underestimation. Apart from this also the high autopsy frequency which is not achieved in other countries make this work a unique study. The cause of death was cancer in 44% of patients. The study convincingly demonstrates the high neoplastic potential in patients with PSC. Unfortunately, up to now there is no method of early detection of cholangiocarcinomas and pancreatic carcinomas available. When the tumors have reached a size that allows detection, the prognosis is very poor.

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References 

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PII: S0168-8278(02)00016-8

Journal of Hepatology
Volume 36, Issue 3 , Pages 433-434, March 2002

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