Primary Sclerosing Cholangitis: Malignancy and Mortality
Primary Sclerosing Cholangitis: Malignancy and Mortality
Background: The outcome of primary sclerosing cholangitis (PSC) has improved by liver transplantation (LT), but patients often develop malignancies. We analysed morbidity and mortality patterns to define strategies to prevent complications.
Methods: Two hundred consecutive patients diagnosed before October 2005 were studied.
Results: Malignancies developed in 40 (20%) and led to death in 28 patients (45.9% of the 61 mortalities). Cholangiocarcinoma (CCa) developed in 13 patients, and was detected shortly after the diagnosis of PSC in 31%. Colorectal carcinomas were documented in 10 and dysplastic adenomas in four patients; eight had ulcerative colitis, two Crohn's colitis, one unclassified inflammatory bowel disease (IBDu), three had no IBD. Five died of colorectal cancer. Three carcinomas and two adenomas were localized in the caecum or ascending colon, but most (n=10) in the recto-sigmoidal region. Hepatocellular carcinoma developed in three patients with advanced fibrosis/cirrhosis, and pancreatic cancer in five. LT has been carried out in 42 patients, 6.1 years (median, 0.5–25) after the diagnosis of PSC. Mortality was due to hepatic complications in 13 patients. Within 5 years of the diagnosis, deaths were because of malignancy in 12 patients and to hepatobiliary decompensation in only three, whereas 18 had been transplanted.
Conclusions: Since the use of transplantation, malignancies are the major cause of death. CCa has to be searched for in any new symptomatic patient. Colorectal malignancy occurs frequently. Colonoscopy at the diagnosis of PSC is obligatory and should be repeated at 1–2 years interval in the patients with IBD and every 5 years in those without IBD.
Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease with inflammation and progressive fibrosis of the bile ducts. It gradually leads to a biliary type of cirrhosis with portal hypertension. The exact cause of the disease remains unknown, but a genetic predisposition exists. Adequate curative treatment is presently not available. Liver transplantation (LT) has greatly altered the dismal prognosis as > 80% of patients survive 5 years after LT. This survival rate is in marked contrast with the natural history of PSC without LT, since 50% of symptomatic patients are dead within approximately 8 years, and 25% of asymptomatic patients within 7 years. The 50% survival rate in a recent study from Germany was <3 years in persistently jaundiced patients and 11–12 years in non-jaundiced PSC patients.
A large proportion (60–80%) of PSC patients has associated inflammatory bowel disease (IBD), most often ulcerative colitis (UC). It is well recognized that patients with PSC run a severe risk to develop cholangiocarcinoma (CCa), but a high incidence of other tumours such as colorectal, hepatic and pancreatic carcinomas has also been reported. We analysed the incidence and nature of malignant diseases and the pattern of mortality in a cohort of 200 consecutive PSC patients with a median follow-up of 12.4 years (CI: [10.3, 14.0]). The aim was to identify the development of malignancies with regards to morbidity and mortality in an era in which LT was available and to try to define strategies to prevent these malignant and other complications.
Abstract and Introduction
Abstract
Background: The outcome of primary sclerosing cholangitis (PSC) has improved by liver transplantation (LT), but patients often develop malignancies. We analysed morbidity and mortality patterns to define strategies to prevent complications.
Methods: Two hundred consecutive patients diagnosed before October 2005 were studied.
Results: Malignancies developed in 40 (20%) and led to death in 28 patients (45.9% of the 61 mortalities). Cholangiocarcinoma (CCa) developed in 13 patients, and was detected shortly after the diagnosis of PSC in 31%. Colorectal carcinomas were documented in 10 and dysplastic adenomas in four patients; eight had ulcerative colitis, two Crohn's colitis, one unclassified inflammatory bowel disease (IBDu), three had no IBD. Five died of colorectal cancer. Three carcinomas and two adenomas were localized in the caecum or ascending colon, but most (n=10) in the recto-sigmoidal region. Hepatocellular carcinoma developed in three patients with advanced fibrosis/cirrhosis, and pancreatic cancer in five. LT has been carried out in 42 patients, 6.1 years (median, 0.5–25) after the diagnosis of PSC. Mortality was due to hepatic complications in 13 patients. Within 5 years of the diagnosis, deaths were because of malignancy in 12 patients and to hepatobiliary decompensation in only three, whereas 18 had been transplanted.
Conclusions: Since the use of transplantation, malignancies are the major cause of death. CCa has to be searched for in any new symptomatic patient. Colorectal malignancy occurs frequently. Colonoscopy at the diagnosis of PSC is obligatory and should be repeated at 1–2 years interval in the patients with IBD and every 5 years in those without IBD.
Introduction
Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease with inflammation and progressive fibrosis of the bile ducts. It gradually leads to a biliary type of cirrhosis with portal hypertension. The exact cause of the disease remains unknown, but a genetic predisposition exists. Adequate curative treatment is presently not available. Liver transplantation (LT) has greatly altered the dismal prognosis as > 80% of patients survive 5 years after LT. This survival rate is in marked contrast with the natural history of PSC without LT, since 50% of symptomatic patients are dead within approximately 8 years, and 25% of asymptomatic patients within 7 years. The 50% survival rate in a recent study from Germany was <3 years in persistently jaundiced patients and 11–12 years in non-jaundiced PSC patients.
A large proportion (60–80%) of PSC patients has associated inflammatory bowel disease (IBD), most often ulcerative colitis (UC). It is well recognized that patients with PSC run a severe risk to develop cholangiocarcinoma (CCa), but a high incidence of other tumours such as colorectal, hepatic and pancreatic carcinomas has also been reported. We analysed the incidence and nature of malignant diseases and the pattern of mortality in a cohort of 200 consecutive PSC patients with a median follow-up of 12.4 years (CI: [10.3, 14.0]). The aim was to identify the development of malignancies with regards to morbidity and mortality in an era in which LT was available and to try to define strategies to prevent these malignant and other complications.