Elsevier

Journal of Hepatology

Volume 50, Issue 1, January 2009, Pages 158-164
Journal of Hepatology

High lifetime risk of cancer in primary sclerosing cholangitis

https://doi.org/10.1016/j.jhep.2008.08.013Get rights and content

Background/Aims

Primary sclerosing cholangitis (PSC) patients are at risk for developing cholangiocarcinoma (CCA) and colorectal carcinoma (CRC). Our aim was to assess the risk of malignancies and their influence on survival.

Methods

Data from PSC patients diagnosed between 1980 and 2006 in two university hospitals were retrieved. The Kaplan–Meier method and a time-dependent Cox regression model were used to calculate risks of malignancies and their influence on survival.

Results

Two hundred and eleven patients were included, 143 (68%) were male and 126 (60%) had inflammatory bowel disease (IBD). Median transplantation-free survival was 14 years. The risk of CCA after 10 and 20 years was 9% and 9%, respectively. In patients with concomitant IBD the 10-year and 20-year risks for CRC were 14% and 31%, which was significantly higher than for patients without IBD (2% and 2% (P = 0.008)). CCA, cholangitis, and age at entry were independent risk factors for the combined endpoint death or liver transplantation. Risk factors for the endpoint death were CCA, CRC, age, and symptomatic presentation.

Conclusions

Patients with PSC and IBD have a high long-term risk of developing CRC and this risk is about threefold higher than the risk for CCA. Both malignancies are associated with decreased survival.

Introduction

Primary sclerosing cholangitis (PSC) is a chronic disease, characterized by inflammation and fibrosis of the intra- and extrahepatic bile ducts [1], [2]. The etiology is unknown and a therapy to stop or reverse progression of the disease is not available. Apart from the development of decompensated liver cirrhosis with transplantation as the only effective treatment, life expectancy of PSC patients is seriously threatened by the unpredictable occurrence of cholangiocarcinoma (CCA) and colorectal cancer (CRC).

The reported overall risk for CCA varies from 8% to 36% [3], [4], [5], [6] and the 10-year cumulative incidence from 11% to 31% [3], [7], [8], [9]. These highly variable results are probably largely explained by differences in patient selection and duration of follow-up. Few studies have assessed the risk of CRC in PSC. Up to 90% of patients with PSC have concurrent inflammatory bowel disease (IBD), a major risk factor for CRC [10], [11]. It is still debated whether PSC carries an additional and an independent risk for CRC. The frequent use of colorectal neoplasia (dysplasia and CRC) instead of CRC as a clinical endpoint of studies contributes to the difficulty to appreciate the actual CRC risk. Broome et al. [12] found cumulative risks for colorectal neoplasia of 9%, 31%, and 50% after an IBD disease duration of 10, 20, and 25 years, respectively. In contrast, others reported no significant difference in CRC risk between patients with PSC-IBD or IBD alone [13], [14], [15]. The aim of this study was to assess the risk of malignancies, in particular CRC and CCA, as well as their impact on survival in a large and long-term follow-up study of Dutch PSC patients.

Section snippets

Patients

All patients diagnosed with PSC in the period January 1980–May 2006 were identified from two databases (Endobase III, Olympus and the central hospital patient registration system) at the University Medical Center of Utrecht (UMCU) and the Erasmus MC University Medical Center Rotterdam, the latter being one of the three liver transplant centers in The Netherlands. PSC patients seen at the UMCU and with an indication for liver transplantation were referred to Rotterdam.

The diagnosis of PSC was

Patient characteristics at diagnosis of PSC

Two hundred and eleven patients (143 males) were included (Table 1). The median age at diagnosis was 33 years (range 11–72) for males and 40 years (range 11–75) for females. Seventy-six (36%) patients were symptomatic at the time of diagnosis. The most prevalent symptom was jaundice (n = 43). In most cases (84%) diagnosis of PSC was based on cholangiographic findings. Histology was available in 148 (70%) patients and showed cirrhosis in 23 cases. Concurrent IBD was present in 126 (60%) patients

Discussion

This large and long-term cohort study showed that PSC-IBD patients have a high lifetime risk for CRC and that this risk is substantially higher than that for CCA. Furthermore, occurrence of CRC in these patients leads to reduced survival chances.

Few and conflicting data on CRC risk in PSC have been reported. Loftus et al. [14] found an actuarial incidence at 10 years of only 4%, whereas Kornfeld et al. [24] reported a 10-year risk of 25%. The latter finding, however, was based on only five CRC

Acknowledgement

We thank R. Stellato, statistician, for her assistance with the analyses.

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    The authors declare that they do not have anything to disclose regarding funding from industries or conflict of interest with respect to this manuscript

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