Screening of primary sclerosing cholangitis patients by quantitative DNA analysis of bile duct specimens in order to schedule patients at high risk for liver transplantation

H Al-Abadi MD^a, R Hintze^b, H Abou-Rebyeh MD^b, S Jonas MD^a, CTIAC Rotter^a, P Neuhaus MD^a

^aDept. General-, Laboratory of Clinical Cytology and DNA-cytometry, Visceral- and Transplantation Surgery, Charité, Berlin, ^bDept. Hepatology and Gastroenterology, Charité, Berlin, Germany

Introduction: Primary sclerosing cholangitis (PSC) is a biliary destructive disease with increased risk for developing cholangiocarcinoma (CC). Today, liver transplantation is the only curative therapy. However, PSC patients at high risk should be accurately selected for transplantation. In an attempt to establish prognostic factors for this selection we investigated the value of quantitative DNA ploidy analysis. Material and Methods: This prospective study included 60 patients afflicted from PSC investigated within a period of four years (09/1998 and 01/2002). In all patients, biliary specimens were obtained by ERC-guided brush cytology. In case of dysplasia, DNA-ploidy was analysed by image cytometry. Follow up periods ranged from 9 to 36 months. Survival was calculated by using the Kaplan-Meier algorithm. Risk factors were identified in a Cox regression analysis. Results: 20% (12/60) of the PSC patients had cytomorphologicaly CC. The DNA-analysis of this patients showed DNA distributions typical for aneuploid tumors. These patients were excluded from transplantation and died within 8-12 months due to tumor progression. The further 80% (48/60) of patients revealed in the brush biopsies different degrees of dysplasia. 11 out of these 48 patients (23%) revealed dysplastic with aneupleuid DNA distribution. These patients received either transplantation (n=8) or liver resection (n=3). 2 of these patients died within 1 year after OLT. 12% (6/48) revealed dysplastic cells with polyploid DNA distribution. Thereof, 2 patients were liver grafted and are so far in good physical condition. 31 out of 48 patients showed dysplastic cells with a normal diploid DNA pattern. Therefore, these patients were followed up clinically and by ERC with brush cytology. Conclusion: Brush biopsy with quantitative DNA analysis in PSC patients could be a screening approach to identify PSC patients at higher risk for CC development. These increased risk PSC patients require either intensified follow up investigations or early liver transplantation.

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in poster session 897 (Precursor lesions).