title: Biliary dysplasia in patients with primary sclerosing cholangitis: additional value of DNA ploidity.
abstract: BACKGROUND
  Detection of biliary dysplasia in PSC is essential for proper timing of liver transplantation to prevent the development of cholangiocancer, which is considered a contraindication for liver transplantation in most centres. In patients with PSC, differential diagnosis of benign, premalignant and malignant biliary strictures is difficult.
  
  
  OBJECTIVE
  This prospective study aimed to evaluate the role of DNA analysis in combination with brush cytology, scored ERCP findings, and tumour markers to detect hepatobiliary dysplasia and malignancy.
  
  
  METHODS
  Brush samples for cytology and for evaluation of DNA content analysed with flow cytometry came from 102 consecutive PSC patients referred for ERCP. Symptoms, serum Ca19-9 and CEA were determined at the time of index biliary examination. ERCP findings were scored for intra- and extrahepatic changes. The end-points were liver transplantation or diagnosis of malignancy or dysplasia.
  
  
  RESULTS
  Most of the patients were asymptomatic at the time of ERCP: 73% had no symptoms, and 12% had only mild symptoms. An aneuploid DNA content was evident in 20 (20%) patients, and cells suspected for malignancy in 22 (21%). Seven patients had both aneuploidity and cytology (7%) suspicious for malignancy. An end-point, diagnosis of malignancy or liver transplantation was achieved in 42 patients. Combining DNA ploidity and cytology in patients at the end-point, sensitivity was 72%, specificity 82%, positive predictive value 86% and negative predictive value 67%.
  
  
  CONCLUSIONS
  In this mostly asymptomatic PSC-patient population, 33% demonstrated abnormal brush cytology or aneuploidity. Determining DNA ploidy and brush cytology during ERCP offers a useful tool for identifying those PSC patients who are at high risk of developing cholangiocancer.
authors.affiliation: Department of Gastroenterologic Surgery, Helsinki University Hospital, Helsinki, Finland. leena.halme@hus.fi
authors.forename: Leena
authors.initials: L
authors.lastname: Halme
authors.forename: Johanna
authors.initials: J
authors.lastname: Arola
authors.forename: Kirsti
authors.initials: K
authors.lastname: Numminen
authors.forename: Leena
authors.initials: L
authors.lastname: Krogerus
authors.forename: Heikki
authors.initials: H
authors.lastname: Mäkisalo
authors.forename: Martti
authors.initials: M
authors.lastname: Färkkilä
mesh_terms: D000328:Adult; D001661:Biliary Tract Neoplasms / Q000175:diagnosis / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000097:blood; D001706:Biopsy / Q000379:methods; D018395:CA-19-9 Antigen / Q000097:blood; D018281:Cholangiocarcinoma / Q000175:diagnosis / Q000235:genetics*; D002760:Cholangiopancreatography, Endoscopic Retrograde; D015209:Cholangitis, Sclerosing / Q000150:complications*; D004273:DNA, Neoplasm / Q000032:analysis*; D005434:Flow Cytometry; D006801:Humans; D011003:Ploidies; D011446:Prospective Studies
chemical_list: D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; D004273:DNA, Neoplasm