Value of Brush Cytology for Dominant Strictures in Primary Sclerosing Cholangitis

 

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Background and Study Aims: Around 10 % of patients with primary sclerosing cholangitis (PSC) develop cholangiocarcinoma, which is cholangiographically often indistinguishable from a benign dominant stricture. The aim of the present study was to assess the value of brush cytology in discriminating between benign and malignant dominant strictures in primary sclerosing cholangitis.

Patients and Methods: The results of all brush cytology specimens from dominant strictures from patients with established primary sclerosing cholangitis, taken at endoscopic retrograde cholangiopancreatography between 1987 and 1996, were compared with the histological diagnosis or clinical status of the patients at least 2 years later.

Results: A total of 47 brush cytology samples, taken between 1987 and 1996, from 43 PSC patients could be in-cluded. Between 1993 and 1996, p53 immunocytochemical examination was done in 27 brush cytology specimens and K-ras mutation analysis in 25 patients. The sensitivity, specificity, positive predictive value, and negative predictive value of brush cytology for detection of malignancy were 60 %, 89 %, 59 %, and 89 %, respectively. These figures were not improved by adding the results of p53 and K-ras analysis. Logistic regression analysis did not reveal any additional benefit of p53 or K-ras analysis either. Prior stenting did not adversely affect specificity.

Conclusions: The sensitivity and positive predictive value of brush cytology for dominant strictures in PSC are rather poor. The specificity and negative predictive value are reasonably good. There was no additional value from p53 immunocytochemistry and K-ras mutation analysis. Prior stenting did not affect the results.

References

• 1 Broomé U, Olsson R, Loof L, et al. Natural history and prognostic factors in 305 Swedish patients with primary sclerosing cholangitis.  Gut. 1996;  38 610-5
  PubMedGoogle Scholar
• 2 Farrant JM, Hayllar KM, Wilkinson ML, et al. Natural history and prognostic variables in primary sclerosing cholangitis.  Gastroenterology. 1991;  100 1710-7
  PubMedGoogle Scholar
• 3 Wiesner RH, Grambsch PM, Dickson ER, et al. Primary sclerosing cholangitis: natural history, prognostic factors and survival analysis.  Hepatology. 1989;  10 430-6
  PubMedGoogle Scholar
• 4 Rosen CB, Nagorney DM, Wiesner RH, et al. Cholangiocarcinoma complicating primary sclerosing cholangitis.  Ann Surg. 1991;  213 21-5
  PubMedGoogle Scholar
• 5 Farrant M, Williams R. Natural history and prognosis in primary sclerosing cholangitis.  Eur J Gastroenterol Hepatol. 1992;  4 272-5
  PubMedGoogle Scholar
• 6 Marsh JW, Iwatsuki S, Makowka L, et al. Orthotopic liver transplantation for primary sclerosing cholangitis.  Ann Surg. 1988;  207 21-5
  PubMedGoogle Scholar
• 7 Nashan B, Schlitt HJ, Tusch G, et al. Biliary malignancies in primary sclerosing cholangitis: timing for liver transplantation.  Hepatology. 1996;  23 1105-11
  PubMedGoogle Scholar
• 8 Abu-Elmagd KM, Selby R, Iwatsuki S, et al. Cholangiocarcinoma and sclerosing cholangitis: clinical characteristics and effect on survival after liver transplantation.  Transplant Proc. 1993;  25 1124-5
  PubMedGoogle Scholar
• 9 Mansfield JC, Griffin SM, Wadehra V, Matthewson K. A prospective evaluation of cytology from biliary strictures.  Gut. 1997;  40 671-7
  PubMedGoogle Scholar
• 10 Rabinovitz M, Zajko AB, Hassanein T, et al. Diagnostic value of brush cytology in the diagnosis of bile duct carcinoma: a study of 65 patients with bile duct strictures.  Hepatology. 1990;  12 747-52
  PubMedGoogle Scholar
• 11 Pugliese V, Conio M, Nicolo G, et al. Endoscopic retrograde forceps biopsy and brush cytology of biliary strictures: a prospective study.  Gastrointest Endosc. 1995;  42 520-6
  PubMedGoogle Scholar
• 12 Kurzawinski T, Deery A, Dooley J, et al. A prospective controlled study comparing brush and bile exfoliative cytology for diagnosing bile duct strictures.  Gut. 1992;  33 1675-7
  PubMedGoogle Scholar
• 13 Ponchon T, Gagnon P, Berger F, et al. Value of endobiliary brush cytology and biopsies for the diagnosis of malignant bile duct stenosis: results of a prospective study.  Gastrointest Endosc. 1995;  42 565-72
  PubMedGoogle Scholar
• 14 Rizzi PM, Ryder SD, Portmann B, et al. p53 Protein overexpression in cholangiocarcinoma arising in primary sclerosing cholangitis.  Gut. 1996;  38 265-8
  PubMedGoogle Scholar
• 15 Levi S, Urbano-Ispizua A, Gill R, et al. Multiple K-ras codon 12 mutations in cholangiocarcinomas demonstrated with a sensitive polymerase chain reaction technique.  Cancer Res. 1991;  51 3497-502
  PubMedGoogle Scholar
• 16 Ohashi K, Tsutsumi M, Nakajima Y, et al. High rates of Ki-ras point mutation in both intra- and extrahepatic cholangiocarcinomas.  Jpn J Clin Oncol. 1994;  24 305-10
  PubMedGoogle Scholar
• 17 Berg van den FM, Tigges AJ, Schipper MEI, et al. Expression of the nuclear oncogene p53 in colon tumours.  J Pathol. 1989;  157 193-9
  PubMedGoogle Scholar
• 18 Hruban RH, Sturm PD, Slebos RJ, et al. Can K-ras codon 12 mutations be used to distinguish benign bile duct proliferations from metastases in the liver? A molecular analysis of 101 liver lesions from 93 patients.  Am J Pathol. 1997;  151 943-9
  PubMedGoogle Scholar
• 19 Caldas C, Hahn SA, Hruban RH, et al. Detection of K-ras mutations in the stool of patients with pancreatic adenocarcinoma and pancreatic ductal hyperplasia.  Canc Res. 1994;  54 3568-73
  PubMedGoogle Scholar
• 20 Lavaissiere L, Jia S, Nishiyama M, et al. Overexpression of human aspartyl(asparaginyl)beta-hydroxylase in hepatocellular carcinoma and cholangiocarcinoma.  J Clin Invest. 1996;  98 1313-23
  PubMedGoogle Scholar

M.D. C. Y. Ponsioen

Dept. of Gastroenterology and Hepatology

Academic Medical Center

Meibergdreef 9

1105 AZ Amsterdam

Netherlands

Phone: + 31-20-6917033

Email: c.y.ponsioen@amc.uva.nl