Endoscopy 2006; 38(6): 561-565
DOI: 10.1055/s-2006-925387
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Diagnostic and Prognostic Implications of DNA Ploidy and S-Phase Evaluation in the Assessment of Malignancy in Biliary Strictures

B.  Lindberg1 , L.  Enochsson2 , B.  Tribukait3 , U.  Arnelo2 , A.  Bergquist4
  • 1 Department of Radiology, Karolinska University Hospital, Karolinska Institutet, Sweden
  • 2 Division of Surgery, Karolinska University Hospital, Karolinska Institutet, Sweden
  • 3 Department of Radiobiology, Karolinska University Hospital, Karolinska Institutet, Sweden
  • 4 Department of Gastroenterology and Hepatology, Karolinska University Hospital, Karolinska Institutet, Sweden
Further Information

Publication History

Submitted 17 May 2005

Accepted after revision 3 September 2005

Publication Date:
27 June 2006 (online)

Background and Study Aims: Brush cytology of biliary strictures has a low sensitivity for diagnosing malignancy, and additional diagnostic tools are needed. The aim of the present study was to assess the diagnostic and prognostic importance of DNA measurements as an adjunct to brush cytology in patients with biliary strictures.
Patients and Methods: All patients (n = 225) with bile duct strictures who underwent endoscopic retrograde cholangiopancreatography (ERCP) between January 1997 and October 2003 at the Department of Radiology at Karolinska University Hospital, Huddinge, Sweden, were included in the study. While 66 patients had an unclear final diagnosis and were therefore excluded, the remaining 159 patients were assessed with brush cytology and DNA flow cytometry.

Results: Sensitivity and specificity of DNA aneuploidy for tumor detection were 43 % and 96 %. Using DNA analysis in addition to brush cytology, the sensitivity was 62 % compared with 57 % for brush cytology alone (not significant). Patients with diploid DNA tumors had a significantly better survival than patients with aneuploid DNA tumors (P = 0.02). The mean survival was 10 months for diploid cancers and 6 months for aneuploid cancers.

Conclusion: DNA ploidy measurement may be a diagnostic method that could supplement brush cytology in the identification of malignancy in biliary strictures. DNA aneuploidy is a marker of poor prognosis in patients with malignant biliary strictures.

References

  • 1 Lammer J, Herlinger H, Zalaudek G, Hofler H. Pseudotumorous pancreatitis.  Gastrointest Radiol. 1985;  10 59-67
  • 2 Verbeek P C, van Leeuwen D J, de Wit L T. et al . Benign fibrosing disease at the hepatic confluence mimicking Klatskin tumors.  Surgery. 1992;  112 866-871
  • 3 Menges M, Lerch M M, Zeitz M. The double duct sign in patients with malignant and benign pancreatic lesions.  Gastrointest Endosc. 2000;  52 74-77
  • 4 Bergquist A, Ekbom A, Olsson R. et al . Hepatic and extrahepatic malignancies in primary sclerosing cholangitis.  J Hepatol. 2002;  36 321-327
  • 5 Ferrari Jr A P , Lichtenstein D R, Slivka A. et al . Brush cytology during ERCP for the diagnosis of biliary and pancreatic malignancies.  Gastrointest Endosc. 1994;  40 140-145
  • 6 Rabinovitz M, Zajko A B, Hassanein T. et al . Diagnostic value of brush cytology in the diagnosis of bile duct carcinoma: a study in 65 patients with bile duct strictures.  Hepatology. 1990;  12 747-752
  • 7 Ryan M E. Cytological brushings of ductal lesions during ERCP.  Gastrointest Endosc. 1991;  37 139-142
  • 8 Sears R J, Duckworth C W, Decaestecker C. et al . Image cytometry as a discriminatory tool for cytologic specimens obtained by endoscopic retrograde cholangiopancreatography.  Cancer. 1998;  84 119-126
  • 9 Rumalla A, Baron T H, Leontovich O. et al . Improved diagnostic yield of endoscopic biliary brush cytology by digital image analysis.  Mayo Clin Proc. 2001;  76 29-33
  • 10 Ryan M E, Baldauf M C. Comparison of flow cytometry for DNA content and brush cytology for detection of malignancy in pancreaticobiliary strictures.  Gastrointest Endosc. 1994;  40 133-139
  • 11 Lindberg B, Arnelo U, Bergquist A. et al . Diagnosis of biliary strictures in conjunction with endoscopic retrograde cholangiopancreaticography, with special reference to patients with primary sclerosing cholangitis.  Endoscopy. 2002;  34 909-916
  • 12 Lundin J, Nordling S, von Boguslawsky K. et al . Prognostic value of Ki-67 expression, ploidy and S-phase fraction in patients with pancreatic cancer.  Anticancer Res. 1995;  15 2659-2668
  • 13 Karlen P, Kornfeld D, Brostrom O. et al . Is colonoscopic surveillance reducing colorectal cancer mortality in ulcerative colitis? A population based case control study.  Gut. 1998;  42 711-714
  • 14 Bergquist A, Lindberg B, Castro J, Tribukait B. Methodologic aspects of evaluating brush samples from biliary strictures by cytology and DNA flow cytometry.  Acta Cytol. 2004;  48 341-347
  • 15 Bohorfoush A, Franco J, Komorowski R. et al . Flow cytometric analysis of bile duct epithelium in primary sclerosing cholangitis potentially assists in timing of liver transplantation [abstract].  Gastrointest Endosc A. 1997;  45 Abstract no 394
  • 16 Baron T H, Harewood G C, Rumalla A. et al . A prospective comparison of digital image analysis and routine cytology for the identification of malignancy in biliary tract strictures.  Clin Gastroenterol Hepatol. 2004;  2 214-219
  • 17 Harewood G C, Baron T H, Stadheim L M. et al . Prospective, blinded assessment of factors influencing the accuracy of biliary cytology interpretation.  Am J Gastroenterol. 2004;  99 1464-1469
  • 18 Brunt E M, Kraemer B B. DNA image analysis study of lesions of the gallbladder and biliary system.  Liver Transpl Surg. 1996;  2 284-289
  • 19 Bergquist A, Tribukait B, Glaumann H, Broomé U. Can DNA cytometry be used for evaluation of malignancy and premalignancy in bile duct strictures in primary sclerosing cholangitis?.  J Hepatol. 2000;  33 873-877
  • 20 Abou-Rebyeh H, Al-Abadi H, Jonas S. et al . DNA analysis of cholangiocarcinoma cells: prognostic and clinical importance.  Cancer Detect Prev. 2002;  26 313-319
  • 21 Yeaton P, Kiss R, Deviere J. et al . Use of cell image analysis in the detection of cancer from specimens obtained during endoscopic retrograde cholangiopancreatography.  Am J Clin Pathol. 1993;  100 497-501
  • 22 Brandsaeter B, Isoniemi H, Broome U. et al . Liver transplantation for primary sclerosing cholangitis; predictors and consequences of hepatobiliary malignancy.  J Hepatol. 2004;  40 815-822
  • 23 Goss J A, Shackleton C R, Farmer D G. et al . Orthotopic liver transplantation for primary sclerosing cholangitis. A 12-year single center experience.  Ann Surg. 1997;  225 472-481

B. Lindberg, M. D., Ph. D.

Department of Radiology

Karolinska University Hospital · S-141 86 Stockholm · Sweden

Fax: +46 8 7114840

Email: bo.lindberg@ki.se

    >