Value of Brush Border Cytology for Dominant Strictures in Primary Sclerosing Cholangitis

Some 8 % of patients with primary sclerosing cholangitis (PSC) develop cholangiocarcinoma, and the incidence of this tumor in patients with end-stage disease attending transplantation centers is even higher [[1]]. Many attempts have therefore been made to identify measures capable of detecting the tumor at an earlier stage in its progress. The imaging methods currently available (endoscopic retrograde cholangiography, computed tomography, magnetic resonance imaging, and magnetic resonance cholangiopancreatography) have not so far been able to accomplish this. Reports describing good sensitivity with intraductal ultrasound [[2]] and positron emission tomography (PET) [[3]] require further confirmation. In the study by the Amsterdam group published in this issue of Endoscopy [[4]], brush cytology samples from dominant strictures in 43 patients were taken on 63 occasions, and the positive and negative predictive values were evaluated. Of the ten patients who ultimately proved to have a tumor, the cytology was positive in only four (40 %). In the 37 patients who had no tumor after two years of observation, four had false-positive cytology samples. The authors therefore conclude that the positive predictive value of this method is poor, while its negative predictive value is limited. This study is in line with others, and it puts an end to optimistic reports suggesting that there might be an easy method of achieving early detection of cholangiocarcinoma in PSC.

The measurement of the tumor markers p53 and K-ras in the brush specimens was of no additional value. Recently, it has been shown that cholangiocarcinoma in PSC was associated with p53 abnormalities in 78.5 % of cases when assessed in surgically obtained tumor tissue [[5]]. Abnormalities in p53 apparently occur at a late stage in the development of the malignant process and are often not found in the brush cytology specimens, so that this marker does not allow early detection of cholangiocarcinoma.

Unfortunately, as other studies have shown, attempts to use markers such as serum carcinoembryonic antigen (CEA) and Ca 19-9 have also proved to be of limited or no value for detection [[6]].

The message from this and other studies is that there is as yet no method of detecting cholangiocarcinomas at an early stage; when the tumors have reached a size that allows detection, the prognosis is very poor. The conclusion that has been drawn at some centers - that such patients should undergo transplantation at very early stages of the disease, at the first look - appears to be the logical conclusion. However, the statistics regarding the outcome in PSC patients after liver transplantation at centers where early transplantation is recommended indicate that after eight years, 20-30% have died due to sequelae of transplantation [[7]]. Carrying out prophylactic transplantation in PSC patients with precirrhotic liver disease in order to prevent cholangiocarcinoma may therefore not be the answer.

As yet, there is no method of early detection available, and there are no prospects for solving the problem once carcinoma has developed. At present, the only hope is that the recent trend in studies using ursodeoxycholic acid, suggesting that patients with PSC who are treated with this bile acid may develop fewer cholangiocarcinomas, will be confirmed in the future [[8] [9]].

References

• 1 Broome U, Olsson R, Lööf L, et al. Natural history and prognostic factors in 305 Swedish patients with primary sclerosing cholangitis.  Gut. 1996;  38 610-5
• 2 Tamada K, Ueno N, Tomiyama T, et al. Characterization of biliary strictures using intraductal ultrasonography: comparison with percutaneous cholangioscopic biopsy.  Gastrointest Endosc. 1998;  47 341-9
• 3 Dahlerup J F, Keiding S, Hansen S B, et al. Detection of cholangiocarcinoma in patients with primary sclerosing cholangitis by positron emission tomography (abstract).  Digestion. 1998;  59 (Suppl. 3) 26
• 4 Ponsioen C IJ, Vrouenraets S ME, van Milligen de Wit A WM, et al. Value of brush border cytology for dominant strictures in primary sclerosing cholangitis.  Endoscopy. 1999;  31 305-9
• 5 Rizzi P M, Portman B, Ramage J K, et al. p53 protein overexpression in cholangiocarcinoma arising in primary sclerosing cholangitis.  Gut. 1996;  38 265-8
• 6 Hultcrantz R, Olson R, Danielson A, et al. J Hepatol 1999 30: 669-73
• 7 Luftus E V, Aguilar H J, Sandborn W, et al. Risk of colorectal neoplasia in patients with primary biliary sclerosing cholangitis and ulcerative colitis following orthotopic liver transplantation.  Hepatology. 1998;  27 685-90
• 8 Lindor K D, Mayo PSC/UDCA Study Group. Ursodiol for the treatment of primary sclerosing cholangitis.  N Engl J Med. 1997;  336 691-5
• 9 Stiehl A, Rudolph G, Sauer P, et al. Efficacy of ursodeoxycholic acid and endoscopic dilation of major duct stenoses in primary sclerosing cholangitis: an 8-year prospective study.  J Hepatol. 1997;  26 560-6