Utility of serum tumor markers, imaging, and biliary cytology for detecting cholangiocarcinoma in primary sclerosing cholangitis†

Abstract

There is limited information on test performance for detecting cholangiocarcinoma in primary sclerosing cholangitis (PSC), particularly when used sequentially. This study aimed to characterize diagnostic performance of serum carbohydrate antigen 19-9 (CA 19-9), ultrasonography, computed tomography, magnetic resonance imaging, cholangiography, and biliary cytologic techniques for detecting cholangiocarcinoma in PSC. All consecutive patients with PSC were screened and followed for development of cholangiocarcinoma from 2000 through 2006. Of 230 patients, 23 developed cytopathologically confirmed cholangiocarcinoma with an annual incidence of 1.2%. The optimal cutoff value for serum CA 19-9 was 20 U/mL, which yielded a sensitivity of 78%, specificity of 67%, positive predictive value (PPV) of 23%, and negative predictive value (NPV) of 96%. Serum CA 19-9 combined with either ultrasonography, computed tomography, or magnetic resonance imaging provided a sensitivity of 91%, 100%, and 96%, specificity of 62%, 38%, and 37%, PPV of 23%, 22%, and 24%, and NPV of 98%, 100%, and 98%, respectively, if at least one method was positive. Subsequent cholangiographic examinations in these patients increased specificity to 69% and PPV to 42% while maintaining sensitivity of 91% and NPV of 96%. Following this group, conventional cytology, aneuploidy detection by digital imaging analysis, and aneusomy detection by fluorescence in situ hybridization in brushing samples of biliary strictures had a sensitivity of 50%, 57%, and 86%, specificity of 97%, 94%, and 83%, PPV of 86%, 89%, and 80%, and NPV of 83%, 74%, and 88%, respectively, for detecting cholangiocarcinoma. Conclusion: Tumor serology combined with cross-sectional liver imaging may be useful as a screening strategy and cholangiography with cytologic examination is helpful for the diagnosis of cholangiocarcinoma in patients with PSC. C holangiocarcinoma occurs with increased frequency in patients with primary sclerosing cholangitis (PSC) and is currently a leading cause of death in these patients. [1][2][3][4] The development of cholangiocarcinoma is unpredictable on the basis of the duration, symptoms, and severity of PSC. 2,4 The cholangiographic appearance of benign strictures of PSC makes the diagnosis of cholangiocarcinoma difficult in this setting. Most patients are diagnosed with advanced unresectable disease, which imparts a dismal prognosis and is a contraindication of liver transplantation. 3 However, innovative approaches using a combination of neoadjuvant chemoradiotherapy and liver transplantation provide excellent outcomes with 5-year survival of 82% in Abbreviations: AUC, area under the curve; CT, computed tomography; DIA, digital From the

Dominant strictures in primary sclerosing cholangitis: A multicenter survey of clinical definitions and practices

“…Multimodal approaches, including a combination of laboratory tests, cross‐sectional imaging, and endoscopic testing, are frequently required for this purpose. Use of serum CA 19‐9 in combination with ultrasonography, computed tomography, or magnetic resonance imaging has been reported to have a sensitivity of 91%, 100%, and 96%, respectively (when at least one modality is positive) 35. Conversely, individual tests generally have suboptimal performance characteristics.…”

“…Conversely, individual tests generally have suboptimal performance characteristics. For example, conventional brush cytology has excellent specificity (nearly 100%) but limited sensitivity (ranging from 18%‐40%) in diagnosing CCA 15, 35, 36, 37, 38, 39. Similarly, while serum CA 19‐9 has a reported sensitivity and specificity of 79% and 98%, respectively, at a cut‐off value of 130 U/mL,40 its levels may become elevated in the setting of nonmalignant obstruction or acute cholangitis, and it is undetectable in Lewis blood antigen‐negative patients (and remains so even in the presence of CCA) 41.…”

Liver transplantation and whipple surgery combined with chemoradiotherapy for treatment of hilar cholangiocarcinoma in patients with primary sclerosing cholangitis

“…5 ERCP with brush cytology and tumor markers has been applied to PSC patients for the detection of CC with limited success. 6 Therefore, the entire biliary epithelium is at risk of a malignant transformation. Bergquist et al 7 showed that more than 60% of patients with PSC have bile duct dysplasia in the liver.…”

Brazilian society of hepatology recommendations for the diagnosis and management of autoimmune diseases of the liver

“…In regard to CC, screening strategies employing imaging techniques, preferentially with MRI, but also ultrasound and computed tomography, in association with tumor biomarkers have been suggested strategies (241,244) , but their accuracy in detecting CC was reported to be low (244,245) . The most commonly employing biomarker for CC in PSC is CA19-9.…”