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10.1245/s10434-007-9650-y
Annals of Surgical Oncology 15:583-589 (2008)
© 2008 Society of Surgical Oncology
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Original Article

Serum Cytokeratin 19 Fragment (CYFRA21-1) as a Prognostic Factor in Intrahepatic Cholangiocarcinoma

Takahiro Uenishi, MD1, Osamu Yamazaki, MD2, Hiromu Tanaka, MD1, Shigekazu Takemura, MD1, Takatsugu Yamamoto, MD1, Shogo Tanaka, MD1, Shuhei Nishiguchi, MD3 and Shoji Kubo, MD1

1 Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
2 Department of Gastrointestinal Surgery, Osaka City General Hospital, Osaka, Japan
3 Division of Hepatobiliary and Pancreatic Diseases, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan

Correspondence: Address correspondence and reprint requests to: Takahiro Uenishi, MD; E-mail: m6877710{at}msic.med.osaka-cu.ac.jp

Background: A high serum cytokeratin 19 fragment (CYFRA21-1) concentration in patients with various cancers is associated with poor prognosis. This study aimed to establish the clinical significance of preoperative serum CYFRA21-1 in patients with intrahepatic cholangiocarcinoma.

Methods: CYFRA21-1, carcinoembryonic antigen (CEA), and carbohydrate antigen (CA) 19-9 concentrations were measured in sera from 71 patients with intrahepatic cholangiocarcinoma. The prognostic significance of serum CYFRA21-1 levels was assessed by univariate and multivariate analyses.

Results: Analysis of the areas under the receiver operator characteristic (ROC) curves clearly showed better discrimination between intrahepatic cholangiocarcinoma and benign liver diseases for CYFRA 21-1 than for CEA or CA 19-9. Based on the maximization of the Youden’s index, the optimal cut-off value was 2.7 ng ml–1 for CYFRA 21-1 (sensitivity, 74.7%; specificity, 92.2%). The serum CYFRA21-1 concentration was related to tumor stage, since the CYFRA21-1 concentrations varied according to tumor size, vascular invasion, and number of tumors. The 3-year recurrence-free survival rates for patients with high and low concentrations of CYFRA21-1 were 25.0% and 76.2%, respectively (log-rank test, p < 0.01). The 3-year overall survival rates for patients with high and low concentrations of CYFRA21-1 were 39.4% and 63.6%, respectively (p = 0.01). On multivariate analysis, a high concentration of CYFRA21-1, nodal metastases, and a microscopic resection margin involvement were independent prognostic factors associated with both tumor recurrence and postoperative death.

Conclusions: A high serum CYFRA21-1 concentration is associated with tumor progression and poor postoperative outcomes in patients with intrahepatic cholangiocarcinoma.

Key Words: Cytokeratin 19 fragment • Tumor marker • Intrahepatic cholangiocarcinoma • Liver resection • Postoperative outcome






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