Annals of Surgical Oncology

, Volume 15, Issue 2, pp 583–589 | Cite as

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

  • Takahiro Uenishi
  • Osamu Yamazaki
  • Hiromu Tanaka
  • Shigekazu Takemura
  • Takatsugu Yamamoto
  • Shogo Tanaka
  • Shuhei Nishiguchi
  • Shoji Kubo
Gastrointestinal Oncology



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.


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.


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.


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


Cytokeratin 19 fragment Tumor marker Intrahepatic cholangiocarcinoma Liver resection Postoperative outcome 


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Copyright information

© Society of Surgical Oncology 2007

Authors and Affiliations

  • Takahiro Uenishi
    • 1
  • Osamu Yamazaki
    • 2
  • Hiromu Tanaka
    • 1
  • Shigekazu Takemura
    • 1
  • Takatsugu Yamamoto
    • 1
  • Shogo Tanaka
    • 1
  • Shuhei Nishiguchi
    • 3
  • Shoji Kubo
    • 1
  1. 1.Department of Hepato-Biliary-Pancreatic SurgeryOsaka City University Graduate School of MedicineOsakaJapan
  2. 2.Department of Gastrointestinal SurgeryOsaka City General HospitalOsakaJapan
  3. 3.Division of Hepatobiliary and Pancreatic Diseases, Department of Internal MedicineHyogo College of MedicineHyogoJapan

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