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CYFRA 21-1 is a fragment of cytokeratin 19 (CK 19). Four patients with large intrahepatic (or peripheral) cholangiocarcinoma (CC) and high serum levels of CYFRA 21-1 (normal, < or = 2 ng/ml) are reported. CYFRA 21-1 levels exceeded 9 ng/ml in all 4 patients. Carcinoembryonic antigen (CEA), was high in 1 (CEA; normal range, < or = 5.0 ng/ml) and carbohydrate antigen 19-9 (CA 19-9) was high in 3 (CA19-9; normal range, < or = 36 U/ml). We also measured serum levels of CYFRA 21-1 in 13 patients with hepatocellular carcinoma (HCC) more than 5 cm in diameter. Levels of CYFRA 21-1 exceeded 2 ng/ml in 9 of the HCC patients and were higher than 9 ng/ml in 2 of the HCC patients. Levels of alpha fetoprotein (AFP) and/or protein induced by vitamin K absence or antagonist II (PIVKA II) were elevated in all HCC patients (AFP, PIVKA II, respectively; normal range, < or = 10.0 ng/ml and < or = 0.1 AU/ml) CYFRA 21-1 levels were measured twice or three times during the clinical course in 2 CC patients and in 6 HCC patients, and increased gradually with tumor growth in the 2 CC patients and in 3 of the 6 HCC patients. Marked increases in serum CYFRA 21-1 levels in patients with large liver cancers, particularly in those with normal levels of AFP and PIVKA II, would suggest the existence of intrahepatic CC rather than HCC.
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