Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

Use of FDP and F1P aldolase to detect tumorous and nontumorous tissue damage by ethanol injection of hepatocellular carcinoma

KN Khan MD PhD 1, K Nakata MD 1, K Nakao MD 1, Y Kato MD 1, K Eguchi MD 1

1 First Dept Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan,

AIMS Changes in serum levels of tumor-specific fructose 1,6-diphosphate (FDP) aldolase and nontumor-specific fructose 1-phosphate (F1P) aldolase activities were analyzed in patients with hepatocellular carcinoma (HCC) to detect the damage of tumorous and nontumorous hepatic cells after percutaneous ethanol injection (PEI). METHODS: Initial PEI was performed in 20 patients containing 22 HCC nodules with a diameter of ÅÖ4 cm. Changes in serum hepatic enzyme activities were measured before and after repeated PEI. FDP and F1P aldolase levels were measured by substrate-specific enzymatic methods. Pre-and post treatment alphafetoprotein (AFP) levels were determined by radioimmunoassay. The consequent changes in the total nontumorous liver volumes after PEI were also analyzed by follow-up CT scans. RESULTS Serum levels of FDP aldolase released by ethanol injection were progressively increased (p<0.0001) until the third PEI and thereafter decreased. In contrast, serum levels of F1P aldolase were continuously elevated even after the third PEI (p<0.0001). Serum levels of transaminases were also elevated after repeated PEI (p<0.0001). The FDP/F1P aldolase ratio decreased significantly with increased volume (ÅÑ20 ml) of injected ethanol (p=0.01) caused by nontumorous liver damage. The elevation of FDP aldolase was markedly associated with a decrease in serum levels of AFP (p<0.001), indicating adequate tumor necrosis. The progression of the total nontumor liver atrophy depended on the volume of injected ethanol and correlated significantly with F1P aldolase levels after PEI (p<0.01) but not with FDP aldolase. CONCLUSIONS These results demonstrated that caution is needed to avoid nontumorous liver damage caused by the large volume of ethanol injection in treating HCC. Measurement of FDP and F1P aldolase activities in serum after PEI is clinically useful to detect the degree of tumorous and nontumorous tissue damage by ethanol.

KEY WORDS: Ethanol injection, hepatocellular carcinoma, aldolases, adjacent tumor tissue damage , liver atrophy.

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Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on prognostic markers.