Biological markers as an aid in the clinical management of patients with liver metastases

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Abstract
Liver metastases due to the more common neoplastic diseases such as colorectal, breast, or bronchogenic carcinoma are a frequent occurrence and are associated with an ominous prognosis. Earlier detection followed by appropriate therapeutic interventions might have a decided effect on the subsequent course of disease. Controversy exists over the selection of tests with the greatest sensitivity, specificity, and potential utility. Preliminary evidence suggest that γ‐glutamyl transpeptidase and 5′‐nucleotidase may be of particular significance. Four enzymes — γ‐glutamyl transpeptidase, 5′‐nucleotidase, leucine aminopeptidase, and alkaline phosphatase plus carcinoembryonic antigen — were compared in the same blood samples from selected patients with breast and small cell carcinoma of the lung. γ‐Glutamyl transpeptidase was the most sensitive test with 28/29 (97%) patients with hepatic metastases having elevated enzymatic activity in their sera. For patients with small cell carcinoma of the lung followed serially, γ‐glutamyl transpeptidase activity was increased an average of 5 months before liver metastases were detected by clinical means. Two factors are important in the interpretation of the results of γ‐glutamyl transpeptidase analysis: (1) Hepatic dysfunction due to diseases other than metastatic tumor involvement can cause a rise in enzyme levels as can (2) medications or ethanol which activate the hepatic microsomal drug metabolizing system. Of particular importance, however, is the fact that antitumor chemotherapy, even intensive and multiple agent, did not appear to effect the enzyme activity in the sera of patients with breast or small cell carcinoma of the lung. γ‐Glutamyl transpeptidase in combination with carcinoembryonic antigen may be of particular value in detecting liver metastases and in assessing subsequent response to therapy.