CAN DETERMINATION OF THE PROLIFERATIVE CAPACITY OF THE NONTUMOR PORTION PREDICT THE RISK OF TUMOR RECURRENCE IN THE LIVER REMNANT AFTER RESECTION OF HUMAN HEPATOCELLULAR-CARCINOMA

To test the hypothesis that increased proliferative capacity of cells in a liver remnant is a risk factor for tumor recurrence in patients w ho have undergone liver resection for hepatocellular carcinoma, DNA fl ow-cytometric measurement and cell-cycle analysis of the nontumor part s of resected hepatocellular carcinomas (tumor size < 5 cm) were perfo rmed. The disease-free survival rates 1, 2, 3 and 4 yr after surgery w ere 64%, 58%, 43%, and 36%, respectively. Proliferative capacity (frac tions of synthetic, postsynthetic and mitotic phases) of the nontumor parts, irrespective of liver pathology, was higher than that of normal liver and statistically lower than that of tumor parts from resected hepatocellular carcinoma specimens. Livers with chronic active hepatit is and with hepatocyte dysplasia had significantly lower proliferative activity than did those with chronic active hepatitis and with hepato cyte dysplasia. We saw no significant difference in proliferative capa city between patients with and without cirrhosis. Disease-free-surviva l analysis showed that the presence of liver pathology (hepatitis B in fection, cirrhosis, chronic active hepatitis and hepatocyte dysplasia) was not the factor linked to tumor recurrence in the liver remnant an d that a marked increase in proliferative capacity (greater-than-or-eq ual-to 18%), regardless of liver pathology, was the risk factor linked to tumor recurrence after liver resection. We conclude that there is some degree of increased proliferative capacity in the nontumor parts of resected hepatocellular carcinomas and that a marked increase in th e proliferative capacity (> 18%) of the nontumor part is a significant risk factor in predicting tumor recurrence in the liver remnant after liver resection.