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?

Abstract

To test the hypothesis that increased proliferative capacity of cells in a liver remnant is a risk factor for tumor recurrence in patients who have undergone liver resection for hepatocellular carcinoma, DNA flow-cytometric measurement and cell-cycle analysis of the nontumor parts of resected hepatocellular carcinomas (tumor size < 5 cm) were performed. The disease-free survival rates 1, 2, 3 and 4 yr after surgery were 64%, 58%, 43%, and 36%, respectively. Proliferative capacity (fractions 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 hepatitis (+) and with hepatocyte dysplasia (-) had significantly lower proliferative activity than did those with chronic active hepatitis (-) and with hepatocyte dysplasia (+), respectively [corrected]. We saw no significant difference in proliferative capacity between patients with and without cirrhosis. Disease-free-survival analysis showed that the presence of liver pathology (hepatitis B infection, cirrhosis, chronic active hepatitis and hepatocyte dysplasia) was not the factor linked to tumor recurrence in the liver remnant and that a marked increase in proliferative capacity (> or = 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 the proliferative capacity (> or = 18%) of the nontumor part is a significant risk factor in predicting tumor recurrence in the liver remnant after liver resection.

Immunohistochemical analysis of tumor biological factors in hepatocellular carcinoma: relationship to clinicopathological factors and prognosis after hepatic resection

“…25,29,30 Recent studies of HCC have revealed candidate pathological and tumor biological factors, by the use of advanced methods for detecting genetic abnormalities. [7][8][9][10][11][12][13][14][15][16][17][18][19] We believe that clarifying the relationship between such factors and patient prognosis should contribute to future classification criteria for HCC. To our knowledge, comprehensive analysis using such factors in relation to tumor recurrence or patient survival has not yet been reported.…”

“…Previous reports have indicated that proliferative activity in noncancerous hepatic tissue may reflect tumor recurrence or the development of tumor in new regions. 5,15 Angiogenesis around and within the tumor may be important to support tumor growth. 32 We first examined the relationship of clinicopathological factors in HCC that may influence recurrence or patient survival.…”

“…Furthermore, such studies may facilitate the prediction of tumor aggressiveness and prognosis. The relationship between patient prognosis and various tumor biological factors, such as the abnormal expression of p53, 7,8 nm23 (tumor suppressor gene), [9][10][11] and interleukin 10; 12 angiogenesis; 13,14 proliferative activity; 5,15,16 growth factors; 17 and DNA ploidy 18 has been reported previously. Recently, Qin and Tang 19 reported a comprehensive analysis of many molecular markers and examined their relationship to prognosis in HCC.…”

Prevention of Second Primary Tumors by an Acyclic Retinoid, Polyprenoic Acid, in Patients with Hepatocellular Carcinoma

“…related to the occurrence of new tumors after the treatment of small hepatomas -including the size and number of the hepatomas treated, the functional reserve of the liver, and the degree of inflammation of liver parenchyma (as measured by the serum alanine aminotransferase activity) [17][18][19][20][21][22][23]30,[32][33][34][35][36][37][38][39][40][41][42] -did not differ between groups. The method of treating the initial hepatoma, whether it was surgical resection or percutaneous injection of ethanol, was also studied in a stratified analysis between the groups.…”

Current status of hepatic resection for hepatocellular carcinoma

“…[48][49][50][51] Further, fibrosis or cirrhosis seems to be associated with poor survival beyond 5 years after surgery. 52…”