Intranodular blood supply correlates well with biological malignancy grade determined by tumor growth rate in pathologically proven hepatocellular carcinoma.

This study was carried out to investigate whether intranodular blood supply in histologically proven well-differentiated hepatocellular carcinomas (HCCs) correlates with tumor growth rates. A total of 52 well-differentiated HCCs were enrolled in this study. Ultrasound angiography with intra-arterial CO(2) microbubble injection was performed in all 52 HCCs and computed tomography during arterial portography was performed in 21 of the 52 HCCs. Tumor volume doubling time (TVDT) was measured in all 52 nodules by B-mode ultrasonography performed at 2- to 3-month intervals for a follow-up period of at least 6 months (range: 6 months to 8 years) with respect to arterial vascularity. In the hypervascular (n = 27), isovascular (n = 9), and hypovascular nodules (n = 16), the mean values of TVDT (mean +/- SD) were 79 +/- 131, 98 +/- 227, and 782 +/- 324 days, respectively (r(s) = 0.722, p < 0.0001). Concerning portal blood supply, the mean TVDT in nodules in which the portal supply was reduced (n = 5) was 178 +/- 78 days compared with 592 +/- 211 days in nodules in which the portal supply was preserved (n = 11), with a significant difference (p < 0.01). Five nodules in which the portal supply was preserved did not enlarge during the follow-up period of 3-5 years. There was a significant correlation among the three groups (r(s) = 0.804, p < 0.05). In conclusion, intranodular blood flow dynamics in patients with well-differentiated HCC reflect the biological malignancy or cancer progression in the process of multistep hepatocarcinogenesis, suggesting the importance of this parameter in deciding on a treatment strategy. In other words, nodules in which arterial vascularity is present and those in which the portal blood flow is reduced should be treated for reasons such as a short doubling time and the risk of rapid progression to artery-dominant classical HCC.