Intranodular Blood Supply Correlates Well with Biological Malignancy Grade Determined by Tumor Growth Rate in Pathologically Proven Hepatocellular Carcinoma

Abstract

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 CO₂ 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.

Anatomical basis and histopathological changes resulting from selective internal radiotherapy for liver metastases

“…In patients with cancer, the application of ultrasound angiography in patients with liver tumours has demonstrated that established malignancy can take its blood supply from the portal venous system as well as the arterial system, but that the arterial blood supply to a malignancy appears to determine its growth rate 20. Investigators studied a group of patients with well differentiated hepatocellular carcinomas, in whom they found that tumours that had a faster rate of progression had a predominantly arterial blood supply 20.…”

Evidence Supporting LI-RADS Major Features for CT- and MR Imaging–based Diagnosis of Hepatocellular Carcinoma: A Systematic Review

“…Well-differentiated HCCs tend to be slow growing, whereas moderately and poorly differentiated HCCs are fast growing, although there is overlap in the reported TVDTs of HCCs with varying degrees of differentiation (93,97,98). Imaging features associated with shorter TVDT include APHE (92,(99)(100)(101), presence of "washout" (100,102), T2 hyperintensity (99), and diameter less than 1 cm at baseline (94,103).…”

“…Measuring maximum tumor diameter on at least two serial studies assesses its doubling time. Physiologically, tumor volume doubling time (TVDT) is an indicator of the biologic potential of a tumor and its blood supply (92). While benign lesions tend to remain stable or grow slowly over time, malignant tumors grow more rapidly.…”

Atypically large well-differentiated hepatocellular carcinoma with extensive fatty metamorphosis: Report of a Case

“…To our knowledge, there are no reports describing such a large well-differentiated HCC (over 40 mm in diameter) with remarkable fatty change. Kudo et al reported that well-differentiated HCCs abundant of arterial blood supply grow more rapidly than those showing poor vascularity (13). In our case, CT image in arterial phase showed irregular enhancement of the tumor.…”