Early Detection and Characterization of Hepatocellular Carcinoma: Value of Imaging Multistep Human Hepatocarcinogenesis

Kudo, Masatoshi

doi:10.1159/000087265

Cited by 14 publications

(12 citation statements)

References 58 publications

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“…these nodules is almost impossible with BUS, CEUS plays an important role in differentiating these lesions because of its ability to demonstrate the vascularity of the lesions [63][64][65] . Regenerative nodules and dysplastic nodules are differentiated from HCC as the former lesions usually do not show enhancement in the arterial phase and are iso-enhanced similar to the surrounding liver parenchyma in the portal and late phases ( Figure 5) [64,65] .…”

Section: A B Cmentioning

confidence: 99%

“…Regenerative nodules and dysplastic nodules are differentiated from HCC as the former lesions usually do not show enhancement in the arterial phase and are iso-enhanced similar to the surrounding liver parenchyma in the portal and late phases ( Figure 5) [64,65] . Nonetheless, regenerative nodules and some dysplastic nodules may also exhibit additional arterial hyper-enhancement; by analysis of the portal venous and late phases it may be possible to differentiate these iso-enhancing nodules from hypo-enhancing HCC [64,65] . CEUS with Sonazoid is more sensitive for detecting arterial vascularity of target nodules than contrastenhanced CT and MRI.…”

Section: A B Cmentioning

confidence: 99%

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Detection of focal liver lesions in cirrhotic liver using contrast-enhanced ultrasound

Wong

Xu²,

Xie³

2009

WJR

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Patients with liver cirrhosis are at increased risk of hepatocellular carcinoma (HCC). Conventional or baseline ultrasound (BUS) is often used as the first-line tool for HCC surveillance or detection, but the accuracy of BUS in HCC detection or differentiation from other focal liver lesions (FLLs) is limited. Contrast-enhanced ultrasound (CEUS) represents a recent revolution in the field of ultrasonography and it has become increasingly important in the detection and evaluation of FLLs. In CEUS, HCC typically exhibits arterial hyper-enhancement and portal-venous washout represented by hypoenhanced lesions in the portal venous and late phases. The detection rate of HCC was significantly higher with CEUS compared with BUS. Even regenerative or some dysplastic nodules may exhibit arterial hyperenhancement as they are differentiated from HCC by its iso-enhancing pattern in portal and late phases. The contrast-enhancement patterns of other different types of benign and malignant FLLs, as well as their detection rates with CEUS, were also discussed.

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Section: A B Cmentioning

confidence: 99%

Section: A B Cmentioning

confidence: 99%

Detection of focal liver lesions in cirrhotic liver using contrast-enhanced ultrasound

Wong

Xu²,

Xie³

2009

WJR

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“…In HCCs, the tumor tissue is supplied by blood from new arteries and the development of rich vasculature occurs in parallel with tumor development (9). VEGF plays a critical role in the process of angiogenesis (10,11).…”

Section: Introductionmentioning

confidence: 99%

Vandetanib, an Inhibitor of VEGF Receptor-2 and EGF Receptor, Suppresses Tumor Development and Improves Prognosis of Liver Cancer in Mice

Inoue

Torimura

Nakamura

et al. 2012

Clinical Cancer Research

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Purpose: VEGF, EGF, and TGF-a are expressed in hepatocellular carcinomas (HCC) and play a role in its growth. Vandetanib, a multikinase inhibitor, suppresses the phosphorylation of VEGF receptor 2 (VEGFR-2) and EGF receptor (EGFR). The aim of this study was to clarify the antitumor effect of vandetanib in mouse HCCs.Experimental Design: We evaluated the effects of vandetanib on proliferation of human umbilical vein endothelial cells (HUVEC) and three hepatoma cell lines, as well as the phosphorylation of VEGFR-2 and EGFR in these cells. Mice were implanted with hepatoma cells subcutaneously or orthotopically in the liver and treated with 50 or 75 mg/kg vandetanib. We analyzed the effects of treatment on tumor cell proliferation and apoptosis, vessel density, phosphorylation of VEGFR-2 and EGFR, and production of VEGF, TGF-a, and EGF in tumor tissues. Adverse events on vandetanib administration were also investigated.Results: Vandetanib suppressed phosphorylation of VEGFR-2 in HUVECs and EGFR in hepatoma cells and inhibited cell proliferation. In tumor-bearing mice, vandetanib suppressed phosphorylation of VEGFR-2 and EGFR in tumor tissues, significantly reduced tumor vessel density, enhanced tumor cell apoptosis, suppressed tumor growth, improved survival, reduced number of intrahepatic metastases, and upregulated VEGF, TGF-a, and EGF in tumor tissues. Treatment with vandetanib was not associated with serious adverse events, including alanine aminotransferase abnormality, bone marrow suppression, or body weight loss.Conclusions: The antitumor effects of vandetanib in mice suggest that it is a potentially suitable and safe chemotherapeutic agent for HCCs.

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“…In any case, the malignancy grade varied among well-differentiated HCCs in the process of multistep hepatocarcinogenesis (fig. 2, 5) [9,10,11,12,13]: lesions in which portal blood flow is preserved despite hypovascular arterial blood flow, those in which both arterial and portal blood flow is reduced, or those with isovascular arterial blood flow. This suggests that the accurate evaluation of intranodular blood flow dynamics is useful for assessing the malignancy grade, providing useful information on the basis of therapeutic strategies can be decided [13].…”

Section: Discussionmentioning

confidence: 99%

“…2, 5) [9,10,11,12,13]: lesions in which portal blood flow is preserved despite hypovascular arterial blood flow, those in which both arterial and portal blood flow is reduced, or those with isovascular arterial blood flow. This suggests that the accurate evaluation of intranodular blood flow dynamics is useful for assessing the malignancy grade, providing useful information on the basis of therapeutic strategies can be decided [13]. A study reported that large, well-differentiated HCC with portal blood flow was benign in nature, and that its therapeutic necessity is low [14].…”

Section: Discussionmentioning

confidence: 99%

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

Kudo

Tochio

2008

Oncology

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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.

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Early Detection and Characterization of Hepatocellular Carcinoma: Value of Imaging Multistep Human Hepatocarcinogenesis

Cited by 14 publications

References 58 publications

Detection of focal liver lesions in cirrhotic liver using contrast-enhanced ultrasound

Detection of focal liver lesions in cirrhotic liver using contrast-enhanced ultrasound

Vandetanib, an Inhibitor of VEGF Receptor-2 and EGF Receptor, Suppresses Tumor Development and Improves Prognosis of Liver Cancer in Mice

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

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