Clinical implication of hypovascular hepatocellular carcinoma studied in 4,474 patients with solitary tumour equal or less than 3 cm

Kenichi Takayasu, Shigeki Arii, Michiie Sakamoto, Yutaka Matsuyama, Masatoshi Kudo, Takafumi Ichida, Osamu Nakashima, Osamu Matsui, Namiki Izumi, Yonson Ku, Norihiro Kokudo, Masatoshi Makuuchi

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Background & Aims: To clarify the biological behaviour of small hypovascular hepatocellular carcinoma (HCC) because of insufficient evidence even though frequently encountered. Methods: The study covered naïve 4,474 patients who met solitary HCC ≤3 cm (mean, 2.1 cm), histopathologically proven and Child Pugh A or B. Macroscopic vascular invasion and distant metastasis were excluded. The hypovascularity of tumour was defined as hypo- or iso-enhancement in arterial phase of multiple dynamic imaging techniques. Results: Of them, 802 (18%) were hypovascular. The ratio of hypovascular HCC decreased as tumour size increased (P < 0.001) and most of them developed to hypervascular type when they grew over 1.5 cm. Hypovascular group showed a significantly higher ratio of well differentiated grade (P < 0.001) and marginally less incidence of microvascular invasion and metastases compared with hypervascular group. The histologic dedifferentiation (less differentiation) developed step-by-step as tumour size increased in hyper- and even hypovascular group. The des-γ-carboxy prothrombin (DCP) value ≥ 300mAU/ml was closely correlated with increase of tumour size in both groups. Logistic regression analysis revealed five variables were independent predictors for hypovascular HCC; tumour size ≤1.5 cm, alpha-fetoprotein < 200 ng/ml, DCP < 40mAU/ml, well differentiated grade, and positivity for hepatitis C virus antibody. Conclusions: Hypovascular HCC was biologically less aggressive and developed with stepwise dedifferentiation and transformation to hypervascular appearance along with tumour growth. These results will help in leading correct diagnosis of small hypovascular tumour and assessing optimal treatment for hypovascular HCC≤3 cm.

Original languageEnglish
Pages (from-to)762-770
Number of pages9
JournalLiver International
Volume33
Issue number5
DOIs
Publication statusPublished - 2013 May

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Hepatocellular Carcinoma
Neoplasms
Prothrombin
Neoplasm Metastasis
Hepatitis C Antibodies
alpha-Fetoproteins
Blood Vessels
Logistic Models
Regression Analysis
Incidence
Growth

Keywords

  • Arterial tumour hypervascularization
  • Des-γ-carboxy prothrombin (DCP)
  • Histologic differentiation
  • Hypovascular hepatocellular carcinoma (HCC)
  • Multistep hepatocarcinogenesis

ASJC Scopus subject areas

  • Hepatology

Cite this

Clinical implication of hypovascular hepatocellular carcinoma studied in 4,474 patients with solitary tumour equal or less than 3 cm. / Takayasu, Kenichi; Arii, Shigeki; Sakamoto, Michiie; Matsuyama, Yutaka; Kudo, Masatoshi; Ichida, Takafumi; Nakashima, Osamu; Matsui, Osamu; Izumi, Namiki; Ku, Yonson; Kokudo, Norihiro; Makuuchi, Masatoshi.

In: Liver International, Vol. 33, No. 5, 05.2013, p. 762-770.

Research output: Contribution to journalArticle

Takayasu, K, Arii, S, Sakamoto, M, Matsuyama, Y, Kudo, M, Ichida, T, Nakashima, O, Matsui, O, Izumi, N, Ku, Y, Kokudo, N & Makuuchi, M 2013, 'Clinical implication of hypovascular hepatocellular carcinoma studied in 4,474 patients with solitary tumour equal or less than 3 cm', Liver International, vol. 33, no. 5, pp. 762-770. https://doi.org/10.1111/liv.12130
Takayasu, Kenichi ; Arii, Shigeki ; Sakamoto, Michiie ; Matsuyama, Yutaka ; Kudo, Masatoshi ; Ichida, Takafumi ; Nakashima, Osamu ; Matsui, Osamu ; Izumi, Namiki ; Ku, Yonson ; Kokudo, Norihiro ; Makuuchi, Masatoshi. / Clinical implication of hypovascular hepatocellular carcinoma studied in 4,474 patients with solitary tumour equal or less than 3 cm. In: Liver International. 2013 ; Vol. 33, No. 5. pp. 762-770.
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AU - Takayasu, Kenichi

AU - Arii, Shigeki

AU - Sakamoto, Michiie

AU - Matsuyama, Yutaka

AU - Kudo, Masatoshi

AU - Ichida, Takafumi

AU - Nakashima, Osamu

AU - Matsui, Osamu

AU - Izumi, Namiki

AU - Ku, Yonson

AU - Kokudo, Norihiro

AU - Makuuchi, Masatoshi

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N2 - Background & Aims: To clarify the biological behaviour of small hypovascular hepatocellular carcinoma (HCC) because of insufficient evidence even though frequently encountered. Methods: The study covered naïve 4,474 patients who met solitary HCC ≤3 cm (mean, 2.1 cm), histopathologically proven and Child Pugh A or B. Macroscopic vascular invasion and distant metastasis were excluded. The hypovascularity of tumour was defined as hypo- or iso-enhancement in arterial phase of multiple dynamic imaging techniques. Results: Of them, 802 (18%) were hypovascular. The ratio of hypovascular HCC decreased as tumour size increased (P < 0.001) and most of them developed to hypervascular type when they grew over 1.5 cm. Hypovascular group showed a significantly higher ratio of well differentiated grade (P < 0.001) and marginally less incidence of microvascular invasion and metastases compared with hypervascular group. The histologic dedifferentiation (less differentiation) developed step-by-step as tumour size increased in hyper- and even hypovascular group. The des-γ-carboxy prothrombin (DCP) value ≥ 300mAU/ml was closely correlated with increase of tumour size in both groups. Logistic regression analysis revealed five variables were independent predictors for hypovascular HCC; tumour size ≤1.5 cm, alpha-fetoprotein < 200 ng/ml, DCP < 40mAU/ml, well differentiated grade, and positivity for hepatitis C virus antibody. Conclusions: Hypovascular HCC was biologically less aggressive and developed with stepwise dedifferentiation and transformation to hypervascular appearance along with tumour growth. These results will help in leading correct diagnosis of small hypovascular tumour and assessing optimal treatment for hypovascular HCC≤3 cm.

AB - Background & Aims: To clarify the biological behaviour of small hypovascular hepatocellular carcinoma (HCC) because of insufficient evidence even though frequently encountered. Methods: The study covered naïve 4,474 patients who met solitary HCC ≤3 cm (mean, 2.1 cm), histopathologically proven and Child Pugh A or B. Macroscopic vascular invasion and distant metastasis were excluded. The hypovascularity of tumour was defined as hypo- or iso-enhancement in arterial phase of multiple dynamic imaging techniques. Results: Of them, 802 (18%) were hypovascular. The ratio of hypovascular HCC decreased as tumour size increased (P < 0.001) and most of them developed to hypervascular type when they grew over 1.5 cm. Hypovascular group showed a significantly higher ratio of well differentiated grade (P < 0.001) and marginally less incidence of microvascular invasion and metastases compared with hypervascular group. The histologic dedifferentiation (less differentiation) developed step-by-step as tumour size increased in hyper- and even hypovascular group. The des-γ-carboxy prothrombin (DCP) value ≥ 300mAU/ml was closely correlated with increase of tumour size in both groups. Logistic regression analysis revealed five variables were independent predictors for hypovascular HCC; tumour size ≤1.5 cm, alpha-fetoprotein < 200 ng/ml, DCP < 40mAU/ml, well differentiated grade, and positivity for hepatitis C virus antibody. Conclusions: Hypovascular HCC was biologically less aggressive and developed with stepwise dedifferentiation and transformation to hypervascular appearance along with tumour growth. These results will help in leading correct diagnosis of small hypovascular tumour and assessing optimal treatment for hypovascular HCC≤3 cm.

KW - Arterial tumour hypervascularization

KW - Des-γ-carboxy prothrombin (DCP)

KW - Histologic differentiation

KW - Hypovascular hepatocellular carcinoma (HCC)

KW - Multistep hepatocarcinogenesis

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