Hepatic arterial embolization for unresectable hepatocellular carcinomas: do technical factors affect prognosis?

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    Hepatic arterial embolization for unresectable hepatocellularcarcinomas: do technical factors affect prognosis?

    Koichiro Yamakado Shiro Miyayama Shozo Hirota Kimiyoshi Mizunuma

    Kenji Nakamura Yoshitaka Inaba Akihiro Maeda Kunihiro Matsuo Norifumi Nishida

    Takeshi Aramaki Hiroshi Anai Shinichi Koura Shigeo Oikawa Ken Watanabe

    Taku Yasumoto Kinya Furuichi Masato Yamaguchi

    Received: 4 April 2012 / Accepted: 10 May 2012 / Published online: 30 May 2012

    Japan Radiological Society 2012


    Purpose To evaluate retrospectively whether technical

    factors of hepatic arterial embolization affect the prognosis

    of patients with hepatocellular carcinoma (HCC).

    Materials and methods Inclusion criteria of this study

    were the following: (1) patients received embolization as

    the initial treatment during 20032004, (2) Child A or B

    liver profile, (3) five or fewer HCCs with maximum

    diameter of 7 cm or smaller, and (4) no extrahepatic

    metastasis. Patient data were gathered from 43 centers.

    Prognostic factors were evaluated using univariate and

    multivariate analyses.

    Results Eight hundred fifteen patients were enrolled. The

    1-, 3-, 5-, and 7-year overall survival rates were 92.0 %

    (95 % CI 90.193.9), 62.9 % (95 % CI 59.366.6), 39.0 %

    (95 % CI 35.143.0), and 26.7 % (95 % CI 22.630.8) in all

    patients. Univariate analysis showed a Child-Pugh class-A,

    alpha-fetoprotein level lower than 100 ng/ml, tumor size of

    On behalf of the Clinical Research Group of the Japanese Society for

    Transcatheter Hepatic Arterial Embolization and Japanese Society of

    Interventional Radiology.

    K. Yamakado (&)Department of Interventional Radiology, Mie University School

    of Medicine, 2-174 Edobashi, Tsu 514-8507, Japan

    e-mail: yama@clin.medic.mie-u.ac.jp

    S. Miyayama

    Department of Diagnostic Radiology, Fukui-ken Saiseikai

    Hospital, Fukui, Japan

    S. Hirota A. MaedaDepartment of Radiology, Hyogo College of Medicine,

    Nishinomiya, Japan

    K. Mizunuma

    Department of Radiology, Ohtawara Red Cross Hospital,

    Ohtawara, Japan

    K. Nakamura

    Department of Radiology, Daito Central Hospital, Daito, Japan

    Y. Inaba

    Department of Diagnostic and Interventional Radiology,

    Aichi Cancer Center Hospital, Nagoya, Japan

    K. Matsuo

    Department of Radiology, Narumi Hospital, Hirosaki, Japan

    N. Nishida

    Department of Radiology, Osaka City University, Osaka, Japan

    T. Aramaki

    Department of Diagnostic Radiology, Shizuoka Cancer Center,

    Shizuoka, Japan

    H. Anai

    Department of Radiology, Nara Medical University,

    Kashihara, Japan

    S. Koura

    Department of Radiology, Fukuoka University,

    Fukuoka, Japan

    S. Oikawa

    Department of Radiology, Iwate Prefectural Central Hospital,

    Morioka, Japan

    K. Watanabe

    Department of Radiology, Jikei University, Tokyo, Japan

    T. Yasumoto

    Department of Radiology, Toyonaka Municipal Hospital,

    Toyonaka, Japan

    K. Furuichi

    Department of Radiology, Higashiosaka City General

    Hospital, Higashiosaka, Japan

    M. Yamaguchi

    Department of Radiology, Kobe University, Kobe, Japan


    Jpn J Radiol (2012) 30:560566

    DOI 10.1007/s11604-012-0088-1

  • 3 cm or smaller, tumor number of 3 or fewer, one-lobe tumor

    distribution, nodular tumor type, within the Milan criteria,

    stage I or II, no portal venous invasion, use of iodized oil, and

    selective embolization were significantly better prognostic

    factors. In the multivariate Cox model, the benefit to survival

    of selective embolization remained significant (hazard ratio

    0.68; 95 % CI 0.480.97; p = 0.033).

    Conclusion Selective embolization contributes to sur-

    vival in patients with HCCs.

    Keywords Hepatocellular carcinoma Arterialembolization Prognosis


    The incidence of hepatocellular carcinoma (HCC), the fifth

    most common cancer in the world, is increasing worldwide

    [1]. Curative therapies including resection, liver transplan-

    tation, and percutaneous ablation such as percutaneous eth-

    anol injection (PEI) and radiofrequency (RF) ablation are

    applicable in only 3040 % of patients with HCC [1]. Other

    HCC patients are still not eligible for curative treatment

    because of an advanced tumor stage or poor hepatic func-

    tional reserve. Therefore, a continuing need persists for

    effective palliative treatments. Recently, the benefit to sur-

    vival of undergoing chemoembolization has been shown

    compared with the best supportive care in meta-analyses of

    randomized trials and in two individual trials [25].

    It is important to achieve complete tumor necrosis to

    prolong patient survival [6, 7]. Therefore, some techniques

    have been developed in an attempt to reinforce anticancer

    effects on HCC. These techniques include the use of che-

    motherapeutic agents and iodized oil, and the introduction

    of selective embolization [820]. Although some reports

    have described a benefit to survival of using iodized oil and

    anticancer drugs [11, 12], others have not [810]. Despite

    the accumulation of evidence indicating that selective

    embolization achieves better anticancer effects than non-

    selective embolization, data demonstrating a benefit to

    survival of this technique are lacking [1320].

    Therefore, we conducted this retrospective study to eval-

    uate whether technical factors of transarterial embolization

    have impacts on survival in patients with unresectable HCCs.

    Materials and methods

    Study design

    The Clinical Research Group of the Japanese Society of

    Transcatheter Hepatic Arterial Embolization asked 255

    training centers accredited by the Japanese Society of

    Interventional Radiology to take part in this study. Ques-

    tionnaire sheets were sent to them. Patient data were gathered

    from the 43 institutions (16.9 %, 43/255) that agreed to

    participate. At each institution, IRB approval was obtained

    for this study. Because of the retrospective nature of this

    study, the requirement of obtaining informed consent to take

    part in this study was waived at all but two institutions, where

    informed consent was obtained from living patients.

    Inclusion criteria of this study were the following: (1)

    patients received embolization as the initial treatment

    during 20032004 and followed at least 3 months, (2)

    Child A or B liver profile, (3) five or fewer HCCs with a

    maximum diameter of 7 cm or smaller, and (4) no extra-

    hepatic metastasis.


    In 2003 and 2004, 1290 patients received transarterial

    embolization as the initial treatment of unresectable HCCs at

    the 43 institutions. Of them, 815 patients (63.2 %, 815/1290)

    met the inclusion criteria and were enrolled in this study.

    The diagnosis of HCC was made mainly based on

    imaging modalities using ultrasonography, contrast-

    enhanced computed tomography (CT), magnetic resonance

    (MR) imaging, and angiography, in addition to elevation of

    tumor markers such as a-fetoprotein and des-c-carboxylprothrombin. The typical HCC was depicted as an

    enhanced tumor in the arterial phase and washout in the

    delayed phase in contrast-enhanced CT and MRI, and as a

    hypervascular tumor in digital subtraction angiography

    [21]. Alpha-fetoprotein was positive ([20 ng/ml) in 460patients (60.6 %, 460/759), as was des-c-carboxyl pro-thrombin ([40 mAU/ml) in 371 patients (48.8 %). Biopsywas done in seven patients (0.9 %).

    The decision for unresectable tumor was made by sur-

    geons in each institution taking into account liver function,

    tumor number and location, and patients status, such as

    their age and performance status.

    Patient and tumor characteristics are presented in

    Table 1. The 535 men (65.6 %, 535/815) and 280 women

    (34.4%, 280/815) had a mean age of 69.0 8.4 years

    (standard deviation) (range 4091 years).

    The mean maximum tumor diameter was 3.1 1.5 cm

    (range 0.57.0 cm) and the mean tumor number 1.8 1.1

    (range 15). Based on the Liver Cancer Study Group of Japan

    (LCSGJ) tumor-node-metastasis (TNM) staging system,

    65.6 % (535/815) of patients had stage I or II disease, and

    34.4 % (280/815) of patients had stage III or IVA [22].

    Transarterial embolization

    Transarterial embolization was done using a gelatin sponge

    in all patients (Table 1). Iodized oil was used in 98 % of

    Jpn J Radiol (2012) 30:560566 561


  • patients (799/815) and anticancer drugs in 98.2 % of patients

    (800/815). The iodized oil dose was 115 ml, with a mean

    dose of 3.9 2.1 ml. Anticancer drugs were epirubicin,

    used in 76.9 % of patients (615/800), epirubicin and mito-

    mycin in 17.8 % of patients (142/800), and others in 5.4 % of

    patients (43/800). The epirubicin dose was 590 mg with a

    mean dose of 32.5 14.2 mg. That of mitomycin was

    212 mg with a mean dose of 6.2 2.3 mg.

    The definition of selective embolization was the fol-

    lowing: transarterial embolization performed in the seg-

    mental artery or more peripherally. Even when selective

    embolization was performed at two or more different sites,

    the technique was defined as selective embolization. When

    selective embolization was combined with lobar or whole

    liver embolization, the procedure was not regarded as