Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. HCC develops
in various causes – Viral hepatitis infection, toxins, or other liver conditions - by activation of
oncogenes and/or inactivation of tumor suppressors. Understanding of signal pathways and
protein-protein interactions critical in tumor development may lead to novel treatment strategy.
To evaluate the progression of HCC and effects of potential therapies, various animal models
have been established. Experimental models of HCC provide valuable tools to investigate the
risk factors, new treatment modalities and biologic characteristics. Subcutaneous xenograft
models have been widely used in the past. However, with the advancement of in vivo imaging
technology, investigators are more concerned with the orthotopic models nowadays.
Genetically engineered mouse models have greatly facilitated studies of gene function in
HCC development. Lately, a novel approach for stable gene expression in mouse hepatocytes
by hydrodynamic injection has been developed. Each model has its own advantages and
disadvantages. Therefore, selecting the optimal models based on study objectives is necessary.
In this review, we highlight both the frequently used mouse models and some emerging ones
with emphasis on their merits or defects, and give advices for investigators to choose a ‘‘best-fit’’
animal model in HCC research.
Recently, various combination therapies have been applied to the treatment of hepatocellular
carcinoma (HCC). Among various treatment modalities, transarterial chemoembolization
(TACE) and radiofrequency ablation (RFA) were combined to improve the therapeutic effect of
RFA. The decrease of blood flow by TACE can increase the size of the ablation area by reducing
heat loss during RFA. Based on these theoretical advantages, TACE and RFA combination
therapy have been tried for the treatment of patients with HCC which is not feasible to be
removed by surgery. However, TACE and RFA combination therapy has not been standardized
by various protocols for each study. This review discusses the implications and role of this
treatment, although there are several limitations to clearly demonstrate the indications and
efficacy of TACE and RFA combination therapies.
Jae Young Jang, June Sung Lee, Hyung-Joon Kim, Jae-Jun Shim, Ji Hoon Kim, Bo Hyun Kim, Choon Hyuck Kwon, Seung Duk Lee, Hae Won Lee, Jung Hoon Kim, Woo Kyoung Jeong, Jin-Young Choi, Heung Kyu Ko, Dong Ho Lee, Haeryoung Kim, Baek-hui Kim, Sang Min Yoon, Soon Ho Um
J Liver Cancer. 2017;17(1):19-44. Published online March 31, 2017
The General Rules for the Study of Primary Liver Cancer was published in June 2001 as the first
edition. Since then, the 5th edition of the General Rules for the Study of Primary Liver Cancer
was published by the 17th Committee of the Korean Liver Cancer Association based on the
most recent data. The 5th edition of the General Rules for the Study of Primary Liver Cancer
ranged over numerous topics such as anatomy, medical assessment of the patients, staging
of hepatocellular carcinoma, description of the image findings, summary of hepatic resection,
description of the surgical specimens, liver transplantation, reporting the pathological findings,
pathological examinations of liver specimen, non-surgical treatment, radiotherapy, and
assessment of tumor response after non-surgical treatment of hepatocellular carcinoma. The 5th
General Rules for the Study of Primary Liver Cancer will not only become the basis of academic
development for liver cancer studies in Korea, but also serve as the primary form of national
liver cancer data accumulation based on standardized rules.
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Background/Aims As the optimal stereotactic body radiation therapy (SBRT) modality
for hepatocellular carcinoma (HCC) has not been confirmed, we aimed herein to provide a
practical guideline by our retrospective review.
Methods Thirty-nine patients with primary HCC who underwent liver SBRT via 3 modalities
(helical tomotherapy [HT]: 22, volumetric modulated arc therapy [VMAT]: 13, Cyberknife: 4)
at our institution between July 2014 and July 2015 were included. Modalities were compared
with regard to dose conformity index (CI), homogeneity index (HI), clinical results, and patient
compliance.
Results VMAT SBRT had favorable conformity (CI: 0.7±0.2), homogeneity (HI: 1.1±0.0), and
shortest treatment time (100.2±26.1 seconds). HT SBRT yielded good dosimetric outcomes,
especially in conformity (CI: 1.0±0.2). Although the Cyberknife SBRT synchrony system allowed
real-time tumor targeting, the treatment time was longest (3,015.0±447.3 seconds), invasive
pre-treatment procedures were required, and the HI (1.3±0.0) was lowest.
Conclusions All 3 modalities yielded competent dosimetric planning parameters. VMAT
SBRT was most appropriate for tumors with residual lipiodol or patients with poor conditions.
HT SBRT is available for multiple or irregular targets. Cyberknife SBRT is recommended for
carefully selected patients and tumors indicated for sono-guided fiducial insertion.
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Plan quality analysis of stereotactic ablative body radiotherapy treatment planning in liver tumor Anirut Watcharawipha, Somvilai Chakrabandhu, Anupong Kongsa, Damrongsak Tippanya, Imjai Chitapanarux Journal of Applied Clinical Medical Physics.2023;[Epub] CrossRef
Background/Aims Many recent studies have shown excellent outcomes of surgical resection
for ruptured hepatocellular carcinoma (HCC). In addition, there are several reports suggesting
that a ruptured HCC did not increase the risk for peritoneal dissemination of a tumor after
surgical resection. However, the impact of HCC rupture on recurrence and patient survival has
not yet been clarified.
Methods The medical data of patients who underwent surgical resection for ruptured HCC
in our center between January 2011 and December 2015 were retrospectively reviewed. The
outcomes of the patients were investigated.
Results Among 128 patients who underwent surgical resection for HCC, 5 patients (3.9%) had
a ruptured HCC. All patients underwent elective operation in a stable condition. Transarterial
chemoembolization (TACE) was performed for achieving hemostasis in four patients except
one who achieved spontaneous hemostasis. Two patients had tumor recurrence and one
patient died due to HCC recurrence during the median follow-up duration of 28.3 months
(range, 24.3–62.3 months). One patient who developed late intrahepatic recurrence at 40.0
months after resection was managed well by means of radiofrequency ablation and TACE and
is now alive for 5 years without any evidence of viable tumor. However, the other patient who
showed early peritoneal seeding at 1.9 months after resection finally died despite aggressive
treatments.
Conclusions Rupture of HCC might result in peritoneal seeding of the tumor in the early
postoperative stage, which could lead to a poor result. Nonetheless, surgical resection may be
the best treatment option yielding good survival, even for a ruptured HCC.
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Ruptured Massive Hepatocellular Carcinoma Cured by Transarterial Chemoembolization Ji Eun Lee, Joong-Won Park, In Joon Lee, Bo Hyun Kim, Seoung Hoon Kim, Hyun Beom Kim Journal of Liver Cancer.2020; 20(2): 154. CrossRef
Background/Aims Hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT)
exhibits poor prognosis. The aim of this study is to evaluate factors associated with survival of
HCC patients with PVTT to suggest better therapeutic options.
Methods Patients with HCC which were newly diagnosed at three tertiary hospitals between
January 2004 and December 2012, were reviewed retrospectively. Among them, Barcelona
Clinic of Liver Cancer stage C patients with PVTT were identified. Factors affecting overall
survival (OS) were analyzed and efficacies of the treatment modalities were compared.
Results Four hundred sixty five patients with HCC and PVTT were included. Liver function,
tumor burden, presence of extrahepatic tumor, alfa fetoprotein, and treatment modalities
were significant factors associated with OS. Treatment outcomes were different according
to the initial modalities. OS of the patients who received hepatic resection, radiofrequency
ablation (RFA), transarterial chemoembolization (TACE), hepatic arterial infusion chemotherapy
(HAIC), sorafenib, systemic cytotoxic chemotherapy, radiation therapy (without combination),
and supportive care were 27.8, 7.1, 6.7, 5.3, 2.5, 3.0, 1.8, and 0.9 months, respectively (P<0.001).
Curative-intent treatments such as hepatic resection or RFA were superior to noncurativeintent
treatments (P<0.001). TACE or HAIC was superior to sorafenib or systemic chemotherapy
(P<0.001). Combining radiotherapy to TACE or HAIC did not provide additional benefit on OS
(P=0.096).
Conclusions Treatment modalities as well as baseline factors significantly influenced on
OS of HCC patients with PVTT. Whenever possible, curative intent treatments should be
preferentially considered. If unable, locoregional therapy would be a better choice than
systemic therapy in HCC patients with PVTT.
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Value of surgical resection compared to transarterial chemoembolization in the treatment of hepatocellular carcinoma with portal vein tumor thrombus: A meta-analysis of hazard ratios from five observational studies Keera Kang, Sung Kyu Song, Chul-Woon Chung, Yongkeun Park Annals of Hepato-Biliary-Pancreatic Surgery.2020; 24(3): 243. CrossRef
Hwa-Sun Park, Jae Young Jang, Min Young Baek, Yong Kwon Kim, Hyun Jin Youn, Su Young Back, Soung Won Jeong, Sae Hwan Lee, Sang Gyune Kim, Sang Woo Cha, Young Seok Kim, Young Deok Cho, Hong Soo Kim, Boo Sung Kim
J Liver Cancer. 2017;17(1):72-76. Published online March 31, 2017
Hepatocellular carcinoma (HCC) is the 2nd most common cause of cancer related death
in Korea and well-known malignancy with poor prognosis. Sorafenib is the first-line
molecular targeted agent in patients with extra-hepatic spread of HCC. However, complete
response is extremely rare in patients treated with sorafenib and the disease control rate
is only 43%. We report a 53-year-old man with advanced HCC with pulmonary metastasis
who showed complete response by cytotoxic chemotherapy with doxorubicin and
cisplatin with relatively tolerable adverse effects after failure of treatment with sorafenib.
In hepatocellular carcinoma (HCC), sorafenib is the only approved systemic chemotherapy,
and has been applied for those with advanced HCC especially with systemic metastasis.
However, the treatment results are suboptimal leaving many cases with disease progression
despite the use of optimum dose. There is no established guideline for those that fail to
respond to sorafenib treatment. In this case, a 46-years-old male with metastatic lung cancer
from HCC experienced progression despite sorafenib treatment. Then, the patient received
surgical resection of the metastatic lung mass followed by radiation therapy and achieved
complete remission for 10 months after the surgical treatment and radiation therapy.
Alpha-fetoprotein level was normalized and complete remission has been maintained.
Hepatocellular carcinoma is the third leading cause of cancer related mortality worldwide.
Only 30% of patients are eligible for curative surgical resection at diagnosis. For patients with
advanced hepatocellular carcinoma with accompanying portal vein tumor thrombosis, Sorafenib
is recommended as first-line treatment. However, survival gain from sorafenib is unsatisfactory,
and there is no standard therapy for patients who are intolerable or refractory to sorafenib. Here
we report a case of a 52-year-old man who initially achieved partial response after sorafenib
treatment, but eventually showed disease progression and was treated subsequently with
transarterial chemoembolization (TACE). Multinodular recurrence occurred, but he was treated
with repeated TACE, and has survived for 4 years so far.
Sorafenib is the only approved targeted agent as the first line systemic therapy for treatment of
advanced hepatocellular carcinoma (HCC). However, the improvement of survival duration under
3 months is far from clinical satisfactory and most patients experience disease progression within
6 months after sorafenib therapy. Unfortunately, second line systemic therapy after treatment
failure of sorafenib was not established and there were no clear guidelines for salvage treatment
modalities. Recently, studies suggests that combination of sorafenib and single cytotoxic agent
can be relatively effective and safe strategy that achieves promising rates of local and systemic
control in advanced HCC patients. Based on above suggestions, we herein offer our experience
of a case achieved complete remission by combination therapy of sorafenib and tegafur in the
patient with progressed disease after sorafenib therapy.
Liver cancer is more complex to treat compared to cancers in other organs, since liver function
should be considered. In addition, only a few patients can be applied curative treatment due to
advanced stage at diagnosis. Therefore, early stage detection is important and has been increased
through screening and surveillance programs using image modalities recently. However, it is still
difficult to diagnose small or hypovascular hepatocellular carcinoma (HCC) even using advanced
image modalties. In particular, hypovascular HCCs do not show arterial contrast enhancement
which is a typical finding of HCC on computed tomography (CT) and magnetic resonance
imaging (MRI). Those also account for a considerable portion of early HCC. We present 54 yearsold
man who had recurrent hypervascular and hypovascular nodules on three phase CT and
gadoxetic acid-enhanced MRI. The nodules were removed by surgical resection and confirmed
as combined hepatocellular-cholangiocarcinoma and well differentiated HCC respectively.
Intrahepatic sarcomatoid carcinoma is a rare tumor with poor prognosis due to its highly invasive
and metastatic nature and difficulty for early detection. The most common form of intrahepatic
sarcomatoid carcinoma is the sarcomatoid hepatocellular carcinoma, the development of which is
usually associated with previous treatment for hepatocellular carcinoma. In contrast, sarcomatoid
cholangiocarcinoma is extremely rare and results from spontaneous sarcomatoid transformation
during the development of tumor. Here, we report a case of sarcomatoid cholangiocarcinoma,
in a 58-year-old male, which developed at the site of previous treatment for hepatocellular
carcinoma. A 9 × 7 cm sized tumor which had not been detected in the computed tomography
exam 3 months before diagnosis was newly observed. The tumor rapidly progressed and the
patient died only 31 days after the diagnosis.