Journal of Liver Cancer

Review Article

Animal Models of Liver Cancer: Current Status and Application in Preclinical Research: Hye-Lim Ju, Simon Weonsang Ro; J Liver Cancer. 2017;17(1):1-14. Published online March 31, 2017; DOI: https://doi.org/10.17998/jlc.17.1.1

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Abstract PDF: 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.

Original Article

Diagnostic Performance of Diffusion-weighted Imaging for Hepatic Neuroendocrine Tumor: Comparison with Combined Diffusion-weighted Imaging and Contrast-enhanced Magnetic Resonance Imaging: Suk Ki Jang, Jung Hoon Kim, Mi Hye Yu, Joon Koo Han; J Liver Cancer. 2016;16(2):92-100. Published online September 30, 2016; DOI: https://doi.org/10.17998/jlc.16.2.92

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Abstract PDF: Background/Aim
s: To investigate the diagnostic performance of diffusion-weighted imaging (DWI) for hepatic neuroendocrine tumors (NET) compared with combined DWI and contrastenhanced magnetic resonance imaging (MRI) .
Methods
Fifteen patients with hepatic NET (n=128) underwent enhanced MRI and DWI with multiple-b values. We analyzed three different sets: Precontrast set; DWI set (added DWI); combined set (added enhanced image). Two reviewers rated possibility of NET using a 5-point scale for each image set. Their diagnostic performance was compared using Jackknife alternative free-response ROC (JAFROC).
Results
Diagnostic performance was better on the combined set (figure of merit [FOM]=0.852, 0.761) than the precontrast set (FOM=0.427, 0.572, P<0.05) and the DWI set (FOM=0.682, 0.620, P<0.05). However, DWI improved performance compared with precontrast set without statistical difference. In small NETs (<1 cm), all sets showed low sensitivity (10.7-65.9%) with high specificity (95.4-100%). Interobserver agreement was moderate in all image sets (k=0.521 to 0.589).
Conclusions
Combined DWI and enhanced MRI were more useful for detecting NET. Although statistically insignficant, there was a trend in improved diagnostic performance with DWI.

Review Articles

Obesity and Hepatocellular Carcinoma: Won Sohn; J Liver Cancer. 2016;16(2):86-91. Published online September 30, 2016; DOI: https://doi.org/10.17998/jlc.16.2.86

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Abstract PDF: Obesity is closely associated with hepatocellular carcinoma (HCC) as well as other malignancies. Obesity is an important risk factor for cancer development and overall mortality in HCC. Molecular mechanisms of hepatocarcinogenesis in obesity are adipose tissue remodeling, dysregulation of adipokines, increased reactive oxygen species, insulin resistance or hyperinsulinemia, alteration of gut microbiota, and dysregulation of microRNA. Obesity is the most common cause of non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH). NAFLD or NASH leads to HCC as well as liver cirrhosis. Hepatitis C virus regulates lipid homeostasis in liver. Obesity and its’ related factors (metabolic syndrome and diabetes mellitus) are significantly related to the risk of HCC development in chronic hepatitis C. However, it is not clear whether obesity is a risk factor for HCC in chronic hepatitis B. The relationship between obesity and HCC seems to be different according to etiology of background liver disease. Further studies are needed to clarify the effect of obesity on HCC in different etiologies of chronic liver disease.

Transarterial Chemoembolization in Patients with Hepatocellular Carcinoma and Extrahepatic Metastasis: Jin Su Kim, Su Cheol Park; J Liver Cancer. 2016;16(2):82-85. Published online September 30, 2016; DOI: https://doi.org/10.17998/jlc.16.2.82

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Abstract PDF: Transarterial chemoembolization (TACE) has been widely performed as a treatment for unresectable hepatocellular carcinoma (HCC). Recently extrahepatic metastasis (EHM) of HCC is increasing due to improvement of survival. Sorafenib has been generally accepted as a standard treatment in advanced HCC. However, many HCC patients with EHM are treated with TACE in real-world clinical practice because sorafenib has modest efficacy and the main cause of death in the patients with EHM is hepatic failure. In this review, the usefulness of TACE for the patients with HCC and EHM will be discussed.

Locoregional Treatment of Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis: Sang Youn Hwang, Ryoung-Go Kim, Cheol-Won Choi, Sang Bu Ahn; J Liver Cancer. 2016;16(2):69-81. Published online September 30, 2016; DOI: https://doi.org/10.17998/jlc.16.2.69

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Abstract PDF

Hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) have a extremely poor prognosis. According to the Barcelona Clinic Liver Cancer guideline, sorafenib is a standard therapy in this situation, but many clinicians still select locoregional therapy (LRT) such as transarterial therapy, external beam radiation therapy (EBRT), even surgical resection (SR) or combination of LRTs because the survival improvement by sorafenib is unsatisfactory. Based on recent meta-analysis and prospective study, transarterial chemoembolization (TACE) and transarterial radioembolization seem to be effective and safe therapeutic option that have comparable outcome to sorafenib. Recently large nationwide studies demonstrated that SR can be a potentially curative treatment in selected patients. Hepatic arterial infusion chemotherapy (HAIC) can be also good option, especially in Child class B patients based on small volume prospective studies. Moreover, multidisciplinary strategies based on the combination of LRTs (SR plus TACE, TACE + EBRT, TACE + Sorafenib, HAIC + EBRT etc.) may improve survival of HCC patients with PVTT. Finally we discuss individualized and tailored treatment strategies for different clinical situations.

Citations

Citations to this article as recorded by

Progress in Non-Surgical Treatment of Primary Hepatocellular Carcinoma with Combined Portal Vein Carcinoma Thrombosis
文豪寇
Advances in Clinical Medicine.2023; 13(07): 11779. CrossRef

Case Reports

Hepatic Immunoglobulin G4-related Inflammatory Pseudotumor Mimicking Hepatocellular Carcinoma: Seung Heon Kang, Sang Hoon Park, Ho Hyun Park, Jeong Rok Lee, Won Hyeok Choe, So Dug Lim, Soon Young Ko; J Liver Cancer. 2016;16(2):151-154. Published online September 30, 2016; DOI: https://doi.org/10.17998/jlc.16.2.151

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Abstract PDF: Immunoglobulin G4-related disease is a recently recognized entity characterized by a massforming or regional lesion that contains an extensive infiltration of IgG4-producing plasma cells with dense fibrosis. Immunoglobulin G4-related disease can affect any organ system, but solitary hepatic lesion of Immunoglobulin G4-related disease is very rare. This entity mimics primary malignant hepatic tumor, such as hepatocellular carcinoma or intrahepatic cholangiocarcinoma. We experienced a case of hepatic IgG4-related inflammatory pseudotumor in a 50-year-old woman, mimicking hepatocellular carcinoma.

A Case of Surgical Resection in Hepatocellular Carcinoma with Pulmonary Metastasis: Woo Jin Jung, Jae Young Jang, Jun Seok Park, Hee Jeong Lee, Young Kyu Cho, Soung Won Jeong, Sae Hwan Lee, Snag Gyune Kim, Sang Woo Cha, Young Seok Kim, Young Deok Cho, Hong Soo Kim, Boo Sung Kim; J Liver Cancer. 2016;16(2):145-150. Published online September 30, 2016; DOI: https://doi.org/10.17998/jlc.16.2.145

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Abstract PDF: Hepatocellular carcinoma (HCC) is well known malignancy with poor prognosis, even after resection of the primary tumor. Sorafenib is the first-line treatment in advanced HCC, but the disease control rate of sorafenib is only 43%. Pulmonary metastasectomy in patients with pulmonary metastasis from HCC has been reported to increase long-term survival compared with systemic chemotherapy. Video-assisted thoracic surgery is considered a reliable approach to the diagnosis and treatment of pulmonary diseases with low complication rate. Pulmonary metastasectomy is not universally accepted because of frequent local recurrence, an uncontrollable primary tumor, and frequent multiple pulmonary metastases in HCC, but outcome of pulmonary metastasectomy and adjuvant sorafenib therapy has not been studied. We experienced a patient who had advanced HCC with pulmonary oligometastasis and received surgical resection of the metastatic pulmonary nodule and sorafenib chemotherapy. In advanced HCC with pulmonary oligometastasis, surgical resection of pulmonary metastasis and sorafenib chemotherapy should be considered.

Sarcomatoid Intrahepatic Cholangiocarcinoma: A Rare Case of Primary Liver Cancer: Doo Hyuck Lee, Kyu Hyung Han, Sun Young Ahn, Sang Sun Kim, Hyun Sung Shin, Ki Bae Bang, Jun Ho Choi, Suk Bae Kim, Won Ae Lee, il Han Song; J Liver Cancer. 2016;16(2):139-144. Published online September 30, 2016; DOI: https://doi.org/10.17998/jlc.16.2.139

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3 Citations

Abstract PDF

Sarcomatoid carcinoma arising from intrahepatic cholangiocyte, an extremely rare primary liver cancer, has highly invasive and metastatic potential. The pathogenesis of this tumor is unclear, although histogenetic mechanisms, such as transdifferentiation/dedifferentiation (epithelialmesenchymal transition or metaplastic transformation), biphasic differentiation (combination and collision), and redifferentiation, might be suggested to explain the simultaneous coexistence of carcinoma and sarcoma components in the same tumor. Immunohistochemical staining might be necessary to differentiate whether sarcomatous component is originated from hepatocyte or cholangiocyte. We report a case of sarcomatoid intrahepatic cholangiocarcinoma in a 58 year-old man presenting as an incidentally detected liver mass on regular health examination, which was diagnosed by an application of immunohistochemical methods after surgical resection, with a review of the literature based on 9 cases reported in Korea.

Citations

Citations to this article as recorded by

Pathologic features and clinical treatment of sarcomatoid intrahepatic cholangiocarcinoma
Xiaoli Xie, Nannan Lai, Yuanyuan Yang, Jinwei Zhang, Jianmin Qin, Xia Sheng
Intractable & Rare Diseases Research.2023; 12(4): 267. CrossRef
Clinical diagnosis and treatment strategies for sarcomatoid intrahepatic cholangiocarcinoma
Xia Sheng, Jian-Min Qin
World Chinese Journal of Digestology.2022; 30(14): 614. CrossRef
Analysis of intrahepatic sarcomatoid cholangiocarcinoma: Experience from 11 cases within 17 years
Dong Kyun Kim, Bo Ra Kim, Jin Sook Jeong, Yang Hyun Baek
World Journal of Gastroenterology.2019; 25(5): 608. CrossRef

A Case of Advanced Hepatocellular Carcinoma with Portal Vein Tumor Invasion that Showed Favorable Prognosis after Combined External Radiation Therapy and Sorafenib Therapy: Namyoung Paik, Dong Hyun Sinn, Hee Chul Park, Woo Kyung Jeong, Min Sun Kim, Ji Hye Kim, Bumhee Yang; J Liver Cancer. 2016;16(2):134-138. Published online September 30, 2016; DOI: https://doi.org/10.17998/jlc.16.2.134

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Abstract PDF: A prognosis of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is dismal that the median survival is 2 to 4 months without treatment. Sorafenib, the standard regimen of advanced HCC, can prolong median survival only 1.5 months. A 50-year-old man with a history of chronic hepatitis B was diagnosed advanced HCC with PVTT. By a multidisciplinary medical team approach, the combination of 3-demensional conformal radiation therapy with sequential sorafenib was challenged. 4 months after initiation of treatment, he achieved partial response as modified response evaluation criteria in solid tumors criteria. Sorafenib was continued so far, and stable disease has been maintained up to now, without significant adverse effect.

A Case of Management for Hepatocellular Carcinoma with Lung Metastasis: Han Jo Jeon, Tae Hyung Kim, Soon Ho Um, Yeon Seok Seo, Hyun Seo Kim, Ki Joon Lim, Seung Woon Park, Han Ah Lee, Dong-Sik Kim; J Liver Cancer. 2016;16(2):129-133. Published online September 30, 2016; DOI: https://doi.org/10.17998/jlc.16.2.129

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Abstract PDF: Liver cancer is the 2nd most common cause of cancer related death in Korea. Especially, patients who present extrahepatic spread of hepatocellular carcinoma (HCC) have a shorter life expectancy (50% survival at 1 year and less than 4 months of median overall survival). Molecular target agent like sorafenib was usually mentioned as a treatment for them, but that was still not firmly established. We present a 75 year-old who had expanding nodular type of HCC. The mass was removed by resection and radiofrequency ablation. However, lung metastasis were revealed shortly after surgery. That lesions were treated with lenvatinib and systemic chemotherapy.

A Case of Achieving Complete Remission with Stereotactic Body Radiation Therapy in Patients with Hepatocellular Carcinoma with Macrovascular Invasion after Repeated Transarerial Chemoembolization: Sang Youn Hwang, Seon-Mi Lee, Jong Woo Im, Ki Jeong Jeon, Sang Bu Ahn, Eun Kyeong Ji, Jin-Young Park, Cheol-Won Choi Choi, Gwang-Mo Yang; J Liver Cancer. 2016;16(2):123-128. Published online September 30, 2016; DOI: https://doi.org/10.17998/jlc.16.2.123

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Abstract PDF: Transarterial chemoembolization (TACE) is the worldwide procedure performed for patients with various stage hepatoceullar carcinoma (HCC), but is not yet considered as curative treatment because of relatively high local recurrence rate. Moreover, many clinicians frequently experience treatment failure (incomplete necrosis or stage progression etc.) after repeated TACE, but no clear guidelines have been recommended about salvage treatment modalities for this situation. Recently, studies for combination of radiation therapy and TACE for HCC with TACE refractoriness have been tried and reported better therapeutic efficacy. Based on above suggestions, we herein offer our experience of a patient with macrovascular invasion developed after repeated TACE that achieve complete remission by stereotactic body radiation therapy. Further study, maybe regarding a combination of locoregional and systemic therapy, is necessary on how to manage HCC patients with TACE refractoriness.

A Case of Successful Hepatic Resection after Insufficient Response to Transarterial Chemoembolization and Radiation Therapy in Hepatocellular Carcinoma with Portal Vein Invasion: Seong Kyun Na, Hyung Joon Yim, Sang Jun Suh, Young Kul Jung; J Liver Cancer. 2016;16(2):118-122. Published online September 30, 2016; DOI: https://doi.org/10.17998/jlc.16.2.118

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Abstract PDF: Hepatocellular carcinoma (HCC) with portal vein invasion has a poor prognosis. Treatments such as transarterial chemoembolization (TACE), radiation therapy (RT), sorafenib are done as a first line treatment. But in case of incomplete response to first line treatment, there’s no established guideline about salvage treatment. We present a 47 year-old male who was diagnosed as HCC with portal vein invasion. He was treated with RT and repeated TACE, but remnant viable tumor was observed. Surgical resection was performed as a salvage treatment, and HCC was completely removed. He has been followed up over 3 years, but there was no recurrence.

Original Articles

High-level Expression of Interleukin-17 and C-reactive Protein Predicts Tumor Progression in Unresectable Hepatocellular Carcinoma Treated by Transarterial Chemoembolization: Myeong Jun Song, Sung Won Lee, Eun-Jee Oh, Bohyun Jang, Jeong Won Jang, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon; J Liver Cancer. 2016;16(2):108-117. Published online September 30, 2016; DOI: https://doi.org/10.17998/jlc.16.2.108

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Abstract PDF: Background/Aim
s: Transarterial chemoembolization (TACE) is the standard locoregional treatment in patients with unresectable hepatocellular carcinoma (HCC). Angiogenesis and inflammation play important roles in tumor growth in HCC. In this study, we evaluated the associations between the levels of growth factors and inflammatory markers and clinical prognosis in patients with unresectable HCC treated with TACE.
Methods
The clinical outcomes of 58 HCC patients treated with TACE at the Catholic Medical Centers from January, 2012 to February 2015 were evaluated. Baseline levels of the growth factors vascular endothelial growth factor, fibroblast growth factor, platelet-derived growth factor, and hepatocyte growth factor and the inflammatory cytokines interleukin (IL)-17 and high sensitivity C-reactive protein (hs-CRP) were compared with the treatment outcomes. The primary endpoint was time to progression (TTP); the secondary endpoint was overall survival (OS).
Results
During the 20.8 months of follow-up, TTP was significantly delayed in patients with low levels of hs-CRP (≤0.15) and IL-17 (≤0.94) and a maximal tumor diameter ≤5 cm (P =0.010, P =0.015, and 0.048, respectively). Patients with HCC with low hs-CRP and IL-17 levels had a longer survival than that of those with high hs-CRP levels and IL-17 (35.1 vs. 22.5 months, P =0.000; 41 vs. 21.8 months, P =0.000, respectively). However, any baseline growth factors were not significantly correlated with TTP and OS.
Conclusions
Elevated IL-17 and hs-CRP may be predictive of a poor outcome in patients with HCC treated with TACE. A better understanding of this relationship will require further investigation of the immune mechanisms underlying tumor progression.

Cause of Mortality for Hepatocellular Carcinoma Patients who were Diagnosed within the Milan Criteria: Hyun-Woo Lee, Dong Hyun Sinn, Wonseok Kang, Geum-Youn Gwak, Yong-Han Paik, Moon Seok Choi, Joon Hyeok Lee, Kwang Cheol Koh, Seung Woon Paik; J Liver Cancer. 2016;16(2):101-107. Published online September 30, 2016; DOI: https://doi.org/10.17998/jlc.16.2.101

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7 Citations

Abstract PDF

Background/Aim
s: Hepatocellular carcinoma (HCC) is a unique condition where the cause of death might not only be due to progressive cancer, but also from liver failure. We evaluated specific causes of death for HCC patients who were initially diagnosed within the Milan criteria.
Methods
A retrospective cohort of 147 patients with mortality who were initially diagnosed with HCC within the Milan criteria between January 2008 and December 2012 at a single institution was reviewed.
Results
During follow-up, 104 patients (70.7%) experienced one or more cirrhotic complications, such as ascites, variceal bleeding, or hepatic encephalopathy. Near mortality, cancer progression (exceeding the Milan criteria) was recorded for 102 patients (69.3%), while cirrhosis progression (greater than two-point increase in Child-Pugh score) was noted in 110 (74.8%) patients. Alphafetoprotein, protein-induced by vitamin K antagonist-II levels and treatment modality were associated with cancer progression, while age and Child-Pugh class were associated with cirrhosis progression. There were 61 patients with in-hospital mortality; cancer progression plus liver failure was noted in 34 patients (55.7%), liver failure without cancer progression was seen in 20 patients (32.8%), and only four patients (6.6%) showed mortality from extrahepatic metastasis without liver failure.
Conclusions
Among HCC patients who were diagnosed within the Milan criteria, most of them had cirrhosis progression near mortality, and significant proportion died without uncontrolled cancer growth, mainly due to liver failure. These findings show the importance of liver function that should be considered in managing HCC patients.

Citations

Citations to this article as recorded by

2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma

Journal of Liver Cancer.2023; 23(1): 1. CrossRef
Clinical Outcomes of Hepatitis B Virus–Related Hepatocellular Carcinoma Patients with Undetectable Serum HBV DNA Levels
Jong-In Chang, Dong Hyun Sinn, Hyun Cho, Seonwoo Kim, Wonseok Kang, Geum-Youn Gwak, Yong-Han Paik, Moon Seok Choi, Joon Hyeok Lee, Kwang Cheol Koh, Seung Woon Paik
Digestive Diseases and Sciences.2022; 67(9): 4565. CrossRef
2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma

Clinical and Molecular Hepatology.2022; 28(4): 583. CrossRef
2022 KLCA-NCC Korea Practice Guidelines for the Management of Hepatocellular Carcinoma

Korean Journal of Radiology.2022; 23(12): 1126. CrossRef
Stereotactic Ablative Radiotherapy for Oligometastatic Hepatocellular Carcinoma: A Multi-Institutional Retrospective Study (KROG 20-04)
Tae Hyung Kim, Taek-Keun Nam, Sang Min Yoon, Tae Hyun Kim, Young Min Choi, Jinsil Seong
Cancers.2022; 14(23): 5848. CrossRef
Multidisciplinary approach is associated with improved survival of hepatocellular carcinoma patients
Dong Hyun Sinn, Gyu-Seong Choi, Hee Chul Park, Jong Man Kim, Honsoul Kim, Kyoung Doo Song, Tae Wook Kang, Min Woo Lee, Hyunchul Rhim, Dongho Hyun, Sung Ki Cho, Sung Wook Shin, Woo Kyoung Jeong, Seong Hyun Kim, Jeong Il Yu, Sang Yun Ha, Su Jin Lee, Ho Yeon
PLOS ONE.2019; 14(1): e0210730. CrossRef
Hepatocellular carcinoma with extrahepatic metastasis: Are there still candidates for transarterial chemoembolization as an initial treatment?
Jihye Kim, Dong-Hyun Sinn, Moon Seok Choi, Wonseok Kang, Geum-Youn Gwak, Yong-Han Paik, Joon Hyeok Lee, Kwang Cheol Koh, Seung Woon Paik, Enzo Tagliazucchi
PLOS ONE.2019; 14(3): e0213547. CrossRef

Review Article

Evaluation of the Outcome after Transarterial Chemoembolization; Refinement of Barcelona Clinic Liver Cancer Stage-B from Eastern Point of View: Namiki Izumi; J Liver Cancer. 2016;16(1):7-11. Published online March 31, 2016; DOI: https://doi.org/10.17998/jlc.16.1.7

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Abstract PDF: Transarterial chemoembolization (TACE) is recommended as the first line treatment option for the patients with Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC), however, treatment strategy and evaluation of effects after TACE has not been fully established. Recently, sub-stage of BCLC stage B has been proposed and validated, but it should be validated including a large number of the patients and its refinement should be discussed. We have validated the sub-stage of BCLC stage B (B1-B4) by comparing overall survival after TACE, and there was no statistically significant difference in overall survival after TACE between B1 and B2. After excluding the patients with Child-Pugh point 7 from B1, the overall survival was significantly better than that of B2. Therefore, up-to-seven criteria is shown to be a reliable tool for the treatment strategy in the patients with intermediate stage of HCC. Refinement of sub-stage of BCLC stage B has been proposed by some other institutes, and it is important to establish novel treatment strategy for the patients with BCLC stage B after TACE to improve the prognosis of the patients after TACE, and to define the best timing for conversion to sorafenib or liver transplantation should be discussed. (J Liver Cancer 2016;16:7-11)

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