Journal of Liver Cancer

Volume 18(1); March 2018

Review Articles

Translational Application of Single-cell Transcriptomic Analysis in Hepatocellular Carcinoma: Yoon, Seung Kew; J Liver Cancer. 2018;18(1):1-8. Published online March 31, 2018; DOI: https://doi.org/10.17998/jlc.18.1.1

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Abstract PDF: The emergence of single-cell technology in recent years has made remarkable progress for understanding of biological process in various diseases including cancers. In particular of cancer, single-cell transcriptome analysis provides a powerful tool for comprehensive characterization of cancer cell subpopulations within a heterogeneous bulk populations. Hepatocellular carcinoma (HCC) is a highly heterogeneous cancer and its molecular mechanism is extremely complex associated with a poor prognosis. To date, the molecular mechanisms of hepatocarcinogenesis remain unclear. Here, I review current status of single-cell transcriptome analysis for HCC, focusing on their application for cancer genomics, circulating tumor cells, cancer stem cells and tumor infiltrating cells in HCC.

Tumor Response Evaluation after Treatment and Post-treatment Surveillance of Hepatocellular Carcinoma: Yoon, Jun Sik , Park, Soo Young; J Liver Cancer. 2018;18(1):9-16. Published online March 31, 2018; DOI: https://doi.org/10.17998/jlc.18.1.9

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Abstract PDF: Hepatocellular carcinoma is one of the most prevalent malignancies and frequent causes of death worldwide. Treatment options of hepatocellular carcinoma consist of locoregional therapy, surgical resection, liver transplantation, and systemic therapy. Assessment of tumor response is required in patients receiving locoregional and systemic therapy. The Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 is widely used tumor response evaluation criteria. However, the RECIST does not reflect the extent of tumor necrosis after some locoregional therapies and molecular targeted agents. The Modified RECIST (mRECIST), which has the concept of viable tumor, was introduced in order to overcome this problem. The mRECIST were developed on the basis of RECIST version 1.1 and only tumoral tissue showing contrast uptake in arterial phase of dynamic radiologic imaging techniques was measured to assess tumor response. Recently, immune checkpoint inhibitors have emerged as a promising therapeutic modality for the treatment of hepatocellular carcinoma. To identify tumor response after immunotherapy, immune RECIST (iRECIST) has been proposed as consensusbased criteria. After achieving complete response after curative treatment, optimal surveillance was needed to detect recurrence. Individualized surveillance schedule should be considered, taking into consideration the risk factors of the patient and the risk associated with the treatment modalities.

Systemic Therapy for Advanced Hepatocellular Carcinoma: Targeted Therapy and Immunotherapy: Kim, Bo Hyun , Park, Joong Won; J Liver Cancer. 2018;18(1):17-22. Published online March 31, 2018; DOI: https://doi.org/10.17998/jlc.18.1.17

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Abstract PDF

Systemic therapy for hepatocellular carcinoma (HCC) has markedly changed since 2007, with the approval of sorafenib. Sorafenib improved the overall survival of patients with advanced HCC; however, the modest efficacy and toxicity of this therapy present unmet needs. Subsequently, a variety of molecular targeted agents have been tested as first-line or secondline therapies but have failed, and sorafenib has remained the only approved systemic agent for almost 10 years. Recently, regorafenib significantly improved overall survival and was approved for patients with HCC who have been previously treated with sorafenib. Nivolumab, a programmed death protein-1 inhibitor, was also approved as second-line therapy, based on remarkable response rates.

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Analysis of Existing Guidelines and Randomized, Controlled, Clinical Trials for Development of [Guideline of Clinical Trial on Herbal Medicinal Product for Liver Cancer]
Ga-jin Han, Dong-hun Kim, Eun-joo Park, Sin Seong, Sung-su Kim, Jung-tae Leem
The Journal of Internal Korean Medicine.2019; 40(1): 89. CrossRef

Original Articles

The Feasibility Study of Contrast-enhanced Ultrasound Using a 3 Dimension Transducer for Tumor Volume Measurement in Rabbit Hepatic VX2 Carcinoma Comparison with 2 Dimension Ultrasound and 3 Dimension Ultrasound without Contrast: Preliminary Results: Kim, Jeehyun , Kim, Jung Hoon , Choi, Seo Youn , Han, Joon Koo; J Liver Cancer. 2018;18(1):23-32. Published online March 31, 2018; DOI: https://doi.org/10.17998/jlc.18.1.23

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Abstract PDF: Background/Aims
To investigate the feasibility of tumor volume measurement using contrastenhanced ultrasound (US) with 3 dimension transducer (3D CEUS) in rabbit hepatic VX2 carcinoma.
Methods
Three different tumor volume measurements, including 2D US using the equation, 4/3(π)(abc), 3D US without contrast, and 3D CEUS were performed in 35 rabbit hepatic VX2 carcinomas. With the tumor volume from computerized tomography (CT) as a reference standard, we compared difference between CT volume and each different US tumor volume. The mean difference and correlation coefficient between each US volume measurement and CT volume were analyzed.
Results
Tumor volume measurement using 3D CEUS and 2D US using equation showed no statistical difference compared to CT volume (0.276 cm3, 0.212 cm3, and 0.263 cm3 vs. 0.306 cm3, 0.247 cm3, 0.276 cm3, P>0.05). However, 3D CEUS provided the highest correlation coefficient with CT volume (R=0.835 and 0.720) and the highest intraclass correlation (0.973 and 0.993). 3D CEUS provided a smaller mean difference with CT volume (0.016 cm3 and 0.033 cm3) than 2D US, showing 3D CEUS’s accurate measurement of tumor volume.
Conclusions
Due to its highly accurate, reliable, and reproducible measurements of tumor volume, 3D CEUS may be useful for predicting the therapeutic response evaluation after treatment.

Methionine Adenosyltransferase 1: A Proteomic Surrogate Marker of Early Hepatocellular Carcinoma in Cirrhotic Patients: Lee, Joo Ho , Jun, Mi Jung , Shim, Ju Hyun , Song, Gi Won , Tak, Eunyoung , Oh, Bora , Yu, Eunsil , Choi, Sang Woon , An, Jihyun , Lee, Danbi , Kim, Kang Mo , Lim, Young Suk , Lee, Han Chu , Chung, Young Hwa , Lee, Yung Sang; J Liver Cancer. 2018;18(1):33-43. Published online March 31, 2018; DOI: https://doi.org/10.17998/jlc.18.1.33

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Abstract PDF: Background/Aims
Because there is a lack of effective biomarkers, we aimed to discover proteomic candidate markers for hepatocellular carcinoma (HCC) in cirrhotic patients at the highest-risk of HCC, and to validate the markers. Methods: We collected tumor tissue from 5 cirrhotics with HCC, and from 5 cirrhotics without HCC, who underwent liver resection or transplantation. These tissue samples were analyzed by 2-dimensional difference gel electrophoresis coupled with matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), and potential markers were validated at the transcriptional and translational levels. We also performed western blot assays using other blood samples from 10 cirrhotics with HCC and 10 without HCC. Results: Among the 66 distinguishable spots on 2-D gel images, we identified 15 proteins overexpressed more than 1.5 fold in terms of volume ratio in the tumors. Ten of the over-expressed proteins were identified by MALDI-TOF MS; of those, only methionine adenosyltransferase 1 (MAT1), a protein specific for liver, and acyl-CoA dehydrogenase were significantly up-regulated in tumors in further immunoblotting analyses (Ps<0.05). There was no between-pair difference in MAT1 mRNA measured by real-time polymerase chain reaction (P=0.96). However, in western blots of serum samples, distinct MAT1 bands were observed in all 10 HCC patients, but in only 2 of the non-HCC patients. Conclusions: MAT1 is a potential marker for surveillance in cirrhotic patients with and without prior HCC.

Noninvasive Diagnostic Criteria of the Revised 2014 the Korean Liver Cancer Study Group and the National Cancer Center Guideline for Subcentimetersized Hepatocellular Carcinoma: Is It Too Strict?: Kim, Nam Joong , Sinn, Dong Hyun , Kang, Wonseok , Paik, Yong Han , Choi, Moon Seok , Lee, Joon Hyeok , Koh, Kwang Cheol , Paik, Seung Woon , Gwak, Geum Youn; J Liver Cancer. 2018;18(1):44-50. Published online March 31, 2018; DOI: https://doi.org/10.17998/jlc.18.1.44

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Abstract PDF

Background/Aims
Noninvasive diagnostic criteria for hepatocellular carcinoma (HCC) differ between guidelines, especially for subcentimeter-sized nodules. This study aimed to analyze clinical and radiological characteristics of subcentimeter-sized HCC, and assess the validity of noninvasive diagnostic criteria of the revised 2014 the Korean Liver Cancer Study Group and the National Cancer Center (KLCSG-NCC) guideline for subcentimeter-sized HCC. Methods: A total of 33 consecutive patients (median age, 58.6 years; men, 60.6%; hepatitis B virus-infected, 87.9%) who were diagnosed with HCC between January 2009 and December 2013 and had a maximum tumor diameter less than 1 cm were retrospectively included. Results: Among 33 subcentimeter-sized HCC cases, 6 cases were histologically proven and the remaining 27 patients were diagnosed by radiologically and/or serologically. Initial detection modality was dynamic contrast-enhanced computed tomography (CT) (66.7%, 22/33) or dynamic contrast-enhanced magnetic resonance imaging (MRI) (33.3% 11/33). No case was identified by surveillance ultrasonography. Typical radiological feature of HCC, which is arterial enhancement with delayed washout, was present in 51.7% (15/29 patients) in dynamic contrast-enhanced CT, and 90.9% (30/33 patients) in dynamic contrast-enhanced MRI. When these 33 cases were re-assessed by the revised 2014 KLCSG-NCC guideline, no one has fulfilled the noninvasive diagnostic criteria. Conclusions: None of the cases that were diagnosed as subcentimeter-sized HCC including histologically confirmed cases did not fulfill the noninvasive diagnostic criteria of the revised 2014 KLCSG-NCC guideline. Refinement of the current noninvasive diagnostic criteria for subcentimeter-sized HCC may be required.

Citations

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Clinical practice guideline and real-life practice in hepatocellular carcinoma: A Korean perspective
Myung Ji Goh, Dong Hyun Sinn, Jong Man Kim, Min Woo Lee, Dong Ho Hyun, Jeong Il Yu, Jung Yong Hong, Moon Seok Choi
Clinical and Molecular Hepatology.2023; 29(2): 197. CrossRef

Case Reports

A Case of Hepatocellular Carcinoma in Non-alcoholic Fatty Liver Disease: Seok, Jun , Suk, Ki Tae , Kim, Dong Joon; J Liver Cancer. 2018;18(1):51-54. Published online March 31, 2018; DOI: https://doi.org/10.17998/jlc.18.1.51

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Abstract PDF: Non-alcoholic fatty liver disease (NAFLD) has been one of the causes of cryptogenic hepatocellular carcinoma (HCC). NAFLD-associated HCC (NAFLD-HCC) have clinical features such as high body mass index, deranged lipid profiles, or diabetes mellitus. We experienced a 72-year–old woman with NAFLD associated HCC which was recurred after surgical resection.

Spontaneous Regression of Massive Infiltrative Hepatocellular Carcinoma with Change in Hepatic Contour: A Case Report with Literature Review: Lee, Eun Hwa , Oh, Myung Jin; J Liver Cancer. 2018;18(1):55-62. Published online March 31, 2018; DOI: https://doi.org/10.17998/jlc.18.1.55

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2 Citations

Abstract PDF

Spontaneous regression of hepatocellular carcinoma (HCC) is associated with alcohol abstinence, herbal medication, radiation, ischemia and immune reaction against systemic or local infections. Herein, we report a case of 67-year-old man with spontaneous disappearance of HCC after local infection as a rare cause. The patient had no clinical symptoms except for markedly increased tumor marker of HCC (protein induced by vitamin K absence or antagonist-II: 731 mAU/mL). On computed tomography (CT) and magnetic resonance imaging, massive infiltrating HCC with portal vein invasion was confirmed. During conservative treatment, he was admitted due to suppurative diabetic foot. After medical treatment, HCC disappeared on follow-up CT scans, along with change in hepatic contour. The disappearance of HCC might be a result of immune response by treatment of the diabetic foot and that of ischemia by portal vein tumor thrombosis secondarily. We summarized case reports regarding spontaneous regression of HCC by infection and ischemia.

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What Can Trigger Spontaneous Regression of Breast Cancer?
Nicoletta D’Alessandris, Angela Santoro, Damiano Arciuolo, Giuseppe Angelico, Michele Valente, Giulia Scaglione, Stefania Sfregola, Angela Carlino, Elena Navarra, Antonino Mulè, Gian Franco Zannoni
Diagnostics.2023; 13(7): 1224. CrossRef
The Spontaneous Regression of Primary Gastrointestinal Malignancies: An Observational Review
Carlos D Minacapelli, Philip Leuszkiewicz, Ankoor Patel, Carolyn Catalano, George Abdelsayed, Alexander Lalos, Vinod Rustgi
Cureus.2022;[Epub] CrossRef

Needle-tract Seeding of Hepatocellular Carcinoma at Chest Wall: A Report of Two Cases: Kim, Dae Jung , Kim, Gwangil; J Liver Cancer. 2018;18(1):63-66. Published online March 31, 2018; DOI: https://doi.org/10.17998/jlc.18.1.63

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Abstract PDF: We report two cases of needle-tract seeding after cryoablation and radiofrequency ablation for hepatocellular carcinomas. The seeding nodule appeared 6 and 12 months on the follow-up computed tomographic scan, respectively. In both cases, the seeding nodules were solitary in the chest wall, and could be completely resected.

A Case of Management for Advanced Hepatocellular Carcinoma with Extrahepatic Metastasis by Autologous Natural Killer Cells Combined with Immune Checkpoint Inhibitor: Woo, Ara , Kim, Eun Ju , Shin, Sun Young , Jeon, Hong Jae , Park, Hana , Chon, Young Eun , Lee, Yun Bin , Hwang, Seong Gyu , Rim, Kyu Sung , Lee, Joo Ho; J Liver Cancer. 2018;18(1):67-74. Published online March 31, 2018; DOI: https://doi.org/10.17998/jlc.18.1.67

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63 Downloads

Abstract PDF: Hepatocellular carcinoma (HCC) has extremely poor prognosis. Immunotherapy has emerged as a new treatment for a number of cancers. Adoptive immunotherapy is one of the important cancer immunotherapy, which relies on the various lymphocytes including cytotoxic T lymphocytes, natural killer (NK) and cytokine induced killer cells. Also, there has been advance in techniques of NK cell activation to more effectively kill the cancer cells. Of note, recently the blocking antibodies targeting programmed cell death protein 1 (PD-1) have shown promising results in diverse cancers including HCC. We report our recent experience of a patient accompanying advanced HCC with extrahepatic metastases. Disease progression had occurred after sorafenib administration, while the patient showed local tumor control and tumor marker decrease by NK cell immunotherapy combined with PD-1 inhibitor therapy. Though, there was no definite survival advantage due to impaired liver function, which might be caused by treatment related toxicities as well as cancer progression.

A Case of Complete Response with Biliary Stenosis after Hepatic Arterial Injection and Stereotactic Body Radiotherapy to Hepatoecllular Carcinoma with Portal Vein Thrombosis: Rim, Chai Hong , Im, Hyung Joon , Jung, Young Geol , Chung, Hwan Hoon , Seo, Sang Joon , Yoon, Won Sup; J Liver Cancer. 2018;18(1):75-79. Published online March 31, 2018; DOI: https://doi.org/10.17998/jlc.18.1.75

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Abstract PDF: Curative treatment of hepatocellular carcinoma (HCC) with portal vein invasion is difficult to achieve, and the prognosis is dismal. Combining external beam radiotherapy (EBRT) with hepatic arterial infusion chemotherapy (HAIC) has shown favorable local therapeutic effects for patients with HCC exhibiting portal vein invasion. Stereotactic body radiotherapy (SBRT) is a recently developed EBRT modality that shows excellent tumor control. The combination of SBRT and HAIC for HCC with portal vein invasion has not been well-studied. We report a patient with HCC and portal vein invasion who achieved 15 months of survival with complete response status after combination SBRT and HAIC. The patient later experienced grade 3 biliary stricture and died of liver abscesses of unknown etiologies that subsequently appeared.

A Case of Hepatocellular Carcinoma Treated by Proton Beam Therapy as 1st Choice: Oh, Jinmyeong , Sinn, Dong Hyun , Seong, Gyeol , Chung, Hye Gyo , Heo, Chanmi , Yu, Jeongil , Park, Hee Chul; J Liver Cancer. 2018;18(1):80-85. Published online March 31, 2018; DOI: https://doi.org/10.17998/jlc.18.1.80

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29 Downloads
1 Citation

Abstract PDF

Although first-line treatment option for single, small sized hepatocellular carcinoma in patients with preserved liver function and good performance status is resection or ablation, sometimes these modalities cannot be applied for variable reasons. For them, alternative options such as transarterial chemoeombolization, ethanol injection, and external radiation therapy can be considered, with variable success rates. Herein, we describe 45 year-old male who presented with a single small tumor located at caudate lobe. After multi-disciplinary discussion, the patient was treated with proton beam therapy, which resulted in favorable treatment outcome.

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Carbon ion radiotherapy for patients with hepatocellular carcinoma in the caudate lobe
Shohei Okazaki, Kei Shibuya, Shintaro Shiba, Masahiko Okamoto, Yuhei Miyasaka, Naoto Osu, Motohiro Kawashima, Satoru Kakizaki, Kenichiro Araki, Ken Shirabe, Tatsuya Ohno
Hepatology Research.2021; 51(3): 303. CrossRef

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