Journal of Liver Cancer

Review Article

Intrahepatic cholangiocarcinoma: histological diversity and the role of the pathologist: Mina Komuta; J Liver Cancer. 2024;24(1):17-22. Published online January 3, 2024; DOI: https://doi.org/10.17998/jlc.2023.12.11

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Intrahepatic cholangiocarcinoma (iCCA) is one of the primary liver cancers and presents with tumor heterogeneity. About 50% of iCCAs comprise actionable mutations, which completely change patient management. In addition, the precise diagnosis of iCCA, including subtype, has become crucial, and pathologists play an important role in this regard. This review focuses on iCCA heterogeneity; looking at different perspectives to guide diagnosis and optimal treatment choice.

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Imaging findings of intrahepatic cholangiocarcinoma for prognosis prediction and treatment decision-making: a narrative review
Jun Gu Kang, Taek Chung, Dong Kyu Kim, Hyungjin Rhee
The Ewha Medical Journal.2024;[Epub] CrossRef

Original Article

Diagnostic performance of the 2022 KLCA-NCC criteria for hepatocellular carcinoma on magnetic resonance imaging with extracellular contrast and hepatobiliary agents: comparison with the 2018 KLCA-NCC criteria: Ja Kyung Yoon, Sunyoung Lee, Jeong Ah Hwang, Ji Eun Lee, Seung-seob Kim, Myeong-Jin Kim; J Liver Cancer. 2023;23(1):157-165. Published online February 23, 2023; DOI: https://doi.org/10.17998/jlc.2023.02.07

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Abstract PDF Supplementary Material

Background/Aim
This study aimed to determine the diagnostic performance of 2022 Korean Liver Cancer Association-National Cancer Center (KLCA-NCC) imaging criteria compared with the 2018 KLCA-NCC for hepatocellular carcinoma (HCC) in high-risk patients using magnetic resonance imaging (MRI).
Methods
This retrospective study included 415 treatment-naïve patients (152 patients who underwent extracellular contrast agent [ECA]-MRI and 263 who underwent hepatobiliary agent [HBA]-MRI; 535 lesions, including 412 HCCs) with a high risk of HCC who underwent contrast-enhanced MRI. Two readers evaluated all lesions according to the 2018 and 2022 KLCA-NCC imaging diagnostic criteria, and the per-lesion diagnostic performances were compared.
Results
In “definite” HCC category of both 2018 and 2022 KLCA-NCC, HBA-MRI showed a significantly higher sensitivity for the diagnosis of HCC than ECA-MRI (77.0% vs. 64.3%, P=0.006) without a significant difference in specificity (94.7% vs. 95.7%, P=0.801). On ECAMRI, “definite” or “probable” HCC categories of the 2022 KLCA-NCC had significantly higher sensitivity than those of the 2018 KLCA-NCC (85.3% vs. 78.3%, P=0.002) with identical specificity (93.6%). On HBA-MRI, the sensitivity and specificity of “definite” or “probable” HCC categories of both 2018 and 2022 KLCA-NCC were not significantly different (83.3% vs. 83.6%, P>0.999 and 92.1% vs. 90.8%, P>0.999, respectively).
Conclusions
In “definite” HCC category of both 2018 and 2022 KLCA-NCC, HBA-MRI provides better sensitivity than ECA-MRI without compromising specificity. On ECA-MRI, “definite” or “probable” HCC categories of the 2022 KLCA-NCC may improve sensitivity in the diagnosis of HCC compared with the 2018 KLCA-NCC.

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Impact of the updated KLCA-NCC criteria for diagnosis of “probable HCC” in liver MRI: comparisons between KLCA v2022 and v2018
Jeong Hee Yoon
Journal of Liver Cancer.2023; 23(1): 124. CrossRef

Guideline

2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma: J Liver Cancer. 2023;23(1):1-120. Published online December 9, 2022; DOI: https://doi.org/10.17998/jlc.2022.11.07

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58 Citations

Abstract PDF

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.

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Original Article

The diagnostic value of circulating tumor DNA in hepatitis B virus induced hepatocellular carcinoma: a systematic review and meta-analysis: Young Chang, Soung Won Jeong, Jae Young Jang, Hyuksoo Eun, Young‑Sun Lee, Do Seon Song, Su Jong Yu, Sae Hwan Lee, Won Kim, Hyun Woong Lee, Sang Gyune Kim, Seongho Ryu, Suyeon Park; J Liver Cancer. 2022;22(2):167-177. Published online September 29, 2022; DOI: https://doi.org/10.17998/jlc.2022.09.19

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101 Downloads
2 Citations

Abstract PDF Supplementary Material

Background/Aim
New biomarkers are urgently needed to aid in the diagnosis of early stage hepatocellular carcinoma (HCC). We performed a meta-analysis on the diagnostic utility of circulating tumor DNA (ctDNA) levels in patients with hepatitis B virus-induced HCC.
Methods
We retrieved relevant articles from PubMed, Embase, and the Cochrane Library up to February 8, 2022. Two subgroups were defined; one subset of studies analyzed the ctDNA methylation status, and the other subset combined tumor markers and ctDNA assays. Pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic curve (AUC) were analyzed.
Results
Nine articles including 2,161 participants were included. The overall SEN and SPE were 0.705 (95% confidence interval [CI], 0.629-0.771) and 0.833 (95% CI, 0.769-0.882), respectively. The DOR, PLR, and NLR were 11.759 (95% CI, 7.982-17.322), 4.285 (95% CI, 3.098- 5.925), and 0.336 (0.301-0.366), respectively. The ctDNA assay subset exhibited an AUC of 0.835. The AUC of the combined tumor marker and ctDNA assay was 0.848, with an SEN of 0.761 (95% CI, 0.659-0.839) and an SPE of 0.828 (95% CI, 0.692-0.911).
Conclusions
Circulating tumor DNA has promising diagnostic potential for HCC. It can serve as an auxiliary tool for HCC screening and detection, especially when combined with tumor markers.

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Review Articles

Liquid biopsy for early detection and therapeutic monitoring of hepatocellular carcinoma: Eun-Ji Choi, Young-Joon Kim; J Liver Cancer. 2022;22(2):103-114. Published online September 22, 2022; DOI: https://doi.org/10.17998/jlc.2022.09.08

6,030 Views
177 Downloads
7 Citations

Abstract PDF Supplementary Material

Advances in our knowledge of the molecular characteristics of hepatocellular carcinoma (HCC) have enabled significant progress in the detection and therapeutic prediction of HCC. As a non-invasive alternative to tissue biopsy, liquid biopsy examines circulating cellular components such as exosomes, nucleic acids, and cell-free DNA found in body fluids (e.g., urine, saliva, ascites, and pleural effusions) and provides information about tumor characteristics. Technical advances in liquid biopsy have led to the increasing adoption of diagnostic and monitoring applications for HCC. This review summarizes the various analytes, ongoing clinical trials, and case studies of United States Food and Drug Administrationapproved in vitro diagnostic applications for liquid biopsy, and provides insight into its implementation in managing HCC.

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A clinical and pathological update on hepatocellular carcinoma: Salvatore Lorenzo Renne, Luca Di Tommaso; J Liver Cancer. 2022;22(1):14-22. Published online March 31, 2022; DOI: https://doi.org/10.17998/jlc.2022.03.18

11,824 Views
619 Downloads
14 Citations

Abstract PDF

It is estimated that more than 1 million individuals will be affected annually by hepatocellular carcinoma (HCC) by 2025. HCC can be broadly grouped into two major molecular subgroups, each of which is characterized by specific morphological and phenotypic features that mirror the genetic background. The use of these tissue biomarkers in the daily practice of pathologists promises to better allocate patients with HCC with adequate treatments. In turn, this will likely boost the attitude of clinicians toward obtaining a pre-treatment biopsy.

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Original Article

Diagnostic performance of serum exosomal miRNA-720 in hepatocellular carcinoma: Jeong Won Jang, Ji Min Kim, Hye Seon Kim, Jin Seoub Kim, Ji Won Han, Soon Kyu Lee, Heechul Nam, Pil Soo Sung, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon; J Liver Cancer. 2022;22(1):30-39. Published online March 21, 2022; DOI: https://doi.org/10.17998/jlc.2022.02.25

5,149 Views
157 Downloads
4 Citations

Abstract PDF Supplementary Material

Background/Aim
Hepatocellular carcinoma (HCC) is associated with poor prognosis, largely due to late detection. Highly accurate biomarkers are urgently needed to detect early-stage HCC. Our study aims to explore the diagnostic performance of serum exosomal microRNA (miR)-720 in HCC.
Methods
Exosomal miRNA was measured via quantitative real-time PCR. A correlation analysis of exosomal miR-720 and tumor or clinico-demographic data of patients with HCC was performed. The receiver operating characteristic (ROC) curve was used to assess the diagnostic capacity of serum exosomal miR-720 for HCC, in comparison with α-fetoprotein (AFP) and prothrombin induced by vitamin K absence or antagonist-II (PIVKA-II).
Results
MiR-720 was chosen as a potential HCC marker via miR microarray based on significant differential expression between tumor and non-tumor samples. Serum exosomal miR-720 was significantly upregulated in patients with HCC (n=114) versus other liver diseases (control, n=30), with a higher area under the ROC curve (AUC=0.931) than the other markers. Particularly, serum exosomal miR-720 showed superior performance in diagnosing small HCC (< 5 cm; AUC=0.930) compared with AFP (AUC=0.802) or PIVKA-II (AUC=0.718). Exosomal miR-720 levels showed marginal correlation with tumor size. The proportion of elevated miR-720 also increased with intrahepatic tumor stage progression. Unlike AFP or PIVKA-II showing a significant correlation with aminotransferase levels, the exosomal miR-720 level was not affected by aminotransferase levels.
Conclusions
Serum exosomal miR-720 is an excellent biomarker for the diagnosis of HCC, with better performance than AFP or PIVKA-II. Its diagnostic utility is maintained even in small HCC and is unaffected by aminotransferase levels.

Citations

Citations to this article as recorded by

Diagnostic and Prognostic Significance of Exosomes and Their Components in Patients With Cancers
Zinnat Ara Moni, Zahid Hasan, Md. Shaheen Alam, Nitai Roy, Farhadul Islam
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Prospects of liquid biopsy in the prognosis and clinical management of gastrointestinal cancers
Deepankar Mondal, Sapnita Shinde, Vibha Sinha, Vineeta Dixit, Souvik Paul, Rakesh Kumar Gupta, Suresh Thakur, Naveen Kumar Vishvakarma, Dhananjay Shukla
Frontiers in Molecular Biosciences.2024;[Epub] CrossRef
Emerging role of exosomal microRNA in liver cancer in the era of precision medicine; potential and challenges
Tarek El Hayek, Osama Abdulwahab Alnaser-Almusa, Sulaiman Mamoun Alsalameh, Maya Taofik Alhalabi, Ahmad Nedal Sabbah, Eman Abdullah Alshehri, Tanveer Ahmad Mir, Naresh Kumar Mani, Khaled Al-Kattan, Raja Chinnappan, Ahmed Yaqinuddin
Frontiers in Molecular Biosciences.2024;[Epub] CrossRef
Exosomal non-coding RNAs (ncRNAs) as potential biomarkers in tumor early diagnosis
Jingyue Chang, Lingquan Zhang, Zeting Li, Chungen Qian, Juan Du
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer.2024; 1879(6): 189188. CrossRef

Review Article

Update on Pathologic and Radiologic Diagnosis of Combined Hepatocellular-Cholangiocarcinoma: Hyungjin Rhee, Jae Hyon Park, Young Nyun Park; J Liver Cancer. 2021;21(1):12-24. Published online March 31, 2021; DOI: https://doi.org/10.17998/jlc.21.1.12

7,338 Views
340 Downloads
5 Citations

Abstract PDF

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a malignant primary liver carcinoma characterized by the unequivocal presence of both hepatocytic and cholangiocytic differentiation within the same tumor. Recent research has highlighted that cHCC-CCAs are more heterogeneous than previously expected. In the updated consensus terminology and WHO 2019 classification, “classical type” and “subtypes with stem-cell features” of the WHO 2010 classification are no longer recommended. Instead, it is recommended that the presence and percentages of various histopathologic components and stem-cell features be mentioned in the pathologic report. The new terminology and classification enable the exchange of clearer and more objective information about cHCC-CCAs, facilitating multi-center and multinational research. However, there are limitations to the diagnosis of cHCC-CCA by imaging and biopsy. cHCC-CCAs showing typical imaging findings of HCC could be misdiagnosed as HCC and subjected to inappropriate treatment, if other clinical findings are not sufficiently considered. cHCC-CCAs showing at least one of the CCA-like imaging features or unusual clinical features should be subjected to biopsy. There may be a sampling error for the biopsy diagnosis of cHCC-CCA. An optimized diagnostic algorithm integrating clinical, radiological, and histopathologic information of biopsy is required to resolve these diagnostic pitfalls.

Citations

Citations to this article as recorded by

Enhancing liver cirrhosis varices and CSPH risk prediction with spleen stiffness measurement using 100-Hz probe
Jeong-Ju Yoo, Sun Ah Maeng, Young Chang, Sae Hwan Lee, Soung Won Jeong, Jae Young Jang, Gab Jin Cheon, Young Seok Kim, Hong Soo Kim, Sang Gyune Kim
Scientific Reports.2024;[Epub] CrossRef
MRI features of combined hepatocellular-cholangiocarcinoma
Noor Fatima Majeed, Mathew Macey, Marta Braschi Amirfarzan, Sheida Sharifi, Jeremy R Wortman
Abdominal Radiology.2024; 50(1): 169. CrossRef
Imaging findings of intrahepatic cholangiocarcinoma for prognosis prediction and treatment decision-making: a narrative review
Jun Gu Kang, Taek Chung, Dong Kyu Kim, Hyungjin Rhee
The Ewha Medical Journal.2024;[Epub] CrossRef
Differentiation between hepatic angiomyolipoma and hepatocellular carcinoma in individuals who are not at-risk for hepatocellular carcinoma
Sungtae Park, Myeong-Jin Kim, Kyunghwa Han, Jae Hyon Park, Dai Hoon Han, Young Nyun Park, Jaehyo Kim, Hyungjin Rhee
European Journal of Radiology.2023; 166: 110957. CrossRef
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Soo Young Jun, Hyang Ran Yoon, Ji-Yong Yoon, Su-Jin Jeon, Jeong-Ju Lee, Debasish Halder, Jin-Man Kim, Nam-Soon Kim
Cancers.2021; 13(12): 2925. CrossRef

Original Article

Validation of the Korean Liver Cancer Association-National Cancer Center 2018 Criteria for the Noninvasive Diagnosis of Hepatocellular Carcinoma Using Magnetic Resonance Imaging: Sunyoung Lee, Myeong-Jin Kim; J Liver Cancer. 2020;20(2):120-127. Published online September 30, 2020; DOI: https://doi.org/10.17998/jlc.20.2.120

3,638 Views
91 Downloads
2 Citations

Abstract PDF

Background/Aims
This study aimed to assess the validity and diagnostic performance of the imaging criteria of Korean Liver Cancer Association-National Cancer Center (KLCA-NCC) 2018 using magnetic resonance imaging (MRI) in high-risk patients for HCC.
Methods
This retrospective study included 142 treatment-naïve patients (81 patients who underwent MRI with extracellular contrast agent and 61 who underwent MRI with hepatobiliary agent; 183 lesions including 149 HCCs) with a high risk of HCC who underwent multiphasic contrast-enhanced MRI from January to December 2015. All lesions were categorized according to the KLCA-NCC 2018 imaging diagnostic criteria by two readers, and per-lesion diagnostic performances were compared.
Results
According to the KLCA-NCC 2018, none (0%) of the 13 benign category lesions, 11 (44.0%) of 25 indeterminate category lesions, 15 (93.8%) of 16 probable HCC category lesions, and 97 (99.0%) of 98 definite HCC category lesions were ultimately diagnosed as HCCs. The sensitivity and specificity of definite HCC category were 65.1% and 97.1%, respectively, and those of the combination of definite and probable HCC categories were 75.2% and 94.1%, respectively. The sensitivity of the combination of definite and probable HCC categories was significantly higher than that of definite HCC (P<0.001), but the specificity was not significantly lower (P>0.999).
Conclusions
The noninvasive imaging diagnosis of KLCA-NCC 2018 on MRI is reliable and useful for diagnosing HCC in high-risk patients. Combining definite and probable HCC categories of KLCA-NCC 2018 improves the sensitivity while maintaining a high specificity.

Citations

Citations to this article as recorded by

Intraindividual Comparison of MRIs with Extracellular and Hepatobiliary Contrast Agents for the Noninvasive Diagnosis of Hepatocellular Carcinoma Using the Korean Liver Cancer Association–National Cancer Center 2022 Criteria
Ja Kyung Yoon, Dai Hoon Han, Sunyoung Lee, Jin-Young Choi, Gi Hong Choi, Do Young Kim, Myeong-Jin Kim
Cancer Research and Treatment.2023; 55(3): 939. CrossRef
Diagnostic Performance of KLCA-NCC 2018 Criteria for Hepatocellular Carcinoma Using Magnetic Resonance Imaging: A Systematic Review and Meta-Analysis
Dong Hwan Kim, Bohyun Kim, Seo Yeon Youn, Hokun Kim, Joon-Il Choi
Diagnostics.2021; 11(10): 1763. CrossRef

Case Reports

A Case of Simultaneous Resection of Recurrent Combined Hepatocellular Cholangiocarcinoma and Hypovascular Hepatocellular Carcinoma: Tae Hyung Kim, Soon Ho Um, Sang Jung Park, Seung Woon Park, Han Ah Lee, Yeon Seok Seo, Young Dong Yu, Dong-Sik Kim, Joo Young Kim; J Liver Cancer. 2017;17(1):94-99. Published online March 31, 2017; DOI: https://doi.org/10.17998/jlc.17.1.94

2,084 Views
13 Downloads

Abstract PDF: 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.

Two Cases of Small (< 1 cm) Hepatocellular Carcinoma: Jin Yong Jung, Sun Young Yim, Chang Ha Kim, Jin Dong Kim, Yeon Seok Seo, Hyung Joon Yim, Ho Sang Ryu, Min Ju Kim, Beom Jin Park, Soon Ho Um; Journal of the Korean Liver Cancer Study Group. 2012;12(1):37-41. Published online February 28, 2012

655 Views
2 Downloads

Abstract PDF: Tumor size is one of the most important factors for decision of therapeutic plan and prognosis of hepatocellular carcinoma (HCC). If the diagnosis of HCC is made earlier in its small size, the prognosis is better. However the diagnosis of small HCC is not easy because small HCC lacks the typical clinical and radiologic feature. We experienced two cases of small HCC less than 1 cm that was confirmed after first treatment.

A Case of Small Hepatocellular Carcinoma Less Than 1 cm: Yun Jeong Jo, Young Kul Jung, Dong Hae Chung, Oh Sang Kwon, Yun Soo Kim, Duck Joo Choi, Ju Hyun Kim; Journal of the Korean Liver Cancer Study Group. 2012;12(1):42-46. Published online February 28, 2012

622 Views
1 Download

Abstract PDF: Hepatocellular carcinoma (HCC) is one of the most important causes of cancer death in South Korea. Approximately two thirds of the patients are diagnosed in the advanced stage with multiple metastasis and underlying liver dysfunction, so they are not suitable to undergo curative resection. Small HCC has no consensus about diagnostic criteria but became known early stage HCC that means good prognosis. Cases of small HCC have been increasing with the progress of diagnostic methods. We experienced a case of incidentally found small HCC less than 1 cm from liver cirrhosis by liver dynamic imaging, so reported it.

Review Articles

Changes of Hepatocellular Carcinoma Guidelines during the Last Ten-Year Period: Do Seon Song, Si Hyun Bae; Journal of the Korean Liver Cancer Study Group. 2011;11(2):136-143. Published online September 30, 2011

694 Views
1 Download

Abstract PDF: Hepatocellular carcinoma (HCC) is the third most common cause of cancer death in the world. There has been many advances in diagnosis of HCC during the last ten-year period, especially imaging techniques. The Korean Liver cancer study group (KLCSG), European Association for the Study of the Liver (EASL), American Association for the Study of Liver disease (AASLD) and Asian-Pacific Association for the Study of Liver (APASL) have made and changed HCC guidelines with advances of imaging technique and results of research on HCC. We reviewed the changes of imaging guidelines in HCC diagnosis according to the advances of imaging. In addition, further studies will be needed to solve the controversies in diagnosis of HCC smaller than 1 cm in size.

Diagnosis of Hepatocellular Carcinoma: Jin-Wook Kim; Journal of the Korean Liver Cancer Study Group. 2010;10(1):1-5. Published online June 30, 2010

633 Views
7 Downloads

Abstract PDF: The Korean Liver Cancer Study Group (KLCSG) and the Center for Liver Cancer at the National Cancer Center (NCC) in Korea compiled a clinical practice guideline for the management of hepatocellular carcinoma (HCC) in 2003, and the guideline has been revised in 2009 to incorporate newly published scientific evidence in the diagnosis and treatment of HCC. The surveillance and diagnostic criteria of HCC of the 2009 guideline is reviewed with respect to practical application. Several unresolved issues were also discussed.

Differential Diagnosis of Heaptocellular Carcinoma in Radiology: Jeong-Sik Yu; Journal of the Korean Liver Cancer Study Group. 2003;3(1):21-29. Published online July 31, 2003

760 Views
4 Downloads

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