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Articles in E-pub version are posted online ahead of regular printed publication.

Editorial
Radiofrequency for hepatocellular carcinoma larger than 3 cm: potential for applications in daily practice
Ji Hoon Kim, Pil Soo Sung
Received February 10, 2024  Accepted February 13, 2024  Published online March 14, 2024  
DOI: https://doi.org/10.17998/jlc.2024.02.13    [Epub ahead of print]
  • 66 Views
  • 9 Downloads
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Review Article
Intermediate-stage hepatocellular carcinoma: refining substaging or shifting paradigm?
Bernardo Stefanini, Luca Ielasi, Dante Pio Pallotta, Sofia Penazza, Mariarosaria Marseglia, Fabio Piscaglia
Received January 30, 2024  Accepted February 21, 2024  Published online March 12, 2024  
DOI: https://doi.org/10.17998/jlc.2024.02.21    [Epub ahead of print]
  • 119 Views
  • 17 Downloads
AbstractAbstract PDF
This review explores the evolution of cancer staging, focusing on intermediate hepatocellular carcinoma (HCC), and the challenges faced by physicians. The Barcelona Clinic Liver Cancer (BCLC) staging system, introduced in 1999, was designed to address the limitations associated with providing accurate prognostic information for HCC and allocating specific treatments, to avoid overtreatment. However, criticism has emerged, particularly regarding the intermediate stage of HCC (BCLC-B) and its heterogeneous patient population. To overcome this limitation, various subclassification systems, such as the Bolondi and Kinki criteria, have been proposed. These systems are aimed at refining categorizations within the intermediate stage and have demonstrated varying degrees of success in predicting outcomes through external validation. This study discusses the shift in treatment paradigms, emphasizing the need for a more personalized approach rather than strictly adhering to cancer stages, without dismissing the relevance of staging systems. It assesses the available treatment options for intermediate-stage HCC, highlighting the importance of considering surgical and nonsurgical options alongside transarterial chemoembolization for optimal outcomes. In conclusion, the text advocates for a paradigm shift in staging systems prioritizing treatment suitability over cancer stage. This reflects the evolving landscape of HCC management, where a multidisciplinary approach is crucial for tailoring treatments to individual patients, ultimately aiming to improve overall survival.
Original Articles
Liver resection in selective hepatocellular carcinoma with Vp3 or Vp4 portal vein tumor thrombosis improves prognosis
Manuel Lim, Jongman Kim, Jinsoo Rhu, Gyu-Seong Choi, Jae-Won Joh
Received November 7, 2023  Accepted January 31, 2024  Published online February 14, 2024  
DOI: https://doi.org/10.17998/jlc.2024.01.31    [Epub ahead of print]
  • 245 Views
  • 26 Downloads
AbstractAbstract PDF
Background/Aim
Hepatocellular carcinoma (HCC) tumor thrombi located in the first branch of the portal vein (Vp3) or in the main portal trunk (Vp4) are associated with poor prognosis. This study aimed to investigate the clinicopathological characteristics and risk factors for HCC recurrence and mortality following liver resection (LR) in patients with Vp3 or Vp4 HCC.
Methods
The study included 64 patients who underwent LR for HCC with Vp3 or Vp4 portal vein tumor thrombosis (PVTT).
Results
Fifty-eight patients (90.6%) had Vp3 PVTT, whereas the remaining six patients exhibited Vp4 PVTT. The median tumor size measured 8 cm, with approximately 36% of patients presented with multiple tumors. Fifty-four patients (84.4%) underwent open LR, whereas 10 patients underwent laparoscopic LR. In the Vp4 cases, combined LR and tumor thrombectomy were performed. The 3-year cumulative disease-free survival rate was 42.8% for the Vp3 group and 22.2% for the Vp4 group. The overall survival (OS) rate at 3 years was 47.9% for the Vp3 group and 60.0% for the Vp4 group. Intrahepatic metastasis has been identified as an important contributor to HCC recurrence. High hemoglobin levels are associated with high mortality.
Conclusion
LR is a safe and effective treatment modality for selected patients with Vp3 or Vp4 HCC PVTT. This suggests that LR is a viable option for these patients, with favorable outcomes in terms of OS.
Additional nodules detected using EOB-MRI in patients with resectable single hepatocellular carcinoma: an implication for active treatment strategy
Na Reum Kim, Seoung Yoon Rho, Jonathan Navarro, Chansik An, Dai Hoon Han, Jin Sub Choi, Myeong-Jin Kim, Gi Hong Choi
Received November 9, 2023  Accepted January 25, 2024  Published online February 14, 2024  
DOI: https://doi.org/10.17998/jlc.2024.01.25    [Epub ahead of print]
  • 222 Views
  • 30 Downloads
AbstractAbstract PDF
Background/Aim
Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOBMRI) further enhances the identification of additional hepatic nodules compared with computed tomography (CT) alone; however, the optimal treatment for such additional nodules remains unclear. We investigated the long-term oncological effect of aggressive treatment strategies for additional lesions identified using EOB-MRI in patients with hepatocellular carcinoma (HCC).
Methods
Data from 522 patients diagnosed with solitary HCC using CT between January 2008 and December 2012 were retrospectively reviewed. Propensity score-matched (PSM) analysis was used to compare the oncologic outcomes between patients with solitary HCC and those with additional nodules on EOB-MRI after aggressive treatment (resection or radiofrequency ablation [RFA]).
Results
Among the 383 patients included, 59 had additional nodules identified using EOB-MRI. Compared with patients with solitary HCC, those with additional nodules on EOB-MRI had elevated total bilirubin, aspartate transaminase, and alanine transaminase; had a lower platelet count, higher MELD score, and highly associated with liver cirrhosis (P<0.05). Regarding long-term outcomes, 59 patients with solitary HCC and those with additional nodules after PSM were compared. Disease-free survival (DFS) and overall survival (OS) were comparable between the two groups (DFS, 60.4 vs. 44.3 months, P=0.071; OS, 82.8 vs. 84.8 months, P=0.986).
Conclusion
The aggressive treatment approach, either resection or RFA, for patients with additional nodules identified on EOBMRI was associated with long-term survival comparable with that for solitary HCC. However, further studies are required to confirm these findings.
Letter to the Editor
Reply to the Letter regarding “Treatment options for solitary hepatocellular carcinoma ≤5 cm: surgery vs. ablation: a multicenter retrospective study”
Kazuhiro Nouso, Kazuya Kariyama
Received December 19, 2023  Accepted January 2, 2024  Published online January 19, 2024  
DOI: https://doi.org/10.17998/jlc.2024.01.02    [Epub ahead of print]
  • 212 Views
  • 17 Downloads
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Original Article
Comparison of atezolizumab plus bevacizumab and lenvatinib for hepatocellular carcinoma with portal vein tumor thrombosis
Jeayeon Park, Yun Bin Lee, Yunmi Ko, Youngsu Park, Hyunjae Shin, Moon Haeng Hur, Min Kyung Park, Dae-Won Lee, Eun Ju Cho, Kyung-Hun Lee, Jeong-Hoon Lee, Su Jong Yu, Tae-Yong Kim, Yoon Jun Kim, Tae-You Kim, Jung-Hwan Yoon
Received September 28, 2023  Accepted December 25, 2023  Published online January 19, 2024  
DOI: https://doi.org/10.17998/jlc.2023.12.25    [Epub ahead of print]
  • 602 Views
  • 113 Downloads
AbstractAbstract PDFSupplementary Material
Background/Aim
Atezolizumab plus bevacizumab and lenvatinib are currently available as first-line therapy for the treatment of unresectable hepatocellular carcinoma (HCC). However, comparative efficacy studies are still limited. This study aimed to investigate the effectiveness of these treatments in HCC patients with portal vein tumor thrombosis (PVTT).
Methods
We retrospectively included patients who received either atezolizumab plus bevacizumab or lenvatinib as first-line systemic therapy for HCC with PVTT. Primary endpoint was overall survival (OS), and secondary endpoints included progressionfree survival (PFS) and disease control rate (DCR) determined by response evaluation criteria in solid tumors, version 1.1.
Results
A total of 52 patients were included: 30 received atezolizumab plus bevacizumab and 22 received lenvatinib. The median follow-up duration was 6.4 months (interquartile range, 3.9-9.8). The median OS was 10.8 months (95% confidence interval [CI], 5.7 to not estimated) with atezolizumab plus bevacizumab and 5.8 months (95% CI, 4.8 to not estimated) with lenvatinib (P=0.26 by log-rank test). There was no statistically significant difference in OS (adjusted hazard ratio [aHR], 0.71; 95% CI, 0.34-1.49; P=0.37). The median PFS was similar (P=0.63 by log-rank test), with 4.1 months (95% CI, 3.3-7.7) for atezolizumab plus bevacizumab and 4.3 months (95% CI, 2.6-5.8) for lenvatinib (aHR, 0.93; 95% CI, 0.51-1.69; P=0.80). HRs were similar after inverse probability treatment weighting. The DCRs were 23.3% and 18.2% in patients receiving atezolizumab plus bevacizumab and lenvatinib, respectively (P=0.74).
Conclusion
The effectiveness of atezolizumab plus bevacizumab and lenvatinib was comparable for the treatment of HCC with PVTT.
Review Article
Intrahepatic cholangiocarcinoma: histological diversity and the role of the pathologist
Mina Komuta
Received October 31, 2023  Accepted December 11, 2023  Published online January 3, 2024  
DOI: https://doi.org/10.17998/jlc.2023.12.11    [Epub ahead of print]
  • 400 Views
  • 76 Downloads
AbstractAbstract PDF
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.
Letter to the Editor
Letter regarding “Treatment options for solitary hepatocellular carcinoma ≤5 cm: surgery vs. ablation: a multicenter retrospective study”
Jongman Kim
Received November 21, 2023  Accepted December 4, 2023  Published online December 12, 2023  
DOI: https://doi.org/10.17998/jlc.2023.12.04    [Epub ahead of print]
  • 254 Views
  • 18 Downloads
PDF
Review Article
Complications of immunotherapy in advanced hepatocellular carcinoma
Young-Gi Song, Jeong-Ju Yoo, Sang Gyune Kim, Young Seok Kim
Received October 16, 2023  Accepted November 21, 2023  Published online November 29, 2023  
DOI: https://doi.org/10.17998/jlc.2023.11.21    [Epub ahead of print]
  • 527 Views
  • 51 Downloads
AbstractAbstract PDF
Immune checkpoint inhibitors (ICIs) are highly effective in cancer treatment. However, the risks associated with the treatment must be carefully balanced against the therapeutic benefits. Immune-related adverse events (irAEs) are generally unpredictable and may persist over an extended period. In this review, we analyzed common irAEs reported in highly cited original articles and systematic reviews. The prevalent adverse reactions include fatigue, pyrexia, rash, pruritus, diarrhea, decreased appetite, nausea, abdominal pain, constipation, hepatitis, and hypothyroidism. Therefore, it is crucial to conduct evaluations not only of gastrointestinal organs but also of cardiac, neurologic, endocrine (including the frequently affected thyroid), and ophthalmic systems before commencing ICIs. This review further explores commonly reported types of irAEs, specific irAEs associated with each ICI agent, rare yet potentially fatal irAEs, and available treatment options for managing them.
Case Report
Metastatic papillary renal cell carcinoma with portal vein tumor thrombosis confirmed on blind liver biopsy
Hun Kim, Tae Hoon Roh, Jun Seop Lee, Min Seong Kim, Beom Kyung Kim
Received August 16, 2023  Accepted November 5, 2023  Published online November 29, 2023  
DOI: https://doi.org/10.17998/jlc.2023.11.05    [Epub ahead of print]
  • 595 Views
  • 64 Downloads
AbstractAbstract PDF
Portal vein tumor thrombosis (PVTT) is an uncommon condition in which tumor cells expand into the vessels, causing blood clot formation in the portal vein. PVTT is mainly associated with hepatocellular carcinoma, leading to an unfavorable prognosis; however, it can also develop in patients with other cancer types. Herein, we report a case of metastatic renal cell carcinoma diagnosed by a blind liver biopsy in a patient with dynamic computed tomography-confirmed portal vein thrombosis and cholangiopathy. This case illustrates the importance of systematic surveillance with routine laboratory tests and contrast-enhanced imaging studies on patients with cancer to detect potential liver infiltration of metastatic cancer.
Letter to the Editor
Performance of HCC diagnosis in the KLCA-NCC guidelines: a closer look at MRI contrast agents and HCC imaging hallmarks
Ji Hye Min, Young Kon Kim
Received September 4, 2023  Accepted October 8, 2023  Published online November 6, 2023  
DOI: https://doi.org/10.17998/jlc.2023.10.08    [Epub ahead of print]
  • 379 Views
  • 41 Downloads
PDF
Research Article
Treatment options for solitary hepatocellular carcinoma ≤5 cm: surgery vs. ablation: a multicenter retrospective study
Kazuya Kariyama, Kazuhiro Nouso, Atsushi Hiraoka, Hidenori Toyoda, Toshifumi Tada, Kunihiko Tsuji, Toru Ishikawa, Takeshi Hatanaka, Ei Itobayashi, Koichi Takaguchi, Akemi Tsutsui, Atsushi Naganuma, Satoshi Yasuda, Satoru Kakizaki, Akiko Wakuta, Shohei Shiota, Masatoshi Kudo, Takashi Kumada
Received August 5, 2023  Accepted September 11, 2023  Published online November 6, 2023  
DOI: https://doi.org/10.17998/jlc.2023.09.11    [Epub ahead of print]
  • 608 Views
  • 77 Downloads
AbstractAbstract PDF
Background/Aim
The aim of this study was to compare the therapeutic efficacy of ablation and surgery in solitary hepatocellular carcinoma (HCC) measuring ≤5 cm with a large HCC cohort database.
Methods
The study included consecutive 2,067 patients with solitary HCC who were treated with either ablation (n=1,248) or surgery (n=819). Th e patients were divided into three groups based on the tumor size and compared the outcomes of the two therapies using propensity score matching.
Results
No significant difference in recurrence-free survival (RFS) or overall survival (OS) was found between surgery and ablation groups for tumors measuring ≤2 cm or >2 cm but ≤3 cm. For tumors measuring >3 cm but ≤5 cm, RFS was significantly better with surgery than with ablation (3.6 and 2.0 years, respectively, P=0.0297). However, no significant difference in OS was found between surgery and ablation in this group (6.7 and 6.0 years, respectively, P=0.668).
Conclusion
The study suggests that surgery and ablation can be equally used as a treatment for solitary HCC no more than 3 cm in diameter. For HCCs measuring 3-5 cm, the OS was not different between therapies; thus, ablation and less invasive therapy can be considered a treatment option; however, special caution should be taken to prevent recurrence.

JLC : Journal of Liver Cancer