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You GR, Park SY, Cho SH, Cho SB, Koh YS, Lee CH, Jo HG, Choi SK, Yoon JH. Extrahepatic Recurrence After Surgical Resection of Hepatocellular Carcinoma Without Intrahepatic Recurrence: A Multi-Institutional Observational Study. Cancers (Basel) 2025; 17:1417. [PMID: 40361344 PMCID: PMC12070905 DOI: 10.3390/cancers17091417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2025] [Revised: 04/22/2025] [Accepted: 04/23/2025] [Indexed: 05/15/2025] Open
Abstract
BACKGROUND/OBJECTIVES Extrahepatic recurrence (EHR) is a significant negative prognostic factor in hepatocellular carcinoma (HCC). Although EHR is commonly observed in high-risk patients following HCC hepatectomy, its occurrence without concurrent intrahepatic HCC remains poorly understood. Therefore, this study aims to examine the clinical characteristics and risk factors associated with EHR in patients without intrahepatic HCC at diagnosis. METHODS This study included 1066 treatment-naïve patients who underwent curative hepatectomy for HCC at four tertiary academic centers between January 2004 and December 2019. After excluding those with intrahepatic recurrence (IHR), concurrent EHR, or incomplete clinical records, 569 patients were included in the final analysis. Risk factors for EHR were assessed using multivariate Cox regression over a median follow-up period of 3.91 years. RESULTS Among the cohort, 38 patients developed EHR post-surgery without residual intrahepatic HCC, with a median follow-up of 1.04 years. These patients experienced earlier initial HCC recurrence than those without EHR (1.73 vs. 4.43 years). Multivariate analysis revealed significant associations between EHR and microvascular invasion (hazard ratio [HR]: 2.418, p = 0.020), tumor necrosis (HR: 2.592, p = 0.009), and initial tumor staging beyond the Milan criteria (HR: 3.008, p = 0.001). Moreover, Cox regression analysis revealed that EHR strongly correlated with decreased post-hepatectomy survival (HR: 14.044, p < 0.001). Cumulative EHR and survival rates were closely linked to the number of risk factors present. CONCLUSIONS EHR without detectable IHR is significant and warrants close monitoring in high-risk patients.
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Affiliation(s)
- Ga Ram You
- Department of Gastroenterology and Hepatology, Chonnam National University Hwasun Hospital and Medical School, Hwasun 58128, Republic of Korea; (G.R.Y.); (S.B.C.)
| | - Shin Young Park
- Department of Gastroenterology and Hepatology, Chonnam National University Hospital and Medical School, Gwangju 61469, Republic of Korea; (S.Y.P.); (S.H.C.); (S.K.C.)
| | - Su Hyeon Cho
- Department of Gastroenterology and Hepatology, Chonnam National University Hospital and Medical School, Gwangju 61469, Republic of Korea; (S.Y.P.); (S.H.C.); (S.K.C.)
| | - Sung Bum Cho
- Department of Gastroenterology and Hepatology, Chonnam National University Hwasun Hospital and Medical School, Hwasun 58128, Republic of Korea; (G.R.Y.); (S.B.C.)
| | - Yang Seok Koh
- Department of Surgery, Chonnam National University Hwasun Hospital and Medical School, Hwasun 58128, Republic of Korea;
| | - Chang Hun Lee
- Department of Gastroenterology and Hepatology, Jeonbuk National University Hospital and Medical School, Jeonju 54907, Republic of Korea;
| | - Hoon Gil Jo
- Department of Gastroenterology and Hepatology, Wonkwang University Hospital and Medical School, Iksan 54538, Republic of Korea;
| | - Sung Kyu Choi
- Department of Gastroenterology and Hepatology, Chonnam National University Hospital and Medical School, Gwangju 61469, Republic of Korea; (S.Y.P.); (S.H.C.); (S.K.C.)
| | - Jae Hyun Yoon
- Department of Gastroenterology and Hepatology, Chonnam National University Hospital and Medical School, Gwangju 61469, Republic of Korea; (S.Y.P.); (S.H.C.); (S.K.C.)
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Mortezaei A, Taghlabi KM, Al-Saidi N, Amasa S, Whitehead RE, Hoang A, Yaeger K, Faraji AH, Kadirvel R, Ghozy S. Advanced targeted microsphere embolization for arteriovenous malformations: state-of-the-art and future directions. Neuroradiology 2025; 67:1009-1022. [PMID: 40088307 DOI: 10.1007/s00234-025-03584-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Accepted: 03/04/2025] [Indexed: 03/17/2025]
Abstract
BACKGROUND Arteriovenous malformations (AVMs) present a significant therapeutic challenge, as current treatment modalities frequently fail to achieve complete and rapid obliteration and are associated with substantial morbidity in both the short and long term. This underscores the critical need for innovative therapeutic strategies that enable efficient AVM obliteration while minimizing patient risk. The current review aims to comprehensively assess the role of ATME in AVM management, examining its clinical efficacy, associated risks and benefits, and the economic and ethical implications to provide valuable foundation for future studies and guiding development in treatment strategies for AVMs. RESULTS Advanced targeted microsphere embolization (ATME) has emerged as a promising therapeutic option, initially developed for the localized treatment of AVMs and unresectable tumors, including liver cancer. By providing targeted delivery, ATME offers potential advantages over conventional approaches in achieving effective local control. CONCLUSIONS ATME are safe and effective for vascular disease and cancer. Although evidence for microspheres in AVMs is scarce, results are promising. Future research could refine eligibility criteria, evaluate treatment techniques, and optimize ATME.
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Affiliation(s)
- Ali Mortezaei
- Gonabad University of Medical Sciences, Gonabad, Iran
- Clinical Innovations Laboratory, Department of Neurological Surgery, Houston Methodist Research Institute, Houston, TX, USA
| | - Khaled M Taghlabi
- Clinical Innovations Laboratory, Department of Neurological Surgery, Houston Methodist Research Institute, Houston, TX, USA.
- Department of Neurological Surgery, Houston Methodist Hospital, Houston, TX, USA.
| | - Nadir Al-Saidi
- College of Medicine, Central Michigan University, Mt Pleasant, MI, USA.
| | - Saketh Amasa
- Department of Neurosurgery, The University of Texas Medical Branch, Galveston, TX, USA
| | - Rachael E Whitehead
- Clinical Innovations Laboratory, Department of Neurological Surgery, Houston Methodist Research Institute, Houston, TX, USA
- Department of Neurological Surgery, Houston Methodist Hospital, Houston, TX, USA
| | - Alex Hoang
- Department of Neurological Surgery, Houston Methodist Hospital, Houston, TX, USA
| | - Kurt Yaeger
- Department of Neurological Surgery, Houston Methodist Hospital, Houston, TX, USA
| | - Amir H Faraji
- Clinical Innovations Laboratory, Department of Neurological Surgery, Houston Methodist Research Institute, Houston, TX, USA
- Department of Neurological Surgery, Houston Methodist Hospital, Houston, TX, USA
| | - Ramanathan Kadirvel
- Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, USA
- Department of Radiology, Mayo Clinic, Rochester, MN, USA
| | - Sherief Ghozy
- Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, USA.
- Department of Radiology, Mayo Clinic, Rochester, MN, USA.
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Keshavarz P, Nezami N, Yazdanpanah F, Khojaste-Sarakhsi M, Mohammadigoldar Z, Azami M, Hajati A, Ebrahimian Sadabad F, Chiang J, McWilliams JP, Lu DSK, Raman SS. Prediction of treatment response and outcome of transarterial chemoembolization in patients with hepatocellular carcinoma using artificial intelligence: A systematic review of efficacy. Eur J Radiol 2025; 184:111948. [PMID: 39892373 DOI: 10.1016/j.ejrad.2025.111948] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Revised: 01/10/2025] [Accepted: 01/22/2025] [Indexed: 02/03/2025]
Abstract
PURPOSE To perform a systematic literature review of the efficacy of different AI models to predict HCC treatment response to transarterial chemoembolization (TACE), including overall survival (OS) and time to progression (TTP). METHODS This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines until May 2, 2024. RESULTS The systematic review included 23 studies with 4,486 HCC patients. The AI algorithm receiver operator characteristic (ROC) area under the curve (AUC) for predicting HCC response to TACE based on mRECIST criteria ranged from 0.55 to 0.97. Radiomics-models outperformed non-radiomics models (AUCs: 0.79, 95 %CI: 0.75-0.82 vs. 0.73, 0.61-0.77, respectively). The best ML methods used for the prediction of TACE response for HCC patients were CNN, GB, SVM, and RF with AUCs of 0.88 (0.79-0.97), 0.82 (0.71-0.89), 0.8 (0.60-0.87) and 0.8 (0.55-0.96), respectively. Of all predictive feature models, those combining clinic-radiologic features (ALBI grade, BCLC stage, AFP level, tumor diameter, distribution, and peritumoral arterial enhancement) had higher AUCs compared with models based on clinical characteristics alone (0.79, 0.73-0.89; p = 0.04 for CT + clinical, 0.81, 0.75-0.88; p = 0.017 for MRI + clinical versus 0.6, 0.55-0.75 in clinical characteristics alone). CONCLUSION Integrating clinic-radiologic features enhances AI models' predictive performance for HCC patient response to TACE, with CNN, GB, SVM, and RF methods outperforming others. Key predictive clinic-radiologic features include ALBI grade, BCLC stage, AFP level, tumor diameter, distribution, and peritumoral arterial enhancement. Multi-institutional studies are needed to improve AI model accuracy, address heterogeneity, and resolve validation issues.
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Affiliation(s)
- Pedram Keshavarz
- Department of Radiological Sciences, David Geffen School of Medicine at The University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
| | - Nariman Nezami
- Department of Radiology, MedStar Georgetown University Hospital, Washington, DC 20007, USA; Georgetown University School of Medicine, Washington, DC 20007, USA; Lombardi Comprehensive Cancer Center, Washington, DC 20007, USA
| | | | | | - Zahra Mohammadigoldar
- Department of Radiological Sciences, David Geffen School of Medicine at The University of California, Los Angeles (UCLA), Los Angeles, CA, USA
| | - Mobin Azami
- Department of Diagnostic & Interventional Radiology, New Hospitals Ltd., Tbilisi 0114, Georgia
| | - Azadeh Hajati
- Department of Radiology, Division of Abdominal Imaging, Harvard Medical School, Boston, MA 02114, USA
| | | | - Jason Chiang
- Department of Radiological Sciences, David Geffen School of Medicine at The University of California, Los Angeles (UCLA), Los Angeles, CA, USA
| | - Justin P McWilliams
- Department of Radiological Sciences, David Geffen School of Medicine at The University of California, Los Angeles (UCLA), Los Angeles, CA, USA
| | - David S K Lu
- Department of Radiological Sciences, David Geffen School of Medicine at The University of California, Los Angeles (UCLA), Los Angeles, CA, USA
| | - Steven S Raman
- Department of Radiological Sciences, David Geffen School of Medicine at The University of California, Los Angeles (UCLA), Los Angeles, CA, USA
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Zhang R, Chen W, Peng X, Zhang Z, Yang S, Zhong L. Prognostic significance of combined PCPE-1 and α-fetoprotein for hepatocellular carcinoma. Transl Oncol 2025; 51:102185. [PMID: 39522303 PMCID: PMC11585787 DOI: 10.1016/j.tranon.2024.102185] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Revised: 10/02/2024] [Accepted: 10/29/2024] [Indexed: 11/16/2024] Open
Abstract
PURPOSE Procollagen C-proteinase enhancer 1 (PCPE-1) is associated with liver fibrosis, a major risk factor of hepatocellular carcinoma (HCC). However, its role in HCC remains unclear. MATERIALS AND METHODS The mRNA and protein expression levels of PCPE-1 were analyzed using publicly available datasets of HCC tissues and matched normal tissues. Western blotting was performed to determine PCPE-1 levels in 7 paired HCC tumor and normal tissues. Immunohistochemistry was used to detect PCPE-1 levels in 155 HCC patients. The ROC curve was employed to determine the optimal cutoff value of PCPE-1. Univariate and multivariate analyses identified independent risk factors associated with overall survival (OS) of HCC patients. Kaplan-Meier analysis assessed the relationship between PCPE-1 expression and OS, and a prognostic model was constructed. RESULTS PCPE-1 protein was upregulated in HCC tissues compared to normal tissues and positively correlated with the expression of several procollagens. 78 out of 155 HCC patients exhibited elevated PCPE-1 expression with cytoplasmic staining. High PCPE-1 expression significantly correlated with tumor necrosis (P = 0.045), poorer histologic grade (G3-G4, P = 0.008), and higher α-fetoprotein (AFP) level (>20 ng/ml, P = 0.043). Both univariate and multivariate analyses showed a significant association between elevated PCPE-1 and poorer overall survival (P < 0.001 in both analyses). Remarkably, combined prognostic model with PCPE-1 and AFP effectively stratified the risk for OS in HCC. CONCLUSION Our results demonstrate for the first time that PCPE-1 serves as an independent prognostic marker for HCC, and the combined prognostic model involving PCPE-1 and AFP emerges as a valuable tool for predicting patient outcomes.
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Affiliation(s)
- Ruhua Zhang
- Guangdong Provincial Key Laboratory of Digestive Cancer Research, Center of Digestive Diseases, Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
- State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Wanqi Chen
- Guangdong Provincial Key Laboratory of Digestive Cancer Research, Center of Digestive Diseases, Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Xuelan Peng
- Guangdong Provincial Key Laboratory of Digestive Cancer Research, Center of Digestive Diseases, Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Zhiguang Zhang
- Guangdong Provincial Key Laboratory of Digestive Cancer Research, Center of Digestive Diseases, Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Shangjiu Yang
- Guangdong Provincial Key Laboratory of Digestive Cancer Research, Center of Digestive Diseases, Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Li Zhong
- Guangdong Provincial Key Laboratory of Digestive Cancer Research, Center of Digestive Diseases, Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
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Eid RA, Abdel Fattah AM, Haseeb AF, Hamed AM, Shaker MA. Percutaneous radiofrequency ablation for stage B1 of modified Bolondi’s subclassification for intermediate-stage hepatocellular carcinoma. EGYPTIAN LIVER JOURNAL 2024; 14:81. [DOI: 10.1186/s43066-024-00388-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Accepted: 10/27/2024] [Indexed: 01/03/2025] Open
Abstract
Abstract
Background
Hepatocellular carcinoma is considered the most common cause of hepatic focal lesions in Egypt. TACE is still the recommended treatment approach for patients in the intermediate stage. In the current research, we evaluated the safety and efficacy of percutaneous radiofrequency ablation (RFA) for a selected category in the intermediate stage (BCLC stage B).
Methods
This prospective study was conducted in the Department of Gastroenterology, Hepatology, Faculty of Medicine, Beni-Suef University between September 2022, and March 2024. In addition to AFP, Pelviabdominal ultrasound and computerized tomography (CT) were used for HCC diagnosis. According to the Child–Pugh score plus Milan and up-to-7 criteria, we used Modified Bolondi’s Subclassification (Kinki Criteria), to sub-classifies the BCLC B stage into B1/B2/B3 subcategories. Radiofrequency ablation was done in the interventional ultrasound unit. Treatment efficacy was assessed 6 months after tumor ablation.
Results
One hundred twenty participants were enrolled in our research trial, 72 (60%) were within the intermediate stage, and 48 (40%) had early-stage HCC. Most of our patients were males, 78 (65%). All the early-stage-HCC patients were Child–Pugh Score A (n = 48), while the intermediate-stage (BCLC B) group was classified in both Child–Pugh Score A (n = 59) and B (n = 16). Within the intermediate group (BCLC-stage B), All enrolled cases fell within category “B1” within the Kinki Criteria. Logistic regression analysis illustrated that the pre-treatment level of Platelet count and post-treatment level of AFP shows a statistically significant prediction effect on treatment response rate with p-value (0.028 and 0.007 respectively).
Conclusion
percutaneous radiofrequency ablation is considered an effective treatment option for the B1 subcategory according to Kinki Criteria for intermediate-stage HCC (BCLC-B1) but long-term follow-up is recommended.
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Lee J, Jin YJ, Shin SK, Kwon JH, Kim SG, Yu JH, Lee JW, Kwon OS, Nahm SW, Kim YS. Clinical outcomes of transarterial chemoembolization in Child-Turcotte Pugh class A patients with a single small (≤3 cm) hepatocellular carcinoma. J Gastroenterol Hepatol 2024; 39:1924-1931. [PMID: 38711168 DOI: 10.1111/jgh.16581] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Revised: 03/09/2024] [Accepted: 03/31/2024] [Indexed: 05/08/2024]
Abstract
BACKGROUND AND AIM Transarterial chemoembolization (TACE) is one of the standard modalities used to treat unresectable hepatocellular carcinoma (HCC), but the effectiveness of TACE for treating patients with a solitary small (≤3 cm) HCC and well-preserved liver function has not been definitively established. This study aimed to determine the therapeutic impact of TACE in patients with these characteristics. METHODS This multicenter (four university hospitals) retrospective cohort study analyzed the medical records of 250 patients with a solitary small (≤3 cm) HCC and Child-Turcotte-Pugh (CTP) class A liver function diagnosed over 10 years. Posttreatment outcomes, including overall survival (OS), recurrence-free survival (RFS), and adverse events, were assessed following TACE therapy. RESULTS One hundred and thirty-eight of the 250 patients (55.2%) treated with TACE achieved complete remission (CR). Overall median OS was 77.7 months, and median OS was significantly longer in the CR group than in the non-CR group (89.1 vs. 58.8 months, P = 0.001). Median RFS was 19.1 months in the CR group. Subgroup analysis identified hypertension, an elevated serum albumin level, and achieving CR as significant positive predictors of OS, whereas diabetes, hepatitis c virus infection, and tumor size (>2 cm) were poor prognostic factors of OS. CONCLUSIONS The study demonstrates the effectiveness of TACE as a viable alternative for treating solitary small (≤3 cm) HCC in CTP class A patients.
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Affiliation(s)
- Jungnam Lee
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, South Korea
| | - Young-Joo Jin
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, South Korea
| | - Seung Kak Shin
- Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon, South Korea
| | - Jung Hyun Kwon
- Department of Internal Medicine, The Catholic University of Korea Incheon St. Mary's Hospital, Incheon, South Korea
| | - Sang Gyune Kim
- Department of Internal Medicine, Soonchunhyang University Hospital Bucheon, Bucheon, South Korea
| | - Jung Hwan Yu
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, South Korea
| | - Jin-Woo Lee
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, South Korea
| | - Oh Sang Kwon
- Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon, South Korea
| | - Soon Woo Nahm
- Department of Internal Medicine, The Catholic University of Korea Incheon St. Mary's Hospital, Incheon, South Korea
| | - Young Seok Kim
- Department of Internal Medicine, Soonchunhyang University Hospital Bucheon, Bucheon, South Korea
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Han JW, Sohn W, Choi GH, Jang JW, Seo GH, Kim BH, Choi JY. Evolving trends in treatment patterns for hepatocellular carcinoma in Korea from 2008 to 2022: a nationwide population-based study. JOURNAL OF LIVER CANCER 2024; 24:274-285. [PMID: 39187270 PMCID: PMC11449573 DOI: 10.17998/jlc.2024.08.13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Revised: 08/09/2024] [Accepted: 08/13/2024] [Indexed: 08/28/2024]
Abstract
BACKGROUNDS/AIMS The treatment landscape for hepatocellular carcinoma (HCC) has significantly evolved over the past decade. We aimed to analyze trends in treatment patterns for HCC using a nationwide claims database from the Korean Health Insurance Review and Assessment Service. METHODS This retrospective population-based cohort study analyzed 171,002 newly diagnosed HCC patients between 2008 and 2022. Etiologies and treatment modalities were categorized based on the ICD-10 codes and insurance data. RESULTS The annual incidence decreased from 11,814 in 2008 to 10,443 in 2022. However, patients aged ≥70 increased noticeably, with those aged ≥80 rising from 3.8% in 2008 to 13.1% in 2022. From 2008 to 2022, the predominant cause of hepatitis B virus decreased from 68.9% to 59.7%, whereas nonalcoholic fatty liver disease increased from 8.9% to 15.8%. The initial treatment trends shifted: surgical resection and systemic therapy increased from 12.2% to 21.3% and from 0.2% to 9.6%, whereas transarterial therapy decreased from 49.9% to 36.6%. Best supportive care decreased from 31.7% to 21.3%. In the subgroup analysis, laparoscopic resection rate increased from 10.6% to 60.6% among the surgical resections. Sorafenib initially accounted for 100%, lenvatinib peaked at 36.5% in 2021, and atezolizumab-bevacizumab became the most widely used (63.1%) by 2022 among the systemic therapies. CONCLUSIONS This study demonstrates the temporal changes in the treatment patterns of Korean HCC patients. Surgical resection, particularly laparoscopic liver resection, and systemic therapy has increased significantly. These changes may have been influenced by reimbursement policies and advances in clinical research.
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Affiliation(s)
- Ji Won Han
- The Korean Liver Cancer Association, Seoul, Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Catholic University of Korea Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Won Sohn
- The Korean Liver Cancer Association, Seoul, Korea
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Gwang Hyeon Choi
- The Korean Liver Cancer Association, Seoul, Korea
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Jeong Won Jang
- The Korean Liver Cancer Association, Seoul, Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Catholic University of Korea Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Gi Hyeon Seo
- The Korean Liver Cancer Association, Seoul, Korea
- Health Insurance Review and Assessment Service, Seoul, Korea
| | - Bo Hyun Kim
- The Korean Liver Cancer Association, Seoul, Korea
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
| | - Jong Young Choi
- The Korean Liver Cancer Association, Seoul, Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Catholic University of Korea Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
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Kim JH, Kim YH, Nam HC, Kim CW, Yoo JS, Han JW, Jang JW, Choi JY, Yoon SK, Chun HJ, Oh JS, Kim S, Lee SH, Sung PS. Consistent efficacy of hepatic artery infusion chemotherapy irrespective of PD‑L1 positivity in unresectable hepatocellular carcinoma. Oncol Lett 2024; 28:388. [PMID: 38966587 PMCID: PMC11223005 DOI: 10.3892/ol.2024.14521] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2023] [Accepted: 05/03/2024] [Indexed: 07/06/2024] Open
Abstract
Atezolizumab/bevacizumab is the first line of treatment for unresectable hepatocellular carcinoma (HCC), combining immune checkpoint inhibitor and anti-VEGF monoclonal antibodies. Hepatic arterial infusion chemotherapy (HAIC) is administered when the above-described combination fails to confer sufficient clinical benefit. The present study aimed to explore the association between tumor programmed cell death-ligand 1 (PD-L1) positivity and HAIC response. A total of 40 patients with HCC who had undergone HAIC with available biopsy samples obtained between January 2020 and May 2023 were retrospectively enrolled. Tumor response, progression-free survival (PFS), disease control rate (DCR) and overall survival (OS) were evaluated. PD-L1 expression in tumor samples was assessed using a combined positivity score. The response rates of HAIC-treated patients with advanced HCC after failure of atezolizumab/bevacizumab combination therapy were recorded. OS (P=0.9717) and PFS (P=0.4194) did not differ between patients with and without PD-L1 positivity. The objective response rate (P=0.7830) and DCR (P=0.7020) also did not differ based on PD-L1 status. In conclusion, the current findings highlight the consistent efficacy of HAIC, regardless of PD-L1 positivity.
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Affiliation(s)
- Ji Hoon Kim
- Department of Gastroenterology and Hepatology, Uijeongbu St. Mary's Hospital, The Catholic University of Korea, Uijeongbu, Gyeonggi 11765, Republic of Korea
| | - Young Hoon Kim
- Department of Pathology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Hee-Chul Nam
- Department of Gastroenterology and Hepatology, Uijeongbu St. Mary's Hospital, The Catholic University of Korea, Uijeongbu, Gyeonggi 11765, Republic of Korea
| | - Chang-Wook Kim
- Department of Gastroenterology and Hepatology, Uijeongbu St. Mary's Hospital, The Catholic University of Korea, Uijeongbu, Gyeonggi 11765, Republic of Korea
| | - Jae-Sung Yoo
- Department of Gastroenterology and Hepatology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Ji Won Han
- Department of Gastroenterology and Hepatology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Jeong Won Jang
- Department of Gastroenterology and Hepatology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Jong Young Choi
- Department of Gastroenterology and Hepatology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Seung Kew Yoon
- Department of Gastroenterology and Hepatology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Ho Jong Chun
- Department of Radiology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Jung Suk Oh
- Department of Radiology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Suho Kim
- Department of Radiology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Sung Hak Lee
- Department of Pathology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Pil Soo Sung
- Department of Gastroenterology and Hepatology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul 06591, Republic of Korea
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Lee HL, Kim SH, Kim HY, Lee SW, Song MJ. A refined prediction model for survival in hepatocellular carcinoma patients treated with transarterial chemoembolization. Front Oncol 2024; 14:1354964. [PMID: 38606106 PMCID: PMC11007070 DOI: 10.3389/fonc.2024.1354964] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Accepted: 03/14/2024] [Indexed: 04/13/2024] Open
Abstract
Background/Aims Transarterial chemoembolization (TACE) is widely performed as a major treatment for hepatocellular carcinoma (HCC) patients, and there is a need to stratify patients for whom the most benefit from the treatment. This study aimed to develop a refined prediction model for overall survival (OS) in patients undergoing TACE as a first-line treatment in a large cohort and validate its performance. Methods A total of 2,632 patients with HCC of Barcelona Clinic Liver Cancer stage A or B who underwent TACE between 2008 and 2017 were enrolled. The patients were randomly assigned to a training cohort (n = 1,304) or a validation cohort (n = 1,328). Independent predictors of OS were used to develop a prediction model. Results The median age of patients in the entire cohort was 63 years, with the majority having hepatitis B virus (56.6%) and being classified as Child-Pugh class A (82.4%). We developed a new prognostic model, called the TACE-prognostic (TP) score, based on tumor burden (sum of the largest tumor diameter and tumor number), alpha-fetoprotein, and Albumin-Bilirubin grade. Patients were classified into five risk groups according to TP scores, with median survival significantly differentiated in both training and validation cohorts (P < 0.001). The new model consistently outperformed other currently available models in both the training and validation cohorts. Conclusion This newly developed TP scoring system has the potential to be a useful tool in identifying ideal candidates of TACE and predicting OS with favorable performance and discrimination. However, further external validation is needed to confirm its effectiveness.
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Affiliation(s)
- Hae Lim Lee
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Korean Liver Cancer Study Group, Seoul, Republic of Korea
- Ministry of Health and Welfare, Korea Central Cancer Registry, Goyang-si, Gyeonggi-do, Republic of Korea
| | - Seok Hwan Kim
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Korean Liver Cancer Study Group, Seoul, Republic of Korea
- Ministry of Health and Welfare, Korea Central Cancer Registry, Goyang-si, Gyeonggi-do, Republic of Korea
| | - Hee Yeon Kim
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Korean Liver Cancer Study Group, Seoul, Republic of Korea
- Ministry of Health and Welfare, Korea Central Cancer Registry, Goyang-si, Gyeonggi-do, Republic of Korea
| | - Sung Won Lee
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Korean Liver Cancer Study Group, Seoul, Republic of Korea
- Ministry of Health and Welfare, Korea Central Cancer Registry, Goyang-si, Gyeonggi-do, Republic of Korea
| | - Myeong Jun Song
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Korean Liver Cancer Study Group, Seoul, Republic of Korea
- Ministry of Health and Welfare, Korea Central Cancer Registry, Goyang-si, Gyeonggi-do, Republic of Korea
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10
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Lee HA, Lee M, Yoo JJ, Chun HS, Park Y, Kim HY, Kim TH, Seo YS, Sinn DH. Identification of patients with favorable prognosis after resection in intermediate-stage-hepatocellular carcinoma. Int J Surg 2024; 110:1008-1018. [PMID: 38016294 PMCID: PMC10871631 DOI: 10.1097/js9.0000000000000941] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Accepted: 11/11/2023] [Indexed: 11/30/2023]
Abstract
BACKGROUNDS It is unclear which patients benefit from resection in intermediate-stage-hepatocellular carcinoma (HCC). The authors aimed to identify high-risk patients for early recurrence among patients with resectable intermediate-stage HCC. METHODS This multicenter retrospective study included patients who underwent resection or trans-arterial chemoembolization (TACE) for intermediate-stage HCC (2008-2019). Multivariable Cox proportional analysis was performed to identify high-risk patients when treated with resection. A prediction score for 2-year recurrence-free survival (RFS) was developed using the training cohort and validated. The 2-year RFS in each risk group was compared with that in TACE group, after propensity score matching (PSM). RESULTS A total of 1686 patients were included (480 and 1206 patients in the resection and TACE groups). During a median follow-up of 31.4 months, the 2-year RFS was significantly higher in the resection (47.7%) than in the TACE group (19.8%) [adjusted hazard ratio (aHR)=1.471, 95% CI: 1.199-1.803, P <0.001). On multivariate analysis, alpha-fetoprotein ≥5.0 ng/ml (aHR=0.202), ALBI grade ≥2 (aHR=0.709), tumor number ≥3 (aHR=0.404), and maximal tumor size ≥5 cm (aHR=0.323) were significantly associated with the lower risk of 2-year RFS in the resection group. The newly developed Surgery Risk score in BCLC-B (SR-B score) with four significant risk factors showed an area under the curve of 0.801 for the 2-year RFS and was validated. Based on the SR-B score, low-risk patients had a significantly higher 2-year RFS (training: aHR=5.834; validation: aHR=5.675) than high-risk patients (all P <0.001) did. In a PSM cohort, a low-risk resection group had a significantly higher (aHR=3.891); a high-risk resection group had a comparable 2-year RFS to those treated with TACE (aHR=0.816). CONCLUSIONS Resection may be beneficial for resectable intermediate-stage HCC based on the SR-B score.
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Affiliation(s)
- Han Ah Lee
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Ewha Womans University Medical Center
- The Korean Liver Cancer Association
| | - Minjong Lee
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Ewha Womans University Medical Center
- The Korean Liver Cancer Association
| | - Jeong-Ju Yoo
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Ho Soo Chun
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Ewha Womans University Medical Center
| | - Yewan Park
- Department of Internal Medicine, Kyung Hee University Hospital
| | - Hwi Young Kim
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Ewha Womans University Medical Center
| | - Tae Hun Kim
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Ewha Womans University Medical Center
| | - Yeon Seok Seo
- Department of Internal Medicine, Korea University College of Medicine, Seoul
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine
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11
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Han S, Kim DY, Lim HY, Yoon JH, Ryoo BY, Kim Y, Kim K, Kim BY, Yi SY, Kim DS, Cho DY, Yu J, Kim S, Park JW. Sorafenib for 9,923 Patients with Hepatocellular Carcinoma: An Analysis from National Health Insurance Claim Data in South Korea. Gut Liver 2024; 18:116-124. [PMID: 37334671 PMCID: PMC10791511 DOI: 10.5009/gnl220406] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Revised: 01/18/2023] [Accepted: 01/26/2023] [Indexed: 06/20/2023] Open
Abstract
Background/Aims Sorafenib is the standard of care in the management of advanced hepatocellular carcinoma (HCC). The purpose of this study was to investigate the characteristics, treatment patterns and outcomes of sorafenib among HCC patients in South Korea. Methods This population-based retrospective, single-arm, observational study used the Korean National Health Insurance database to identify patients with HCC who received sorafenib between July 1, 2008, and December 31, 2014. A total of 9,923 patients were recruited in this study. Results Among 9,923 patients, 6,669 patients (68.2%) received loco-regional therapy prior to sorafenib, and 1,565 patients (15.8%) received combination therapy with concomitant sorafenib; 2,591 patients (26.1%) received rescue therapy after sorafenib, and transarterial chemoembolization was the most common modality applied in 1,498 patients (15.1%). A total of 3,591 patients underwent rescue therapy after sorafenib, and the median overall survival was 14.5 months compared to 4.6 months in 7,332 patients who received supportive care after sorafenib. The mean duration of sorafenib administration in all patients was 105.7 days; 7,023 patients (70.8%) received an initial dose of 600 to 800 mg. The longest survival was shown in patients who received the recommended dose of 800 mg, subsequently reduced to 400 mg (15.0 months). The second longest survival was demonstrated in patients with a starting dose of 800 mg, followed by a dose reduction to 400-600 mg (9.6 months). Conclusions Real-life data show that the efficacy of sorafenib seems similar to that observed in clinical trials, suggesting that appropriate subsequent therapy after sorafenib might prolong patient survival.
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Affiliation(s)
- Sojung Han
- Department of Internal Medicine, Uijeongbu Eulji Medical Center, Eulji University College of Medicine, Uijeongbu, Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Ho Yeong Lim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jung-Hwan Yoon
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Baek-Yeol Ryoo
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yujeong Kim
- Health Insurance Review and Assessment, Wonju, Korea
| | - Kookhee Kim
- Health Insurance Review and Assessment, Wonju, Korea
| | - Bo Yeon Kim
- Health Insurance Review and Assessment, Wonju, Korea
| | - So Young Yi
- Health Insurance Review and Assessment, Wonju, Korea
| | - Dong-Sook Kim
- Health Insurance Review and Assessment, Wonju, Korea
| | - Do-Yeon Cho
- Health Insurance Review and Assessment, Wonju, Korea
| | - Jina Yu
- Health Insurance Review and Assessment, Wonju, Korea
| | - Suhyun Kim
- Health Insurance Review and Assessment, Wonju, Korea
| | - Joong-Won Park
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
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12
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Xuan M, Gu X, Li J, Huang D, Xue C, He Y. Polyamines: their significance for maintaining health and contributing to diseases. Cell Commun Signal 2023; 21:348. [PMID: 38049863 PMCID: PMC10694995 DOI: 10.1186/s12964-023-01373-0] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2023] [Accepted: 10/29/2023] [Indexed: 12/06/2023] Open
Abstract
Polyamines are essential for the growth and proliferation of mammalian cells and are intimately involved in biological mechanisms such as DNA replication, RNA transcription, protein synthesis, and post-translational modification. These mechanisms regulate cellular proliferation, differentiation, programmed cell death, and the formation of tumors. Several studies have confirmed the positive effect of polyamines on the maintenance of health, while others have demonstrated that their activity may promote the occurrence and progression of diseases. This review examines a variety of topics, such as polyamine source and metabolism, including metabolism, transport, and the potential impact of polyamines on health and disease. In addition, a brief summary of the effects of oncogenes and signaling pathways on tumor polyamine metabolism is provided. Video Abstract.
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Affiliation(s)
- Mengjuan Xuan
- Department of Infectious Disease, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Erqi District, Zhengzhou, 450052, Henan, China
| | - Xinyu Gu
- Department of Oncology, College of Clinical Medicine, The First Affiliated Hospital, Henan University of Science and Technology, Luoyang, 471000, Henan, China
| | - Juan Li
- Department of Infectious Disease, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Erqi District, Zhengzhou, 450052, Henan, China
| | - Di Huang
- Department of Child Health Care, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, Henan, China
| | - Chen Xue
- Department of Infectious Disease, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Erqi District, Zhengzhou, 450052, Henan, China.
| | - Yuting He
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
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13
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Lee B, Cho JY, Han HS, Yoon YS, Lee HW, Lee JS, Kim M, Jo Y. Laparoscopic anatomical versus non-anatomical liver resection for hepatocellular carcinoma in the posterosuperior segments: a propensity score matched analysis. Hepatobiliary Surg Nutr 2023; 12:824-834. [PMID: 38115923 PMCID: PMC10727829 DOI: 10.21037/hbsn-21-578] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Accepted: 05/13/2022] [Indexed: 12/21/2023]
Abstract
Background Since laparoscopic anatomical resection (LAR) for tumors, especially located in the posterosuperior (PS) segments of the liver remains difficult, laparoscopic non-anatomical resection (LNAR) are generally preferred. To compare the clinical outcomes between LAR and LNAR for hepatocellular carcinoma (HCC) located in the PS segments. Methods We retrospectively reviewed the data for 1,029 patients who underwent hepatectomy for HCC between 2004 and 2019. Of 167 patients who underwent laparoscopic hepatectomy for HCC in PS segments, 64 underwent LNAR and 103 underwent LAR. Patients were matched one-to-one using propensity score matching (46:46). Results LNAR was associated with significantly shorter operation time (P=0.001), lower estimated blood loss (P=0.001), lower transfusion rate (P=0.006) and shorter hospital stay (P=0.012) than LAR. The respective 1- ,3-, and 5-year overall survival rates (LAR: 95.3%, 87.1%, and 77.8%; LNAR: 96.7%, 91.6%, and 85.0%; P=0.262) and recurrence-free survival rates (LAR: 75.7%, 70.3%, and 68.9%; LNAR: 81.8%, 58.3%, and 55.3%; P=0.879) were similar. The intrahepatic recurrence rate was significantly higher in LNAR group than in LAR group (78.6% vs. 57.1%, P=0.023), but the post-recurrence treatments differed significantly between the two groups (P=0.016); the re-resection rate was much greater in the LNAR group (45.0% vs. 0%) group. The respective 1-, 3-, and 5-year post-recurrence survival rates were similar in the LAR and LNAR groups (P=0.212). After recurrence, survival in re-resection group was significantly greater than not (P=0.026). Conclusions LNAR is safe and feasible for HCC located in PS segments, and provided acceptable oncologic outcomes that are comparable to those of LAR. LNAR can be considered for patient with tumor located in PS segment when LAR is not feasible.
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Affiliation(s)
- Boram Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Jai Young Cho
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Ho-Seong Han
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Yoo-Seok Yoon
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Hae Won Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Jun Suh Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Moonhwan Kim
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Yeongsoo Jo
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
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14
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Kim BK, Ahn SH. Prediction model of hepatitis B virus-related hepatocellular carcinoma in patients receiving antiviral therapy. J Formos Med Assoc 2023; 122:1238-1246. [PMID: 37330305 DOI: 10.1016/j.jfma.2023.05.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Revised: 05/15/2023] [Accepted: 05/24/2023] [Indexed: 06/19/2023] Open
Abstract
Chronic hepatitis B virus (HBV) infection, which ultimately leads to liver cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC), remains a significant disease burden worldwide. Despite the use of antiviral therapy (AVT) using oral nucleos(t)ide analogs (NUCs) with high genetic barriers, the risk of HCC development cannot be completely eliminated. Therefore, bi-annual surveillance of HCC using abdominal ultrasonography with or without tumor markers is recommended for at-risk populations. For a more precise assessment of future HCC risk at the individual level, many HCC prediction models have been proposed in the era of potent AVT with promising results. It allows prognostication according to the risk of HCC development, for example, low-vs. intermediate-vs. high-risk groups. Most of these models have the advantage of high negative predictive values for HCC development, allowing exemption from biannual HCC screening. Recently, non-invasive surrogate markers for liver fibrosis, such as vibration-controlled transient elastography, have been introduced as integral components of the equations, providing better predictive performance in general. Furthermore, beyond the conventional statistical methods that primarily depend on multi-variable Cox regression analyses based on the previous literature, newer techniques using artificial intelligence have also been applied in the design of HCC prediction models. Here, we aimed to review the HCC risk prediction models that were developed in the era of potent AVT and validated among independent cohorts to address the clinical unmet needs, as well as comment on future direction to establish the individual HCC risk more precisely.
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Affiliation(s)
- Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea; Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea; Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea.
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15
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Elderkin J, Al Hallak N, Azmi AS, Aoun H, Critchfield J, Tobon M, Beal EW. Hepatocellular Carcinoma: Surveillance, Diagnosis, Evaluation and Management. Cancers (Basel) 2023; 15:5118. [PMID: 37958294 PMCID: PMC10647678 DOI: 10.3390/cancers15215118] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Revised: 10/11/2023] [Accepted: 10/13/2023] [Indexed: 11/15/2023] Open
Abstract
Hepatocellular carcinoma (HCC) ranks fourth in cancer-related deaths worldwide. Semiannual surveillance of the disease for patients with cirrhosis or hepatitis B virus allows for early detection with more favorable outcomes. The current underuse of surveillance programs demonstrates the need for intervention at both the patient and provider level. Mail outreach along with navigation provision has proven to increase surveillance follow-up in patients, while provider-targeted electronic medical record reminders and compliance reports have increased provider awareness of HCC surveillance. Imaging is the primary mode of diagnosis in HCC with The Liver Imaging Reporting and Data System (LI-RADS) being a widely accepted comprehensive system that standardizes the reporting and data collection for HCC. The management of HCC is complex and requires multidisciplinary team evaluation of each patient based on their preference, the state of the disease, and the available medical and surgical interventions. Staging systems are useful in determining the appropriate intervention for HCC. Early-stage HCC is best managed by curative treatment modalities, such as liver resection, transplant, or ablation. For intermediate stages of the disease, transarterial local regional therapies can be applied. Advanced stages of the disease are treated with systemic therapies, for which there have been recent advances with new drug combinations. Previously sorafenib was the mainstay systemic treatment, but the recent introduction of atezolizumab plus bevacizumab proves to have a greater impact on overall survival. Although there is a current lack of improved outcomes in Phase III trials, neoadjuvant therapies are a potential avenue for HCC management in the future.
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Affiliation(s)
- Jessica Elderkin
- Wayne State University School of Medicine, Detroit, MI 48201, USA;
| | - Najeeb Al Hallak
- Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA; (N.A.H.); (A.S.A.)
| | - Asfar S. Azmi
- Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA; (N.A.H.); (A.S.A.)
| | - Hussein Aoun
- Department of Radiology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA; (H.A.); (J.C.)
| | - Jeffrey Critchfield
- Department of Radiology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA; (H.A.); (J.C.)
| | - Miguel Tobon
- Department of Surgery, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA;
| | - Eliza W. Beal
- Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA; (N.A.H.); (A.S.A.)
- Department of Surgery, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA;
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16
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Jang S, Jin YJ, Lee JW, Kwon D, Yu JH. Risk factors associated with late hepatocellular carcinoma detection in patients undergoing regular surveillance. Medicine (Baltimore) 2023; 102:e34637. [PMID: 37565915 PMCID: PMC10419803 DOI: 10.1097/md.0000000000034637] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Accepted: 07/17/2023] [Indexed: 08/12/2023] Open
Abstract
Hepatocellular carcinoma (HCC) has a very poor prognosis with a 5-year survival rate of < 20%; hence, early diagnosis is crucial. Despite regular checkups for high-risk groups of HCC, there are a few cases in which it is discovered as a late-stage HCC. Therefore, this study aimed to investigate the characteristics of patients with delayed HCC detection during regular surveillance. Between January 2010 and December 2020, we analyzed patients with newly diagnosed HCCs who underwent HCC surveillance by ultrasound or computed tomography scan at least twice and were followed up for more than 1 year for hepatitis B, hepatitis C, and chronic liver disease. The mean age of 223 HCC patients was 70 years, of which 152 were male, accounting for 68.1%. Among them, 196 patients (87%) were diagnosed with Barcelona clinic liver cancer stage 0 or A, while 27 (13%) were diagnosed with Barcelona clinic liver cancer stages B and C. When classified according to the TNM criteria, 154 patients (69%) were in stage I, and 69 (31%) were in stage II or higher. Multivariate analysis was performed to identify the risk factors for patients diagnosed with late-stage HCC. The Child-Turcotte-Pugh (CTP) score was identified as a highly significant factor (P = .002, HR 1.547, 95% CI 1.177-2.032), whereas the presence of cirrhosis, body mass index, and sex had no significant effect. We found that in patients with chronic liver disease who were screened regularly, those with higher CTP scores were more likely to be diagnosed with HCC in the late-stages. Therefore, although the presence of cirrhosis is also important for HCC surveillance, careful attention is needed in patients with high CTP scores.
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Affiliation(s)
- Sangmi Jang
- Digestive Disease Center, Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, South Korea
| | - Young-Joo Jin
- Digestive Disease Center, Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, South Korea
| | - Jin-Woo Lee
- Digestive Disease Center, Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, South Korea
| | - Dam Kwon
- Digestive Disease Center, Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, South Korea
| | - Jung Hwan Yu
- Digestive Disease Center, Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, South Korea
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Lyu T, Wang J, Tong X, Mi T, An C, Zou Y. Efficacy and safety of CalliSpheres® Microsphere transcatheter-arterial chemoembolization versus conventional TACE in treating renal angiomyolipoma patients. J Cancer Res Ther 2023; 19:933-938. [PMID: 37675719 DOI: 10.4103/jcrt.jcrt_2135_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/08/2023]
Abstract
Objective Transcatheter-arterial chemoembolization (TACE) is a well-established interventional technique for various tumor treatments, whereas its application in renal angiomyolipoma (RAML) is seldom reported. Conventional TACE (cTACE) with bleomycin-lipiodol emulsion is effective and tolerable for RAML treatment. In this study, we aimed to further explore the efficacy and safety between bleomycin-loaded CalliSpheres® microsphere TACE (CSM-TACE) and cTACE in treating RAML patients. Methods We retrospectively analyzed the data of 54 RAML patients treated by CSM-TACE (n = 17) or cTACE (n = 37). Data on tumor size, tumor volume reduction ratio, patient percentage with tumor size reduction, white blood cells (WBCs), creatinine (Cre) after treatment, complications, and adverse events were retrieved. Results Tumor size (88.66 vs. 81.19 cm3, P = 0.970), patient percentage with tumor size reduction (12 [70.59%] vs. 30 [81.08%], P = 0.486) after treatment, WBCs (P = 0.114), Cre (P = 0.659), and change in Cre after treatment (P = 0.947) were not significantly different between groups, whereas tumor volume reduction ratio was slightly lower in the CSM-TACE group than in the cTACE group (12 ± 34% vs. 32 ± 31%, P = 0.047). The most common postoperative complication was a post-embolization syndrome, including fever, nausea, and abdominal pain, which occurred in 9 (52.94%) and 14 (37.84%) patients from the CSM-TACE and cTACE groups, respectively (P = 0.347). Conclusion CSM-TACE is effective in and well tolerated by RAML patients, implying its potential as an alternative therapy.
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Affiliation(s)
- Tianshi Lyu
- Department of Interventional and Vascular Surgery, Peking University First Hospital, Beijing, China
| | - Jian Wang
- Department of Interventional and Vascular Surgery, Peking University First Hospital, Beijing, China
| | - Xiaoqiang Tong
- Department of Interventional and Vascular Surgery, Peking University First Hospital, Beijing, China
| | - Tianai Mi
- Lianren Digital Health Technology Company, LTD, Beijing, China
| | - Chao An
- Lianren Digital Health Technology Company, LTD, Beijing, China
| | - Yinghua Zou
- Department of Interventional and Vascular Surgery, Peking University First Hospital, Beijing, China
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Hur MH, Cho Y, Kim DY, Lee JS, Kim GM, Kim HC, Sinn DH, Hyun D, Lee HA, Seo YS, Lee IJ, Park JW, Kim YJ. Transarterial radioembolization versus tyrosine kinase inhibitor in hepatocellular carcinoma with portal vein thrombosis. Clin Mol Hepatol 2023; 29:763-778. [PMID: 37254488 PMCID: PMC10366806 DOI: 10.3350/cmh.2023.0076] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 05/24/2023] [Accepted: 05/24/2023] [Indexed: 06/01/2023] Open
Abstract
BACKGROUND/AIMS Transarterial radioembolization (TARE) has shown promising results in treating advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). However, whether TARE can provide superior or comparable outcomes to tyrosine kinase inhibitor (TKI) in patients with HCC and PVTT remains unclear. We compared the outcomes of TARE and TKI therapy in treatment-naïve patients with locally advanced HCC and segmental or lobar PVTT. METHODS This multicenter study included 216 patients initially treated with TARE (n=124) or TKI (sorafenib or lenvatinib; n=92) between 2011 and 2021. Baseline characteristics were balanced using propensity score matching (PSM) or inverse probability of treatment weighting (IPTW). The primary outcome was overall survival (OS). The secondary outcomes included progression-free survival (PFS) and objective response rate (ORR). RESULTS In the unmatched cohort, the median OS of the TARE and TKI groups were 28.2 and 7.2 months, respectively (p<0.001), and the TARE group experienced significantly and independently longer OS compared to the TKI group (adjusted hazard ratio=0.41, 95% confidence interval=0.28-0.60, p<0.001). Similar results were observed in the study cohorts balanced with IPTW (p=0.003) or PSM (p=0.004). Although PFS was comparable between the two groups, the TARE group showed a trend of prolonged PFS in a subpopulation of patients with Vp1 or Vp2 PVTT (p=0.052). In the matched cohorts, the ORR of the TARE group was 53.0-56.7%, whereas that of the TKI group was 12.3-15.0%. CONCLUSION For patients with advanced HCC with segmental or lobar PVTT and well-preserved liver function, TARE may provide superior OS compared to sorafenib or lenvatinib.
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Affiliation(s)
- Moon Haeng Hur
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Yuri Cho
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
| | - Do Young Kim
- Department of Internal Medicine and Yonsei Liver Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Jae Seung Lee
- Department of Internal Medicine and Yonsei Liver Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Gyoung Min Kim
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Hyo-Cheol Kim
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Dong Hyun Sinn
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Dongho Hyun
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Han Ah Lee
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Yeon Seok Seo
- Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea
| | - In Joon Lee
- Department of Radiology, National Cancer Center, Goyang, Korea
| | - Joong-Won Park
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
| | - Yoon Jun Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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19
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Long J, Chen B, Liu Z. Comparative efficacy and safety of molecular targeted agents combined with transarterial chemoembolization in the treatment of unresectable hepatocellular carcinoma: a network meta-analysis. Front Oncol 2023; 13:1179431. [PMID: 37265792 PMCID: PMC10230082 DOI: 10.3389/fonc.2023.1179431] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Accepted: 05/09/2023] [Indexed: 06/03/2023] Open
Abstract
Objective At present, several molecular targeted agents(MTAs) combined with transarterial chemoembolization (TACE) have been employed to treat unresectable hepatocellular carcinoma (HCC). In this meta-analysis, we compared the efficacy and safety of different MTAs combined with TACE to enable effective decision-making for the clinical treatment of unresectable HCC. Methods Pubmed, Web of Science, EMBASE, and Cochrane Library were retrieved to evaluate the efficacy and safety of different MTAs combined with TACE in cohort studies and randomized controlled trials. The hazard ratios and 95% confidence intervals (CIs) were calculated to investigate the impact of various therapies on overall survival (OS) and progression-free survival. However, the objective response rate (ORR), disease control rate (DCR), adverse events (AEs), and ≥grade-3 adverse events (≥G3-AEs) were calculated using odd ratios and 95% CIs. The node-splitting approach was used to test the heterogeneity. The funnel plot was utilized to analyze the publication bias. Additionally, according to the ranking plots, we ranked various treatments. Results A total of 45 studies involving 10,774 patients with 8 treatment strategies were included in our network meta-analysis. Our network meta-analysis showed that apatinib+TACE provided the highest OS (62.2%), ORR (44.7%), and DCR (45.6%), while and lenvatinib+TACE offered the best PFS (78.9%). Besides, there was no statistically significant difference in AEs and ≥G3-AEs among treatment options. Conclusion Apatinib+TACE demonstrated the best OS, ORR, and DCR with no additional AEs and ≥G3-AEs. Therefore, for the treatment scheme of MTAs combined with TACE, apatinib+TACE may be the best option for patients with unresectable HCC. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023388609.
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Affiliation(s)
- Jiaye Long
- Department of Interventional Radiology, Inner Mongolia Forestry General Hospital, The Second Clinical Medical School of Inner Mongolia University for The Nationalities, Yakeshi, Inner Mongolia, China
| | - Baoxiang Chen
- Department of Interventional Radiology, Inner Mongolia Forestry General Hospital, The Second Clinical Medical School of Inner Mongolia University for The Nationalities, Yakeshi, Inner Mongolia, China
| | - Zhaohui Liu
- Department of Urology, Inner Mongolia Forestry General Hospital, The Second Clinical Medical School of Inner Mongolia University for The Nationalities, Yakeshi, Inner Mongolia, China
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20
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Wu JS, Hong TC, Wu HT, Lin YJ, Chang TT, Wang CT, Liu WC, Hsieh MT, Wu IC, Chen PJ, Chen CY, Lin SH, Chuang CH, Han MZ, Chen HP, Tsai HM, Kuo HY. Hepatic arterial infusion chemotherapy and immune checkpoint inhibitors, alone or in combination, in advanced hepatocellular carcinoma with macrovascular invasion: a single-centre experience in Taiwan. J Gastrointest Oncol 2023; 14:849-862. [PMID: 37201085 PMCID: PMC10186549 DOI: 10.21037/jgo-22-858] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Accepted: 04/04/2023] [Indexed: 05/20/2023] Open
Abstract
Background The presence of vascular invasion is associated with poor survival in advanced hepatocellular carcinoma (HCC). We compared the effectiveness of hepatic arterial infusion chemotherapy (HAIC) and immune checkpoint inhibitors (ICIs), alone or in combination, in patients with advanced HCC. Methods We retrospectively reviewed medical records of adult patients with unresectable HCC and macrovascular invasion (MVI) who were treated with HAIC or ICIs alone or in combination at a single centre in Taiwan. Overall tumour response, vascular thrombi response, overall survival (OS) and progression-free survival (PFS) in 130 patients were analysed. Results The treatment group showed no significant effect on the overall tumour response [objective response rate (ORR), 22.86% for HAIC, 26.09% for ICI, 50.00% for HAIC+ICI; P=0.111], but showed a significant effect on vessel response (objective response rate of tumour thrombi (ORRT), 38.57% for HAIC, 45.65% for ICI, 78.57% for HAIC+ICI; P=0.023). Post-hoc comparisons followed by Bonferroni correction revealed that vessel ORRT was significantly different between the HAIC+ICI and HAIC groups (P=0.014). A significant effect of treatment group on portal vein tumour thrombus (PVTT) was also detected (ORRT, 40.00% for HAIC, 50.00% for ICI, 90.00% for HAIC; P=0.013), with significant difference between the HAIC+ICI and HAIC groups (P=0.005). Patients treated with HAIC, ICI, and HAIC+ICI respectively had 12-month OS rates of 44.9%, 31.4%, and 67.5% (P=0.127) and 12-month PFS rates of 21.2%, 24.6%, and 33.2% (P=0.091). In multivariate analysis of PFS, HAIC+ICI was associated with reduced risk of progression or death compared with HAIC alone (adjusted hazard ratio: 0.46; 95% confidence interval: 0.23-0.94; P=0.032). Conclusions HAIC combined with ICIs had a superior response of PVTT compared to HAIC alone, and was associated with reduced risk of progression or death. Future studies are needed to address the survival benefit of the combination therapy in advanced HCC with MVI.
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Affiliation(s)
- Juei-Seng Wu
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan
| | - Tzu-Chun Hong
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan
| | - Hung-Tsung Wu
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan
| | - Yih-Jyh Lin
- Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan
| | - Ting-Tsung Chang
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan
| | - Chung-Teng Wang
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan
| | - Wen-Chun Liu
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan
| | - Ming-Tsung Hsieh
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan
| | - I-Chin Wu
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan
| | - Po-Jun Chen
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan
| | - Chiung-Yu Chen
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan
| | - Sheng-Hsiang Lin
- Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan
- Department of Public Health, College of Medicine, National Cheng Kung University, Tainan
- Biostatistics Consulting Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan
| | - Chiao-Hsiung Chuang
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan
| | - Meng-Zhi Han
- Department of Internal Medicine, An Nan Hospital, China Medical University, Tainan
| | - Huang-Pin Chen
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan
| | - Hong-Ming Tsai
- Department of Diagnostic Radiology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan
| | - Hsin-Yu Kuo
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan
- Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan
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21
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Bosi C, Rimini M, Casadei-Gardini A. Understanding the causes of recurrent HCC after liver resection and radiofrequency ablation. Expert Rev Anticancer Ther 2023; 23:503-515. [PMID: 37060290 DOI: 10.1080/14737140.2023.2203387] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/16/2023]
Abstract
INTRODUCTION Surgical resection and radiofrequency ablation are preferred options for early-stage disease, with 5-year recurrence rates as high as 70% when patients are treated according to guidelines. With increasing availability of therapeutic options, including but not limited to, immune-checkpoint inhibitors (ICI), tyrosine kinase inhibitors, antiangiogenics, and adoptive cell therapies, understanding the causes of recurrence and identifying its predictors should be priorities in the hepatocellular carcinoma (HCC) research agenda. AREAS COVERED Current knowledge of HCC predictors of recurrence is reviewed, and recent insights about its underlying mechanisms are presented. In addition, results from recent clinical trials investigating treatment combinations are critically appraised. EXPERT OPINION HCC recurrence is either due to progressive growth of microscopic residual disease, or to de novo cancer development in the context of a diseased liver, each occurring in an early (<2years) vs. late (≥2 years) fashion. Collectively, morphological, proteomic, and transcriptomic data suggest vascular invasion and angiogenesis as key drivers of HCC recurrence. Agents aimed at blocking either of these two hallmarks should be prioritized at the moment of early-stage HCC clinical trial design. Emerging results from clinical trials testing ICI in early-stage HCC underscore the importance of defining the best treatment sequence and the most appropriate combination strategies. Lastly, as different responses to systemic therapies are increasingly defined according to the HCC etiology, patient enrolment into clinical trials should take into account the biological characteristics of their inherent disease.
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Affiliation(s)
- Carlo Bosi
- Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, 20132, Italy
- Vita-Salute San Raffaele University School of Medicine, Milan, 20132, Italy
| | - Margherita Rimini
- Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, 20132, Italy
- Vita-Salute San Raffaele University School of Medicine, Milan, 20132, Italy
| | - Andrea Casadei-Gardini
- Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, 20132, Italy
- Vita-Salute San Raffaele University School of Medicine, Milan, 20132, Italy
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22
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Calderon-Martinez E, Landazuri-Navas S, Vilchez E, Cantu-Hernandez R, Mosquera-Moscoso J, Encalada S, Al lami Z, Zevallos-Delgado C, Cinicola J. Prognostic Scores and Survival Rates by Etiology of Hepatocellular Carcinoma: A Review. J Clin Med Res 2023; 15:200-207. [PMID: 37187717 PMCID: PMC10181349 DOI: 10.14740/jocmr4902] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Accepted: 04/14/2023] [Indexed: 05/17/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a common cancer and ranks sixth among all malignancies worldwide. Risk factors for HCC can be classified as infectious or behavioral. Viral hepatitis and alcohol abuse are currently the most common risk factors for HCC; however, nonalcoholic liver disease is expected to become the most common cause of HCC in upcoming years. HCC survival rates vary according to the causative risk factors. As in any malignancy, staging is crucial in making therapeutic decisions. The selection of a specific score should be individualized according to patient characteristics. In this review, we summarize the current data on epidemiology, risk factors, prognostic scores, and survival in HCC.
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Affiliation(s)
| | | | | | - Raul Cantu-Hernandez
- Department of Internal Medicine, Monterrey Institute of Technology and Higher Studies, Mexico
| | | | - Sebastian Encalada
- Department of Internal Medicine, University of the Americas, Quito, Ecuador
| | - Zahraa Al lami
- Department of Internal Medicine, University of Baghdad, College of Medicine, Iraq
| | | | - John Cinicola
- Department of Internal Medicine, UPMC Harrisburg, Harrisburg, PA, USA
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23
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Kwon MJ, Chang S, Kim JH, Han JW, Jang JW, Choi JY, Yoon SK, Sung PS. Factors associated with the survival outcomes of patients with untreated hepatocellular carcinoma: An analysis of nationwide data. Front Oncol 2023; 13:1142661. [PMID: 37035191 PMCID: PMC10073541 DOI: 10.3389/fonc.2023.1142661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Accepted: 03/13/2023] [Indexed: 04/11/2023] Open
Abstract
INTRODUCTION In this study, we examined the natural course of untreated hepatocellular carcinoma (HCC) and identified predictors of survival in an area where hepatitis B is the predominant cause of HCC. METHODS We identified 1,045 patients with HCC who did not receive HCC treatment and were registered in the Korean Primary Liver Cancer Registry between 2008 and 2014, and were followed-up up to December 2018. Thereafter, we analyzed the clinical characteristics of patients who survived for <12 or ≥12 months. A Cox proportional regression model was used to identify the variables associated with patient survival. RESULTS AND DISCUSSION The mean age of the untreated patients at HCC diagnosis was 59.6 years, and 52.1% of patients had hepatitis B. Most untreated patients (94.2%) died during the observation period. The median survival times for each Barcelona Clinic Liver Cancer (BCLC) stage were as follows: 31.0 months for stage 0/A (n = 123), 10.0 months for stage B (n = 96), 3.0 months for stage C (n = 599), and 1.0 month for stage D (n = 227). Multivariate Cox regression analysis demonstrated that BCLC stage D (hazard ratio, 4.282; P < 0.001), model for end-stage liver disease (MELD) score ≥10 (HR, 1.484; P < 0.001), and serum alpha-fetoprotein (AFP) level ≥1,000 ng/mL (HR, 1.506; P < 0.001) were associated with poor survival outcomes in patients with untreated HCC. In untreated patients with HCC, advanced stage BCLC, serum AFP level ≥1,000 ng/mL, and MELD score ≥10 were significantly associated with overall survival.
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Affiliation(s)
- Min Jung Kwon
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Soy Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Ji Hoon Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Ji Won Han
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jeong Won Jang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jong Young Choi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Seung Kew Yoon
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Pil Soo Sung
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
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24
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Wong JK, Lim HJ, Tam VC, Burak KW, Dawson LA, Chaudhury P, Abraham RJ, Meyers BM, Sapisochin G, Valenti D, Samimi S, Ramjeesingh R, Mujoomdar A, Martins I, Dixon E, Segedi M, Liu DM. Clinical consensus statement: Establishing the roles of locoregional and systemic therapies for the treatment of intermediate-stage hepatocellular carcinoma in Canada. Cancer Treat Rev 2023; 115:102526. [PMID: 36924644 DOI: 10.1016/j.ctrv.2023.102526] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 02/12/2023] [Accepted: 02/14/2023] [Indexed: 03/06/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) a leading cause of cancer mortality worldwide and approximately one-third of patients present with intermediate-stage disease. The treatment landscape of intermediate-stage HCC is rapidly evolving due to developments in local, locoregional and systemic therapies. Treatment recommendations focused on this heterogenous disease stage and that take into account the Canadian reality are lacking. To address this gap, a pan-Canadian group of experts in hepatology, transplant, surgery, radiation therapy, nuclear medicine, interventional radiology, and medical oncology came together to develop consensus recommendations on management of intermediate-stage HCC relevant to the Canadian context. METHODS A modified Delphi framework was used to develop consensus statements with strengths of recommendation and supporting levels of evidence graded using the AHA/ACC classification system. Tentative consensus statements were drafted based on a systematic search and expert input in a series of iterative feedback cycles and were then circulated via online survey to assess the level of agreement. RESULTS & CONCLUSION The pre-defined ratification threshold of 80 % agreement was reached for all statements in the areas of multidisciplinary treatment (n = 4), intra-arterial therapy (n = 14), biologics (n = 5), radiation therapy (n = 3), surgical resection and transplantation (n = 7), and percutaneous ablative therapy (n = 4). These generally reflected an expansion in treatment options due to developments in previously established or emergent techniques, introduction of new and more active therapies and increased therapeutic flexibility. These developments have allowed for greater treatment tailoring and personalization as well as a paradigm shift toward strategies with curative intent in a wider range of disease settings.
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Affiliation(s)
- Jason K Wong
- University of Calgary, 2500 University Dr NW, Calgary, AB T2N 1N4, Canada.
| | - Howard J Lim
- BC Cancer Agency, 600 West 10th Avenue, Vancouver, BC V5Z 4E6, Canada.
| | - Vincent C Tam
- Tom Baker Cancer Centre, University of Calgary, 1331 29 St NW, Calgary, AB T2N 4N2, Canada.
| | - Kelly W Burak
- University of Calgary, 2500 University Dr NW, Calgary, AB T2N 1N4, Canada.
| | - Laura A Dawson
- Princess Margaret Cancer Centre, University of Toronto, 610 University Ave, Toronto, ON M5G 2C1, Canada.
| | | | - Robert J Abraham
- Department of Diagnostic Radiology, Dalhousie University, 6299 South St, Halifax, NS B3H 4R2, Canada.
| | - Brandon M Meyers
- Juravinski Cancer Centre, 699 Concession St, Hamilton, ON L8V 5C2, Canada.
| | | | - David Valenti
- McGill University, 845 Rue Sherbrooke O, Montréal, QC H3A 0G4, Canada.
| | - Setareh Samimi
- Hopital Sacre-Coeur de Montreal, University of Montreal, 5400 Boul Gouin O, Montréal, QC H4J 1C5, Canada.
| | - Ravi Ramjeesingh
- Department of Medicine, Dalhousie University, 6299 South St, Halifax, NS B3H 4R2, Canada.
| | - Amol Mujoomdar
- Western University, 1151 Richmond Street, London, ON N6A 5B9, Canada.
| | - Ilidio Martins
- Kaleidoscope Strategic, Inc. 1 King Street W, Suite 4800 - 117, Toronto, ON M5H 1A1, Canada.
| | - Elijah Dixon
- University of Calgary, 2500 University Dr NW, Calgary, AB T2N 1N4, Canada.
| | - Maja Segedi
- Department of Surgery, Vancouver General Hospital, Jim Pattison Pavilion, 899 W 12th Ave, Vancouver, BC V5Z 1M9, Canada.
| | - David M Liu
- School of Biomedical Engineering, University of British Columbia, 2329 West Mall Vancouver, BC V6T 1Z4, Canada.
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25
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Abasseri M, Hoque S, Slavica Kochovska BA, Caldwell K, Sheahan L, Zekry A. Barriers to palliative care in hepatocellular carcinoma: A review of the literature. J Gastroenterol Hepatol 2023. [PMID: 36634200 DOI: 10.1111/jgh.16107] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2022] [Revised: 01/09/2023] [Accepted: 01/11/2023] [Indexed: 01/14/2023]
Abstract
Hepatocellular carcinoma (HCC) is a deadly and burdensome form of liver cancer with an increasing global prevalence. Its course is unpredictable as it frequently occurs in the context of underlying end-stage liver disease, and the associated symptoms and adverse effects of treatment cause severe suffering for patients. Palliative care (PC) is a medical specialty that addresses the physical, emotional, and spiritual needs of patients and their carers in the context of life-limiting illness. In other cancers, a growing body of evidence has demonstrated that the early introduction of PC at diagnosis improves patient and carer outcomes. Despite this, the integration of palliative care at the diagnosis of HCC remains suboptimal, as patients usually receive PC only at the very terminal phase of their disease, even when diagnosed early. Significant barriers to the uptake of palliative care in the treatment algorithm of hepatocellular carcinoma fall under four main themes: data limitations, disease, clinician, and patient factors. Barriers relating to data limitations mainly encapsulated the risk of bias inherent in published work in the field of PC. Clinician-reported barriers related to negative attitudes towards PC and a lack of time for PC discussions. Barriers related to the disease align with prognostic uncertainty due to the unpredictable course of HCC. Significantly, there exists a paucity of evidence exploring patient-perceived barriers to timely PC implementation in HCC. Given that patients are often the underrepresented stakeholder in the delivery of PC, future research should explore the patient perspective in adequately designed qualitative studies as the first step.
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Affiliation(s)
- Mostafa Abasseri
- School of Medicine and Health, UNSW, Sydney, New South Wales, Australia
| | - Shakira Hoque
- Gastroenterology and Hepatology Department, St George Hospital, Sydney, New South Wales, Australia
| | - B A Slavica Kochovska
- Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, New South Wales, Australia.,IMPACCT, Faculty of Health, University of Technology, Sydney, New South Wales, Australia
| | - Kim Caldwell
- Palliative Medicine, Calvary Hospital Kogarah, Kogarah, New South Wales, Australia
| | - Linda Sheahan
- Clinical Ethics Service, South Eastern Sydney Local Health District, Randwick, New South Wales, Australia.,Sydney Health Ethics, The University of Sydney, Camperdown, New South Wales, Australia.,UNSW Medicine & Health, St George and Sutherland Clinical Campus.,Palliative Medicine Department, St George Hospital, Sydney, New South Wales, Australia
| | - Amany Zekry
- School of Medicine and Health, UNSW, Sydney, New South Wales, Australia.,Gastroenterology and Hepatology Department, St George Hospital, Sydney, New South Wales, Australia.,UNSW Medicine & Health, St George and Sutherland Clinical Campus
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Yun B, Ahn SH, Oh J, Yoon JH, Kim BK. Post-operative recurrence of liver cancer according to antiviral therapy for detectable hepatitis B viremia: A nationwide study. Eur J Intern Med 2023; 107:66-72. [PMID: 36347739 DOI: 10.1016/j.ejim.2022.10.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Revised: 10/18/2022] [Accepted: 10/20/2022] [Indexed: 11/06/2022]
Abstract
BACKGROUND High postoperative recurrence of hepatitis B virus (HBV)-infected hepatocellular carcinoma (HCC) remains a significant challenge. Here, we aimed to compare the postoperative HCC recurrence between patients with AVT for detectable serum HBV-DNA vs. those without. METHODS Data of patients undergoing curative resection of HBV-infected HCC as an initial therapy from 2015 to 2017 were obtained from the National Health Insurance Service database in South Korea. AVT was initiated when serum HBV-DNA was detectable. The primary outcome was HCC recurrence. The cumulative risk of HCC recurrence between AVT users and non-users was estimated using the Kaplan-Meier method. RESULTS During follow-up (median 2.7 years) with 3034 patients, 25.7% and 23.6% of AVT users and non-users experienced HCC recurrence, respectively. The 1-, 2-, and 3-year cumulative recurrence rates were similar (p = 0.57): 15.6%, 23.3%, and 26.4% in AVT users versus 15.3%, 22.0%, and 24.9% in non-users, respectively. After adjusting for covariates, multivariable Cox regression analysis showed comparable outcomes between the two groups with adjusted hazard ratios (aHR 1.08, 95% confidence interval [CI] 0.89-1.31; p = 0.439). Similar outcomes between the two groups were reproduced after stratification of liver cirrhosis. Inverse probability treatment weighting analysis also showed comparable outcomes between the two groups in the subgroups with liver cirrhosis (aHR 1.01, 95% CI 0.80-1.29; p = 0.92) and non-cirrhosis (aHR 1.08, 95% CI 0.87-1.34; p = 0.472). CONCLUSIONS Initiating AVT based on detectable serum HBV-DNA provided the similar risk of postoperative HCC recurrence in HBV-infected HCC patients with and without detectable serum HBV-DNA.
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Affiliation(s)
- Byungyoon Yun
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea; Yonsei Liver Centre, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea
| | - Juyeon Oh
- Department of Public Health, Graduate School, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jin-Ha Yoon
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; The Institute for Occupational Health, Yonsei University College of Medicine, Seoul, Republic of Korea.
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea; Yonsei Liver Centre, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea.
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Cho Y, Kim BH, Park JW. The emerging age-pattern changes of patients with hepatocellular carcinoma in Korea. Clin Mol Hepatol 2023; 29:99-101. [PMID: 36300329 PMCID: PMC9845682 DOI: 10.3350/cmh.2022.0321] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Accepted: 10/25/2022] [Indexed: 02/02/2023] Open
Affiliation(s)
- Yuri Cho
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
| | - Bo Hyun Kim
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
| | - Joong-Won Park
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea,Corresponding author : Joong-Won Park Division of Gastroenterology, Department of Internal Medicine, Center for Liver and Pancreatobiliary Cancer, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 10408, Korea Tel: +82-31-920-1605, Fax: +82-31-920-1520, E-mail:
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Lee JS, Lim TS, Lee HW, Kim SU, Park JY, Kim DY, Ahn SH, Lee HW, Lee JI, Kim JK, Min IK, Kim BK. Suboptimal Performance of Hepatocellular Carcinoma Prediction Models in Patients with Hepatitis B Virus-Related Cirrhosis. Diagnostics (Basel) 2022; 13:3. [PMID: 36611295 PMCID: PMC9818663 DOI: 10.3390/diagnostics13010003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 12/14/2022] [Accepted: 12/14/2022] [Indexed: 12/24/2022] Open
Abstract
This study aimed to evaluate the predictive performance of pre-existing well-validated hepatocellular carcinoma (HCC) prediction models, established in patients with HBV-related cirrhosis who started potent antiviral therapy (AVT). We retrospectively reviewed the cases of 1339 treatment-naïve patients with HBV-related cirrhosis who started AVT (median period, 56.8 months). The scores of the pre-existing HCC risk prediction models were calculated at the time of AVT initiation. HCC developed in 211 patients (15.1%), and the cumulative probability of HCC development at 5 years was 14.6%. Multivariate Cox regression analysis revealed that older age (adjusted hazard ratio [aHR], 1.023), lower platelet count (aHR, 0.997), lower serum albumin level (aHR, 0.578), and greater LS value (aHR, 1.012) were associated with HCC development. Harrell’s c-indices of the PAGE-B, modified PAGE-B, modified REACH-B, CAMD, aMAP, HCC-RESCUE, AASL-HCC, Toronto HCC Risk Index, PLAN-B, APA-B, CAGE-B, and SAGE-B models were suboptimal in patients with HBV-related cirrhosis, ranging from 0.565 to 0.667. Nevertheless, almost all patients were well stratified into low-, intermediate-, or high-risk groups according to each model (all log-rank p < 0.05), except for HCC-RESCUE (p = 0.080). Since all low-risk patients had cirrhosis at baseline, they had unneglectable cumulative incidence of HCC development (5-year incidence, 4.9−7.5%). Pre-existing risk prediction models for patients with chronic hepatitis B showed suboptimal predictive performances for the assessment of HCC development in patients with HBV-related cirrhosis.
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Affiliation(s)
- Jae Seung Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul 03722, Republic of Korea
| | - Tae Seop Lim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Division of Gastroenterology, Department of Internal Medicine, Yongin Severance Hospital, Yonsei University Health System, Gyeonggi-do, Seoul 03722, Republic of Korea
| | - Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul 03722, Republic of Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul 03722, Republic of Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul 03722, Republic of Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul 03722, Republic of Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul 03722, Republic of Korea
| | - Hyun Woong Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Division of Gastroenterology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University Health System, Seoul 06273, Republic of Korea
| | - Jung Il Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Division of Gastroenterology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University Health System, Seoul 06273, Republic of Korea
| | - Ja Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Division of Gastroenterology, Department of Internal Medicine, Yongin Severance Hospital, Yonsei University Health System, Gyeonggi-do, Seoul 03722, Republic of Korea
| | - In Kyung Min
- Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul 03722, Republic of Korea
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Lee H, Yoo JJ, Ahn SH, Kim BK. New Evidence of Oral Branched-Chain Amino Acid Supplementation on the Prognosis of Patients With Advanced Liver Disease. Clin Transl Gastroenterol 2022; 13:e00542. [PMID: 36250703 PMCID: PMC9780118 DOI: 10.14309/ctg.0000000000000542] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Accepted: 10/12/2022] [Indexed: 01/31/2023] Open
Abstract
INTRODUCTION Oral branched-chain amino acids (BCAAs) might benefit patients with advanced liver disease. We assess its effects on prognosis compared with control from the meta-analysis. METHODS Study end points were development of hepatic encephalopathy (HE), hepatocellular carcinoma (HCC), mortality, and overall liver-related events (LREs). Risk ratios (RRs) and hazard ratios (HRs) were calculated using random effects model and heterogeneity using I 2 statistic. RESULTS Twenty-eight studies were included in this meta-analysis; 1,578 and 1,727 patients in oral BCAAs and control groups, respectively. From studies using RRs as outcome measures, oral BCAAs were better in preventing HE and LRE than controls, with RRs 0.684 (95% confidence interval [CI] 0.497-0.941; P = 0.019) and 0.788 (95% CI 0.585-0.810; P < 0.001), respectively. Oral BCAAs had marginal effect on preventing HCC compared with control, with RR 0.791 (95% CI 0.619-1.011; P = 0.061); no significant difference in mortality was detected. From studies using HRs as outcome measures, oral BCAAs were superior to control in preventing LRE with adjusted HR 0.497 (95% CI 0.321-0.770; P = 0.002). In subgroups undergoing HCC resection, oral BCAAs had beneficial effect in preventing HE (RR 0.716, 95% CI 0.514-0.996; P = 0.047) and LRE (RR 0.716, 95% CI 0.595-0.860; P < 0.001). DISCUSSION Oral BCAAs could afford clinical benefits in reducing HE and LRE risks, especially among patients undergoing HCC resection.
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Affiliation(s)
- Hankil Lee
- College of Pharmacy, Ajou University, Suwon, Gyeonggi-do, Republic of Korea
| | - Jeong-Ju Yoo
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyaung University College of Medicine, Bucheon, Republic of Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea
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30
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Yang D, Su Y, Zhao F, Hu Y, Zhao K, Xiong X, Zhu M, Pei J, Ding Y. Low-grade hepatocellular carcinoma characteristics, a practical nomogram and risk stratification system: a SEER population-based study. Expert Rev Gastroenterol Hepatol 2022; 16:1115-1123. [PMID: 36412566 DOI: 10.1080/17474124.2022.2150610] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
BACKGROUND The purpose of this study is to establish a nomogram and risk stratification system to predict OS in patients with low-grade HCC. RESEARCH DESIGN AND METHODS Data were extracted from the SEER database. C-index, time-dependent AUCs, and calibration plots were used to evaluate the effective performance of the nomogram. NRI, IDI, and DCA curves were adopted to compare the clinical utility of nomogram with AJCC. RESULTS 3415 patients with low-grade HCC were available. The C-indices for the training and validation cohorts were 0.773 and 0.772. The time-dependent AUCs in the training cohort were 0.821, 0.817, and 0.846 at 1, 3 and 5 years. Calibration plots for 1-, 3- and 5-year OS showed good consistency between actual observations and that predicted by the nomogram. The values of NRI at 1, 3, and 5 years were 0.37, 0.66, and 0.64. The IDI values at 1, 3, and 5 years were 0.11, 0.16, and 0.23 (P< 0.001). DCA curves demonstrated that the nomogram showed better ability of predicting 1-, 3-, and 5-year OS probabilities than AJCC. CONCLUSIONS A nomogram and risk stratification system for predicting OS in patients with low-grade HCC were established and validated.
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Affiliation(s)
- Dashuai Yang
- Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Yang Su
- Department of Gastrointestinal Surgery, Tongji Hospital, Tongji Medical College in Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Fangrui Zhao
- Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Yong Hu
- Departments of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Kailiang Zhao
- Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Xiangyun Xiong
- Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Mingqiang Zhu
- Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Junpeng Pei
- Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Youming Ding
- Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
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Yun B, Ahn SH, Oh J, Yoon JH, Kim BK. Prognostic Impact of MAFLD Following Surgical Resection of Hepatitis B Virus-Related Hepatocellular Carcinoma: A Nationwide Cohort Study. Cancers (Basel) 2022; 14:5002. [PMID: 36291786 PMCID: PMC9599346 DOI: 10.3390/cancers14205002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Revised: 10/12/2022] [Accepted: 10/12/2022] [Indexed: 11/16/2022] Open
Abstract
The association between the metabolic effects of hepatic steatosis as a part of postoperative outcomes of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) has rarely been studied. This study aimed to assess the relationship between metabolic dysfunction-associated fatty liver disease (MAFLD) and patients’ prognoses following curative resection of HBV-related HCC. Patients who underwent surgical resection for HBV-related HCC between 2009 and 2015 were recruited. The study endpoints were postoperative hepatocellular carcinoma (HCC) recurrence and all-cause mortality. Adjusted hazard ratios (aHRs) for the outcomes were estimated using multivariate Cox regression models. The mean age of the 2032 enrolled patients was 55.0 years, and 77.9% were men. During follow-up (median 5.3 years), HCC recurrence and all-cause mortality occurred in 954 (47.0%) and 422 (20.8%) patients, respectively. HCC recurrence and all-cause mortality were significantly associated with MAFLD, with aHRs of 1.22 (p = 0.003) and 1.44 (p < 0.001), respectively. Propensity score matching and inverse probability treatment weighting analyses confirmed similar results (p < 0.05). MAFLD was associated with significantly poor prognoses in terms of HCC recurrence and all-cause mortality following surgical resection of HBV-related HCC. Further studies are needed to develop an effective preventive strategy through the management of metabolic health.
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Affiliation(s)
- Byungyoon Yun
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul 03722, Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Korea
- Yonsei Liver Centre, Severance Hospital, Yonsei University Health System, Seoul 03722, Korea
| | - Juyeon Oh
- Department of Public Health, Yonsei University Graduate School, Seoul 03722, Korea
| | - Jin-Ha Yoon
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul 03722, Korea
- The Institute for Occupational Health, Yonsei University College of Medicine, Seoul 03722, Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Korea
- Yonsei Liver Centre, Severance Hospital, Yonsei University Health System, Seoul 03722, Korea
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Yoon JH, Choi SK, Cho SB, Kim HJ, Ko YS, Jun CH. Early extrahepatic recurrence as a pivotal factor for survival after hepatocellular carcinoma resection: A 15-year observational study. World J Gastroenterol 2022; 28:5351-5363. [PMID: 36185633 PMCID: PMC9521522 DOI: 10.3748/wjg.v28.i36.5351] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 08/11/2022] [Accepted: 09/08/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Surgical resection is one of the most widely used modalities for the treatment of hepatocellular carcinoma (HCC). Early extrahepatic recurrence (EHR) of HCC after surgical resection is considered to be closely associated with poor prognosis. However, data regarding risk factors and survival outcomes of early EHR after surgical resection remain scarce. AIM To investigate the clinical features and risk factors of early EHR and elucidate its association with survival outcomes. METHODS From January 2004 to December 2019, we enrolled treatment-naïve patients who were ≥ 18 years and underwent surgical resection for HCC in two tertiary academic centers. After excluding patients with tumor types other than HCC and/or ineligible data, this retrospective study finally included 779 patients. Surgical resection of HCC was performed according to the physicians' decisions and the EHR was diagnosed based on contrast-enhanced computed tomography or magnetic resonance imaging, and pathologic confirmation was performed in selected patients. Multivariate Cox regression analysis was performed to identify the variables associated with EHR. RESULTS Early EHR within 2 years after surgery was diagnosed in 9.5% of patients during a median follow-up period of 4.4 years. The recurrence-free survival period was 5.2 mo, and the median time to EHR was 8.8 mo in patients with early EHR. In 52.7% of patients with early EHR, EHR occurred as the first recurrence of HCC after surgical resection. On multivariate analysis, serum albumin < 4.0 g/dL, serum alkaline phosphatase > 100 U/L, surgical margin involvement, venous and/or lymphatic involvement, satellite nodules, tumor necrosis detected by pathology, tumor size ≥ 7 cm, and macrovascular invasion were determined as risk factors associated with early EHR. After sub-categorizing the patients according to the number of risk factors, the rates of both EHR and survival showed a significant correlation with the risk of early EHR. Furthermore, multivariate analysis revealed that early EHR was associated with substantially worse survival outcomes (Hazard ratio, 6.77; 95% confidence interval, 4.81-9.52; P < 0.001). CONCLUSION Early EHR significantly deteriorates the survival of patients with HCC, and our identified risk factors may predict the clinical outcomes and aid in postoperative strategies for improving survival.
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Affiliation(s)
- Jae Hyun Yoon
- Department of Gastroenterology and Hepatology, Chonnam National University Hospital and College of Medicine, Gwangju 61469, South Korea
| | - Sung Kyu Choi
- Department of Gastroenterology and Hepatology, Chonnam National University Hospital and College of Medicine, Gwangju 61469, South Korea
| | - Sung Bum Cho
- Department of Gastroenterology and Hepatology, Hwasun Chonnam National University Hospital and College of Medicine, Hwasun 58128, South Korea
| | - Hee Joon Kim
- Department of Surgery, Chonnam National University Hospital and College of Medicine, Gwangju 61469, South Korea
| | - Yang Seok Ko
- Department of Surgery, Hwasun Chonnam National University Hospital and College of Medicine, Hwasun 58128, South Korea
| | - Chung Hwan Jun
- Department of Internal Medicine, Mokpo Hankook Hospital, Mokpo 58643, South Korea
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Yao M, Cheng S, Zhai X, Zhao H, Hong J, Li X, Meng Y, Chen W. Prognostic Comparison between cTACE and H101-TACE in Unresectable Hepatocellular Carcinoma (HCC): A Propensity-Score Matching Analysis. Appl Bionics Biomech 2022; 2022:9084852. [PMID: 36091626 PMCID: PMC9463032 DOI: 10.1155/2022/9084852] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Accepted: 08/12/2022] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Transarterial chemoembolization (TACE) is the most common treatment for patients with HCC who are unsuitable for radical therapies. Conventional TACE (cTACE) takes advantage of the preferential hepatic arterial supply of HCC for the targeted delivery of chemotherapeutic agents suspended in lipiodol, followed by embolization or reduction of arterial flow using various types of particles while sparing the surrounding liver parenchyma. Aims and Objectives. The current study is aimed at comparing the efficacy and safety profiles of transarterial infusion of recombinant human type-5 adenovirus (H101-TACE) with conventional transarterial chemoembolization (cTACE) in patients with unresectable hepatocellular carcinoma (HCC). METHODS Unresectable HCC patients that received H101-based TACE or cTACE from August 2018 to September 2021 were retrospectively evaluated. Propensity score matching (PSM) has a 1 : 1 ratio to eliminate possible confounder imbalances across cohorts. The main outcome was overall survival (OS), while secondary outcomes were progression-free survival (PFS) and tumor response. RESULTS This study included 111 patients classified across two cohorts: the H101-TACE cohort (n = 37) and the cTACE cohort (n = 74). Median OS within the H101-TACE cohort was 9.0 months longer than within the cTACE cohort before PSM (22.1 vs. 13.1 months, P = 0.043) and 9.3 months longer following PSM (22.1 vs. 12.8 months, P = 0.004). The median PFS within the H101-TACE cohort was 3.2 months longer compared to the cTACE cohort before PSM (6.5 vs. 3.3 months, P = 0.046) and 2.5 months after PSM (6.5 vs. 4.0 months, P = 0.012). The disease control rate for H101 and control cohorts was 81.1% and 59.5%, accordingly (P = 0.039). CONCLUSION The present study demonstrated that the H101-TACE is safe and efficient and can considerably enhance prognostic results for unresectable HCC compared to cTACE.
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Affiliation(s)
- Man Yao
- Department of Integrative Oncology, The First Affiliated Hospital of Navy Military Medical University, Shanghai 200433, China
| | - Simo Cheng
- School of Traditional Chinese Medicine, Navy Medical University, Shanghai 200433, China
| | - Xiaofeng Zhai
- Department of Integrative Oncology, The First Affiliated Hospital of Navy Military Medical University, Shanghai 200433, China
| | - Hetong Zhao
- School of Traditional Chinese Medicine, Navy Medical University, Shanghai 200433, China
| | - Jing Hong
- Department of Radiology, The First Affiliated Hospital of Navy Military Medical University, Shanghai 200433, China
| | - Xiaoyan Li
- Department of Integrative Oncology, The First Affiliated Hospital of Navy Military Medical University, Shanghai 200433, China
| | - Yongbin Meng
- Department of Integrative Oncology, The First Affiliated Hospital of Navy Military Medical University, Shanghai 200433, China
| | - Wei Chen
- Department of Radiology, The First Affiliated Hospital of Navy Military Medical University, Shanghai 200433, China
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Lee B, Cho JY, Han HS, Yoon YS, Lee HW, Lee JS, Kim M, Jo Y. Effect of postoperative administration of nafamostat mesilate on posthepatectomy liver failure. HPB (Oxford) 2022; 24:1569-1576. [PMID: 35477649 DOI: 10.1016/j.hpb.2022.03.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 03/16/2022] [Accepted: 03/29/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND To investigate whether the administration of nafamostat mesilate (NM) reduces the risk of posthepatectomy liver failure (PHLF) in patients undergoing hepatectomy for hepatocellular carcinoma (HCC). METHODS We retrospectively reviewed the 1114 patients who underwent hepatectomy for HCC between 2004 and 2020. NM was selectively administered to patients undergoing major hepatectomy with an estimated blood loss of >500 mL. NM group was administered via intravenous of 20 mg of NM from immediately after surgery until postoperative day 4. We performed 1:1 propensity score matching and included 56 patients in each group. PHLF was defined according to the International Study Group of Liver Surgery (ISGLS). RESULTS The incidence of PHLF was lower in the NM group than control group (P = 0.018). The mean peak total bilirubin (P = 0.006), aspartate transaminase (P = 0.018), and alanine aminotransferase (P = 0.018) levels postoperatively were significantly lower in the NM group. The mean hospital stays (P = 0.012) and major complication rate (P = 0.023) were also significantly lower in the NM group. CONCLUSION Prophylactic administration of NM reduced the risks of complication and decreased the frequency of PHLF after hepatectomy. A further prospective study is needed to verify our findings.
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Affiliation(s)
- Boram Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, South Korea
| | - Jai Young Cho
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, South Korea.
| | - Ho-Seong Han
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, South Korea
| | - Yoo-Seok Yoon
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, South Korea
| | - Hae Won Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, South Korea
| | - Jun Suh Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, South Korea
| | - Moonhwan Kim
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, South Korea
| | - Yeongsoo Jo
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, South Korea
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Long-Term Outcomes of Laparoscopic Liver Resection for Centrally Located Hepatocellular Carcinoma. MEDICINA (KAUNAS, LITHUANIA) 2022; 58:medicina58060737. [PMID: 35744000 PMCID: PMC9230051 DOI: 10.3390/medicina58060737] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Revised: 05/24/2022] [Accepted: 05/26/2022] [Indexed: 12/07/2022]
Abstract
Background and Objectives: The feasibility of laparoscopic liver resection (LLR) for centrally located hepatocellular carcinoma (cHCC 1 cm of the hilum, major hepatic veins, and inferior vena cava) is still controversial. This study aims to evaluate the feasibility and safety of LLR for cHCC and compare the perioperative outcomes with those of open liver resection (OLR). Materials and Methods: This retrospective study included 110 patients who underwent LLR (n = 59) or open liver resection (OLR) (n = 51) for cHCC between January 2004 and September 2018. LLR group was divided into the following two subgroups according to the date of operation: Group 1 (n = 19) and Group 2 (n = 40), to account for the advancement in the laparoscopic techniques. Results: No mortality within 3 months was observed. There were no significant differences in operation time (285 vs. 280 min; p = 0.938) and postoperative complication rate (22.0% vs. 27.5%; p = 0.510) between both groups. However, intraoperative blood loss (500 vs. 700 mL; p < 0.001), transfusion rate (10.2% vs. 31.4%; p = 0.006), and hospital stay (6 vs. 10 days; p < 0.001) were significantly lower in the LLR group than in the OLR group. In the LLR group, Group 2, showed a shorter hospital stay than Group 1 (6 vs. 8 days; p = 0.006). There were improvements in the operation time (280 vs. 360 min; p = 0.036) and less intraoperative blood loss (455 vs. 500 mL; p = 0.075) in Group 2. Conclusions: We demonstrated that LLR can be safely performed in highly selected patients with cHCC.
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A Case-Matched Analysis of Laparoscopic Liver Resection for Hepatocellular Carcinoma Located in Posterosuperior Segments of the Liver According to Adaption of Developed Techniques. MEDICINA (KAUNAS, LITHUANIA) 2022; 58:medicina58040543. [PMID: 35454381 PMCID: PMC9032568 DOI: 10.3390/medicina58040543] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Revised: 04/11/2022] [Accepted: 04/12/2022] [Indexed: 12/07/2022]
Abstract
Background and Objectives: Laparoscopic liver resection (LLR) for the hepatocellular carcinoma (HCC) located in posterosuperior (PS) segment is technically demanding, but has been overcome by accumulated experiences and technological improvements. We analyzed peri-and post-operative results before and after the adaptation of the enhanced techniques. Materials and Methods: We retrospectively reviewed 246 patients who underwent LLR for HCC in PS segments from September 2003 to December 2019. According to the introduction of advanced techniques including intercostal trocars, Pringle maneuver, and semi-lateral French position, the patients were divided into Group 1 (n = 43), who underwent LLR from September 2003 to December 2011, and Group 2 (n = 203), who underwent LLR from January 2012 to December 2019. Among these cases, 136 patients (Group 1 = 34, Group 2 = 102) were selected by case-matched analysis using perioperative variables. Results: Mean operation time (362 min vs. 291 min) and hospital stay (11 days vs. 8 days, p = 0.023) were significantly longer in Group 1 than Group 2. Otherwise, disease-free survival (DFS) rate was shorter and resection margin (1.3 mm vs. 0.7 mm, p = 0.034) were smaller in Group 2 than Group 1. However, there was no difference in type of complication (p = 0.084), severity of complication graded by the Clavien–Dindo grade system (p = 0.394), and 5-year overall survival (OS) rates (p = 0.986). In case-matched analysis, operation time (359 min vs. 266 min p = 0.002) and hospital stay (11.5 days vs. 8.0 days, p = 0.032) were significantly different, but there was no significant difference in resection margin, DFS, and OS. Conclusions: The adaptation of improved techniques has reduced the complexity of LLR in PS segments.
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D'Silva M, Cho JY, Han HS, Yoon YS, Lee HW, Lee JS, Lee B, Kim M, Jo Y. Association between achieving textbook outcomes and better survival after laparoscopic liver resection in the anterolateral segments in patients with hepatocellular carcinoma. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2022; 29:855-862. [PMID: 35389551 DOI: 10.1002/jhbp.1148] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Revised: 02/05/2022] [Accepted: 02/15/2022] [Indexed: 12/07/2022]
Abstract
BACKGROUND The quality of surgical procedures are assessed by textbook outcomes (TO). LLR is considered a standard treatment for HCC in the anterolateral segments of the liver. The main objective of this study was to evaluate the factors affecting achievement of TO for laparoscopic liver resection (LLR) and its impact on survival. METHODS We conducted a retrospective cohort study of patients who underwent LLR for lesions located in the anterolateral segments (n=309). Patients were divided into TO and non-TO group. RESULTS A TO was achieved in 55.0% of patients (n=170). In multivariable analysis, Model for End-stage Liver Disease (MELD) score >10 (odds ratio[OR] 3.076; 95% confidence interval[CI] 1.134-8.342), absence of diabetes mellitus (OR 2.325; 95% CI 1.227-4.407) and thrombocytopenia (OR 2.115; 95% CI 1.134-8.342) were independently associated with not achieving TO. The 5-year overall (82.9% vs. 72.8%, P=0.017) and recurrence-free (48.8% vs. 35.4%; P=0.036) survival rates were significantly greater in the TO group than in the non-TO group. CONCLUSION The MELD score, thrombocytopenia, and hypoalbuminemia were independent risk factors influencing the achievement of TO. TO influences the short- and long-term outcomes after LLR for HCC.
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Affiliation(s)
- Mizelle D'Silva
- Department of Gastrointestinal Surgery, Jaslok Hospital and Research Centre, 15, Peddar Road, IT Colony, Tardeo, Mumbai, Maharashtra, India.,Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Gumi-ro 173, Bundang-gu, Gyeonggi-do, Seongnam-si, Republic of Korea
| | - Jai Young Cho
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Gumi-ro 173, Bundang-gu, Gyeonggi-do, Seongnam-si, Republic of Korea
| | - Ho-Seong Han
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Gumi-ro 173, Bundang-gu, Gyeonggi-do, Seongnam-si, Republic of Korea
| | - Yoo-Seok Yoon
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Gumi-ro 173, Bundang-gu, Gyeonggi-do, Seongnam-si, Republic of Korea
| | - Hae Won Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Gumi-ro 173, Bundang-gu, Gyeonggi-do, Seongnam-si, Republic of Korea
| | - Jun Suh Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Gumi-ro 173, Bundang-gu, Gyeonggi-do, Seongnam-si, Republic of Korea
| | - Boram Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Gumi-ro 173, Bundang-gu, Gyeonggi-do, Seongnam-si, Republic of Korea
| | - Moonhwan Kim
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Gumi-ro 173, Bundang-gu, Gyeonggi-do, Seongnam-si, Republic of Korea
| | - Yeongsoo Jo
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Gumi-ro 173, Bundang-gu, Gyeonggi-do, Seongnam-si, Republic of Korea
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Kim BK, Cheon J, Kim H, Kang B, Ha Y, Kim DY, Hwang SG, Chon YE, Chon HJ. Atezolizumab/Bevacizumab vs. Lenvatinib as First-Line Therapy for Unresectable Hepatocellular Carcinoma: A Real-World, Multi-Center Study. Cancers (Basel) 2022; 14:1747. [PMID: 35406518 PMCID: PMC8996911 DOI: 10.3390/cancers14071747] [Citation(s) in RCA: 47] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Revised: 03/25/2022] [Accepted: 03/28/2022] [Indexed: 12/12/2022] Open
Abstract
Lenvatinib (LENV) and atezolizumab/bevacizumab (ATE/BEV) have been approved as first-line regimens for the treatment of unresectable hepatocellular carcinoma (HCC). We aimed to compare their clinical efficacy and safety. Patients receiving ATE/BEV (n = 86) or LENV (n = 146) as first-line treatment were recruited from three academic hospitals in Korea. Overall survival (OS), progression-free survival (PFS), and radiological response were assessed according to the Response Evaluation Criteria in Solid Tumors. Clinical features of the two groups were balanced through propensity score (PS) matching with a 1:1 ratio and inverse probability of treatment weighting (IPTW) analyses. The median age was 62 years, with male predominance (83.6%). There was no significant difference in the objective response rate between the ATE/BEV and LENV groups (32.6% vs. 31.5%; p = 0.868). Neither median OS (not reached vs. 12.8 months; p = 0.357) nor PFS (5.7 vs. 6.0 months; p = 0.738) was different between ATE/BEV and LENV groups. PS-matched and IPTW analyses yielded comparable results in terms of OS and PFS (all p > 0.05). Grade ≥ 3 adverse events occurred in 42.8% and 21.9% of patients in the ATE/BEV and LENV groups, respectively (p = 0.141). The two first-line therapy regimens for unresectable HCC had comparable clinical efficacy and safety in real-world practice settings. Further studies with a larger sample size and longer follow-up are needed to validate these results.
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Affiliation(s)
- Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea; (B.K.K.); (D.Y.K.)
| | - Jaekyung Cheon
- Department of Medical Oncology, CHA Bundang Medical Center, CHA University, Seongnam 13496, Korea; (J.C.); (B.K.)
| | - Hyeyeong Kim
- Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 44033, Korea;
| | - Beodeul Kang
- Department of Medical Oncology, CHA Bundang Medical Center, CHA University, Seongnam 13496, Korea; (J.C.); (B.K.)
| | - Yeonjung Ha
- Department of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam 13496, Korea; (Y.H.); (S.G.H.)
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea; (B.K.K.); (D.Y.K.)
| | - Seong Gyu Hwang
- Department of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam 13496, Korea; (Y.H.); (S.G.H.)
| | - Young Eun Chon
- Department of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam 13496, Korea; (Y.H.); (S.G.H.)
| | - Hong Jae Chon
- Department of Medical Oncology, CHA Bundang Medical Center, CHA University, Seongnam 13496, Korea; (J.C.); (B.K.)
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Choe WH. Is multidisciplinary treatment effective for hepatocellular carcinoma with portal vein tumor thrombus? JOURNAL OF LIVER CANCER 2022; 22:1-3. [PMID: 37383530 PMCID: PMC10035715 DOI: 10.17998/jlc.2022.03.15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/06/2022] [Revised: 03/14/2022] [Accepted: 03/14/2022] [Indexed: 06/30/2023]
Affiliation(s)
- Won Hyeok Choe
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
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Kim DS, Kim BK, Lee JS, Lee HW, Park JY, Kim DY, Ahn SH, Kim SU. Validation of Pre-/Post-TACE-Predict Models among Patients with Hepatocellular Carcinoma Receiving Transarterial Chemoembolization. Cancers (Basel) 2021; 14:67. [PMID: 35008231 PMCID: PMC8750487 DOI: 10.3390/cancers14010067] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Revised: 12/17/2021] [Accepted: 12/20/2021] [Indexed: 11/17/2022] Open
Abstract
This study attempted to validate the prognostic performance of the proposed Pre- and Post-TACE (transarterial chemoembolization)-Predict models, in comparison with other models for prognostication. One-hundred-and-eighty-seven patients with HCC who underwent TACE were recruited. Regarding overall survival (OS), the predictive performance of the Pre-TACE-Predict model (one-year integrated area under the curve (iAUC) 0.685 (95% confidence interval (CI) 0.593-0.772)) was better than that of the Post-TACE-Predict model (iAUC 0.659 (95% CI 0.580-0.742)). However, there was no significant statistical difference between two models at any time point. For comparison between models using pre-treatment factors, the modified hepatoma arterial embolization prognostic (mHAP)-II model demonstrated significantly better predictive performance at one year (iAUC 0.767 (95% CI 0.683-0.847)) compared with Pre-TACE-Predict. For comparison between models using first TACE response, the SNACOR model was significantly more predictive at one year (iAUC 0.778 (95% CI 0.687-0.866) vs. 0.659 (95% CI 0.580-0.742), respectively) and three years (iAUC 0.707 (95% CI 0.646-0.770) vs. 0.624 (95% CI 0.564-0.688), respectively) than the Post-TACE-Predict model. mHAP-II and SNACOR may be preferred over the Pre- and Post-TACE-Predict models, respectively, considering their similar or better performance and the ease of application.
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Affiliation(s)
- David Sooik Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea; (D.S.K.); (B.K.K.); (J.S.L.); (H.W.L.); (J.Y.P.); (D.Y.K.); (S.H.A.)
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea; (D.S.K.); (B.K.K.); (J.S.L.); (H.W.L.); (J.Y.P.); (D.Y.K.); (S.H.A.)
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Korea
- Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul 03722, Korea
| | - Jae Seung Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea; (D.S.K.); (B.K.K.); (J.S.L.); (H.W.L.); (J.Y.P.); (D.Y.K.); (S.H.A.)
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Korea
- Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul 03722, Korea
| | - Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea; (D.S.K.); (B.K.K.); (J.S.L.); (H.W.L.); (J.Y.P.); (D.Y.K.); (S.H.A.)
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Korea
- Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul 03722, Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea; (D.S.K.); (B.K.K.); (J.S.L.); (H.W.L.); (J.Y.P.); (D.Y.K.); (S.H.A.)
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Korea
- Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul 03722, Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea; (D.S.K.); (B.K.K.); (J.S.L.); (H.W.L.); (J.Y.P.); (D.Y.K.); (S.H.A.)
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Korea
- Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul 03722, Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea; (D.S.K.); (B.K.K.); (J.S.L.); (H.W.L.); (J.Y.P.); (D.Y.K.); (S.H.A.)
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Korea
- Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul 03722, Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea; (D.S.K.); (B.K.K.); (J.S.L.); (H.W.L.); (J.Y.P.); (D.Y.K.); (S.H.A.)
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Korea
- Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul 03722, Korea
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Kim JM, Rhu J, Ha SY, Choi GS, Kwon CHD, Kim G, Joh JW. Realization of improved outcomes following liver resection in hepatocellular carcinoma patients aged 75 years and older. Ann Surg Treat Res 2021; 101:257-265. [PMID: 34796141 PMCID: PMC8564081 DOI: 10.4174/astr.2021.101.5.257] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 09/01/2021] [Accepted: 09/24/2021] [Indexed: 01/27/2023] Open
Abstract
Purpose Little is known about liver resection (LR) in hepatocellular carcinoma (HCC) patients older than 75 years of age. This study aimed to compare the postoperative and long-term outcomes of hepatectomy in this patient population according to operation period. Methods This study included 130 elderly patients who underwent LR for solitary treatment-naïve HCC between November 1998 and March 2020. Group 1 included patients who underwent LR before 2016 (n = 68) and group 2 included those who underwent LR during or after 2016 (n = 62). Results The proportion of major LR, anatomical LR, and laparoscopic LR (LLR) in group 1 was significantly lower than those in group 2. Also, the median operation time, amount of blood loss, hospitalization length, rates of intraoperative blood transfusion, and complications in group 2 were less than those in group 1. In the subgroup analysis of group 1, high proteins induced by vitamin K absence or antagonist-II, long hospitalization, and LLR were closely associated with mortality. In the subgroup analysis of group 2, however, none of the factors increased mortality. Nevertheless, the presence of tumor grade 3 or 4 and the incidence of microvascular invasion were higher in group 1 than in group 2, and the disease-free survival and overall survival were better in group 2 than in group 1 because of minimized blood loss and quicker recovery period by increased surgical techniques and anatomical approach, and LLR. Conclusion LR in elderly HCC patients has been frequently performed recently, and the outcomes have improved significantly compared to the past.
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Affiliation(s)
- Jong Man Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jinsoo Rhu
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sang Yun Ha
- Department of Pathology and Translational Genomics, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Gyu-Seong Choi
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Choon Hyuck David Kwon
- Department of Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Gaabsoo Kim
- Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jae-Won Joh
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Feasibility and safety of a novel indwelling catheter system via the femoral artery for intermittent transarterial therapy for treating malignant liver tumors. Jpn J Radiol 2021; 40:326-333. [PMID: 34699022 DOI: 10.1007/s11604-021-01202-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Accepted: 09/21/2021] [Indexed: 10/20/2022]
Abstract
PURPOSE An indwelling arterial access system via the brachial artery, System-i, has been previously reported. We have modified the technique for the femoral artery approach. This study aimed to evaluate the feasibility and safety of the modified System-i for patients with malignant liver tumors. MATERIALS AND METHODS The modified System-i is an indwelling catheter that provides vascular access for inserting a microcatheter without repeated punctures to the femoral artery. Between 2018 and 2020, the system was implanted for 50 patients with malignant liver tumors. We used the system for patients with difficulty in inserting the conventional indwelling catheter system. To place the system, a side-holed catheter was implanted in the femoral artery, and the tip of the catheter was placed in the superficial femoral artery through the contralateral iliac artery. Using this system, transcatheter arterial chemoembolization or hepatic arterial infusion chemotherapy was performed. A shaped high-flow microcatheter and a non-tapered microcatheter were used with the system. The technical aspects and outcomes of the system were also assessed. RESULTS Implantation of the system was successful in all patients. The median implantation time was 40 min. The main reason for implantation was obstruction or stenosis of the hepatic artery. Among the 50 patients, 11 (22%) showed complications, of which four had major complications/class C based on the SIR criteria. CONCLUSION The modified System-i is a safe system that can be a feasible repeated interventional radiological treatment via the femoral approach. We need to evaluate the efficacy of this system in the treatment of advanced cancers in the future. The modified System-i is a novel indwelling catheter system that allows vascular access to perform intermittent transarterial therapy, such as transcatheter arterial chemoembolization and hepatic arterial infusion chemotherapy via the femoral approach. In this study, we report the technical details and safety of the system.
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Kim TS, Lee M, Park M, Kim SY, Shim MS, Lee CY, Choi DH, Cho Y. Metformin and Dichloroacetate Suppress Proliferation of Liver Cancer Cells by Inhibiting mTOR Complex 1. Int J Mol Sci 2021; 22:ijms221810027. [PMID: 34576192 PMCID: PMC8467948 DOI: 10.3390/ijms221810027] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Revised: 09/13/2021] [Accepted: 09/14/2021] [Indexed: 12/15/2022] Open
Abstract
The Warburg effect is important for cancer cell proliferation. This phenomenon can be flexible by interaction between glycolysis and mitochondrial oxidation for energy production. We aimed to investigate the anticancer effects of the pyruvate dehydrogenase kinase inhibitor, dichloroacetate (DCA) and the mitochondrial respiratory complex I inhibitor metformin in liver cancer cells. The anticancer effect of DCA and/or metformin on HepG2, PLC/PRF5 human liver cancer cell lines, MH-134 murine hepatoma cell lines, and primary normal hepatocytes using MTT assay. Inhibition of lactate/ATP production and intracellular reactive oxygen species generation by DCA and metformin was investigated. Inhibition of PI3K/Akt/mTOR complex I was evaluated to see whether it occurred through AMPK signaling. Anticancer effects of a combination treatment of DCA and metformin were evaluated in HCC murine model. The results showed that metformin and DCA effectively induced apoptosis in liver cancer cells. A combination treatment of metformin and DCA did not affect viability of primary normal hepatocytes. Metformin upregulated glycolysis in liver cancer cells, thereby increasing sensitivity to the DCA treatment. Metformin and DCA inhibited mTOR complex I signaling through upregulated AMPK-independent REDD1. In addition, metformin and DCA increased reactive oxygen species levels in liver cancer cells, which induced apoptosis. A combination treatment of metformin and DCA significantly suppressed the tumor growth of liver cancer cells using in vivo xenograft model. Taken together, the combined treatment of metformin and DCA suppressed the growth of liver cancer cells. This strategy may be effective for patients with advanced liver cancer.
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Affiliation(s)
- Tae Suk Kim
- Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon 24341, Korea; (T.S.K.); (C.Y.L.); (D.H.C.)
| | - Minjong Lee
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul 07804, Korea;
- Department of Internal Medicine, Ewha Womans University Medical Center, Seoul 07804, Korea
- Correspondence: (M.L.); (Y.C.); Tel.: +82-2-6986-1761 (M.L.); +82-31-920-1605 (Y.C.)
| | - Minji Park
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul 07804, Korea;
- Department of Internal Medicine, Ewha Womans University Medical Center, Seoul 07804, Korea
- Department of Internal Medicine, CHA Gangnam Medical Center, CHA University School of Medicine, Seoul 06135, Korea
| | - Sae Yun Kim
- Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea;
| | - Min Suk Shim
- Division of Bioengineering, Incheon National University, Incheon 22012, Korea;
| | - Chea Yeon Lee
- Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon 24341, Korea; (T.S.K.); (C.Y.L.); (D.H.C.)
| | - Dae Hee Choi
- Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon 24341, Korea; (T.S.K.); (C.Y.L.); (D.H.C.)
| | - Yuri Cho
- Department of Internal Medicine, CHA Gangnam Medical Center, CHA University School of Medicine, Seoul 06135, Korea
- Center for Liver and Pancreatobiliary Cancer, Research Institute and Hospital, National Cancer Center, Goyang 10408, Korea
- Correspondence: (M.L.); (Y.C.); Tel.: +82-2-6986-1761 (M.L.); +82-31-920-1605 (Y.C.)
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