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Cheah DS, Tsai K, Kawano F, Kemprecos HJ, Salirrosas O, Tigranyan A, Cohen MS, Polites G, Kutlu OC, Mise Y, Saiura A, Conrad C. Are More Young, Western Patients Also Developing Hepatocellular Carcinoma? Ann Surg Oncol 2025; 32:3924-3932. [PMID: 40063237 DOI: 10.1245/s10434-025-17042-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Accepted: 02/05/2025] [Indexed: 04/16/2025]
Abstract
BACKGROUND While the incidence of early-onset cancers is rising, it is unclear whether this is the case for early-onset hepatocellular carcinoma (eHCC). Even the definition of eHCC remains unclear. This study was designed to identify an age cutoff for eHCC and to explore trends in its incidence, clinical presentation, surgical outcomes, and long-term survival compared to typical-onset HCC (tHCC). METHODS The National Cancer Database was queried for HCC patients (2010-2021). Both eHCC (< 50 years) and tHCC (≥ 50 years) were statistically defined. Propensity score matching adjustment, multivariate hazard ratios, and stage-dependent Kaplan-Meier survival analysis were calculated. RESULTS Among 207,653 patients, 10,128 (4.88%) had eHCC, with decreasing incidence from 2010 to 2021 (7.50% to 3.83%). eHCC had higher grade, synchronous metastasis, and nodal involvement. Independent predictors of worse 5-year survival included tHCC, uninsured, and higher TNM staging. Despite worse clinical characteristics, eHCC had improved survival across all stages (p < 0.001). After matching, eHCC had improved outcomes for stage I, II (p < 0.001, p = 0.004), and T1-T3 tumors (p < 0.001, p = 0.002, p = 0.045), but not T4. Minority status, lack of insurance, lower income, and greater distance to the hospital are independent predictors of eHCC. CONCLUSIONS After defining a novel, evidence-based age cutoff for eHCC, data indicate that while cancer incidence among younger patients is generally rising, the incidence of eHCC is declining. Although eHCC are more advanced cancers, they have improved outcomes compared to tHCC when undergoing surgery. In this context, especially young patients with stage I, II, or tumor ≤ T3 have favorable outcomes following resection.
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Affiliation(s)
- Daniel S Cheah
- Carle Illinois College of Medicine, University of Illinois Urbana-Champaign, Urbana, IL, USA
| | - Kathryn Tsai
- Carle Illinois College of Medicine, University of Illinois Urbana-Champaign, Urbana, IL, USA
| | - Fumihiro Kawano
- Carle Foundation Hospital, Urbana, IL, USA
- Juntendo University Hospital, Tokyo, Japan
| | - Helen J Kemprecos
- Carle Illinois College of Medicine, University of Illinois Urbana-Champaign, Urbana, IL, USA
| | | | - Annie Tigranyan
- Carle Illinois College of Medicine, University of Illinois Urbana-Champaign, Urbana, IL, USA
| | - Mark S Cohen
- Carle Illinois College of Medicine, University of Illinois Urbana-Champaign, Urbana, IL, USA
- Carle Foundation Hospital, Urbana, IL, USA
| | - Gregory Polites
- Carle Illinois College of Medicine, University of Illinois Urbana-Champaign, Urbana, IL, USA
- Carle Foundation Hospital, Urbana, IL, USA
| | - Onur C Kutlu
- Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA
| | | | | | - Claudius Conrad
- Carle Illinois College of Medicine, University of Illinois Urbana-Champaign, Urbana, IL, USA.
- Carle Foundation Hospital, Urbana, IL, USA.
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Wen J, Xia M, Luo H, Zhu L, Li M, Hou Y. Global, regional, and national burden of liver cancer in adolescents and young adults from 1990 to 2021: an analysis of the global burden of disease study 2021 and forecast to 2040. Front Public Health 2025; 13:1547106. [PMID: 40129589 PMCID: PMC11931027 DOI: 10.3389/fpubh.2025.1547106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Accepted: 02/17/2025] [Indexed: 03/26/2025] Open
Abstract
Background The global burden of liver cancer among adolescents and young adults (AYAs) has often been underestimated, despite significant shifts in its etiology. This study analyzes the disease burden of liver cancer in AYAs from 1990 to 2021 and forecasts trends up to 2040 using data from the Global Burden of Disease Study 2021. Our goal is to provide insights that can inform resource allocation and policy planning. Methods Incidence, mortality, and disability-adjusted life years (DALYs) data were extracted and estimated annual percentage changes calculated to assess trends. Correlation between age-standardized rates and sociodemographic index (SDI) was analyzed using Spearman correlation, and future trends were predicted using the Bayesian age-period-cohort model. Findings Globally, there were 24,348 new liver cancer cases and 19,270 deaths among AYAs in 2021, with decreases in age-standardized rates for incidence, mortality, and DALYs from 1990 to 2021. East Asia bears the highest burden, with males experiencing significantly higher rates than females. The burden increases with age, peaking at 35-39 years. Higher SDI is associated with lower incidence, mortality, and DALYs. While HBV remains the leading cause, NASH is the fastest-growing contributor to liver cancer incidence and mortality. Projections indicate a continued decline in liver cancer burden among AYAs, though female cases are expected to rise. Interpretation Despite a gradual decline in liver cancer burden among AYAs, NASH is emerging as a significant and rising cause of incidence and mortality. Regional and gender disparities persist, highlighting the need for tailored prevention and healthcare strategies to alleviate the liver cancer AYA's burden globally.
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Affiliation(s)
- Jingyu Wen
- Department of Medical Insurance, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Mingge Xia
- State Key Laboratory of Quality Research in Chinese Medicines, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao SAR, China
| | - Han Luo
- Department of Hepatobiliary Surgery, Zigong Fourth People's Hospital, Zigong, China
| | - Luwei Zhu
- Department of Medical Insurance, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Min Li
- Department of Medical Insurance, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Yifu Hou
- Department of Organ Transplantation, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
- School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
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Lee HA. Management of hepatocellular carcinoma in elderly and adolescent/young adult populations. JOURNAL OF LIVER CANCER 2025; 25:52-66. [PMID: 40108768 PMCID: PMC12010824 DOI: 10.17998/jlc.2025.02.28] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/01/2025] [Revised: 02/26/2025] [Accepted: 02/28/2025] [Indexed: 03/22/2025]
Abstract
Hepatocellular carcinoma (HCC) presents unique challenges in both the elderly and adolescent/young adult (AYA) populations, requiring distinct management approaches. Recent epidemiological data show an increasing incidence of HCC in both age groups, with elderly cases rising significantly and AYA cases showing trends in specific regions. The clinical characteristics and treatment considerations vary substantially among these populations. Elderly patients with HCC typically present with hepatitis C virus infection, metabolic dysfunction-associated steatotic liver disease, well-differentiated tumors, and multiple comorbidities. In contrast, AYA patients with HCC often present with more aggressive tumor characteristics and predominantly with hepatitis B virus-related diseases. Treatment decisions for elderly patients with HCC require careful consideration of physiological reserves, comprehensive geriatric assessments, and potential complications. Recent studies have demonstrated that elderly patients can achieve outcomes comparable to younger patients across various treatment modalities when properly selected. While surgical outcomes are comparable to those of younger patients with proper selection, less-invasive options such as radiofrequency ablation or transarterial therapies may be more appropriate for some elderly patients. The treatment approach for AYA HCC emphasizes curative intent while considering long-term effects. AYA patients require specialized attention to their psychosocial needs, fertility preservation, and long-term health maintenance. Although data on AYA patients remain limited, they are known to have relatively favorable prognoses despite exhibiting more aggressive tumor characteristics. Management of HCC in both the elderly and AYA populations requires individualized approaches that consider age-specific factors. Both groups benefit from multidisciplinary team involvement and careful consideration of quality of life.
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Affiliation(s)
- Han Ah Lee
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
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Kirihata N, Nakano Y, Moriyoshi K, Miyamoto S. Ruptured hepatocellular carcinoma developed in a normal liver in a young patient with a body mass index of 33 kg/m 2. BMJ Case Rep 2024; 17:e262841. [PMID: 39950627 DOI: 10.1136/bcr-2024-262841] [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: 05/09/2025] Open
Abstract
Hepatocellular carcinoma (HCC) in young patients is rare, and the most common cause is hepatitis B viral infection. We report a case of ruptured HCC in a man in his 30s with a body mass index of 33 kg/m² without hepatitis viral infection. He had multiple HCC with distant metastases at the first visit. On the 6th day after admission, he underwent transcatheter arterial embolisation for HCC rupture, but died the following day. Pathological autopsy revealed moderately to poorly differentiated HCC without evidence of fibrolamellar carcinoma, which is common in young patients with HCC. Based on his history of obesity and fatty liver, we presumed that he had metabolic dysfunction-associated steatohepatitis. However, his non-neoplastic liver was normal. The HCC might have developed from metabolic dysfunction-associated steatotic liver disease, followed by regression of the underlying hepatic steatosis as the patient lost weight owing to HCC progression.
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Affiliation(s)
- Naoki Kirihata
- Gastroenterology, National Hospital Organisation Kyoto Medical Center, Kyoto, Kyoto, Japan
| | - Yoshiko Nakano
- Gastroenterology, National Hospital Organisation Kyoto Medical Center, Kyoto, Kyoto, Japan
| | - Koki Moriyoshi
- Diagnostic Pathology, National Hospital Organisation Kyoto Medical Center, Kyoto, Kyoto, Japan
| | - Shin'ichi Miyamoto
- Gastroenterology, National Hospital Organisation Kyoto Medical Center, Kyoto, Kyoto, Japan
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Guan Y, Gan Y, An J. Clinical Characteristics and Prognosis of Early-Onset Hepatocellular Carcinoma: A Retrospective Cohort Study Based on Population Data. Dig Dis Sci 2024; 69:3563-3573. [PMID: 38965157 DOI: 10.1007/s10620-024-08549-9] [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: 01/24/2024] [Accepted: 06/22/2024] [Indexed: 07/06/2024]
Abstract
BACKGROUND The incidence of young patients diagnosed with hepatocellular carcinoma (HCC) is projected to rise. This study aimed to investigate the distinctive characteristics of adolescent and young adult (AYA) patients with HCC and identify the risk factors that impact their survival. METHODS This study included 1005 AYA patients and 55,435 older adult (OA) patients with HCC, using data from the Surveillance, Epidemiology, and End Results database. Propensity score matching was used to adjust for baseline differences in patient characteristics. The Kaplan-Meier curve and log-rank test are utilized to compare the overall survival between the two groups. The Cox proportional hazards regression model was used for subgroup analysis to identify risk factors for overall survival in AYA patients. RESULTS AYA patients exhibited a higher proportion of advanced clinical stage (49.15% vs 37.57%, P < 0.001) and fibrolamellar hepatocellular carcinoma (14.13% vs 0.09%, P < 0.001), but a lower incidence of alpha-fetoprotein positivity (32.04% vs 45.32%, P < 0.001) and cirrhosis (8.86% vs 18.32%, P < 0.001). The subgroup analysis results indicated that AYA patients had a more favorable prognosis than OA patients in most subgroups. Undifferentiated carcinoma emerged as the predominant risk factor for AYA patients (Hazard Ratio [HR], 6.08 [2.53-14.62]), whereas partial hepatectomy was determined to be the most advantageous factor (HR, 0.29 [0.23-0.37]). CONCLUSIONS AYA patients with HCC exhibit more aggressive characteristics but demonstrate a better prognosis compared to the OA group, necessitating personalized surveillance and treatment.
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Affiliation(s)
- Yufan Guan
- Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, 169 Changle Xi Lu, Xi'an, 710032, China
| | - Yu Gan
- Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, 169 Changle Xi Lu, Xi'an, 710032, China
| | - Jiaze An
- Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, 169 Changle Xi Lu, Xi'an, 710032, China.
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Qin R, Jin T, Xu F. Biomarkers predicting the efficacy of immune checkpoint inhibitors in hepatocellular carcinoma. Front Immunol 2023; 14:1326097. [PMID: 38187399 PMCID: PMC10770866 DOI: 10.3389/fimmu.2023.1326097] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2023] [Accepted: 12/11/2023] [Indexed: 01/09/2024] Open
Abstract
In recent years, immune checkpoint inhibitors (ICIs) have emerged as a transformative approach in treating advanced hepatocellular carcinoma (HCC). Despite their success, challenges persist, including concerns about their effectiveness, treatment costs, frequent occurrence of treatment-related adverse events, and tumor hyperprogression. Therefore, it is imperative to identify indicators capable of predicting the efficacy of ICIs treatment, enabling optimal patient selection to maximize clinical benefits while minimizing unnecessary toxic side effects and economic losses. This review paper categorizes prognostic biomarkers of ICIs treatment into the following categories: biochemical and cytological indicators, tumor-related markers, imaging and personal features, etiology, gut microbiome, and immune-related adverse events (irAEs). By organizing these indicators systematically, we aim to guide biomarker exploration and inform clinical treatment decisions.
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Affiliation(s)
| | - Tianqiang Jin
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China
| | - Feng Xu
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China
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Guo C, Liu Z, Lin C, Fan H, Zhang X, Wang H, Han X, Li Y, Mu L, Yu S, Zhang T. Global epidemiology of early-onset liver cancer attributable to specific aetiologies and risk factors from 2010 to 2019. J Glob Health 2023; 13:04167. [PMID: 38085217 PMCID: PMC10715628 DOI: 10.7189/jogh.13.04167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2023] Open
Abstract
Background Considering its emergence as a public health concern worldwide, with potential spatial-temporal heterogeneities, we aimed to determine the global burden of early-onset liver cancer attributable to aetiologies and concomitant risk factors. Methods We used data from the Global Burden of Diseases Study 2019 to determine age-standardised disability-adjusted life-year (DALY) rates for early-onset liver cancer by aetiologies and the population DALYs attributable to concomitant risk factors between 2010 and 2019. We also calculated estimated annual percentage changes (EAPCs) to measure temporal trends. Results There were 2.9 million DALYs related to early-onset liver cancer globally in 2019. East Asia contributed over half of DALYs, which increased annually by 1.23% (95% confidence interval (CI) = 0.71, 1.76) between 2010 and 2019. Non-alcoholic steatohepatitis was the only growing aetiology. The proportion of DALYs attributed to metabolic risks increased by 22.50% (95% CI = 14.33, 38.13), while behavioral risks remained stable. Obesity surpassed smoking as the most prevalent nondeterministic aetiological risk factor from 2010 to 2019, while the population DALY attributable to hepatitis B combined with obesity increased by 29.93% (95% CI = 8.49, 60.77) in the same period, making it the principal joint contributor. Conclusions Early-onset liver cancer poses considerable disability and continues to increase in many regions, especially in East Asia. Metabolic risk factors, particularly when hepatitis B and obesity coexist, are the fastest-growing contributors to this type of cancer. More targeted interventions are imperative to curb the growing burden of early-onset liver cancer due to metabolic risks.
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Affiliation(s)
- Chengnan Guo
- Shanghai Institute of Infectious Disease and Biosecurity, School of Public Health, Fudan University, Shanghai, China
- Department of Epidemiology, School of Public Health, Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, Fudan University, Shanghai, China
| | - Zhenqiu Liu
- State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Chunqing Lin
- National Clinical Research Center for Cancer, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hong Fan
- Shanghai Institute of Infectious Disease and Biosecurity, School of Public Health, Fudan University, Shanghai, China
- Department of Epidemiology, School of Public Health, Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, Fudan University, Shanghai, China
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Xin Zhang
- Shanghai Institute of Infectious Disease and Biosecurity, School of Public Health, Fudan University, Shanghai, China
- Department of Epidemiology, School of Public Health, Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, Fudan University, Shanghai, China
| | - Haili Wang
- Shanghai Institute of Infectious Disease and Biosecurity, School of Public Health, Fudan University, Shanghai, China
- Department of Epidemiology, School of Public Health, Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, Fudan University, Shanghai, China
| | - Xinyu Han
- Shanghai Institute of Infectious Disease and Biosecurity, School of Public Health, Fudan University, Shanghai, China
- Department of Epidemiology, School of Public Health, Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, Fudan University, Shanghai, China
| | - Yi Li
- Shanghai Institute of Infectious Disease and Biosecurity, School of Public Health, Fudan University, Shanghai, China
- Department of Epidemiology, School of Public Health, Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, Fudan University, Shanghai, China
| | - Lina Mu
- Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, State University of New York (SUNY), Buffalo, New York, USA
| | - Shunzhang Yu
- Department of Epidemiology, School of Public Health, Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, Fudan University, Shanghai, China
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Tiejun Zhang
- Shanghai Institute of Infectious Disease and Biosecurity, School of Public Health, Fudan University, Shanghai, China
- Department of Epidemiology, School of Public Health, Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, Fudan University, Shanghai, China
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
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Lee KI, Liang PC, Hsu PY, Jang TY, Wei YJ, Huang CI, Hsieh MY, Lin ZY, Yeh ML, Huang CF, Huang JF, Dai CY, Chuang WL, Yu ML. Unawareness of hepatitis B infection and lack of surveillance are associated with severity of hepatocellular carcinoma. Kaohsiung J Med Sci 2023; 39:1145-1154. [PMID: 37658712 DOI: 10.1002/kjm2.12744] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 07/06/2023] [Accepted: 07/20/2023] [Indexed: 09/03/2023] Open
Abstract
Unawareness of hepatitis B virus (HBV) infection and lack of surveillance may serve as major barriers to HBV control and contributors to severe hepatocellular carcinoma (HCC) at presentation. This study evaluated the risk of HBV unawareness and its relationship with HCC severity. This retrospective study was conducted in a tertiary hospital in Taiwan. Patients with HBV-related HCC diagnosed from 2011 to 2021 were enrolled. The demographic, clinical, and HCC characteristics were collected and compared between patients with HBV unawareness and awareness with and without surveillance. Of 501 HBV-related HCC patients enrolled, 105 (21%) patients were unaware of HBV infection at the time of HCC diagnosis. Patients with HBV unawareness were significantly younger and had poorer liver function than those with HBV awareness. Patients with HBV unawareness also had a significantly higher rate of detectable HBV DNA and an advanced stage of HCC. Ninety-one (23%) of the HBV-aware patients did not receive regular surveillance. Patients with HBV unawareness and awareness without surveillance shared similar clinical characteristics with more severe HCC status. Further regression analysis demonstrated that HBV awareness with periodic surveillance was associated with early stage HCC. Meanwhile, we observed that there was no change in the proportion of HBV awareness over the past 10 years. Patients with surveillance also had better HCC survival than patients without surveillance or unawareness. HBV unawareness and lack of regular surveillance correlated with advanced HCC at presentation. Efforts to improve HBV education, disease awareness, and HCC surveillance are needed.
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Affiliation(s)
- Kuan-I Lee
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Po-Cheng Liang
- Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Po-Yau Hsu
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Tyng-Yuan Jang
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Yu-Ju Wei
- Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Ching-I Huang
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Ming-Yen Hsieh
- Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Zu-Yau Lin
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- School of Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung, Taiwan
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Wilbaux M, Demanse D, Gu Y, Jullion A, Myers A, Katsanou V, Meille C. Contribution of machine learning to tumor growth inhibition modeling for hepatocellular carcinoma patients under Roblitinib (FGF401) drug treatment. CPT Pharmacometrics Syst Pharmacol 2022; 11:1122-1134. [PMID: 35728123 PMCID: PMC9381917 DOI: 10.1002/psp4.12831] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Revised: 05/13/2022] [Accepted: 05/16/2022] [Indexed: 12/19/2022] Open
Abstract
Machine learning (ML) opens new perspectives in identifying predictive factors of efficacy among a large number of patients’ characteristics in oncology studies. The objective of this work was to combine ML with population pharmacokinetic/pharmacodynamic (PK/PD) modeling of tumor growth inhibition to understand the sources of variability between patients and therefore improve model predictions to support drug development decisions. Data from 127 patients with hepatocellular carcinoma enrolled in a phase I/II study evaluating once‐daily oral doses of the fibroblast growth factor receptor FGFR4 kinase inhibitor, Roblitinib (FGF401), were used. Roblitinib PKs was best described by a two‐compartment model with a delayed zero‐order absorption and linear elimination. Clinical efficacy using the longitudinal sum of the longest lesion diameter data was described with a population PK/PD model of tumor growth inhibition including resistance to treatment. ML, applying elastic net modeling of time to progression data, was associated with cross‐validation, and allowed to derive a composite predictive risk score from a set of 75 patients’ baseline characteristics. The two approaches were combined by testing the inclusion of the continuous risk score as a covariate on PD model parameters. The score was found as a significant covariate on the resistance parameter and resulted in 19% reduction of its variability, and 32% variability reduction on the average dose for stasis. The final PK/PD model was used to simulate effect of patients’ characteristics on tumor growth inhibition profiles. The proposed methodology can be used to support drug development decisions, especially when large interpatient variability is observed.
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Affiliation(s)
| | - David Demanse
- Early Development Analytics, Novartis, Basel, Switzerland
| | - Yi Gu
- Pharmacokinetic Sciences, Novartis Institutes for Biomedical Research, Cambridge, USA
| | - Astrid Jullion
- Early Development Analytics, Novartis, Basel, Switzerland
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Wang W, Wang F, Chen Q, Ouyang S, Iwamoto Y, Han X, Lin L, Hu H, Tong R, Chen YW. Phase Attention Model for Prediction of Early Recurrence of Hepatocellular Carcinoma With Multi-Phase CT Images and Clinical Data. FRONTIERS IN RADIOLOGY 2022; 2:856460. [PMID: 37492657 PMCID: PMC10365106 DOI: 10.3389/fradi.2022.856460] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 02/24/2022] [Indexed: 07/27/2023]
Abstract
Hepatocellular carcinoma (HCC) is a primary liver cancer that produces a high mortality rate. It is one of the most common malignancies worldwide, especially in Asia, Africa, and southern Europe. Although surgical resection is an effective treatment, patients with HCC are at risk of recurrence after surgery. Preoperative early recurrence prediction for patients with liver cancer can help physicians develop treatment plans and will enable physicians to guide patients in postoperative follow-up. However, the conventional clinical data based methods ignore the imaging information of patients. Certain studies have used radiomic models for early recurrence prediction in HCC patients with good results, and the medical images of patients have been shown to be effective in predicting the recurrence of HCC. In recent years, deep learning models have demonstrated the potential to outperform the radiomics-based models. In this paper, we propose a prediction model based on deep learning that contains intra-phase attention and inter-phase attention. Intra-phase attention focuses on important information of different channels and space in the same phase, whereas inter-phase attention focuses on important information between different phases. We also propose a fusion model to combine the image features with clinical data. Our experiment results prove that our fusion model has superior performance over the models that use clinical data only or the CT image only. Our model achieved a prediction accuracy of 81.2%, and the area under the curve was 0.869.
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Affiliation(s)
- Weibin Wang
- Graduate School of Information Science and Engineering, Ritsumeikan University, Kusatsu, Japan
| | - Fang Wang
- Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
| | - Qingqing Chen
- Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
| | - Shuyi Ouyang
- College of Computer Science and Technology, Zhejiang University, Hangzhou, China
| | - Yutaro Iwamoto
- Graduate School of Information Science and Engineering, Ritsumeikan University, Kusatsu, Japan
| | - Xianhua Han
- Graduate School of Information Science and Engineering, Yamaguchi University, Yamaguchi-shi, Japan
| | - Lanfen Lin
- College of Computer Science and Technology, Zhejiang University, Hangzhou, China
| | - Hongjie Hu
- Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
| | - Ruofeng Tong
- College of Computer Science and Technology, Zhejiang University, Hangzhou, China
- Zhejiang Lab, Research Center for Healthcare Data Science, Hangzhou, China
| | - Yen-Wei Chen
- Graduate School of Information Science and Engineering, Ritsumeikan University, Kusatsu, Japan
- College of Computer Science and Technology, Zhejiang University, Hangzhou, China
- Zhejiang Lab, Research Center for Healthcare Data Science, Hangzhou, China
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11
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Dong D, Zhu X, Wang H, Li L, Wan M, Li S, Zhang Y, Geng J, Li Y, Wang W. Prognostic significance of albumin-bilirubin score in patients with unresectable hepatocellular carcinoma undergoing combined immunotherapy and radiotherapy. J Med Imaging Radiat Oncol 2022; 66:662-670. [PMID: 35243796 DOI: 10.1111/1754-9485.13398] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Revised: 01/17/2022] [Accepted: 02/15/2022] [Indexed: 01/27/2023]
Abstract
INTRODUCTION We aimed to explore the prognostic value of albumin-bilirubin (ALBI) scores in unresectable hepatocellular carcinoma (HCC) treated with combined immune checkpoint inhibitors (ICIs) and radiotherapy (RT). METHODS Patients with unresectable HCC receiving combined ICI and RT (July 2018 to February 2021) were retrospectively enrolled and analysed. Cox regression modelling was implemented to identify prognostic factors. Survival analysis was performed using the Kaplan-Meier method. Survival was compared using log-rank tests. RESULTS A total of 38 patients were enrolled. The median follow-up was 16.5 months (range: 6.7-29.9). The objective response rate (ORR) was 28.9%, including complete response in three (7.9%) patients. The median progression-free survival (PFS) was 5.6 months (95% confidence interval (CI): 3.2-8.0), and the median overall survival (OS) was 12.9 months (95% CI: 8.3-17.6). In the multivariate Cox regression analysis, ALBI score and age were identified as independent prognostic factors for PFS and OS. Patients with grade 1 ALBI scores who were ≥53 years of age (the low-risk group) had statistically significantly higher ORRs (50.0% vs. 13.6%) and prolonged median PFS (15.3 vs. 2.7 months) and OS (not reached vs. 10.1 months). Grade 3 haematological toxicities and/or liver function abnormalities occurred in 15 (39.5%) patients; treatment was not interrupted. No grade 4 or higher side effects were observed. CONCLUSION Combined ICI and RT is an effective modality for treating unresectable HCC with moderate side effects. ALBI scores merits consideration when applying this combined treatment modality. These results should be validated within large cohort studies.
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Affiliation(s)
- Dezuo Dong
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Xianggao Zhu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Hongzhi Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Lijuan Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Meng Wan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Shuai Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Yangzi Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Jianhao Geng
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Yongheng Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Weihu Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, China
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12
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Yan H, Wang X, Liu X, Wang P, Yu L, Zhou D, Yang Z. The survival strength of younger patients in BCLC stage 0-B of hepatocellular carcinoma: basing on competing risk model. BMC Cancer 2022; 22:185. [PMID: 35180841 PMCID: PMC8855543 DOI: 10.1186/s12885-022-09293-x] [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: 01/30/2021] [Accepted: 02/09/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The number of young patients with hepatocellular carcinoma (HCC) is increasing, but whether patients of different ages have a survival advantage is unclear. This study was conducted to investigate whether age differences in the Barcelona Clinic Liver Cancer (BCLC) classification system contribute to the long-term survival outcomes of patients with HCC. METHODS A total of 1602 patients with HCC admitted to the Beijing Ditan Hospital was included in this study. Patients were divided into younger (≤45 years) and older (> 45 years) groups. Factors determining overall survival and progression-free survival were analyzed using univariate and multivariate analyses with the Kaplan-Meier method and Cox proportional hazard regression model. We calculated the cumulative incidence function using the Fine-Gray model. The effect of mortality on age was also estimated using a restricted cubic spline. RESULTS After matching, overall survival and progression-free survival were significantly better in younger patients than in older patients with BCLC stage 0-B (p = 0.015 and p = 0.017, respectively). In BCLC stage 0-B, all-cause mortality increased with age and increased rapidly around the age of 40 years (non-linear, p < 0.05). In BCLC stages 0-B, HCC-related and non-HCC-related deaths significantly differed between younger and older individuals (p = 0.0019). CONCLUSION In stage BCLC 0-B, age affects the long-term prognosis of patients.
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Affiliation(s)
- Huiwen Yan
- Center of Integrative Medicine, Capital Medical University Affiliated Beijing Ditan Hospital, No. 8 Jing Shun East Street, Beijing, 100015, People's Republic of China.,Dongzhimen Hospital, Beijing University of Chinese Medicine, Chaoyang District, Beijing, 100029, People's Republic of China
| | - Xinhui Wang
- Center of Integrative Medicine, Capital Medical University Affiliated Beijing Ditan Hospital, No. 8 Jing Shun East Street, Beijing, 100015, People's Republic of China
| | - Xiaoli Liu
- Center of Integrative Medicine, Capital Medical University Affiliated Beijing Ditan Hospital, No. 8 Jing Shun East Street, Beijing, 100015, People's Republic of China
| | - Peng Wang
- Center of Integrative Medicine, Capital Medical University Affiliated Beijing Ditan Hospital, No. 8 Jing Shun East Street, Beijing, 100015, People's Republic of China
| | - Lihua Yu
- Center of Integrative Medicine, Capital Medical University Affiliated Beijing Ditan Hospital, No. 8 Jing Shun East Street, Beijing, 100015, People's Republic of China
| | - Dongdong Zhou
- Center of Integrative Medicine, Capital Medical University Affiliated Beijing Ditan Hospital, No. 8 Jing Shun East Street, Beijing, 100015, People's Republic of China
| | - Zhiyun Yang
- Center of Integrative Medicine, Capital Medical University Affiliated Beijing Ditan Hospital, No. 8 Jing Shun East Street, Beijing, 100015, People's Republic of China.
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13
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Yang C, Feng H, Dai C. Development and validation of an immune‐related prognosis signature associated with hypoxia and ferroptosis in hepatocellular carcinoma. Cancer Med 2022; 11:2329-2341. [PMID: 35092175 PMCID: PMC9160815 DOI: 10.1002/cam4.4556] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Revised: 01/05/2022] [Accepted: 01/06/2022] [Indexed: 12/24/2022] Open
Abstract
Background Hypoxia and ferroptosis are crucial in the occurrence and development of hepatocellular carcinoma (HCC), and they both affect the immune status of the tumor microenvironment. Previous studies have also shown a link between hypoxia and ferroptosis. Patients and methods In all, 814 HCC cases from The Cancer Genome Atlas and Gene Expression Omnibus databases were used as the discovery cohort, and 230 HCC cases from the International Cancer Genome Consortium database were used as the validation cohort. Hypoxia subtypes and ferroptosis subtypes were identified by consensus cluster analysis according to 174 hypoxia‐related genes and 193 ferroptosis‐related genes. The prognostic signature was constructed using the Cox and LASSO regression analyses, and two risk groups were identified. A comprehensive analysis of the clinical and immune characteristics between the two risk groups was further performed. Results Two hypoxia subtypes and two ferroptosis subtypes were distinguished and verified; subsequently, a five‐gene prognostic signature was constructed and the risk score could be acquired by the following formula: risk score = 0.0604*Expression (CA9)−0.0714*Expression (ANXA10) + 0.1501*Expression (CDC20)−0.0853*Expression (CYP7A1) + 0.0530*Expression (SPP1). Compared with the low‐risk group, the high‐risk group had a worse prognosis. The high‐risk group also showed a higher level of immune infiltration than the low‐risk group, and immune checkpoints were generally upregulated in the high‐risk group. The antigen presentation ability of the low‐risk group was poor, which may be related to the immune escape mechanism. Drug sensitivity analysis indicated that the high‐ and low‐risk groups were sensitive to tyrosine kinase inhibitors and chemotherapeutic drugs, respectively. Conclusion The hypoxia‐, ferroptosis‐, and immune‐associated prognostic signature we constructed could stratify patients with HCC and guide precise treatment.
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Affiliation(s)
- Chun‐Bo Yang
- Department of General Surgery Shengjing Hospital of China Medical University Shenyang Liaoning China
| | - Han‐Xin Feng
- Department of General Surgery Shengjing Hospital of China Medical University Shenyang Liaoning China
| | - Chao‐Liu Dai
- Department of General Surgery Shengjing Hospital of China Medical University Shenyang Liaoning China
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14
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Pu JL, Chen Z, Yao LQ, Feng JY, Diao YK, Guan MC, Li JD, Chen ZL, Zhou YH, Wang H, Gu WM, Li J, Li C, Wang MD, Zhu H, Liang YJ, Shen F, Pawlik TM, Lau WY, Yang T. Long-term oncological prognosis after curative-intent liver resection for hepatocellular carcinoma in the young versus the elderly: multicentre propensity score-matching study. BJS Open 2022; 6:zrab145. [PMID: 35086147 PMCID: PMC8794648 DOI: 10.1093/bjsopen/zrab145] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 12/17/2021] [Accepted: 12/20/2021] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the most common malignancy in the elderly worldwide, but it is also common among younger individuals in areas with endemic hepatitis B virus infection. The differences in long-term oncological prognosis of young versus elderly patients after R0 liver resection for HCC were explored in this study. METHODS Using a Chinese multicentre database, consecutive patients who underwent R0 liver resection for HCC between 2007 and 2019 were analysed retrospectively. After excluding middle-aged (36-69 years old) patients, overall survival (OS), cancer-specific survival (CSS), and recurrence were compared between young (35 years or younger) and elderly (70 years or older) patients using propensity score matching (PSM). RESULTS Among 531 enrolled patients, there were 192 (36.2 per cent) and 339 (63.8 per cent) patients categorized as young and elderly respectively. PSM created 140 pairs of matched patients. In the PSM cohort, 5-year OS was comparable for young versus elderly patients (51.7 versus 52.3 per cent, P = 0.533). Young patients, however, had a higher 5-year cumulative recurrence rate (62.1 versus 51.6 per cent, P = 0.011) and a worse 5-year CSS rate (54.0 versus 64.3 per cent, P = 0.034) than elderly patients. On multivariable Cox regression analyses, young patient age remained independently associated with an increased recurrence rate (hazard ratio 1.62, P = 0.016) and a decreased CSS rate (hazard ratio 1.69, P = 0.021) compared with older age. CONCLUSION Following R0 liver resection for HCC, younger patients were at a higher risk of recurrence, and elderly patients had a better CSS rate. Thus, enhanced surveillance for HCC recurrence should be implemented for young patients.
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Affiliation(s)
- Jia-Le Pu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Nantong University, Nantong, Jiangsu, China
| | - Zhong Chen
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Nantong University, Nantong, Jiangsu, China
| | - Lan-Qing Yao
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Ji-Ye Feng
- Department of Hepatobiliary & Pancreatic Surgery, The Affiliated People’s Hospital of Ningbo University, Ningbo, Zhejiang, China
| | - Yong-Kang Diao
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Ming-Cheng Guan
- Department of Medical Oncology, The First Affiliated Hospital of Soochow University, Soochow, Jiangsu, China
| | - Ju-Dong Li
- Department of Pancreatic-biliary Surgery, Changzheng Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Zheng-Liang Chen
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Ya-Hao Zhou
- Department of Hepatobiliary Surgery, Pu’er People’s Hospital, Pu’er, Yunnan, China
| | - Hong Wang
- Department of General Surgery, Liuyang People’s Hospital, Liuyang, Hunan, China
| | - Wei-Min Gu
- The First Department of General Surgery, The Fourth Hospital of Harbin, Harbin, Heilongjiang, China
| | - Jie Li
- Department of Hepatobiliary Surgery, Fuyang People’s Hospital, Fuyang, Anhui, China
| | - Chao Li
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Ming-Da Wang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Hong Zhu
- Department of Medical Oncology, The First Affiliated Hospital of Soochow University, Soochow, Jiangsu, China
| | - Ying-Jian Liang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Feng Shen
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Timothy M. Pawlik
- Department of Surgery, Ohio State University, Wexner Medical Center, Columbus, Ohio, USA
| | - Wan Yee Lau
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
- Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China
| | - Tian Yang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China
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15
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Sohn W, Chang Y, Cho YK, Hong YS, Shin H, Ryu S. Liver fibrosis scores and risk of liver-related mortality in young adults with chronic hepatitis B: A cohort study. J Viral Hepat 2022; 29:69-77. [PMID: 34582599 DOI: 10.1111/jvh.13618] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Revised: 09/21/2021] [Accepted: 09/23/2021] [Indexed: 12/14/2022]
Abstract
The predictive role of noninvasive liver fibrosis scores on liver-related mortality in patients with chronic hepatitis B below 40 years of age remains unclarified. We examined the association of liver fibrosis scores with liver-related mortality in young (<40 years) and older adults with hepatitis B virus (HBV) infection. A cohort study was performed in 21,360 HBsAg-positive Korean adults without liver cirrhosis or liver cancer at baseline who were followed up for up to 18 years. The liver fibrosis scores were determined using the fibrosis-4 score (FIB-4) and aspartate transaminase to platelet ratio index (APRI). Patients' vital status and cause of death were ascertained through the National Death Records. During a median follow-up of 10.2 years, 283 liver-related deaths were identified (liver-related mortality, 127.4/105 person-years). The liver fibrosis scores were significantly associated with increased risks of liver-related mortality; this association did not differ by age group (<40 vs. ≥40 years). The multivariable-adjusted hazard ratios with 95% confidence intervals for liver-related mortality comparing intermediate and high to low FIB-4 scores were 4.23 (1.99-9.00), and 15.16 (5.18-44.38), respectively, among individuals under 40, and 4.46 (3.03-6.56) and 22.47 (15.11-33.41), respectively, among older individuals. These associations were similar in analyses using APRI. In this cohort of HBsAg-positive individuals, the liver fibrosis scores were associated with increased risks of liver-related mortality in young and older adults. The liver fibrosis scores have a role in predicting liver mortality, even in young adults with HBV.
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Affiliation(s)
- Won Sohn
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Yoosoo Chang
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, School of Medicine, Sungkyunkwan University, Seoul, South Korea.,Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, School of Medicine, Sungkyunkwan University, Seoul, South Korea.,Department of Clinical Research Design & Evaluation, SAIHST, Sungkyunkwan University, Seoul, South Korea
| | - Yong Kyun Cho
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea.,Department of Clinical Research Design & Evaluation, SAIHST, Sungkyunkwan University, Seoul, South Korea
| | - Yun Soo Hong
- Department of Epidemiology and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
| | - Hocheol Shin
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, School of Medicine, Sungkyunkwan University, Seoul, South Korea.,Department of Family Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Seungho Ryu
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, School of Medicine, Sungkyunkwan University, Seoul, South Korea.,Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, School of Medicine, Sungkyunkwan University, Seoul, South Korea.,Department of Clinical Research Design & Evaluation, SAIHST, Sungkyunkwan University, Seoul, South Korea
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16
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Goh MJ, Kang W, Kim KM, Sinn DH, Gwak GY, Paik YH, Choi MS, Lee JH, Koh KC, Paik SW. Incidence and risk factors for development of hepatocellular carcinoma at young age in patients with chronic hepatitis B. Scand J Gastroenterol 2022; 57:70-77. [PMID: 34731072 DOI: 10.1080/00365521.2021.1988700] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Some young adults with chronic hepatitis B virus (HBV) infection might be at high risk for hepatocellular carcinoma (HCC), enough to justify regular HCC surveillance despite the young age of the patients. However, ways to identify at-risk individuals who may benefit from HCC surveillance need further evaluations. METHODS A hospital-based retrospective cohort of 2757 chronic HBV mono-infected young adults (median age: 34 years, males 66%) were analyzed. The primary outcome was young-onset HCC, defined as a diagnosis made under 40 years of age. We calculated the HCC incidence/1000 person-years in the overall cohort and pre-defined subgroups of patients assessed the independent risk factors that can be used to identify surveillance targets. RESULTS The HCC incidence was low (2.55/1000 person-years) in the overall cohort. However, the HCC incidence varied widely according to baseline characteristics: lowest among young adults with FIB-4 ≤ 0.70 (0.17/1000 person-years) and highest in young adults with radiological cirrhosis (30.7/1000 person-years). In multivariable analysis, radiological cirrhosis, the FIB-4 index, and serum HBV DNA level were independent factors associated with HCC development at a young age. Performance for prediction of young-onset HCC in radiological cirrhotic patients showed the highest specificity but sensitivity was <70%. Combination with FIB-4 index and HBV DNA levels increased sensitivity to 90%. CONCLUSION Risk stratification using FIB-4 index, HBV DNA levels, and either combining radiological cirrhosis or gender and AFP levels would be helpful to stratify young patients who would and would not benefit from regular HCC surveillance.
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Affiliation(s)
- Myung Ji Goh
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Wonseok Kang
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.,Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Sungkyunkwan University, Seoul, South Korea.,Research Institute for Future Medicine, Samsung Medicine Center, Seoul, Korea
| | - Kwang Min Kim
- Department of Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, South Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Geum-Youn Gwak
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Yong-Han Paik
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Moon Seok Choi
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Joon Hyeok Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Kwang Cheol Koh
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Seung Woon Paik
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
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17
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Diao YK, Liu JW, Wu H, Wang MD, Fan XP, Chen TH, Wang JY, Zhou YH, Gu WM, Wang H, Li J, Liang YJ, Chen ZY, Lau WY, Liang L, Li C, Zhang CW, Shen F, Huang DS, Yang T. Long-term oncologic outcomes of liver resection for hepatocellular carcinoma in adolescents and young adults: A multicenter study from a hepatitis B virus-endemic area. Am J Surg 2021; 222:751-758. [PMID: 33741185 DOI: 10.1016/j.amjsurg.2021.03.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 02/08/2021] [Accepted: 03/05/2021] [Indexed: 12/19/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is common among adolescents and young adults (AYAs) in areas with endemic hepatitis B virus infection. We sought to characterize clinical features and long-term outcomes among AYAs versus older adults (OAs) who underwent HCC resection. METHODS From a Chinese multicenter database, patients were categorized as AYA (aged 13-39 years) versus OA (aged ≥40 years). Patient clinical features, perioperative outcomes, overall survival (OS) and time-to-recurrence (TTR) were compared. Multivariable Cox-regression analyses were performed to identify the impact of age on OS and TTR. RESULTS Among 1952 patients, 354(22.2%) were AYAs. AYAs were less likely to have cirrhosis yet were likely to have advanced tumor pathological characteristics than OAs. Postoperative morbidity and mortality were comparable. Compared with OAs, AYAs had a comparable OS but a decreased TTR. Multivariable analyses identified that young age (<40 years) was independently associated with poorer TTR. CONCLUSIONS Compared with OAs, AYAs had a higher incidence of recurrence following liver resection among patients with HCC, suggesting that enhanced surveillance for postoperative recurrence may be required among AYAs.
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Affiliation(s)
- Yong-Kang Diao
- Department of Hepatobiliary Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou, Zhejiang, China; School of Clinical Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Jun-Wei Liu
- Department of Hepatobiliary Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou, Zhejiang, China; School of Clinical Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Han Wu
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Ming-Da Wang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Xin-Ping Fan
- Department of General Surgery, Pingxiang Mining Group General Hospital, Jiangxi, China
| | - Ting-Hao Chen
- Department of General Surgery, Ziyang First People's Hospital, Sichuan, China
| | - Jian-Yu Wang
- Department of General Surgery, Ziyang First People's Hospital, Sichuan, China
| | - Ya-Hao Zhou
- Department of Hepatobiliary Surgery, Pu'er People's Hospital, Yunnan, China
| | - Wei-Min Gu
- The First Department of General Surgery, The Fourth Hospital of Harbin, Heilongjiang, China
| | - Hong Wang
- Department of General Surgery, Liuyang People's Hospital, Hunan, China
| | - Jie Li
- Department of Hepatobiliary Surgery, Fuyang People's Hospital, Fuyang, Anhui, China
| | - Ying-Jian Liang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Harbin Medical University, Heilongjiang, China
| | - Zhi-Yu Chen
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Wan Yee Lau
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China; Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China
| | - Lei Liang
- Department of Hepatobiliary Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou, Zhejiang, China; School of Clinical Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Chao Li
- Department of Hepatobiliary Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou, Zhejiang, China; School of Clinical Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Cheng-Wu Zhang
- Department of Hepatobiliary Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou, Zhejiang, China
| | - Feng Shen
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Dong-Sheng Huang
- Department of Hepatobiliary Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou, Zhejiang, China; School of Clinical Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, China.
| | - Tian Yang
- Department of Hepatobiliary Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou, Zhejiang, China; School of Clinical Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, China; Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China.
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18
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Li C, Chen K, Liu X, Liu HT, Liang XM, Liang GL, Tang ST, Huo RR, Ma L, Xiang BB, Zhong JH, Li LQ. Analysis of Clinicopathological Characteristics and Prognosis of Young Patients with Hepatocellular Carcinoma after Hepatectomy. J Clin Transl Hepatol 2020; 8:285-291. [PMID: 33083251 PMCID: PMC7562805 DOI: 10.14218/jcth.2020.00021] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Revised: 06/26/2020] [Accepted: 07/17/2020] [Indexed: 01/27/2023] Open
Abstract
Background and Aims: This study was designed to analyze the effects of age and clinicopathological characteristics on prognosis of Chinese patients with hepatocellular carcinoma (HCC). Methods: The clinical data of 2032 HCC patients who were first diagnosed with HCC and underwent curative hepatectomy in our hospital between January 2006 and January 2011 were retrospectively analyzed. Results: Younger HCC patients (age <40 years, n=465) had a significantly higher hepatitis B infection rate, larger tumors, higher alpha-fetoprotein levels, higher preoperative liver function, and more frequent vascular invasions than older patients. Most younger patients were suitable for anatomical hepatectomy, and their tumors were found to be at a highly advanced stage. The recurrence-free survival and overall survival rates of younger HCC patients were significantly worse than those of older patients but this difference disappeared after propensity score matching. Multivariate analysis of pre-matched samples showed that age ≤40 years was one of the independent risk factors associated with poor overall survival. Conclusions: Younger patients showed different clinicopathological characteristics than older patients, such as higher rates of hepatitis B infection and advanced tumors. The recurrence-free survival and overall survival rates of younger HCC patients after hepatectomy may be similar to those of older patients.
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Affiliation(s)
- Chuan Li
- Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Kang Chen
- Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Xu Liu
- Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Hao-Tian Liu
- Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Xiu-Mei Liang
- Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Guang-Lan Liang
- Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Shao-Tong Tang
- Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Rong-Rui Huo
- Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Liang Ma
- Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Bang-Be Xiang
- Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Jian-Hong Zhong
- Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Le-Qun Li
- Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
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Zeng J, Lin K, Liu H, Huang Y, Guo P, Zeng Y, Zeng J, Liu J. Prognosis Factors of Young Patients Undergoing Curative Resection for Hepatitis B Virus-Related Hepatocellular Carcinoma: A Multicenter Study. Cancer Manag Res 2020; 12:6597-6606. [PMID: 32848453 PMCID: PMC7425652 DOI: 10.2147/cmar.s261368] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2020] [Accepted: 06/30/2020] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND The prognosis of young and older patients with hepatocellular carcinoma (HCC) is controversial. We aim to compare the clinicopathological features and prognosis of young (age ≤40 years) versus older patients (aged >40 years) with hepatitis B virus (HBV)-related HCC after curative resection. METHODS A total of 4504 patients with HBV-related HCC who underwent curative resection were included in this study and divided into young group (n=699) and older group (n=3805). Subgroup analyses were conducted to compare. Independent risk factors were identified by Cox regression analysis. RESULTS Young patients had better ALBI grade, lower rates of liver cirrhosis, higher rates of elevated serum AFP levels, larger tumor size, higher rates of microvascular invasion and macrovascular invasion, higher rates of Edmondson grade III-IV, lower rates of tumor capsular, more advanced AJCC TNM stages and more advanced BCLC stages than older patients (All p<0.05). Meanwhile, young patients had a worse overall survival (OS) rate (p=0.0091) and a worse recurrence-free survival (RFS) rate (p=0.045) than older patients. Multivariate analysis revealed that AFP, resection margin, tumor size, tumor capsular, and macrovascular invasion were associated with OS. The independent risk factors associated with RFS were ALB, tumor size, microvascular invasion, and macrovascular invasion. CONCLUSION Young patients had better liver function, more aggressive tumor characteristics, and worse prognosis than older patients. A tumor size of ≥5 cm and macrovascular invasion were associated with poor OS and RFS in young patients. If tumors could be detected at the early stage by more frequent surveillance, long-term survival can be expected in the young patients.
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Affiliation(s)
- Jianxing Zeng
- Department of Hepatic Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou350025, People’s Republic of China
- The First Affiliated Hospital of Fujian Medical University, Fuzhou350005, People’s Republic of China
- The Liver Center of Fujian Province, Fujian Medical University, Fuzhou350025, People’s Republic of China
| | - Kongying Lin
- Southeast Big Data Institute of Hepatobiliary Health, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou350025, People’s Republic of China
| | - Huocheng Liu
- Department of Hepatic Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou350025, People’s Republic of China
| | - Yao Huang
- Department of Hepatic Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou350025, People’s Republic of China
- The First Affiliated Hospital of Fujian Medical University, Fuzhou350005, People’s Republic of China
- The Liver Center of Fujian Province, Fujian Medical University, Fuzhou350025, People’s Republic of China
| | - Pengfei Guo
- Southeast Big Data Institute of Hepatobiliary Health, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou350025, People’s Republic of China
| | - Yongyi Zeng
- Department of Hepatic Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou350025, People’s Republic of China
- The First Affiliated Hospital of Fujian Medical University, Fuzhou350005, People’s Republic of China
- The Liver Center of Fujian Province, Fujian Medical University, Fuzhou350025, People’s Republic of China
| | - Jinhua Zeng
- Department of Hepatic Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou350025, People’s Republic of China
- The First Affiliated Hospital of Fujian Medical University, Fuzhou350005, People’s Republic of China
- The Liver Center of Fujian Province, Fujian Medical University, Fuzhou350025, People’s Republic of China
| | - Jingfeng Liu
- Department of Hepatic Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou350025, People’s Republic of China
- The First Affiliated Hospital of Fujian Medical University, Fuzhou350005, People’s Republic of China
- The Liver Center of Fujian Province, Fujian Medical University, Fuzhou350025, People’s Republic of China
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Wang W, Chen Q, Iwamoto Y, Han X, Zhang Q, Hu H, Lin L, Chen YW. Deep Learning-Based Radiomics Models for Early Recurrence Prediction of Hepatocellular Carcinoma with Multi-phase CT Images and Clinical Data. ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. ANNUAL INTERNATIONAL CONFERENCE 2020; 2019:4881-4884. [PMID: 31946954 DOI: 10.1109/embc.2019.8856356] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common malignancy in the world and the second most common cause of cancer-related death. By surgically removing hepatocellular carcinoma, the patients may have the early recurrence within one year. Recently, CT radiomics signatures have been demonstrated to be effective on predicting early recurrence of HCC. However, the radiomics signatures are based on hand-crafted low-level features, such as density and texture. In this paper, we propose a deep learning-based radiomics approach for predicting early recurrence of hepatocellular carcinoma with multi-phase computed tomography (CT) images. We also propose several models to combine the high-level radiomics features with clinical data to improve the prediction accuracy. The area under the curve (AUC) of receiver operating characteristic curve (ROC) is 0.825.
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Baek MY, Yoo JJ, Jeong SW, Jang JY, Kim YK, Jeong SO, Lee SH, Kim SG, Cha SW, Kim YS, Cho YD, Kim HS, Kim BS, Kim YJ, Park SY. Clinical outcomes of patients with a single hepatocellular carcinoma less than 5 cm treated with transarterial chemoembolization. Korean J Intern Med 2019; 34:1223-1232. [PMID: 30360019 PMCID: PMC6823578 DOI: 10.3904/kjim.2018.058] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2018] [Accepted: 05/21/2018] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND/AIMS Transarterial chemoembolization (TACE) is performed for single hepatocellular carcinoma (HCC) that are not eligible for surgery or ablation therapy. We investigated the clinical outcomes of patients with a single HCC ≤ 5 cm treated with TACE. METHODS This study analyzed 175 consecutive patients who underwent TACE as an initial treatment for single HCC ≤ 5 cm. Predictive factors for complete response (CR), recurrence after CR, and overall survival (OS) were evaluated. RESULTS Total 119 patients (68%) achieved CR after TACE. Tumor size < 3 cm and hepatitis B virus infection were significant predictors of CR (p < 0.05). Recurrent HCC was detected in 73 patients (61.3%) after CR. Age > 65 years and absence of liver cirrhosis were predictive factors for non-recurrence after CR (p < 0.05). The OS for all patients was 80.7 ± 5.6 months, and the 1-, 3-, and 5-year OS rates were 88.1%, 64.8%, and 49.9%, respectively. In multivariate analysis for OS, CR (hazard ratio [HR], 0.467; 95% confidence interval [CI], 0.292 to 0.747) and Child class A (HR, 0.390; 95% CI, 0.243 to 0.626) were significant factors. The OS for the CR and Child class A group were 92 and 93.6 months, respectively, and that of the non-CR and Child B, C group were 53.3 and 50.7 months, respectively (p < 0.001). CONCLUSION TACE can be a valid treatment in patients with a single HCC ≤ 5 cm not suitable for curative treatment, especially in patients with Child class A and CR after TACE.
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Affiliation(s)
- Min Young Baek
- Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Seoul, Korea
| | - Jeong-Ju Yoo
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Soung Won Jeong
- Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Seoul, Korea
- Correspondence to Soung Won Jeong, M.D. Department of Internal Medicine, Institute for Digestive Research and Digestive Disease Center, Soonchunhyang University Seoul Hospital, 59 Daesagwan-ro, Yongsan-gu, Seoul 04401, Korea Tel: +82-2-710-3076 Fax: +82-2-709-9696 E-mail:
| | - Jae Young Jang
- Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Seoul, Korea
| | - Yong Kwon Kim
- Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Seoul, Korea
| | - Shin Ok Jeong
- Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Seoul, Korea
| | - Sae Hwan Lee
- Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Korea
| | - Sang Gyune Kim
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Sang-Woo Cha
- Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Seoul, Korea
| | - Young Seok Kim
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Young Deok Cho
- Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Seoul, Korea
| | - Hong Soo Kim
- Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Korea
| | - Boo Sung Kim
- Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Seoul, Korea
| | - Yong Jae Kim
- Department of Radiology, Soonchunhyang University Seoul Hospital, Seoul, Korea
| | - Su Yeon Park
- Department of Biostatistics, Soonchunhyang University Seoul Hospital, Seoul, Korea
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High Expression of MicroRNA-196a is Associated with Progression of Hepatocellular Carcinoma in Younger Patients. Cancers (Basel) 2019; 11:cancers11101549. [PMID: 31614906 PMCID: PMC6826650 DOI: 10.3390/cancers11101549] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Revised: 10/10/2019] [Accepted: 10/11/2019] [Indexed: 12/24/2022] Open
Abstract
MicroRNAs are small RNAs involved in various biological processes and cancer metastasis. miR-196a was associated with aggressive behaviors in several cancers. The role of miR-196a in hepatocellular carcinoma (HCC) metastasis remains unknown. This study aimed to examine the role of miR-196a in HCC progression. Expression of miR-196a was measured in 83 human HCC samples. The HCC patients with high miR-196a expression had younger ages, lower albumin levels, higher frequency with alpha-fetoprotein (AFP) levels ≥20 ng/mL, more macrovascular invasion, and non-early stages. Kaplan-Meier analysis showed that high miR-196a expression was associated with lower recurrence-free survival. Knockdown of miR-196a decreased transwell invasiveness, sphere formation, transendothelial invasion, and Slug, Twist, Oct4, and Sox2 expression, suppressed angiogenesis, and reduced sizes of xenotransplants and number of pulmonary metastasis. Down-regulation of miR-196a decreased Runx2 and osteopontin (OPN) levels. Knockdown of Runx2 in vitro resulted in comparable phenotypes with miR-196a down-regulation. Restoration of Runx2 in miR-196a-knockdown HCC reverted tumor phenotypes. This study showed that high expression of miR-196a is associated with HCC progression in a subset of younger patients. miR-196a mediates HCC progression via upregulation of Runx2, OPN, epithelial-mesenchymal transition (EMT) regulators, and stemness genes. We proposed that miR-196a can be used as a prognostic marker and a potential therapeutic target.
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A nomogram predicting the prognosis of young adult patients diagnosed with hepatocellular carcinoma: A population-based analysis. PLoS One 2019; 14:e0219654. [PMID: 31295310 PMCID: PMC6623961 DOI: 10.1371/journal.pone.0219654] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2019] [Accepted: 06/28/2019] [Indexed: 02/08/2023] Open
Abstract
Background Few studies have reported the clinical characteristics and outcomes of young adult patients diagnosed with hepatocellular carcinoma (HCC). This study aimed to formulate a nomogram to predict the prognosis of young adult HCC patients. Methods Young adult patients diagnosed with HCC from 2004 to 2015 were screened from the Surveillance, Epidemiology, and End Results (SEER) database. Based on the multivariate analysis results, a nomogram was constructed. The concordance index (c-index) and calibration were used to assess the predictive performance of the nomogram. The clinical benefit was measured by using decision curve analysis (DCA). Results The mean follow-up time of the patients was 25.0±34.0 months. Gender, race, AFP level, Edmondson–Steiner classification, treatment and TNM stage were selected as independent prognostic factors and integrated into the nomogram. The c-indexes of the two sets were 0.786 and 0.775, respectively. The calibration curves showed good agreement between the nomogram-predicted probability and the actual observations. Furthermore, the DCA indicated that the nomogram had positive net benefits compared with the conventional staging system. Conclusions The nomogram could accurately predict the prognosis of young adult HCC patients.
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Sinn DH, Kang D, Kang M, Paik SW, Guallar E, Cho J, Gwak GY. Late presentation of hepatitis B among patients with newly diagnosed hepatocellular carcinoma: a national cohort study. BMC Cancer 2019; 19:286. [PMID: 30922251 PMCID: PMC6440099 DOI: 10.1186/s12885-019-5508-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2018] [Accepted: 03/22/2019] [Indexed: 01/16/2023] Open
Abstract
Background Recently, the concept of “late presentation with viral hepatitis” was introduced to help quantify the proportion of patients missing timely diagnosis and treatment for viral hepatitis. The clinical implications of late presentation of hepatitis B at the population level, however, are largely unexplored. Methods Using newly-diagnosed hepatitis B related hepatocellular carcinoma (HCC) patients (N = 1276) from the Korean National Health Insurance Service-National Sample Cohort, a nationally representative cohort study was conducted between 2002 and 2013. HCC patients were classified into 3 groups: late presentation of hepatitis B (no prior clinic visits for hepatitis B before HCC diagnosis), irregular visits (irregular pattern of outpatient clinic visits), and regular visits (regular pattern of outpatient clinic visits). Results The proportion of patients with late presentation decreased from 50.8% in 2003 to 23.1% in 2013. In multivariable analysis compared with patients in the regular visits group, patients with late presentation were more likely to be younger and to be in lower income percentiles. After adjusting for age, sex, year of HCC diagnosis, income percentile, and initial treatment, the hazard ratios (95% confidence intervals) for all-cause mortality comparing the late presentation and irregular visits groups to the regular visits group were 1.76 (1.42–2.18) and 1.31 (1.06–1.61), respectively. Conclusion Timely diagnosis and treatment for hepatitis B related HCC was suboptimal at the population level. More intensive strategies to minimize late presentation for hepatitis B are needed, with special attention to younger people and lower income levels.
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Affiliation(s)
- Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea
| | - Danbee Kang
- Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea
| | - Minwoong Kang
- Center for Clinical Epidemiology, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea
| | - Seung Woon Paik
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea
| | - Eliseo Guallar
- Center for Clinical Epidemiology, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea.,Departments of Epidemiology and Medicine and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institution, Baltimore, MD, USA
| | - Juhee Cho
- Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea. .,Center for Clinical Epidemiology, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea. .,Departments of Epidemiology and Medicine and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institution, Baltimore, MD, USA.
| | - Geum-Youn Gwak
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea.
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Shen J, Li C, Yan L, Li B, Xu M, Yang J, Wang W, Wen T. Short- and Long-term Outcomes between Young and Older HCC Patients Exceeding The Milan Criteria after Hepatectomy. Ann Hepatol 2018; 17:134-143. [PMID: 29311397 DOI: 10.5604/01.3001.0010.7545] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
AIM The objective of this study was to evaluate short- and long-term survival after surgical treatment between young and older hepatocellular carcinoma (HCC) patients beyond the Milan criteria. MATERIAL AND METHODS One hundred fifty-seven HCC patients (≤ 55 years old) were categorized into group A, and one hundred fifty-eight HCC patients (> 55 years old) were categorized into group B. Postoperative complications and overall survival were retrospectively analyzed. RESULTS Older HCC patients had a higher rate of delayed extubation after surgery and suffered more complications after surgery, especially major complications. Intraoperative blood transfusion, liver fibrosis/cirrhosis and delayed extubation were risk factors related to postoperative complications. Microvascular invasion (MVI), tumor diameter, postoperative alpha-fetoprotein and the presence of satellites were independent risk factors for long-term survival. Young patients had more advanced tumors. Overall survival rates at 1, 3 and 5-years were 78.1%, 45.1% and 27.4% for young patients, respectively, and 86.5%, 57.5% and 42.4% for older patients, respectively (p = 0.007). CONCLUSION The category A group had poorer tumor characteristics and worse prognoses than the category B group.
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Affiliation(s)
- Junyi Shen
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University. China
| | - Chuan Li
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University. China
| | - Lvnan Yan
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University. China
| | - Bo Li
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University. China
| | - Mingqing Xu
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University. China
| | - Jiayin Yang
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University. China
| | - Wentao Wang
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University. China
| | - Tianfu Wen
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University. China
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Mehinovic L, Islamagic E, Husic-Selimovic A, Kurtovic-Kozaric A, Vukobrat-Bijedic Z, Suljevic D. Evaluation of Diagnostic Efficiency of Alpha-Fetoprotein in Patients with Liver Cirrhosis and Hepatocellular Carcinoma: Single-Center Experience. Open Access Maced J Med Sci 2018; 6:1668-1673. [PMID: 30337985 PMCID: PMC6182518 DOI: 10.3889/oamjms.2018.344] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2018] [Revised: 08/22/2018] [Accepted: 08/28/2018] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND AFP serum levels are considered as diagnostic and specific for hepatocellular carcinoma (HCC) in patients with liver cirrhosis (LC). AIM This study aimed to examine the diagnostic value of AFP in the distinguishing of patients with HCC from patients with LC, and to analyse the potential correlation between AFP levels and liver disease stages. MATERIAL AND METHODS Fifty patients with LC and fifty patients with HCC were included in this study. The majority of the patients were males, while the HBV aetiology was dominant. RESULTS Significant differences between LC and HCC patients were detected for AST, ALT, GGT, bilirubin, AFP and AP. Patients with HCC had higher AFP values compared to LC. There was no significant correlation between the size of the tumour lesion and serum AFP levels. A positive correlation between AFP concentration and GGT activity was determined, as was the negative correlation between AFP and age of the subjects. The AFP value of 23.34 ng/m showed high sensitivity (84%) and specificity (82%). CONCLUSION The size of the surface below the ROC curve (AUC) was 0.877 (0.80-0.95), which makes AFP a good biomarker and this diagnostic test is sufficient to separate patients with HCC and LC.
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Affiliation(s)
- Lejla Mehinovic
- Department of Biology, Faculty of Science, University of Sarajevo, Sarajevo, Bosnia and Herzegovina
| | - Erna Islamagic
- Department of Biology, Faculty of Science, University of Sarajevo, Sarajevo, Bosnia and Herzegovina
| | - Azra Husic-Selimovic
- Clinic for Gastroenterohepatology, Clinical Center of the University of Sarajevo, Sarajevo, Bosnia and Herzegovina
| | - Amina Kurtovic-Kozaric
- Department of Clinical Pathology, Cytology and Human Genetics, Clinical Center of the University of Sarajevo, Sarajevo, Bosnia and Herzegovina
| | | | - Damir Suljevic
- Department of Biology, Faculty of Science, University of Sarajevo, Sarajevo, Bosnia and Herzegovina
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Role of liver resection in treating intermediate and advanced stage adolescent and young adult hepatocellular carcinoma patients: A propensity-matching cohort study. Int J Surg 2018; 54:259-264. [PMID: 29602016 DOI: 10.1016/j.ijsu.2018.03.051] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2017] [Revised: 01/22/2018] [Accepted: 03/21/2018] [Indexed: 01/27/2023]
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Song P, Cai Y, Tang H, Li C, Huang J. The clinical management of hepatocellular carcinoma worldwide: A concise review and comparison of current guidelines from 2001 to 2017. Biosci Trends 2018; 11:389-398. [PMID: 28904327 DOI: 10.5582/bst.2017.01202] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the second leading cause of cancer-related mortality worldwide. In this review, we made a review on current guidelines published from January 2001 to June 2017 worldwide with a focus on the clinical management of HCC. The electronic databases MEDLINE, the Chinese SinoMed, and the Japanese CiNii were systematically searched. A total of 18 characteristic guidelines for HCC management were finally included, including 8 guidelines from Asia, 5 from Europe, and 5 from the United States of America (USA). If guidelines were published in multiple versions, the most recent update was included, and surveillance, diagnosis, and treatment were compared. The composition of and recommendations in current guidelines on HCC varied, so these guidelines were regrouped and diagnostic and treatment algorithms were summarized graphically to provide the latest information to clinicians. The diagnostic criteria were grouped into 2 categories of a "Size-based pathway" and a "Non-size-based pathway." The treatment criteria were divided into 4 categories: i) Criteria based on the Barcelona Clinic Liver Cancer staging system; ii) Criteria based on the modified Union of International Cancer Control staging system; iii) Criteria based on the Child-Pugh class of liver function; and iv) Criteria based on tumor resectability. Findings from comparison of current guidelines might help target and concentrate efforts to improve the clinical management of HCC. However, further studies are needed to improve the management and outcomes of HCC. More straightforward or refined guidelines would help guide doctors to make better decisions in the treatment of HCC in the future.
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Affiliation(s)
- Peipei Song
- Graduate School of Frontier Sciences, The University of Tokyo
| | - Yulong Cai
- Department of Bile Duct Surgery, West China Hospital, Sichuan University
| | - Haowen Tang
- Hospital and Institute of Hepatobiliary Surgery, Chinese PLA General Hospital
| | - Chuan Li
- Department of Liver Surgery, Liver Transplantation Division, West China Hospital, Sichuan University
| | - Jiwei Huang
- Department of Liver Surgery, Liver Transplantation Division, West China Hospital, Sichuan University
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Ang C, Shields A, Xiu J, Gatalica Z, Reddy S, Salem ME, Farhangfar C, Hwang J, Astsaturov I, Marshall JL. Molecular characteristics of hepatocellular carcinomas from different age groups. Oncotarget 2017; 8:101591-101598. [PMID: 29254188 PMCID: PMC5731898 DOI: 10.18632/oncotarget.21353] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2017] [Accepted: 08/31/2017] [Indexed: 01/01/2023] Open
Abstract
While most patients in Western countries who are diagnosed with HCC are in their 50s and 60s, HCCs diagnosed at extremes of the age spectrum (i.e., < 40 years and ≥ 75 years) are less common and have been linked with distinct geographic locations and etiologies. Using multiplatform profiling, we identified differences in genetic alterations and protein expression in different age groups within a large cohort of HCC patients (N = 421). Young adult HCC patients (18-39 years' old) were more likely to be female, living in the West and Midwestern United States, and showed decreased androgen receptor, drug resistance and pro-angiogenic protein expression compared to older patients. TP53 mutations were the most frequent alteration in young adults (19%), whereas CTNNB1 mutations occurred in 30-33% of patients ≥ 40 years' old. The overall frequency of pathogenic and presumed pathogenic mutations was observed to increase significantly with advancing age. To our knowledge, these data represent one of the only studies to analyze age-specific molecular profiles in HCC, and provide a basis for further exploration and validation of these findings with respect to their clinical and therapeutic implications.
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Affiliation(s)
- Celina Ang
- Department of Medicine, Hematology/Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Anthony Shields
- Department of Oncology, Molecular Imaging & Diagnostics Program, Karmanos Cancer Center, Wayne State University, Detroit, MI, USA
| | - Joanne Xiu
- Department of Medical Affairs, Caris Life Sciences, Phoenix, AZ, USA
| | - Zoran Gatalica
- Department of Pathology, Caris Life Sciences, Phoenix, AZ, USA
| | - Sandeep Reddy
- Department of Medical Affairs, Caris Life Sciences, Phoenix, AZ, USA
| | - Mohamed E Salem
- Hematology/Oncology, Lombardi Comprehensive Cancer Center, Georgetown, University, Washington, DC, USA
| | - Carol Farhangfar
- Levine Cancer Institute, Carolinas Healthcare System, Charlotte, NC, USA
| | - Jimmy Hwang
- Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA
| | - Igor Astsaturov
- Department of Medical Affairs, Caris Life Sciences, Phoenix, AZ, USA.,Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA
| | - John L Marshall
- Hematology/Oncology, Lombardi Comprehensive Cancer Center, Georgetown, University, Washington, DC, USA
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Guo H, Wu T, Lu Q, Dong J, Ren YF, Nan KJ, Lv Y, Zhang XF. Hepatocellular carcinoma in elderly: Clinical characteristics, treatments and outcomes compared with younger adults. PLoS One 2017; 12:e0184160. [PMID: 28886106 PMCID: PMC5590882 DOI: 10.1371/journal.pone.0184160] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2017] [Accepted: 08/18/2017] [Indexed: 12/13/2022] Open
Abstract
The number of elderly patients diagnosed with hepatocellular carcinoma (HCC) is expected to increase. The present study aims to evaluate the role of age on treatments and outcome of HCC patients. 1530 patients firstly diagnosed with HCC were retrospectively included and classified as older (≥65 years, n = 318, 21%) and younger patients (<65 years, n = 1212, 79%). The two groups were compared with clinical characteristics, tumor burden, Barcelona Clinics Liver Cancer (BCLC) stage, treatments and long-term prognosis. Elderly patients were more HCV infected, had more diabetes, poorer performance status, and were less aggressively treated. The proportion of HCC within BCLC stage 0-A, B or C was similar between the two groups, but elderly patients were more presented with BCLC stage D. The overall survival of older patients was poorer compared to younger patients before and after propensity score matching. However, elderly patients were less often effectively treated with surgery and loco-regional therapies across different BCLC stages. After stratified by BCLC stages or treatments, older patients showed comparable long-term outcome to younger patients. Performance status, BCLC stages and effective treatments, rather than age, was independent factors determining prognosis in the whole cohort and only elderly patients by multivariate analysis. In conclusion, older could have comparable survival to younger patients within the same tumor stage or after similar treatments. Thus, equally active treatments should be encouraged to elderly patients.
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Affiliation(s)
- Hui Guo
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Department of Oncology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Tao Wu
- Department of Oncology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Qiang Lu
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Institute of Advanced Surgical Technology and Engineering, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, China
| | - Jian Dong
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Institute of Advanced Surgical Technology and Engineering, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, China
| | - Yi-Fan Ren
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Institute of Advanced Surgical Technology and Engineering, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, China
| | - Ke-Jun Nan
- Department of Oncology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Yi Lv
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Institute of Advanced Surgical Technology and Engineering, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, China
| | - Xu-Feng Zhang
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Institute of Advanced Surgical Technology and Engineering, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, China
- * E-mail:
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CT-based radiomics signature: a potential biomarker for preoperative prediction of early recurrence in hepatocellular carcinoma. Abdom Radiol (NY) 2017; 42:1695-1704. [PMID: 28180924 DOI: 10.1007/s00261-017-1072-0] [Citation(s) in RCA: 161] [Impact Index Per Article: 20.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
PURPOSE To develop a CT-based radiomics signature and assess its ability for preoperatively predicting the early recurrence (≤1 year) of hepatocellular carcinoma (HCC). METHODS A total of 215 HCC patients who underwent partial hepatectomy were enrolled in this retrospective study, and all the patients were followed up at least within 1 year. Radiomics features were extracted from arterial- and portal venous-phase CT images, and a radiomics signature was built by the least absolute shrinkage and selection operator (LASSO) logistic regression model. Preoperative clinical factors associated with early recurrence were evaluated. A radiomics signature, a clinical model, and a combined model were built, and the area under the curve (AUC) of operating characteristics (ROC) was used to explore their performance to discriminate early recurrence. RESULTS Twenty-one radiomics features were chosen from 300 candidate features to build a radiomics signature that was significantly associated with early recurrence (P < 0.001), and they presented good performance in the discrimination of early recurrence alone with an AUC of 0.817 (95% CI: 0.758-0.866), sensitivity of 0.794, and specificity of 0.699. The AUCs of the clinical and combined models were 0.781 (95% CI: 0.719-0.834) and 0.836 (95% CI: 0.779-0.883), respectively, with the sensitivity being 0.784 and 0.824, and the specificity being 0.619 and 0.708, respectively. Adding a radiomics signature into conventional clinical variables can significantly improve the accuracy of the preoperative model in predicting early recurrence (P = 0.01). CONCLUSIONS The radiomics signature was a significant predictor for early recurrence in HCC. Incorporating radiomics signature into conventional clinical factors performed better for preoperative estimation of early recurrence than with clinical variables alone.
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Prognostic nomogram for hepatocellular carcinoma in adolescent and young adult patients after hepatectomy. Oncotarget 2017; 8:106393-106404. [PMID: 29290957 PMCID: PMC5739742 DOI: 10.18632/oncotarget.18192] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2017] [Accepted: 04/11/2017] [Indexed: 02/05/2023] Open
Abstract
Background Hepatocellular carcinoma (HCC) was rarely discussed in adolescent and young adult (AYA) patients. This study aimed to discuss the character of AYA HCC patients and establish an effective prognostic nomogram for patients after hepatectomy. Results For all of the patients, the median OS was 57 months with 5-year OS rate 60.4%, and DFS was 48 months with 5-year DFS rate 51.4%. The tumor size, vascular invasion status and the pathological differentiation were the independent predictors for both OS and DFS. Except for that, gender, Neutrophil-lymphocyte ratio, HbeAg, and α-Fetoprotein were the predictors for OS. The c-index for OS prognostic nomogram was 0.75 (95% CI, 0.71 to 0.79), and c-index was 0.70 (95% CI, 0.66 to 0.74) for DFS prognostic nomogram, which was better than American Joint Commission on Cancer 2002 and 2010, Okuda staging system, the Japanese Integrated Staging system, and Tokyo staging system. Materials And Methods This study was based on 423 AYA HCC patients (younger than 40 years old) undergoing hepatectomy in West China Hospital between 2008 to 2014. Based on the multivariate risk factors, the nomogram was constructed for predict the possibility for overall survival (OS) and disease-free survival (DFS) rate. Harrel’s concordance index (c-index) was used to compare the predictive accuracy and discriminative ability between the nomogram and eight contemporary staging systems. Conclusions Our prognostic nomogram could accurately and preciously provide individual prediction for AYA HCC patients in OS and DFS after hepatectomy.
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Thomas SM, Moke D, Lopez R, Hanna R, Kabbany MN, Alkhouri N. Liver Transplantation for Hepatocellular Carcinoma in Young Adults: A United Network for Organ Sharing Study. J Adolesc Young Adult Oncol 2016; 6:286-293. [PMID: 27996360 DOI: 10.1089/jayao.2016.0048] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
PURPOSE Orthotopic liver transplantation (OLT) is curative for hepatocellular carcinoma (HCC). HCC is typically a disease of older adults (OAs); therefore, characteristics and outcomes of OLT for young adults (YAs) (ages 18-40) are not described. The objective of this study was to assess the characteristics and outcomes of YAs with HCC receiving OLT and compare these to OAs (ages >40 years). METHODS YAs with HCC who had OLT from the United Network for Organ Sharing (UNOS) database were included in this study. As a comparison group, OAs with HCC were matched 4:1 to the YA group. Descriptive statistics of demographics, comorbidities, and outcomes were generated. Kaplan-Meier product limit estimates were used to assess patient and graft survival. Conditional logistic regression and Cox proportional hazards frailty models were used to compare the groups. RESULTS A total of 464 YAs received OLT for HCC. The most common underlying liver diseases were hepatitis C virus (21.3%), hepatitis B virus (HBV, 15.5%), and autoimmune/cholestatic disease (12.3%). An increased number of YAs received OLT for HCC after implementation of model for end-stage liver disease scoring. One thousand two hundred eighty OAs served as the comparison group. Post-transplant 5-year survival was 73.1% in YAs with a retransplantation rate of 7.8%. In OAs, survival and retransplantation rates were lower (68.6% p = 0.093; 4.3% p = 0.001). CONCLUSION Four hundred sixty-four YAs with HCC received OLT in the UNOS database. Compared to the older population, survival and retransplantation rates were higher. HBV, which is vaccine preventable, is a frequent contributor to HCC in YAs.
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Affiliation(s)
- Stefanie M Thomas
- 1 Children's Center for Cancer and Blood Disease , Children's Hospital Los Angeles, Los Angeles, California
- 2 Division of Hematology, Oncology and Blood and Marrow Transplantation, Department of Pediatrics, Keck School of Medicine, University of Southern California , Los Angeles, California
| | - Diana Moke
- 1 Children's Center for Cancer and Blood Disease , Children's Hospital Los Angeles, Los Angeles, California
| | - Rocio Lopez
- 3 Department of Quantitative Health Sciences, Cleveland Clinic , Cleveland, Ohio
| | - Rabi Hanna
- 4 Department of Pediatric Hematology, Oncology and Blood and Marrow Transplantation, Cleveland Clinic Children's , Cleveland, Ohio
| | - Mohammad Nasser Kabbany
- 5 Department of Pediatric Gastroenterology and Hepatology, Cleveland Clinic , Cleveland, Ohio
| | - Naim Alkhouri
- 5 Department of Pediatric Gastroenterology and Hepatology, Cleveland Clinic , Cleveland, Ohio
- 6 Digestive Disease Institute , Cleveland Clinic, Cleveland, Ohio
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Ha SY, Sohn I, Hwang SH, Yang JW, Park CK. The prognosis of hepatocellular carcinoma after curative hepatectomy in young patients. Oncotarget 2016; 6:18664-73. [PMID: 26093092 PMCID: PMC4621918 DOI: 10.18632/oncotarget.4330] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2015] [Accepted: 05/26/2015] [Indexed: 01/28/2023] Open
Abstract
Age at diagnosis is a reported prognostic factor in a variety of solid cancers. In hepatocellular carcinomas (HCCs), several previous studies focused on patient age, but demonstrated inconclusive results on prognosis of young patients. Clinical outcome may differ according to the balance between tumor's own biologic behavior and underlying liver function thus explaining the inconclusive results in previous studies. In this study, we enrolled 282 patients who underwent curative hepatectomy for primary HCCs and had Child Pugh Class A, representing good liver function. Clinicopathologic features were compared between patients aged ≤40 years (young age group) and those aged >40 years (old age group). Thirty-five patients (12.4%) were classified as the young age group and showed larger tumor size (>5cm), higher Edmondson grade, more frequent intrahepatic metastasis and higher alpha-fetoprotein level (>200ng/mL) than old age group. Young age group showed shorter disease specific survival than the old age group. Symptomatic presentation without surveillance was more frequent in the young age group than old age group (45.7% vs. 23.9%). In gene expression profiling analysis, 69 differentially expressed genes between young and old age groups were generated and these genes were mostly associated with cell cycle or cell division. Mitotic rate was significantly higher in HCCs of young patients than those of old patients. In conclusion, HCCs in young patients have distinct clinicopathologic features. Poor prognosis in the young age group could be explained by late detection as well as their own aggressive tumor biology.
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Affiliation(s)
- Sang Yun Ha
- Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Insuk Sohn
- Biostatistics and Clinical Epidemiology Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Korea
| | - Soo Hyun Hwang
- Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jung Wook Yang
- Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Cheol-Keun Park
- Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Chen QW, Teng WJ, Chen Q. Chest wall hernia induced by high intensity focused ultrasound treatment of unresectable massive hepatocellular carcinoma: A case report. Oncol Lett 2016; 12:627-630. [PMID: 27347191 DOI: 10.3892/ol.2016.4618] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2015] [Accepted: 02/11/2016] [Indexed: 12/20/2022] Open
Abstract
In the present study, a case of unresectable massive hepatocellular carcinoma (HCC) treated with high intensity focused ultrasound (HIFU) alone is reported. Although the treatment induced chest wall hernia, its efficacy in treating the HCC was demonstrated. The medical records of a patient with an unresectable massive tumor that was effectively treated with serial HIFU ablation were retrospectively studied. Chest wall hernia was detected as a complication of the HIFU treatment, which has not been reported thus far in the literature. The patient has survived for 44 months since the first diagnosis in September 2010. Treatment resulted in partial remission of the tumor, pain relief, decreased levels of alpha-fetoprotein and chest wall hernia, as a complication. Therefore, HIFU may be an effective approach for the treatment of unresectable HCC, although it may occasionally cause complications.
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Affiliation(s)
- Qi-Wen Chen
- Department of Integrated Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China
| | - Wen-Jing Teng
- Cancer Center, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai 200041, P.R. China
| | - Qian Chen
- Department of Obstetrics of Chongqing Haifu Hospital, Non-Invasive and Minimally Invasive Therapeutic Research Center for Uterine Benign Diseases of Chongqing, Chongqing 401121, P.R. China
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Lee JS, Kim JM, Lee S, Choi JY, Cho W, Choi GS, Park JB, Kwon CHD, Kim SJ, Joh JW. The prognosis in cases of hepatocellular carcinoma after hepatectomy: young patients versus older patients. KOREAN JOURNAL OF HEPATO-BILIARY-PANCREATIC SURGERY 2015; 19:154-60. [PMID: 26693234 PMCID: PMC4683919 DOI: 10.14701/kjhbps.2015.19.4.154] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/27/2015] [Revised: 09/25/2015] [Accepted: 09/30/2015] [Indexed: 01/27/2023]
Abstract
BACKGROUNDS/AIMS Hepatocellular carcinoma (HCC) is uncommon in young adults and the prognosis of these patients is still unclear. In this retrospective study, we compared the clinicopathological characteristics and outcomes of young patients with HCC with those of older patients with HCC. METHODS We retrospectively reviewed the clinicopathological characteristics of a total of 1,124 patients with HCC who underwent hepatectomy at our institution between 2006 and 2010. Patients ≤40 years of age at the time of HCC diagnosis were classified in the younger group. RESULTS One hundred and three patients (9.2%) were classified in the younger group. whereas, 1021 patients were classified in the older group. The incidences of hepatitis B virus infection, alpha-fetoprotein (AFP) levels, and indocyanine green retention test were all higher in younger patients than in older patients (p<0.05). Disease-free survival and overall survival were longer in older patients than in younger patients, without statistical significance. In younger patients, increased levels of protein induced by vitamin K antagonist-II (PIVKA-II) and alkaline phosphatase, portal vein tumor thrombosis, and intrahepatic metastasis were all predisposing factors for tumor recurrence after hepatectomy. CONCLUSIONS Although the AFP levels were higher in younger patients with HCC than in older patients with HCC, disease-free survival and overall survival after liver resection were not significantly different between the two groups.
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Affiliation(s)
- Ji Soo Lee
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jong Man Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Seunghwan Lee
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jin-Yong Choi
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Wontae Cho
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Gyu-Seoung Choi
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jae Berm Park
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Choon Hyuck David Kwon
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sung Joo Kim
- Department of Surgery, 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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Gerli S, Favilli A, Giordano C, Donini A, Di Renzo GC. Mixed hepatocellular carcinoma and cholangiocarcinoma during pregnancy: a case report. Eur J Obstet Gynecol Reprod Biol 2015; 187:76-7. [PMID: 25736194 DOI: 10.1016/j.ejogrb.2015.02.010] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2014] [Accepted: 02/06/2015] [Indexed: 12/13/2022]
Affiliation(s)
- Sandro Gerli
- Department of Obstetrics and Gynecology, University of Perugia, Perugia, Italy.
| | - Alessandro Favilli
- Department of Obstetrics and Gynecology, University of Perugia, Perugia, Italy
| | - Claudia Giordano
- Department of Obstetrics and Gynecology, University of Perugia, Perugia, Italy
| | - Annibale Donini
- Department of General and Emergency Surgery, University of Perugia, Perugia, Italy
| | - Gian Carlo Di Renzo
- Department of Obstetrics and Gynecology, University of Perugia, Perugia, Italy
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Mikhail S, Cosgrove D, Zeidan A. Hepatocellular carcinoma: systemic therapies and future perspectives. Expert Rev Anticancer Ther 2014; 14:1205-18. [PMID: 25199765 DOI: 10.1586/14737140.2014.949246] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Hepatocellular carcinoma is (HCC) the most common primary malignancy of the liver in adults. It is also the fifth most common solid cancer worldwide and the third leading cause of cancer-related deaths. Treatment options for HCC include liver transplantation, surgical resection, locoregional therapies and chemotherapy. The median survival time of patients following the diagnosis of unresectable disease is approximately 6-20 months, whereas the 5-year survival is less than 5%. Given the projected increase in incidence of HCC due to hepatitis C virus infection and obesity related cirrhosis, there is an urgent need for more intensive research in this cancer. In this article, we review the systemic options available for patients with HCC, its molecular pathogenesis and future therapeutic directions with special emphasis on immune-based and molecularly-targeted therapy.
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Affiliation(s)
- Sameh Mikhail
- Wexner Medical Center, Ohio State University, 320 W.10th Street, Columbus, Ohio, 43210, USA
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Clinical characteristics, treatment patterns and survival outcome of hepatocellular carcinoma patients aged 70 years or older: a single-center retrospective study from China. Aging Clin Exp Res 2014; 26:123-30. [PMID: 24129805 DOI: 10.1007/s40520-013-0142-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2013] [Accepted: 09/04/2013] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS The information about clinical presentation and outcome of elderly hepatocellular carcinoma (HCC) patients is limited. We performed this study to assess the impact of age on potential differences in clinical characteristics, treatment patterns and outcome in HCC patients. METHODS Clinical data of 164 "elderly" (≥70 years old) and 531 "younger" (<70 years old) HCC patients treated at a Chinese tertiary university-affiliated medical center between April 2004 and April 2012 were collected and compared using various parameters. RESULTS Compared with younger patients, the elderly patients had a higher proportion of females (32.9 % vs. 18.1 %, p < 0.001), less hepatitis B virus (HBV) infection (40.9 % vs. 76.6 %, p < 0.001), more hepatitis C virus (HCV) infection (23.8 % vs. 5.6 %, p < 0.001), less liver cirrhosis (68.3 % vs. 76.8 %, p = 0.03) and massive tumors (12.8 % vs. 21.8 %, p = 0.01). There was no significant difference between the two groups in Child-Pugh class and tumor stages. The elderly patients received less surgical resection (14.6 % vs. 29.6 %, p < 0.001) and more supportive care (48.8 % vs. 37.9 %, p = 0.01) than younger patients. The overall survival was not significantly different between the two groups (26.2 mo. vs. 28.3 mo., p = 0.75). CONCLUSION Characteristics that distinguish elderly from younger HCC patients included more female, less HBV infection, more HCV infection, less liver cirrhosis and massive tumors. Significant differences were observed in therapeutic strategies utilized with the two groups, but the overall survival was not significantly different.
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Hirokawa F, Hayashi M, Miyamoto Y, Asakuma M, Shimizu T, Komeda K, Inoue Y, Takeshita A, Shibayama Y, Uchiyama K. Surgical outcomes and clinical characteristics of elderly patients undergoing curative hepatectomy for hepatocellular carcinoma. J Gastrointest Surg 2013; 17:1929-37. [PMID: 24002762 DOI: 10.1007/s11605-013-2324-0] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2013] [Accepted: 08/17/2013] [Indexed: 02/08/2023]
Abstract
BACKGROUND The aim of this study was to investigate the clinical characteristics and outcomes of elderly patients (≥ 70 years old) undergoing curative hepatectomy for hepatocellular carcinoma (HCC). METHODS Clinicopathological data and treatment outcomes in 100 elderly patients (≥ 70 years old) and 120 control patients (≤ 70 years old) with HCC who underwent curative hepatectomy between 2000 and 2011 were retrospectively collected and compared. RESULTS The overall survival rate was similar between the two groups, but the disease-free survival rate was worse in the elderly group when compared with the control group. Prognostic factors for overall and disease-free survival were the same when comparing the two groups. The elderly group had higher rate of females (p = 0.0230), higher hepatitis C virus infection rate (p = 0.0090), higher postoperative pulmonary complication rate (p = 0.0484), lower rate of response to interferon (IFN) therapy (p = 0.0203) and shorter surgical time (p = 0.0337) when compared with the control group. The overall recurrence rate was higher in the elderly group than in the control group (p = 0.0346), but the rate of recurrence within 2 years after the operation was similar when comparing the two groups. CONCLUSION The survival of elderly patients with HCC was similar to that of younger patients. However, the disease-free survival was worse in elderly patients than in younger patients. Aggressive antiviral therapy (e.g. IFN therapy) may be necessary to improve the disease-free survival, even in elderly patients. Additionally, clinicians should be aware of the risk of pulmonary complications in elderly patients after hepatectomy.
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Affiliation(s)
- Fumitoshi Hirokawa
- Department of General and Gastroenterological Surgery, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki City, Osaka, 569-8686, Japan,
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Azarpira N, Dehghanian A, Safarian A, Kazemi K. Case report of skull metastasis from hepatocellular carcinoma after a liver transplant. EXP CLIN TRANSPLANT 2013; 12:265-8. [PMID: 23745813 DOI: 10.6002/ect.2013.0019] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
A solitary skull metastasis from hepatocellular carcinoma is rare. A 38-year-old man with hepatocellular carcinoma presented to our institution with a palpable temporal scalp mass. We took a magnetic resonance image, and discovered an enhanced and osteolytic skull tumor. The tumor was removed by an occipital craniectomy, and the histologic diagnosis was a cranial metastasis owing to hepatocellular carcinoma. A skull metastasis owing to hepatocellular carcinoma should be considered in the differential diagnosis in patients with a subcutaneous scalp mass. Although a distant metastasis can affect the prognosis of the patient, early treatment may improve survival.
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Affiliation(s)
- Negar Azarpira
- Transplant Research Center, Department of Pathology, Shiraz University of Medical Science, Shiraz, IR Iran
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Shimada S, Kamiyama T, Yokoo H, Wakayama K, Tsuruga Y, Kakisaka T, Kamachi H, Taketomi A. Clinicopathological characteristics and prognostic factors in young patients after hepatectomy for hepatocellular carcinoma. World J Surg Oncol 2013; 11:52. [PMID: 23452898 PMCID: PMC3599395 DOI: 10.1186/1477-7819-11-52] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2012] [Accepted: 02/06/2013] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND The aim of this study was to analyze the clinicopathological characteristics and the prognostic factors for survival and recurrence of young patients who had undergone hepatectomy for hepatocellular carcinoma. METHODS Between 1990 and 2010, 31 patients aged 40 years or younger (younger patient group) among 811 consecutive patients with hepatocellular carcinoma who had undergone primary hepatectomy were analyzed with regard to patient factors, including liver function, tumor factors and operative factors. The clinicopathological characteristics of the younger patients were compared with those of patients over the age of 40 (older patient group). Then the prognostic factors of the younger patients were analyzed. Continuous variables were expressed as the means ± standard deviation and compared using the χ2 test for categorical variables. Overall survival and recurrence-free survival rates were determined by the Kaplan-Meier method and analyzed by the log-rank test. The Cox proportional hazards model was used for multivariate analysis. RESULTS In the younger patients, the rates of HBs-antigen-positivity, high alpha-fetoprotein, portal invasion, intrahepatic metastasis, large tumors, low indocyanin green retention rate at 15 minutes, and anatomical resection were significantly higher than the same measures in the older patients. The five-year overall survival rate of the young patients was 49.6%. The prognostic factors of survival were HCV-antibody-positivity and low albumin status. Prognostic factors of recurrence were multiple tumors and the presence of portal invasion. CONCLUSIONS In younger patients, survival appeared to be primarily affected by liver function, while recurrence was affected by tumor factors. Young patients with hepatocellular carcinoma should be aggressively treated with hepatectomy due to their good pre-surgical liver function.
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Affiliation(s)
- Shingo Shimada
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Kita15-Nishi7, Kita-Ku, 060-8638, Sapporo, Hokkaido, Japan.
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Clinicopathologic features and prognosis of young patients with hepatocellular carcinoma in a large German cohort. J Clin Gastroenterol 2012; 46:775-8. [PMID: 22914348 DOI: 10.1097/mcg.0b013e31826102cc] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
GOALS AND BACKGROUND Hepatocellular carcinoma in non-hepatitis B virus endemic areas is rare in patients younger than 40 years of age. The aim of this study was to characterize young patients in a large German cohort in comparison with older patients with regard to underlying liver disease, clinical management, and survival. STUDY We analyzed the clinical data and medical records of 1108 consecutive patients with confirmed hepatocellular carcinoma. Twenty-five patients (2%) were younger than 40 years of age. We compared this subgroup with patients older than 40 years of age. RESULTS Underlying chronic liver disease was less common in young patients and detectable in only 56% of patients. Fibrolamellar carcinoma was more frequent in young versus old patients (20% vs. 0.7%; P<0.001). There was a trend toward more potentially curative treatment options in young patients, and overall survival was longer in the young group compared with older patients (56.0 vs. 15.2 mo; P=0.048). CONCLUSIONS This western cohort of young patients is distinctly different from described Asian cohorts, especially with regard to a lower rate of underlying liver disease and particularly hepatitis B virus. Young patients had a better overall survival than older patients.
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Kim YJ, Jang BK, Kim ES, Chung WJ, Park KS, Cho KB, Hwang JS. Hepatocellular carcinoma in the elderly: clinical characteristics, treatment, survival analysis in Korean patients older than 70 years. J Korean Med Sci 2012; 27:1147-54. [PMID: 23091310 PMCID: PMC3468749 DOI: 10.3346/jkms.2012.27.10.1147] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2012] [Accepted: 07/23/2012] [Indexed: 12/18/2022] Open
Abstract
The prevalence of hepatocellular carcinoma (HCC) has increased in recent years. However, HCC remains poorly characterized in elderly patients, and comprehensive data are limited. This study aimed to investigate the clinical characteristics, prognostic features and survival outcome of elderly HCC patients. We retrospectively analyzed 992 HCC patients treated at Dongsan Hospital from January 2003 to December 2007. The patients were divided into two age groups: < 70 yr (n = 813) and ≥ 70 yr (n = 179). Elderly HCC patients, compared to younger patients, had significantly higher incidence of females (31.3% vs 18.9%, P = 0.001), hepatitis C-related disease (HCV antibody positivity 26.3% vs 9.2%, P = 0.001) and comorbid condition (53.6% vs 32.1%), but lower rates of hepatitis B-related disease (HBs antigen positivity 31.3% vs 69.4%, P = 0.001). There were no significant differences in underlying liver function, stage and survival outcomes. Factors significantly influencing the prognosis of HCC were Child-Pugh grade, number of HCC, level of alpha-fetoprotein, presence of metastasis. The survival outcome of older patients with HCC was not different from that of younger patients. There were no differences between groups in independent factors influencing the prognosis of HCC. Therefore, determining the optimal management strategy for elderly HCC patients is important to improve survival and long-term outcomes.
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Affiliation(s)
- Yun Jung Kim
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Byoung Kuk Jang
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Eun Soo Kim
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Woo Jin Chung
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Kyung Sik Park
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Kwang Bum Cho
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Jae Seok Hwang
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
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Lee CR, Lim JH, Kim SH, Ahn SH, Park YN, Choi GH, Choi JS, Kim KS. A comparative analysis of hepatocellular carcinoma after hepatic resection in young versus elderly patients. J Gastrointest Surg 2012; 16:1736-43. [PMID: 22810298 DOI: 10.1007/s11605-012-1966-7] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2012] [Accepted: 07/06/2012] [Indexed: 01/31/2023]
Abstract
PURPOSE The aim of this study was to investigate the clinical outcomes after surgical treatment of hepatocellular carcinoma (HCC) in the elderly patients compared with younger patients. METHODS Clinicopathological data and treatment outcomes in 61 elderly (≥70 years old) and 90 younger (≤40 years old) patients with HCC who underwent curative liver resection between 2000 and 2010 were retrospectively collected and compared using various parameters. RESULTS The older HCC group was more likely to have hepatitis C virus and non-B non-C hepatitis virus infection, higher values of indocyanine green retention at 15 min (ICGR)(15), more preoperative comorbidities, and more postoperative complications. There were no significant differences in intraoperative parameters and pathologic features. The recurrence rate, overall survival and disease-free survival rates were similar amongst the two groups. The only independent prognostic factor of overall survival was postoperative complications. CONCLUSION Our findings suggest that age by itself does not have an adverse effect on operative outcomes, including long-term prognosis. For young and elderly HCC patients, hepatic resection is a safe and effective treatment.
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Affiliation(s)
- Cho Rok Lee
- Department of Surgery, Yonsei University College of Medicine, 50 Yonseiro, Seodaemun-gu, Seoul, South Korea
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Park CH, Jeong SH, Yim HW, Kim JD, Bae SH, Choi JY, Yoon SK. Family history influences the early onset of hepatocellular carcinoma. World J Gastroenterol 2012; 18:2661-7. [PMID: 22690075 PMCID: PMC3370003 DOI: 10.3748/wjg.v18.i21.2661] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2011] [Revised: 12/19/2011] [Accepted: 04/28/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the relationship between a positive family history of primary liver cancer and hepatocellular carcinoma (HCC) development in Korean HCC patients.
METHODS: We studied a total of 2242 patients diagnosed with HCC between January 1990 and July 2008, whose family history of primary liver cancer was clearly described in the medical records.
RESULTS: Of the 2242 patients, 165 (7.4%) had a positive family history of HCC and 2077 (92.6%) did not. The male to female ratio was 3.6:1, and the major causes of HCC were chronic hepatitis B virus (HBV) infection in 75.1%, chronic hepatitis C virus infection in 13.2% and alcohol in 3.1%. The median ages at diagnosis in the positive- and negative-history groups were 52 years (range: 29-79 years) and 57 years (range: 18-89 years), respectively (P < 0.0001). Furthermore, among 1713 HCC patients with HBV infection, the number of patients under 45 years of age out of 136 patients with positive family history was 26 (19.1%), whereas those out of 1577 patients with negative family history was 197 (12.5%), suggesting that a positive family history may be associated with earlier development of HCC in the Korean population (P = 0.0028).
CONCLUSION: More intensive surveillance maybe recommended to those with a positive family history of HCC for earlier diagnosis and proper management especially when HBV infection is present.
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Wang Q, Luan W, Villanueva GA, Rahbari NN, Yee HT, Manizate F, Hiotis SP. Clinical prognostic variables in young patients (under 40 years) with hepatitis B virus-associated hepatocellular carcinoma. J Dig Dis 2012; 13:214-8. [PMID: 22435506 DOI: 10.1111/j.1751-2980.2012.00577.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE The aim of this study was to determine the impact of hepatocelluar carcinoma (HCC) screening in chronic hepatitis B patients who did not meet the current screening recommendations. METHODS Patients who were admitted to Bellevue Hospital Center with HCC were assessed for risk factors, cirrhosis and tumor-specific factors. Eligibility for liver transplantation or resection with favorable outcome was determined by applying Milan criteria. RESULTS In all 93 patients were diagnosed with hepatitis B virus (HBV)-associated HCC, 18 of whom were under 40 years. Cirrhosis was infrequently associated with HCC in this group, with most cancers occurring in non-cirrhotic patients (12/18, 66.7%). No patient developed HCC outside the American Association for the Study of Liver Diseases (AASLD) cancer screening recommendations (young age, non-cirrhotic) were eligible for liver transplantation or resection with favorable outcomes (within Milan criteria). However, HCC patients who were diagnosed within AASLD screening recommendations did meet Milan criteria in 17.3% (14/81) patients. CONCLUSIONS Current guidelines for HCC screening in patients with HBV may lead to a delay in diagnosis in non-cirrhotic patients under 40 years. Consideration should be given to modifying current recommendations to advocate entering HBV patients into a cancer-screening program at young age.
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Affiliation(s)
- Qin Wang
- Division of Surgical Oncology, Mount Sinai School of Medicine, New York, NY 10029, USA
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Choi KK, Hong YJ, Choi SB, Park YN, Choi JS, Lee WJ, Kim KS. Hepatocellular carcinoma during pregnancy: is hepatocellular carcinoma more aggressive in pregnant patients? JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2011; 18:422-31. [PMID: 21116657 DOI: 10.1007/s00534-010-0345-6] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND/PURPOSE Hepatocellular carcinoma (HCC) during pregnancy is a very rare condition and is believed to have a worse prognosis than HCC in non-pregnant women. We evaluated the prognosis and the diagnostic and therapeutic strategies for HCC in pregnant women. METHODS We retrospectively analyzed 4 cases in our hospital and 44 cases described in the medical literature since 1957; we also compared the cases reported before 1995 and those reported during/after 1995. RESULTS The overall 6-month and 1-, 2-, and 3-year survival rates in the patients reported in the literature were 50, 29.5, 18.2, and 13.6%, respectively (n = 44). The mean ages at diagnosis before and during/after 1995 were 31.4 ± 7.2 and 28.9 ± 4.4 years, respectively (P = 0.113). The following characteristics were significantly more common in the later group: fewer pregnancies; the absence of advanced signs or symptoms; receipt of therapy; tendency to undergo surgery; and higher 6-month and 1-, 2-, and 3-year survival rates. The median survivals of the groups before and during/after 1995 were 18 and 25.5 months, respectively (P < 0.001). CONCLUSIONS The morbidity and mortality of HCC during pregnancy has improved over time, as diagnoses have tended to be made earlier and patients have tended to receive surgical and other treatments.
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Affiliation(s)
- Kang Kook Choi
- Kwandong Graduate School of Medicine, Gangneung-si, Gangwon-do, Korea
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Wan DW, Tzimas D, Smith JA, Kim S, Araujo J, David R, Lobach I, Sarpel U. Risk factors for early-onset and late-onset hepatocellular carcinoma in Asian immigrants with hepatitis B in the United States. Am J Gastroenterol 2011; 106:1994-2000. [PMID: 21912436 DOI: 10.1038/ajg.2011.302] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Routine screening for hepatocellular carcinoma (HCC) is recommended in chronic hepatitis B (HBV) patients with cirrhosis and select non-cirrhotic HBV populations including Asian males ages 40 and older and females ages 50 and older. However, many younger HBV patients develop HCC and there have been few studies examining this group. Additionally, studies of HCC in the Asian immigrant population in the United States have been limited. The objective of this study was to determine the associated risk factors for the development of early-onset (males and females under ages 40 and 50, respectively) and late-onset HCC in immigrants with chronic HBV in the United States. METHODS Clinical, demographic, and laboratory data were retrospectively collected on all Asian immigrants with HBV at Bellevue Hospital Center from 2003 to 2009. Patients with HCC were identified within this cohort. Features of early-onset and late-onset HCC cases were compared with age-matched HBV controls without HCC. RESULTS We identified 168 cases of HCC in Asians with HBV. In all, 74% (124/168) of cases were late-onset, and 26% (44/168) were early-onset. When comparing the 124 late-onset HCC cases with 199 age-matched HBV controls, gender (odds ratio (OR)=4.4; P<0.05) and cirrhosis (OR=9.6; P<0.05) or surrogate labs (i.e., platelets, international normalized ratio, total bilirubin, albumin) were found to be associated with HCC development. When comparing the 44 early-onset HCC cases with 432 age-matched HBV controls, family history of HCC (OR=2.7; P<0.05), and smoking history (OR=3.4; P<0.05) were independently associated risk factors in addition to gender (OR=2.7; P<0.05), and cirrhosis (OR=19.5; P<0.05) or surrogate labs. In all, 54.8% of late-onset HCC cases were cirrhotic and 29.5% of early-onset HCC cases were cirrhotic. CONCLUSIONS HCC occurs in Asian immigrant HBV patients younger than currently recommended screening guidelines. A large majority of these early-onset patients did not have cirrhosis at the time of their HCC diagnosis; therefore, factors other than cirrhosis need to be considered when evaluating HCC risk in young patients. Factors associated with HCC development across all ages include cirrhosis and male gender, while family history and smoking history may identify younger Asian immigrant HBV patients at risk for HCC. Prospective validation, including cost-effectiveness evaluation, is necessary, but our results suggest that younger Asian HBV patients, especially those with a smoking history or family history of HCC, appear to have an increased risk for HCC and should be considered for enrollment in early screening programs regardless of their age.
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Affiliation(s)
- David W Wan
- Division of Gastroenterology, Department of Medicine, NYU Langone Medical Center, New York, New York 10016, USA
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Takeishi K, Shirabe K, Muto J, Toshima T, Taketomi A, Maehara Y. Clinicopathological features and outcomes of young patients with hepatocellular carcinoma after hepatectomy. World J Surg 2011; 35:1063-71. [PMID: 21380583 DOI: 10.1007/s00268-011-1017-7] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND There are few reports about hepatectomy for young patients with hepatocellular carcinoma (HCC), and the significance of resection for young patients remains unknown. The present study aimed to investigate retrospectively the clinicopathological features and outcomes after hepatectomy of young HCC patients. METHODS Among 610 patients who underwent curative hepatectomy for HCC between January 1987 and December 2007, 13 patients younger than 40 years of age were defined as the young group. Because none of the young group had hepatitis C virus antibodies (HCVAb), 246 patients aged above 40 years without HCVAb were defined as the older group. The clinicopathological findings and outcomes after hepatectomy were compared between the two groups. RESULTS In the young group, 7 patients had hepatitis B surface antigen and 3 other patients had hepatitis B core antibodies. The young group had better liver function but more advanced HCC, with a large tumor size and a high incidence of portal vein invasion compared with the older group. Major hepatectomy was more frequently chosen in the young group than in the older group. There was no significant difference in the incidences of postoperative complications. The overall survival tended to be better in the young group than in the older group (p=0.057). CONCLUSIONS Hepatitis B virus-related HCC was common in the younger group of patients reported here. Although the young patients had advanced HCC, there were no significant differences in the complication rate and the overall survival rate of the young and older groups. Aggressive hepatic resection for young patients would contribute to improved survival and should be recommended.
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Affiliation(s)
- Kazuki Takeishi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
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