|
1
|
Torimura T, Iwamoto H. Treatment and the prognosis of hepatocellular carcinoma in Asia. Liver Int 2022; 42:2042-2054. [PMID: 34894051 DOI: 10.1111/liv.15130] [Citation(s) in RCA: 58] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Accepted: 12/07/2021] [Indexed: 12/24/2022]
Abstract
Hepatocellular carcinoma is the most common type of malignant tumour in Asia. Treatment is decided according to the staging system with information on tumour burden and liver function. The Barcelona Clinic Liver Cancer staging system is the most commonly used staging system for the selection of appropriate treatments worldwide, and although it is highly evidenced-base, it has very strict guidelines for treatment. In Asian countries, many efforts have been made to expand the indications of each treatment and combination therapies as well as alternative therapies for better outcomes. The guidelines in Asia are less evidence-based than those in Western countries. More aggressive treatments for hepatocellular carcinoma are generally employed in the guidelines of Asian countries. Surgical resection is frequently employed for selected hepatocellular carcinoma patients with the Barcelona Clinic Liver Cancer stages B and C, and combination therapies are sometimes selected, which are contrary to the recommendations of American and European association for the study of the liver guidelines. Recently, a paradigm shift in treatments for advanced hepatocellular carcinoma has occurred with molecular targeted agents, antibodies and immune checkpoint inhibitors in Asia. Atezolizumab+bevacizumab therapy has become the first-line systemic treatment ineligible for radical treatment or transarterial chemoembolization in Asian countries. The overall survival of patients with hepatocellular carcinoma varies substantially across Asia. Taiwan and Japan have the best clinical outcomes for patients with hepatocellular carcinoma worldwide. Intensive surveillance programmes and the development of radical and non-radical treatments are indispensable for the improvement of prognosis in patients with hepatocellular carcinoma.
Collapse
Affiliation(s)
- Takuji Torimura
- Division of Gastroenterology Department of Medicine, Kurume University School of Medicine, Research Center for Innovative Cancer Therapy Kurume University, Kurume City, Japan
| | - Hideki Iwamoto
- Division of Gastroenterology Department of Medicine, Kurume University School of Medicine, Research Center for Innovative Cancer Therapy Kurume University, Kurume City, Japan
| |
Collapse
|
|
2
|
Greten TF, Abou-Alfa GK, Cheng AL, Duffy AG, El-Khoueiry AB, Finn RS, Galle PR, Goyal L, He AR, Kaseb AO, Kelley RK, Lencioni R, Lujambio A, Mabry Hrones D, Pinato DJ, Sangro B, Troisi RI, Wilson Woods A, Yau T, Zhu AX, Melero I. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of hepatocellular carcinoma. J Immunother Cancer 2021; 9:e002794. [PMID: 34518290 PMCID: PMC8438858 DOI: 10.1136/jitc-2021-002794] [Citation(s) in RCA: 47] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/02/2021] [Indexed: 12/11/2022] Open
Abstract
Patients with advanced hepatocellular carcinoma (HCC) have historically had few options and faced extremely poor prognoses if their disease progressed after standard-of-care tyrosine kinase inhibitors (TKIs). Recently, the standard of care for HCC has been transformed as a combination of the immune checkpoint inhibitor (ICI) atezolizumab plus the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab was shown to offer improved overall survival in the first-line setting. Immunotherapy has demonstrated safety and efficacy in later lines of therapy as well, and ongoing trials are investigating novel combinations of ICIs and TKIs, in addition to interventions earlier in the course of disease or in combination with liver-directed therapies. Because HCC usually develops against a background of cirrhosis, immunotherapy for liver tumors is complex and oncologists need to account for both immunological and hepatological considerations when developing a treatment plan for their patients. To provide guidance to the oncology community on important concerns for the immunotherapeutic care of HCC, the Society for Immunotherapy of Cancer (SITC) convened a multidisciplinary panel of experts to develop a clinical practice guideline (CPG). The expert panel drew on the published literature as well as their clinical experience to develop recommendations for healthcare professionals on these important aspects of immunotherapeutic treatment for HCC, including diagnosis and staging, treatment planning, immune-related adverse events (irAEs), and patient quality of life (QOL) considerations. The evidence- and consensus-based recommendations in this CPG are intended to give guidance to cancer care providers treating patients with HCC.
Collapse
Affiliation(s)
- Tim F Greten
- Thoracic and GI Malignancies Branch, National Cancer Institute, Bethesda, Maryland, USA
| | - Ghassan K Abou-Alfa
- Memorial Sloan Kettering Cancer Center, New York, New York, USA
- Weill Medical College at Cornell University, New York, New York, USA
| | - Ann-Lii Cheng
- Department of Medical Oncology, National Taiwan University Cancer Center and National Taiwan University Hospital, Taipei, Taiwan
| | - Austin G Duffy
- The Mater Hospital/University College Dublin, Dublin, Ireland
| | - Anthony B El-Khoueiry
- Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California, USA
| | - Richard S Finn
- David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA
| | | | - Lipika Goyal
- Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Aiwu Ruth He
- Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia, USA
| | - Ahmed O Kaseb
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Robin Kate Kelley
- Department of Medicine (Hematology/Oncology), UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California, USA
| | - Riccardo Lencioni
- Department of Radiology, University of Pisa School of Medicine, Pisa, Italy
- Miami Cancer Institute, Miami, Florida, USA
| | - Amaia Lujambio
- Oncological Sciences Department, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Donna Mabry Hrones
- Thoracic and GI Malignancies Branch, National Cancer Institute, Bethesda, Maryland, USA
| | - David J Pinato
- Department of Surgery & Cancer, Imperial College London, London, UK
| | - Bruno Sangro
- Clinica Universidad de Navarra-Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | | | - Andrea Wilson Woods
- Blue Faery: The Adrienne Wilson Liver Cancer Association, Birmingham, Alabama, USA
| | - Thomas Yau
- Queen Mary Hospital, The University of Hong Kong, Hong Kong, Hong Kong
| | - Andrew X Zhu
- Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA
- Jiahui Health, Jiahui International Cancer Center, Shanghai, China
| | - Ignacio Melero
- Clinica Universidad de Navarra-Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Spain
- Foundation for Applied Medical Research (FIMA), Pamplona, Spain
- Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Madrid, Spain
| |
Collapse
|
|
3
|
Zhang L, Hu J, Hou J, Jiang X, Guo L, Tian L. Radiomics-based model using gadoxetic acid disodium-enhanced MR images: associations with recurrence-free survival of patients with hepatocellular carcinoma treated by surgical resection. Abdom Radiol (NY) 2021; 46:3845-3854. [PMID: 33733337 DOI: 10.1007/s00261-021-03034-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Revised: 02/28/2021] [Accepted: 03/03/2021] [Indexed: 02/07/2023]
Abstract
PURPOSE To develop a prediction model that combined magnetic resonance images (MRI)-based radiomics features with clinical factors to predict recurrence-free survival (RFS) of hepatocellular carcinoma (HCC) patients treated with surgical resection. METHODS HCC patients treated with surgical resection (n = 153) were randomly divided into training (n = 107) and validation (n = 46) datasets. The volumes of interest were manually outlined around the lesion and additional 2 mm and 5 mm peritumoral areas were created with automated dilatation in MRI to extract tumoral (T) and peritumoral (PT) radiomics features. The radiomics models were constructed using least absolute shrinkage and selection operator Cox regression. The combined model incorporated clinical factors and radiomics features using multivariable Cox regression based on the Akaike information criterion principle. Predictive performance of different models were evaluated by receiver operating characteristic (ROC) curves, decision curves, and calibration curves. RESULTS Among the radiomics models, similar performance was observed in the 2 mm and 5 mm PT models (C-index both 0.657), which were better than the T model or T + PT model (C-index 0.607 and 0.641, respectively) in the validation dataset, whereas the model combined with the three identified clinical risk factors showed the best performance (C-index 0.725). Results of the ROC curves, decision curves, and the calibration curves indicated that the combined model and the derived nomogram had better prediction performance, greater clinical benefits, and fair calibration efficiency. CONCLUSION The prediction model that combined MRI radiomics signatures with clinical factors can effectively predict the prognosis of patients with HCC treated with surgical resection.
Collapse
Affiliation(s)
- Ling Zhang
- Department of Radiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China
| | - Jianming Hu
- Department of Radiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China
| | - Jingyu Hou
- Department of Liver Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China
| | - Xinhua Jiang
- Department of Radiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China
| | - Lei Guo
- Department of Radiology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, China.
| | - Li Tian
- Department of Radiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
| |
Collapse
|
|
4
|
Kudo M, Kawamura Y, Hasegawa K, Tateishi R, Kariyama K, Shiina S, Toyoda H, Imai Y, Hiraoka A, Ikeda M, Izumi N, Moriguchi M, Ogasawara S, Minami Y, Ueshima K, Murakami T, Miyayama S, Nakashima O, Yano H, Sakamoto M, Hatano E, Shimada M, Kokudo N, Mochida S, Takehara T. Management of Hepatocellular Carcinoma in Japan: JSH Consensus Statements and Recommendations 2021 Update. Liver Cancer 2021; 10:181-223. [PMID: 34239808 PMCID: PMC8237791 DOI: 10.1159/000514174] [Citation(s) in RCA: 429] [Impact Index Per Article: 107.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Accepted: 12/23/2020] [Indexed: 02/06/2023] Open
Abstract
The Clinical Practice Manual for Hepatocellular Carcinoma was published based on evidence confirmed by the Evidence-based Clinical Practice Guidelines for Hepatocellular Carcinoma along with consensus opinion among a Japan Society of Hepatology (JSH) expert panel on hepatocellular carcinoma (HCC). Since the JSH Clinical Practice Guidelines are based on original articles with extremely high levels of evidence, expert opinions on HCC management in clinical practice or consensus on newly developed treatments are not included. However, the practice manual incorporates the literature based on clinical data, expert opinion, and real-world clinical practice currently conducted in Japan to facilitate its use by clinicians. Alongside each revision of the JSH Guidelines, we issued an update to the manual, with the first edition of the manual published in 2007, the second edition in 2010, the third edition in 2015, and the fourth edition in 2020, which includes the 2017 edition of the JSH Guideline. This article is an excerpt from the fourth edition of the HCC Clinical Practice Manual focusing on pathology, diagnosis, and treatment of HCC. It is designed as a practical manual different from the latest version of the JSH Clinical Practice Guidelines. This practice manual was written by an expert panel from the JSH, with emphasis on the consensus statements and recommendations for the management of HCC proposed by the JSH expert panel. In this article, we included newly developed clinical practices that are relatively common among Japanese experts in this field, although all of their statements are not associated with a high level of evidence, but these practices are likely to be incorporated into guidelines in the future. To write this article, coauthors from different institutions drafted the content and then critically reviewed each other's work. The revised content was then critically reviewed by the Board of Directors and the Planning and Public Relations Committee of JSH before publication to confirm the consensus statements and recommendations. The consensus statements and recommendations presented in this report represent measures actually being conducted at the highest-level HCC treatment centers in Japan. We hope this article provides insight into the actual situation of HCC practice in Japan, thereby affecting the global practice pattern in the management of HCC.
Collapse
Affiliation(s)
- Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan,*Masatoshi Kudo,
| | | | - Kiyoshi Hasegawa
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Ryosuke Tateishi
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kazuya Kariyama
- Department of Gastroenterology, Okayama City Hospital, Okayama, Japan
| | - Shuichiro Shiina
- Department of Gastroenterology, Juntendo University, Tokyo, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Gifu, Japan
| | - Yasuharu Imai
- Department of Gastroenterology, Ikeda Municipal Hospital, Osaka, Japan
| | - Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Masafumi Ikeda
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan
| | - Namiki Izumi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Michihisa Moriguchi
- Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Sadahisa Ogasawara
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Yasunori Minami
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Kazuomi Ueshima
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Takamichi Murakami
- Department of Radiology, Kobe University Graduate School of Medicine, Hyogo, Japan
| | - Shiro Miyayama
- Department of Diagnostic Radiology, Fukui-ken Saiseikai Hospital, Fukui, Japan
| | - Osamu Nakashima
- Department of Clinical Laboratory Medicine, Kurume University Hospital, Kurume, Japan
| | - Hirohisa Yano
- Department of Pathology, Kurume University School of Medicine, Kurume, Japan
| | - Michiie Sakamoto
- Department of Pathology, Keio University School of Medicine, Tokyo, Japan
| | - Etsuro Hatano
- Department of Gastroenterological Surgery, Hyogo College of Medicine, Nishinomiya, Japan
| | - Mitsuo Shimada
- Department of Surgery, Tokushima University, Tokushima, Japan
| | - Norihiro Kokudo
- Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan
| | - Satoshi Mochida
- Department of Gastroenterology and Hepatology, Saitama Medical University, Saitama, Japan
| | - Tetsuo Takehara
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
| |
Collapse
|
|
5
|
Vitale A, Farinati F, Finotti M, Di Renzo C, Brancaccio G, Piscaglia F, Cabibbo G, Caturelli E, Missale G, Marra F, Sacco R, Giannini EG, Trevisani F, Cillo U, Associazione Italiana per lo Studio del Fegato (AISF) HCC Special Interest Group, Italian Liver Cancer (ITA.LI.CA) Study Group. Overview of Prognostic Systems for Hepatocellular Carcinoma and ITA.LI.CA External Validation of MESH and CNLC Classifications. Cancers (Basel) 2021; 13:1673. [PMID: 33918125 PMCID: PMC8037197 DOI: 10.3390/cancers13071673] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 03/23/2021] [Accepted: 03/25/2021] [Indexed: 02/07/2023] Open
Abstract
Prognostic assessment in patients with HCC remains an extremely difficult clinical task due to the complexity of this cancer where tumour characteristics interact with degree of liver dysfunction, patient general health status, and a large span of available treatment options. Several prognostic systems have been proposed in the last three decades, both from the Asian and European/North American countries. Prognostic scores, such as the CLIP score and the recent MESH score, have been generated on a solid statistical basis from real life population data, while staging systems, such as the BCLC scheme and the recent CNLC classification, have been created by experts according to recent HCC prognostic evidences from the literature. A third category includes combined prognostic systems that can be used both as prognostic scores and staging systems. A recent example is the ITA.LI.CA prognostic system including either a prognostic score and a simplified staging system. This review focuses first on an overview of the main prognostic systems for HCC classified according to the above three categories, and, second, on a comprehensive description of the methodology required for a correct comparison between different systems in terms of prognostic performance. In this second section the main studies in the literature comparing different prognostic systems are described in detail. Lastly, a formal comparison between the last prognostic systems proposed for each of the above three categories is performed using a large Italian database including 6882 HCC patients in order to concretely apply the comparison rules previously described.
Collapse
Affiliation(s)
- Alessandro Vitale
- Department of Surgery, Oncology and Gastroenterology, University of Padua, 35121 Padua, Italy; (A.V.); (F.F.); (C.D.R.); (U.C.)
| | - Fabio Farinati
- Department of Surgery, Oncology and Gastroenterology, University of Padua, 35121 Padua, Italy; (A.V.); (F.F.); (C.D.R.); (U.C.)
| | - Michele Finotti
- Department of Surgery, Oncology and Gastroenterology, University of Padua, 35121 Padua, Italy; (A.V.); (F.F.); (C.D.R.); (U.C.)
| | - Chiara Di Renzo
- Department of Surgery, Oncology and Gastroenterology, University of Padua, 35121 Padua, Italy; (A.V.); (F.F.); (C.D.R.); (U.C.)
| | - Giuseppina Brancaccio
- Infectious Diseases Unit, Department of Internal Medicine, Padua University Hospital, 35123 Padua, Italy;
| | - Fabio Piscaglia
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy;
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy
| | - Giuseppe Cabibbo
- Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, PROMISE, Gastroenterology & Hepatology Unit, University of Palermo, 90127 Palermo, Italy;
| | | | - Gabriele Missale
- Infectious Diseases and Hepatology Unit, Azienda Ospedaliero-Universitaria of Parma, 43126 Parma, Italy;
| | - Fabio Marra
- Internal Medicine and Hepatology Unit, Department of Experimental and Clinical Medicine, University of Firenze, 50139 Firenze, Italy;
| | - Rodolfo Sacco
- Gastroenterology and Digestive Endoscopy Unit, Foggia University Hospital, 71122 Foggia, Italy;
| | - Edoardo G. Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy;
| | - Franco Trevisani
- Division of Semeiotics, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Umberto Cillo
- Department of Surgery, Oncology and Gastroenterology, University of Padua, 35121 Padua, Italy; (A.V.); (F.F.); (C.D.R.); (U.C.)
| | | | | |
Collapse
|
|
6
|
Hachiya H, Aoki T, Iso Y, Shimizu T, Tago K, Park KH, Sakuraoka Y, Shiraki T, Mori S, Kubota K. Effects of branched-chain amino acids on postoperative tumor recurrence in patients undergoing curative resection for hepatocellular carcinoma: A randomized clinical trial. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2020; 27:819-829. [PMID: 32949091 DOI: 10.1002/jhbp.830] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Revised: 08/07/2020] [Accepted: 08/10/2020] [Indexed: 12/17/2022]
Abstract
BACKGROUND/PURPOSE No effective postoperative adjuvant therapies have been established for patients with hepatocellular carcinoma (HCC). The aim of this study was to investigate the effect of oral administration of branched-chain amino acids (BCAA) on the recurrence-free survival (RFS) after hepatic resection in HCC patients. METHODS In this randomized clinical trial, HCC patients undergoing curative resections were randomly assigned in a 1:1 ratio to the BCAA group or surgery-alone group. The BCAA group received BCAA (Livact® ) for up to 4 years. The primary endpoint was RFS. The secondary endpoint was overall survival (OS). Multivariate analysis was performed to detect the clinical characteristics significantly associated with RFS. RESULTS Between January 2010 and October 2014, 156 patients (75 in BCAA group and 81 in surgery-alone group) were enrolled in the study. Of these, two patients were excluded from the efficacy analysis. Comparison of the survival curves by the log rank test demonstrated no significant difference in the RFS (P = .579) or OS (P = .268) between the BCAA and the control group. Multivariate analysis revealed that the RFS was significantly associated with age and number of tumors. A beneficial effect of BCAA on the RFS was found in patients younger than 72 years old with a HbA1c level of < 6.4%. CONCLUSIONS Oral BCAA supplementation could not reduce the risk of recurrence after hepatic resection in HCC patients; however, the results suggested that BCAA supplementation may be beneficial for selected patients who were younger and had mildly impaired glucose tolerance.
Collapse
Affiliation(s)
- Hiroyuki Hachiya
- Second Department of Surgery, Dokkyo Medical University, Tochigi, Japan
| | - Taku Aoki
- Second Department of Surgery, Dokkyo Medical University, Tochigi, Japan
| | - Yukihiro Iso
- Second Department of Surgery, Dokkyo Medical University, Tochigi, Japan
| | - Takayuki Shimizu
- Second Department of Surgery, Dokkyo Medical University, Tochigi, Japan
| | - Kazuma Tago
- Second Department of Surgery, Dokkyo Medical University, Tochigi, Japan
| | - Kyung Hwa Park
- Second Department of Surgery, Dokkyo Medical University, Tochigi, Japan
| | - Yuhki Sakuraoka
- Second Department of Surgery, Dokkyo Medical University, Tochigi, Japan
| | - Takayuki Shiraki
- Second Department of Surgery, Dokkyo Medical University, Tochigi, Japan
| | - Shozo Mori
- Second Department of Surgery, Dokkyo Medical University, Tochigi, Japan
| | - Keiichi Kubota
- Second Department of Surgery, Dokkyo Medical University, Tochigi, Japan
| |
Collapse
|
|
7
|
Tsukamoto M, Imai K, Yamashita YI, Kitano Y, Okabe H, Nakagawa S, Nitta H, Chikamoto A, Ishiko T, Baba H. Endoscopic hepatic resection and endoscopic radiofrequency ablation as initial treatments for hepatocellular carcinoma within the Milan criteria. Surg Today 2019; 50:402-412. [PMID: 31680205 DOI: 10.1007/s00595-019-01903-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2019] [Accepted: 10/08/2019] [Indexed: 12/17/2022]
Abstract
PURPOSES The indication of endoscopic (laparoscopic and thoracoscopic) hepatic resection (HR) has been expanded in the past decade because of its low invasiveness. However, the indications of endoscopic HR and radiofrequency ablation (RFA) have not yet been determined. METHODS Among the 906 patients hospitalized for the initial treatment of hepatocellular carcinoma (HCC) between 2000 and 2017, 77 underwent endoscopic partial HR (E-pHR), and 94 underwent endoscopic RFA (E-RFA). We compared the short- and long-term outcomes between the E-pHR and E-RFA groups. RESULTS The patients in the E-RFA group were characterized primarily by an impaired liver function. Among the patients with liver damage B or C, the overall survival (OS) in the E-pHR group was significantly worse than in the E-RFA group (3-year OS: 36% vs. 82%, p = 0.003). CONCLUSION E-RFA may be recommended for the initial treatment of HCC in patients with a severely impaired liver function. However, E-pHR should be avoided as the initial treatment of HCC in such patients.
Collapse
Affiliation(s)
- Masayo Tsukamoto
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Katsunori Imai
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
| | - Yo-Ichi Yamashita
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Yuki Kitano
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Hirohisa Okabe
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Shigeki Nakagawa
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Hidetoshi Nitta
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Akira Chikamoto
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Takatoshi Ishiko
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| |
Collapse
|
|
8
|
Burkhart RA, Pawlik TM. Staging and Prognostic Models for Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma. Cancer Control 2018; 24:1073274817729235. [PMID: 28975828 PMCID: PMC5937249 DOI: 10.1177/1073274817729235] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
There are several important roles that staging systems and prognostic models play in the modern medical care of patients with cancer. First, accurate staging systems can assist clinicians by identifying optimal treatment selection based on the scope of disease at the time of diagnosis. Second, both physicians and patients may infer prognostic information from staging and models that may help decision makers identify appropriate therapies for individual patients. Third, in research, there is benefit to classifying patients with disease into subgroups ensuring greater parity between experimental and control arms. Staging systems in most solid organ malignancies rely heavily on an accurate pathologic assessment of the tumor (size, site, number of tumors, locoregional spread, and distant spread). Another consideration in primary liver cancer, such as hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), is the fact that the underlying liver function can significantly impact patient survival. In HCC, there are at least a dozen options that have been proposed for staging the disease. Herein, we review the most widely used systems and discuss their strengths and weaknesses. Prognostic models and nomograms are also discussed for a variety of subpopulations with HCC. Interestingly, until 2010, the staging system proposed by the American Joint Committee on Cancer for ICC was identical to HCC. The modern staging system, unique to ICC, is reviewed, and future modifications are identified with the primary supporting literature discussed.
Collapse
Affiliation(s)
| | - Timothy M Pawlik
- 2 Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| |
Collapse
|
|
9
|
Tokumitsu Y, Sakamoto K, Tokuhisa Y, Matsui H, Matsukuma S, Maeda Y, Sakata K, Wada H, Eguchi H, Ogihara H, Fujita Y, Hamamoto Y, Iizuka N, Ueno T, Nagano H. A new prognostic model for hepatocellular carcinoma recurrence after curative hepatectomy. Oncol Lett 2018; 15:4411-4422. [PMID: 29556288 PMCID: PMC5844062 DOI: 10.3892/ol.2018.7821] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2017] [Accepted: 10/10/2017] [Indexed: 02/06/2023] Open
Abstract
We previously reported the effectiveness of the product of tumor number and size (NxS factor) for the prognosis of hepatocellular carcinoma (HCC) in patients following hepatectomy. The present study aimed to propose a new score based on the NxS factor to predict HCC recurrence following hepatectomy. A total of 406 patients who underwent hepatectomy for HCC at Osaka University Graduate School of Medicine were retrospectively analyzed to develop the new score. Among clinicopathological factors, including the NxS factor, the marker subset that achieved the best performance for prediction of early recurrence was assessed, and a prognostic model for HCC recurrence after curative hepatectomy (REACH) was developed. As the validation set, 425 patients who underwent hepatectomy for HCC at Yamaguchi University Graduate School of Medicine and Shimonoseki Medical Center were analyzed, and the prognostic ability of the REACH score was compared with that of well-known staging systems. Following analysis, the REACH score was constructed using six covariates (NxS factor, microscopic hepatic vein invasion, differentiation, serum albumin, platelet count and indocyanine green retention rate at 15 min). In the validation set, the REACH score predicted early recurrence in 73 of 81 samples, with a sensitivity of 89% and a specificity of 58%. The area under the curve (AUC) of the receiver operating characteristic curve of the REACH score was 0.78 and 0.74, respectively, for 1- and 2-year recurrence after hepatectomy; each AUC was higher than that of any of the other staging systems. Survival analysis indicated the REACH score had the best predictive value in disease-free and overall survival. The present findings demonstrated that the REACH score may be used to classify patients with HCC into high- and low-risk of recurrence, and to predict subsequent survival following hepatic resection.
Collapse
Affiliation(s)
- Yukio Tokumitsu
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan
| | - Kazuhiko Sakamoto
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan
| | - Yoshihiro Tokuhisa
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan
| | - Hiroto Matsui
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan
| | - Satoshi Matsukuma
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan
| | - Yoshinari Maeda
- Department of Surgery, Kanmon Medical Center, National Hospital Organization, Shimonoseki, Yamaguchi 752-8510, Japan
| | - Koichiro Sakata
- Department of Surgery, Shimonoseki Medical Center, Japan Community Health Care Organization, Shimonoseki, Yamaguchi 750-0061, Japan
| | - Hiroshi Wada
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
| | - Hiroyuki Ogihara
- Department of Biomolecular Engineering Applied Molecular Bioscience, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8611, Japan
| | - Yusuke Fujita
- Department of Information Science and Engineering, Yamaguchi University Graduate School of Sciences and Technology for Innovation, Ube, Yamaguchi 755-8611, Japan
| | - Yoshihiko Hamamoto
- Department of Information Science and Engineering, Yamaguchi University Graduate School of Sciences and Technology for Innovation, Ube, Yamaguchi 755-8611, Japan
| | - Norio Iizuka
- Department of Kampo Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan
| | - Tomio Ueno
- Department of Digestive Surgery, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan
| | - Hiroaki Nagano
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan
| |
Collapse
|
|
10
|
Hiraoka A, Michitaka K, Kumada T, Izumi N, Kadoya M, Kokudo N, Kubo S, Matsuyama Y, Nakashima O, Sakamoto M, Takayama T, Kokudo T, Kashiwabara K, Kudo M. Validation and Potential of Albumin-Bilirubin Grade and Prognostication in a Nationwide Survey of 46,681 Hepatocellular Carcinoma Patients in Japan: The Need for a More Detailed Evaluation of Hepatic Function. Liver Cancer 2017; 6:325-336. [PMID: 29234636 PMCID: PMC5704689 DOI: 10.1159/000479984] [Citation(s) in RCA: 231] [Impact Index Per Article: 28.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND/AIM Recently, albumin-bilirubin (ALBI) scoring/grading, consisting of only albumin and total bilirubin, has been proposed. We examined the efficacy of this grading system for determining hepatic function in patients with hepatocellular carcinoma (HCC). METHODS/MATERIALS The prognoses of 46,681 HCC patients based on results obtained from a nationwide survey conducted in Japan from 2001 to 2007 were evaluated using (1) Japan Integrated Staging (JIS), consisting of Child-Pugh classification and TNM staging (TNM), (2) modified JIS (m-JIS), consisting of liver damage grading and TNM, and (3) ALBI-TNM (ALBI-T), consisting of ALBI grading and TNM, and the results were compared. A subanalysis was also performed to define a cutoff value for ALBI scores for a more detailed stratification of hepatic function. RESULTS ALBI-T, JIS, and m-JIS each showed good capacity for the stratification of prognoses. Although the Akaike information criterion for ALBI-T was nearly equal to that for JIS and m-JIS, the Kaplan-Meier curves and median survival times obtained with ALBI-T were always superior to the corresponding scores. When the indocyanine green retention test (<30%) was used as an additional cutoff value for ALBI score (-2.270, area under the curve 0.828) to divide ALBI grade into 4 levels (modified ALBI [mALBI] grade), mALBI grade was able to stratify the prognosis of patients at any TNM stage in order of grade. Modified ALBI-T (mALBI-T), using mALBI grading and TNM, produced a more detailed stratification for prognosis. CONCLUSION The predictive value for prognosis of ALBI-T was found to be equal to that of JIS and m-JIS. In addition, mALBI grading and mALBI-T, as proposed in the present study, might provide a more detailed assessment of the hepatic function and prognosis of HCC patients.
Collapse
Affiliation(s)
- Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama
| | - Kojiro Michitaka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama
| | - Takashi Kumada
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki
| | - Namiki Izumi
- Department of Gastroenterology, Musashino Red Cross Hospital, Tokyo
| | - Masumi Kadoya
- Department of Radiology, Shinshu University School of Medicine, Matsumoto
| | | | - Shoji Kubo
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka
| | - Yutaka Matsuyama
- Department of Biostatistics, School of Public Health, University of Tokyo, Tokyo
| | - Osamu Nakashima
- Department of Clinical Laboratory Medicine, Kurume University Hospital, Kurume
| | | | - Tadatoshi Takayama
- Department of Digestive Surgery, Nihon University School of Medicine and Hepato-Biliary-Pancreatic Surgery Division
| | | | - Kosuke Kashiwabara
- Department of Biostatistics, School of Public Health, Graduate School of Medicine, University of Tokyo, Tokyo
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University School of Medicine, Osaka, Japan
| |
Collapse
|
|
11
|
Harimoto N, Yoshizumi T, Sakata K, Nagatsu A, Motomura T, Itoh S, Harada N, Ikegami T, Uchiyama H, Soejima Y, Maehara Y. Prognostic significance of combined albumin-bilirubin and tumor-node-metastasis staging system in patients who underwent hepatic resection for hepatocellular carcinoma. Hepatol Res 2017; 47:1289-1298. [PMID: 28169483 DOI: 10.1111/hepr.12868] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2016] [Revised: 02/02/2017] [Accepted: 02/04/2017] [Indexed: 12/13/2022]
Abstract
BACKGROUND In recent years, the establishment of new staging systems for hepatocellular carcinoma (HCC) has been reported worldwide. The system combining albumin-bilirubin (ALBI) with tumor-node-metastasis stage, developed by the Liver Cancer Study Group of Japan, was called the ALBI-T score. METHODS Patient data were retrospectively collected for 357 consecutive patients who had undergone hepatic resection for HCC with curative intent between January 2004 and December 2015. The overall survival and recurrence-free survival were compared by the Kaplan-Meier method, using different staging systems: the Japan integrated staging (JIS), modified JIS, and ALBI-T. RESULTS Multivariate analysis identified five poor prognostic factors (higher age, poor differentiation, the presence of microvascular invasion, the presence of intrahepatic metastasis, and blood transfusion) that influenced overall survival, and four poor prognostic factors (the presence of intrahepatic metastasis, serum α-fetoprotein level, blood transfusion, and each staging system (JIS, modified JIS, and ALBI-T score)) that influenced recurrence-free survival. Patients for each these three staging system had a significantly worse prognosis regarding recurrence-free survival, but not with overall survival. The modified JIS score showed the lowest Akaike information criteria statistic value, indicating it had the best ability to predict overall survival compared with the other staging systems. CONCLUSIONS This retrospective analysis showed that, in post-hepatectomy patients with HCC, the ALBI-T score is predictive of worse recurrence-free survival, even when adjustments are made for other known predictors. However, modified JIS is better than ALBI-T in predicting overall survival.
Collapse
Affiliation(s)
- Norifumi Harimoto
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Tomoharu Yoshizumi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kazuhito Sakata
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Akihisa Nagatsu
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takashi Motomura
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Shinji Itoh
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Noboru Harada
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Toru Ikegami
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Hideaki Uchiyama
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yuji Soejima
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yoshihiko Maehara
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| |
Collapse
|
|
12
|
Li JW, Goh BBG, Chang PE, Tan CK. Barcelona Clinic Liver Cancer outperforms Hong Kong Liver Cancer staging of hepatocellular carcinoma in multiethnic Asians: Real-world perspective. World J Gastroenterol 2017; 23:4054-4063. [PMID: 28652658 PMCID: PMC5473124 DOI: 10.3748/wjg.v23.i22.4054] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2017] [Revised: 03/28/2017] [Accepted: 05/09/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To compare the Barcelona Clinic Liver Cancer (BCLC) and Hong Kong Liver Cancer (HKLC) classification systems when applied to HCC patients from the largest tertiary-level centre in Singapore.
METHODS One thousand two hundred and seventy hepatocellular carcinoma (HCC) patients prospectively enrolled in a tertiary-level centre registry in Singapore since 1988 were studied. Patients were grouped into their respective BCLC and HKLC stages. Data such as demography, aetiology of HCC and type of treatment were collected. Survival data was based on census with the National Registry of Births and Deaths on 31st October 2015. Statistical analyses were done using SPSS version 21 (Chicago, IL, United States). Survival analyses were done by the Kaplan-Meier method. Differences in survival rates were compared using the log-rank test.
RESULTS The median age at presentation was 63 years (range 13-94); male 82.4%; Chinese 89.4%, Malay 7.1%, Indian, 2.8%. Hepatitis B was the predominant aetiology (75.0%; Hepatitis C 7.2%, Hepatitis B and C co-infection 3.8%, non-viral 14.0%). Both BCLC and HKLC staging systems showed good separation with overall log rank test confirming significant survival differences between stages in our cohort (P < 0.001). 206 out of the 240 patients (85.8%) assigned for curative treatment by the BCLC treatment algorithm received curative therapy for HCC [Stage 0 93.2% (68/73); Stage A 82.6% (138/167)]. In contrast, only 341/558 (61.1%) patients received curative treatment despite being assigned for curative treatment by the HKLC treatment algorithm [Stage I 72.7% (264/363); Stage II 40.2% (66/164); Stage Va 35.5% (11/31)]. Patients who were assigned to curative treatment by HKLC but did not receive curative treatment had significantly poorer ECOG (P < 0.001), higher Child-Pugh status (P < 0.001) and were older (median age 66 vs 61, P < 0.001) than those who received curative therapy. Median overall survival in patients assigned to curative treatment groups by BCLC and HKLC were 6.1 and 2.6 years respectively (P < 0.001). When only patients receiving curative treatment were analyzed, BCLC still predicted overall median survival better than HKLC (7.1 years vs 5.5 years, P = 0.037).
CONCLUSION BCLC performs better than HKLC in our multiethnic Asian population in allocating patients to curative treatment in a real-life situation as well as in predicting survival.
Collapse
|
|
13
|
Hansmann J, Ray CE. Overview of Staging Systems for Hepatocellular Carcinoma and Implications for Interventional Radiology. Semin Intervent Radiol 2017; 34:213-219. [PMID: 28579689 DOI: 10.1055/s-0037-1602757] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Jan Hansmann
- Department of Radiology, University of Illinois at Chicago College of Medicine, Chicago, Illinois
| | - Charles E Ray
- Department of Radiology, University of Illinois at Chicago College of Medicine, Chicago, Illinois
| |
Collapse
|
|
14
|
Majumdar A, Roccarina D, Thorburn D, Davidson BR, Tsochatzis E, Gurusamy KS. Management of people with early- or very early-stage hepatocellular carcinoma: an attempted network meta-analysis. Cochrane Database Syst Rev 2017; 3:CD011650. [PMID: 28351116 PMCID: PMC6464490 DOI: 10.1002/14651858.cd011650.pub2] [Citation(s) in RCA: 49] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (primary liver cancer) is classified in many ways. The Barcelona Clinic Liver Cancer (BCLC) group staging classifies the cancer based on patient's life expectancy. People with very early- or early-stage hepatocellular carcinoma have single tumour or three tumours of maximum diameter of 3 cm or less, Child-Pugh status A to B, and performance status 0 (fully functional). Management of hepatocellular carcinoma is uncertain. OBJECTIVES To assess the comparative benefits and harms of different interventions used in the treatment of early or very early hepatocellular carcinoma through a network meta-analysis and to generate rankings of the available interventions according to their safety and efficacy. However, it was not possible to assess whether the potential effect modifiers were similar across different comparisons. Therefore, we did not perform the network meta-analysis and instead assessed the benefits and harms of different interventions versus each other or versus sham or no intervention using standard Cochrane methodology. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, and trials registers to September 2016 to identify randomised clinical trials (RCTs) on hepatocellular carcinoma. SELECTION CRITERIA We included only RCTs, irrespective of language, blinding, or publication status, in participants with very early- or early-stage hepatocellular carcinoma, irrespective of the presence of cirrhosis, portal hypertension, aetiology of hepatocellular carcinoma, size and number of the tumours, and future remnant liver volume. We excluded trials including participants who were previously liver transplanted. We considered interventions compared with each other, sham, or no intervention. DATA COLLECTION AND ANALYSIS We calculated the odds ratio, mean difference, rate ratio, or hazard ratio with 95% confidence intervals using both fixed-effect and random-effects models based on available-participant analysis with Review Manager 5. We assessed the risk of bias according to Cochrane, controlled risk of random errors with Trial Sequential Analysis using Stata, and the quality of the evidence using GRADE. MAIN RESULTS Eighteen trials met the inclusion criteria for this review. Four trials (593 participants; 574 participants included for one or more analyses) compared surgery versus radiofrequency ablation in people with early hepatocellular carcinoma, eligible to undergo surgery. Fourteen trials (2533 participants; 2494 participants included for various analyses) compared different non-surgical interventions in people with early hepatocellular carcinoma, not eligible to undergo surgery. Overall, the quality of evidence was low or very low for all outcomes for both comparisons. Surgery versus radiofrequency ablationThe majority of participants had cirrhotic livers, and the hepatocellular carcinoma was of viral aetiology. The trials did not report the participants' portal hypertension status or whether they received adjuvant antiviral treatment or adjuvant immunotherapy. The average follow-up ranged from 29 months to 42 months (3 trials).There was no evidence of a difference in all-cause mortality at maximal follow-up for surgery versus radiofrequency ablation (hazard ratio 0.80, 95% confidence interval (CI) 0.60 to 1.08; 574 participants; 4 trials; I2 = 68). Cancer-related mortality was lower in the surgery group (20/115 (17.4%)) than in the radiofrequency ablation group (43/115 (37.4%)) (odds ratio 0.35, 95% CI 0.19 to 0.65; 230 participants; 1 trial). Serious adverse events (number of participants) was higher in the surgery group (14/60 (23.3%)) than in the radiofrequency ablation group (1/60 (1.7%)) (odds ratio 17.96, 95% CI 2.28 to 141.60; 120 participants; 1 trial). The number of serious adverse events was higher in the surgery group (adjusted rate 11.3 events per 100 participants) than in the radiofrequency ablation group (3/186 (1.6 events per 100 participants)) (rate ratio 7.02, 95% CI 2.29 to 21.46; 391 participants; 2 trials; I2 = 0%). None of the trials reported health-related quality of life. One trial was funded by a party with vested interests; three trials were funded by parties without any vested. Non-surgical interventionsThe majority of participants had cirrhotic livers, and the hepatocellular carcinoma was of viral aetiology. Most trials did not report the portal hypertension status of the participants, and none of the trials reported whether the participants received adjuvant antiviral treatment or adjuvant immunotherapy. The average follow-up ranged from 6 months to 37 months (11 trials). Trial participants, who were not eligible for surgery, were treated with radiofrequency ablation, laser ablation, microwave ablation, percutaneous acetic acid injection, percutaneous alcohol injection, a combination of radiofrequency ablation with systemic chemotherapy, a combination of radiofrequency ablation with percutaneous alcohol injection, a combination of transarterial chemoembolisation with percutaneous alcohol injection, or a combination of transarterial chemoembolisation with radiofrequency ablation.The mortality at maximal follow-up was higher in the percutaneous acetic acid injection (hazard ratio 1.77, 95% CI 1.12 to 2.79; 125 participants; 1 trial) and percutaneous alcohol injection (hazard ratio 1.49, 95% CI 1.18 to 1.88; 882 participants; 5 trials; I2 = 57%) groups compared with the radiofrequency ablation group. There was no evidence of a difference in all-cause mortality at maximal follow-up for any of the other comparisons. The proportion of people with cancer-related mortality at maximal follow-up was higher in the percutaneous alcohol injection group (adjusted proportion 16.8%) compared with the radiofrequency ablation group (20/232 (8.6%)) (odds ratio 2.18, 95% CI 1.22 to 3.89; 458 participants; 3 trials; I2 = 0%). There was no evidence of a difference in any of the comparisons that reported serious adverse events (number of participants or number of events). None of the trials reported health-related quality of life. Five trials were funded by parties without any vested interest; the source of funding was not available in the remaining trials. AUTHORS' CONCLUSIONS The evidence was of low or very low quality. There was no evidence of a difference in all-cause mortality at maximal follow-up between surgery and radiofrequency ablation in people eligible for surgery. All-cause mortality at maximal follow-up was higher with percutaneous acetic acid injection and percutaneous alcohol injection than with radiofrequency ablation in people not eligible for surgery. There was no evidence of a difference in all-cause mortality at maximal follow-up for the other comparisons. High-quality RCTs designed to assess clinically important differences in all-cause mortality and health-related quality of life, and having an adequate follow-up period (approximately five years) are needed.
Collapse
Affiliation(s)
- Avik Majumdar
- Sheila Sherlock Liver Centre, Royal Free Hospital and the UCL Institute of Liver and Digestive Health, Pond Street, London, UK, NW3 2QG
| | - Davide Roccarina
- Sheila Sherlock Liver Centre, Royal Free Hospital and the UCL Institute of Liver and Digestive Health, Pond Street, London, UK, NW3 2QG
| | - Douglas Thorburn
- Sheila Sherlock Liver Centre, Royal Free Hospital and the UCL Institute of Liver and Digestive Health, Pond Street, London, UK, NW3 2QG
| | - Brian R Davidson
- Department of Surgery, Royal Free Campus, UCL Medical School, Pond Street, London, UK, NW3 2QG
| | - Emmanuel Tsochatzis
- Sheila Sherlock Liver Centre, Royal Free Hospital and the UCL Institute of Liver and Digestive Health, Pond Street, London, UK, NW3 2QG
| | | |
Collapse
|
|
15
|
Roccarina D, Majumdar A, Thorburn D, Davidson BR, Tsochatzis E, Gurusamy KS. Management of people with intermediate-stage hepatocellular carcinoma: an attempted network meta-analysis. Cochrane Database Syst Rev 2017; 3:CD011649. [PMID: 28281295 PMCID: PMC6464331 DOI: 10.1002/14651858.cd011649.pub2] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
BACKGROUND There is significant uncertainty in the treatment of intermediate-stage hepatocellular carcinoma which is defined by the Barcelona Clinic Liver Cancer (BCLC) as hepatocellular carcinoma stage B with large, multi-nodular, Child-Pugh status A to B, performance status 0 to 2, and without vascular occlusion or extrahepatic disease. OBJECTIVES To assess the comparative benefits and harms of different interventions used in the treatment of intermediate-stage hepatocellular carcinoma (BCLC stage B) through a network meta-analysis and to generate rankings of the available interventions according to their safety and efficacy. However, we found only one comparison. Therefore, we did not perform the network meta-analysis, and we assessed the comparative benefits and harms of different interventions versus each other, or versus placebo, sham, or no intervention (supportive treatment only) using standard Cochrane methodology. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and randomised clinical trials registers to September 2016 to identify randomised clinical trials on hepatocellular carcinoma. SELECTION CRITERIA We included only randomised clinical trials, irrespective of language, blinding, or publication status, in participants with intermediate-stage hepatocellular carcinoma, irrespective of the presence of cirrhosis, size, or number of the tumours (provided they met the criteria of intermediate-stage hepatocellular carcinoma), of presence or absence of portal hypertension, of aetiology of hepatocellular carcinoma, and of the future remnant liver volume. We excluded trials which included participants who had previously undergone liver transplantation. We considered any of the various interventions compared with each other or with no active intervention (supportive treatment only). We excluded trials which compared variations of the same intervention: for example, different methods of performing transarterial chemoembolisation. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. We calculated the hazard ratio (HR) with 95% confidence intervals (CI) using both fixed-effect and random-effects models based on available-participant analysis with Review Manager. We assessed risk of bias according to Cochrane, controlled risk of random errors with Trial Sequential Analysis using Stata, and assessed the quality of the evidence using GRADE. MAIN RESULTS Three randomised clinical trials, including 430 participants, met the inclusion criteria for this review; however, data from two trials with 412 participants could be included in only one primary outcome (i.e. mortality). All three trials were at high risk of bias. All three trials included supportive care as cointervention. The comparisons included in the two trials reporting on mortality were: systemic chemotherapy with sorafenib versus no active intervention; and transarterial chemoembolisation plus systemic chemotherapy with sorafenib versus transarterial chemoembolisation alone. The trials did not report the duration of follow-up; however, it appeared that the participants were followed up for a period of about 18 to 30 months. The majority of the participants in the trials had cirrhotic livers. The trials included participants with intermediate-stage hepatocellular carcinoma arising from viral and non-viral aetiologies. The trials did not report the portal hypertension status of the participants. The mortality was 50% to 70% over a median follow-up period of 18 to 30 months. There was no evidence of difference in mortality at maximal follow-up between systemic chemotherapy versus no chemotherapy (hazard ratio 0.85, 95% CI 0.60 to 1.18; participants = 412; studies = 2; I2 = 0%; very low quality evidence). A subgroup analysis performed by stratifying the analysis by the presence or absence of transarterial chemoembolisation as cointervention did not alter the results. None of the trials reported on serious adverse events other than mortality, health-related quality of life, recurrence of hepatocellular carcinoma, or length of hospital stay. One of the trials providing data was funded by the pharmaceutical industry, the other did not report the source of funding, and the trial with no data for the review was also funded by the pharmaceutical industry. We found two ongoing trials. AUTHORS' CONCLUSIONS Currently, there is no evidence from randomised clinical trials that people with intermediate-stage hepatocellular carcinoma would benefit from systemic chemotherapy with sorafenib either alone or when transarterial chemoembolisation was used as a cointervention (very low quality evidence). We need high-quality randomised clinical trials designed to measure differences in clinically important outcomes (e.g. all-cause mortality or health-related quality of life).
Collapse
Affiliation(s)
- Davide Roccarina
- Sheila Sherlock Liver Centre, Royal Free Hospital and the UCL Institute of Liver and Digestive Health, London, UK, NW3 2QG
| | - Avik Majumdar
- Sheila Sherlock Liver Centre, Royal Free Hospital and the UCL Institute of Liver and Digestive Health, London, UK, NW3 2QG
| | - Douglas Thorburn
- Sheila Sherlock Liver Centre, Royal Free Hospital and the UCL Institute of Liver and Digestive Health, London, UK, NW3 2QG
| | - Brian R Davidson
- Department of Surgery, Royal Free Campus, UCL Medical School, Pond Street, London, UK, NW3 2QG
| | - Emmanuel Tsochatzis
- Sheila Sherlock Liver Centre, Royal Free Hospital and the UCL Institute of Liver and Digestive Health, London, UK, NW3 2QG
| | | |
Collapse
|
|
16
|
Choo SP, Tan WL, Goh BKP, Tai WM, Zhu AX. Comparison of hepatocellular carcinoma in Eastern versus Western populations. Cancer 2016; 122:3430-3446. [PMID: 27622302 DOI: 10.1002/cncr.30237] [Citation(s) in RCA: 212] [Impact Index Per Article: 23.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2016] [Revised: 06/23/2016] [Accepted: 06/28/2016] [Indexed: 01/27/2023]
Abstract
Hepatocellular carcinoma (HCC) is a heterogeneous disease that remains highly prevalent in many Asian countries and is the second most common cause of cancer-related mortality worldwide. Significant differences exist between Eastern and Western populations on many key aspects of HCC, contributing to the potential different treatment outcomes and challenges of clinical trial design and data interpretation. In this review, the authors compare HCC in Asia versus the West and highlight 1) differences in terms of epidemiology and trends and their correlation with etiology, 2) differences in genetics and how they relate to underlying etiology, 3) differences in treatment approaches based on existing guidelines and consensus statements, and 4) differences in clinical outcomes for Asian versus non-Asian patients with HCC in clinical trials and the implications for future clinical trial design. Cancer 2016;122:3430-3446. © 2016 American Cancer Society.
Collapse
Affiliation(s)
- Su Pin Choo
- Department of Medical Oncology, National Cancer Center, Singapore
| | - Wan Ling Tan
- Department of Medical Oncology, National Cancer Center, Singapore
| | - Brian K P Goh
- Department of Hepato-Pancreaticobiliary Surgery, Singapore General Hospital, Singapore
| | - Wai Meng Tai
- Department of Medical Oncology, National Cancer Center, Singapore
| | - Andrew X Zhu
- Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts
| |
Collapse
|
|
17
|
Takahara T, Wakabayashi G, Beppu T, Aihara A, Hasegawa K, Gotohda N, Hatano E, Tanahashi Y, Mizuguchi T, Kamiyama T, Ikeda T, Tanaka S, Taniai N, Baba H, Tanabe M, Kokudo N, Konishi M, Uemoto S, Sugioka A, Hirata K, Taketomi A, Maehara Y, Kubo S, Uchida E, Miyata H, Nakamura M, Kaneko H, Yamaue H, Miyazaki M, Takada T. Long-term and perioperative outcomes of laparoscopic versus open liver resection for hepatocellular carcinoma with propensity score matching: a multi-institutional Japanese study. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2015; 22:721-727. [PMID: 26096910 DOI: 10.1002/jhbp.276] [Citation(s) in RCA: 196] [Impact Index Per Article: 19.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/17/2015] [Accepted: 06/17/2015] [Indexed: 12/07/2022]
Abstract
BACKGROUND The aim of this study was to compare the long-term outcomes and perioperative outcomes of laparoscopic liver resection (LLR) with those of open liver resection (OLR) for hepatocellular carcinoma (HCC) between well-matched patient groups. METHODS Hepatocellular carcinoma patients underwent primary liver resection between 2000 and 2010, were collected from 31 participating institutions in Japan and were divided into LLR (n = 436) and OLR (n = 2969) groups. A one-to-one propensity case-matched analysis was used with covariates of baseline characteristics, including tumor characteristics and surgical procedures of hepatic resections. Long-term and short-term outcomes were compared between the matched two groups. RESULTS The two groups were well balanced by propensity score matching and 387 patients were matched. There were no significant differences in overall survival and disease-free survival between LLR and OLR. The median blood loss (158 g vs. 400 g, P < 0.001) was significantly less with LLR, and the median postoperative hospital stay (13 days vs. 16 days, P < 0.001) was significantly shorter for LLR. Complication rate (6.7% vs. 13.0%, P = 0.003) was significantly less in LLR. CONCLUSION Compared with OLR, LLR in selected patients with HCC showed similar long-term outcomes, associated with less blood loss, shorter hospital stay, and fewer postoperative complications.
Collapse
Affiliation(s)
- Takeshi Takahara
- Department of Surgery, Iwate Medical University School of Medicine, Iwate, Japan
| | - Go Wakabayashi
- Department of Surgery, Iwate Medical University School of Medicine, Iwate, Japan
| | - Toru Beppu
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Arihiro Aihara
- Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Kiyoshi Hasegawa
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Naoto Gotohda
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
| | - Etsuro Hatano
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Yoshinao Tanahashi
- Department of Surgery, Fujita Health University School of Medicine, Aichi, Japan
| | - Toru Mizuguchi
- Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Toshiya Kamiyama
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Tetsuo Ikeda
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Shogo Tanaka
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Nobuhiko Taniai
- Department of Gastrointestinal Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Minoru Tanabe
- Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Norihiro Kokudo
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Masaru Konishi
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
| | - Shinji Uemoto
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Atsushi Sugioka
- Department of Surgery, Fujita Health University School of Medicine, Aichi, Japan
| | - Koichi Hirata
- Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Akinobu Taketomi
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Yoshihiko Maehara
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Shoji Kubo
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Eiji Uchida
- Department of Gastrointestinal Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan
| | - Hiroaki Miyata
- Department of Healthcare Quality Assessment, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Masafumi Nakamura
- Department of Digestive Surgery, Kawasaki Medical School, Okayama, Japan
| | - Hironori Kaneko
- Department of Surgery, Toho University Faculty of Medicine, Tokyo, Japan
| | - Hiroki Yamaue
- Second Department of Surgery, Wakayama Medical University, School of Medicine, Wakayama, Japan
| | - Masaru Miyazaki
- Department of General Surgery, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Tadahiro Takada
- Japanese Society of Hepato-biliary-Pancreatic Surgery, Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan
| |
Collapse
|
|
18
|
Lee DY, Park JW, Kim TH, Lee JH, Kim BH, Woo SM, Kim SS, Lee WJ, Kim DY, Kim CM. Prognostic indicators for radiotherapy of abdominal lymph node metastases from hepatocellular carcinoma. Strahlenther Onkol 2015; 191:835-44. [PMID: 26174506 DOI: 10.1007/s00066-015-0873-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2015] [Accepted: 06/23/2015] [Indexed: 02/06/2023]
Abstract
PURPOSE To identify prognostic indicators in patients treated with radiotherapy (RT) for metastases from hepatocellular carcinoma (HCC) in abdominal lymph nodes (LNs). PATIENTS AND METHODS RT was used to treat 65 patients for metastases from HCC in abdominal LNs. Total radiation dose was 30-60 Gy (median 52.8 Gy), with fraction size 1.8-3 Gy. RT was administered five times per week to an equivalent dose in 2-Gy fractions (EQD2; Gy10) of 32.5-65 Gy10 (median 54 Gy10) and an α/βratio for tumor and acute effects of normal tissue of 10. RESULTS Median overall survival (OS) in all patients was 8.1 months. LN responders had significantly higher median OS than nonresponders (14.5 vs. 3.7 months, p < 0.05). Multivariate analysis showed that Child-Pugh classification, status of intrahepatic tumor, number of metastatic LNs, and LN response were independently predictive of OS (p < 0.05 each). Based on results of multivariate analysis, patients were prognostically stratified according to pretreatment risk factors, including Child-Pugh classification, intrahepatic tumor status, and number of metastatic LNs; with the expected median OS in patients with ≥ 2, 1, and 0 risk factors being 2.9, 9.8, and 27.6 months, respectively (p < 0.05). CONCLUSION Our data showed that LN response to RT was an independent prognostic factor for OS in advanced HCC patients with abdominal LN metastases, and suggested that RT for metastatic LNs might improve OS in these patients. In addition, our data suggest that Child-Pugh classification, intrahepatic tumor status, and number of metastatic LNs may be useful prognostic and therapeutic indicators for selecting treatment strategies.
Collapse
Affiliation(s)
- Doo Yeul Lee
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 410-769, Republic of Korea, Goyang, Korea
| | - Joong-Won Park
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 410-769, Republic of Korea, Goyang, Korea
| | - Tae Hyun Kim
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 410-769, Republic of Korea, Goyang, Korea.
| | - Ju Hee Lee
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 410-769, Republic of Korea, Goyang, Korea
| | - Bo Hyun Kim
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 410-769, Republic of Korea, Goyang, Korea
| | - Sang Myung Woo
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 410-769, Republic of Korea, Goyang, Korea
| | - Sang Soo Kim
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 410-769, Republic of Korea, Goyang, Korea
| | - Woo Jin Lee
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 410-769, Republic of Korea, Goyang, Korea
| | - Dae Yong Kim
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 410-769, Republic of Korea, Goyang, Korea
| | - Chang-Min Kim
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 410-769, Republic of Korea, Goyang, Korea
| |
Collapse
|
|
19
|
Tokumitsu Y, Tamesa T, Matsukuma S, Hashimoto N, Maeda Y, Tokuhisa Y, Sakamoto K, Ueno T, Hazama S, Ogihara H, Fujita Y, Hamamoto Y, Oka M, Iizuka N. An accurate prognostic staging system for hepatocellular carcinoma patients after curative hepatectomy. Int J Oncol 2014; 46:944-52. [PMID: 25524574 PMCID: PMC4324590 DOI: 10.3892/ijo.2014.2798] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2014] [Accepted: 11/12/2014] [Indexed: 02/07/2023] Open
Abstract
The aim of this study was to develop an accurate predictive system for prognosis of hepatocellular carcinoma (HCC) patients after hepatectomy. We pooled data of clinicopathological features of 234 HCC patients who underwent curative hepatectomy. On the basis of the pooled data, we established a simple predictive staging system (PS score) scored by the mathematical product of tumor number and size, and degree of liver function. We compared the prognostic abilities of the PS score (score 0-3) with those of six well-known clinical staging systems. Then, we found that there were significant differences (P<0.05) in both disease-free survival (DFS) and overall survival (OS) between patients with different PS scores (PS score 0 vs. 1; PS score 1 vs. 2), and there was a significant difference in DFS, but not OS, between patients with PS score 2 and those with PS score 3. Moreover, the PS score had smaller values of the Akaike information criterion for both DFS and OS than any of the six well-known clinical staging systems. These results suggest that the PS score serves as a simple, accurate predictor for the prognosis of HCC patients after hepatectomy.
Collapse
Affiliation(s)
- Yukio Tokumitsu
- Department of Digestive Surgery and Surgical Oncology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
| | - Takao Tamesa
- Department of Digestive Surgery and Surgical Oncology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
| | - Satoshi Matsukuma
- Department of Digestive Surgery and Surgical Oncology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
| | - Noriaki Hashimoto
- Department of Digestive Surgery and Surgical Oncology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
| | - Yoshinari Maeda
- Department of Digestive Surgery and Surgical Oncology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
| | - Yoshihiro Tokuhisa
- Department of Digestive Surgery and Surgical Oncology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
| | - Kazuhiko Sakamoto
- Department of Digestive Surgery and Surgical Oncology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
| | - Tomio Ueno
- Department of Digestive Surgery and Surgical Oncology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
| | - Shoichi Hazama
- Department of Digestive Surgery and Surgical Oncology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
| | - Hiroyuki Ogihara
- Department of Biomolecular Engineering Applied Molecular Bioscience, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
| | - Yusuke Fujita
- Department of Biomolecular Engineering Applied Molecular Bioscience, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
| | - Yoshihiko Hamamoto
- Department of Biomolecular Engineering Applied Molecular Bioscience, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
| | | | - Norio Iizuka
- Department of Digestive Surgery and Surgical Oncology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
| |
Collapse
|
|
20
|
An C, Choi GH, Lee HS, Kim MJ. Assessment of preoperative magnetic resonance imaging staging in patients with hepatocellular carcinoma undergoing resection compared with the seventh American Joint Committee on Cancer System. Invest Radiol 2013; 47:634-41. [PMID: 22814590 DOI: 10.1097/rli.0b013e3182630e8d] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES The aim of this study was to compare the prognostic utility of a staging system using magnetic resonance imaging (MRI) with the seventh American Joint Committee on Cancer (AJCC) staging system in patients with hepatocellular carcinoma (HCC) who underwent hepatic resection. MATERIALS AND METHODS A total of 175 consecutive patients with HCC who underwent curative hepatic resection after MRI between January 2000 and December 2007 were analyzed. In lieu of microvascular invasion, which is used by the AJCC staging system, we devised an MRI staging system in which a size criterion of 2 cm was used to differentiate between tumor stages 1 and 2. All patients were retrospectively staged using the seventh AJCC staging system and the preoperative MRI staging system. Differences in disease-free and overall survival rates between different stages by the MRI and AJCC staging systems were analyzed using the Kaplan-Meier method with log-rank testing. The predictive accuracy of the 2 staging systems was directly compared using the time-dependent receiver operating characteristic curve analysis. RESULTS Median follow-up period was 222.9 weeks. During the follow-up period, 74 (42.3%) patients experienced tumor recurrence and 22 (12.6%) died. The median disease-free survival and overall survival were 131.1 and 222.9 weeks, respectively. Both staging systems were excellent for the prediction of disease-free survival across different tumor stages but failed to predict overall survival differences between stages 1 and 2. For disease-free and overall survivals, the time-dependent receiver operating characteristic curve analysis revealed no significant differences in predictive accuracy between the 2 staging systems. CONCLUSION A preoperative MRI staging system using a size threshold instead of microvascular invasion may predict the prognosis of HCC patients undergoing hepatic resection as accurately as the seventh AJCC tumor-node-metastasis staging system.
Collapse
Affiliation(s)
- Chansik An
- Department of Diagnostic Radiology, Research Institute of Radiological Science, Medical Research Center, Yonsei University College of Medicine, Seoul, Korea
| | | | | | | |
Collapse
|
|
21
|
Prognosis predictability of hepatocellular carcinoma according to staging systems in hepatitis B virus-endemic area. Clin Res Hepatol Gastroenterol 2012; 36:357-64. [PMID: 22326248 DOI: 10.1016/j.clinre.2011.12.018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2011] [Revised: 12/15/2011] [Accepted: 12/26/2011] [Indexed: 02/04/2023]
Abstract
BACKGROUND There is no worldwide consensus on clinical application of staging systems that have been proposed for hepatocellular carcinoma (HCC). This study evaluated the predictors of survival and compared the prognosis predictability according to staging systems of HCC. PATIENTS AND METHODS We analyzed the medical records of 142 patients who were consecutively diagnosed as HCC in hepatitis B virus (HBV)-endemic area. To analyze the survival predictors and probability of staging systems, Kaplan-Meier method and Cox proportional hazard model were used. And to compare the discriminatory ability and predictive power of staging systems for prognosis and survival, likelyhood ratio χ(2) test and Akaike information criterion were applied. RESULTS Overall median survival of HCC patients was 24 months and 1-, 2-, and 3-year survival rate was 61.3, 49.4, and 45.7%, respectively. Child-Pugh classification (P=0.038) and portal vein thrombosis (PVT) (P=0.022) were ascertained as independent predictors of survival. Although all the staging systems showed a progressive decrease in survival as the tumor stage progressively advanced, the Japan Integrated Staging (JIS) and Chinese University Prognostic Index (CUPI) showed the highest homogeneity (small differences in survival among patients in the same stages), and the best monotonicity of gradient (the survival of patients in earlier stages is longer than the survival of patients in more advanced stages within the same system), respectively. CONCLUSION In HBV-endemic area, Child-Pugh classification and PVT were independent predictors for survival, and JIS and CUPI were the most powerful staging systems to predict the prognosis of HCC.
Collapse
|
|
22
|
Nanashima A, Taura N, Abo T, Ichikawa T, Sakamoto I, Nagayasu T, Nakao K. Tumor marker levels before and after curative treatment of hepatocellular carcinoma as predictors of patient survival. Dig Dis Sci 2011; 56:3086-100. [PMID: 21706206 DOI: 10.1007/s10620-011-1796-6] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2011] [Accepted: 06/08/2011] [Indexed: 01/20/2023]
Abstract
BACKGROUND α-fetoprotein (AFP) is used as a marker for hepatocellular carcinoma (HCC), which is influenced by hepatitis. Protein-induced vitamin K absence or antagonist II (PIVKA-II) is a sensitive diagnostic marker. Changes in these markers after treatment may reflect curability and predict outcome. METHODS We conducted an analysis of prognosis in 470 HCC patients who received curative treatments, and examined the relationship between changes in AFP and PIVKA-II levels after 1 month of treatment in 156 patients. Subjects were divided into three groups according to changes in both levels: (1) normal (L) group before treatment, (2) normalization (N) or (3) decreased but still above normal level or unchanged (ANU) group after treatment. RESULTS High AFP and PIVKA-II levels were significantly associated with poor tumor-free and overall survival. The presence of large size and advanced stage were significantly associated with prevalence of DU group. Overall survival in the AFP-L group was significantly better than that of other groups and overall survival in PIVKA-II-L and N groups were significantly better than that of the PIVKA-II-ANU groups. The combination of changes in the AFP- ANU and PIVKA-II- ANU groups showed the worst tumor-free and overall survivals. Multivariate analysis identified high pre-treatment levels of AFP and PIVKA-II and combination of AFP- ANU and PIVKA-II- ANU as significant determinants of poor tumor-free and overall survival, particularly in patients who underwent hepatectomy. CONCLUSION We conclude that high levels of AFP or PIVKA-II after treatment for HCC did not sufficiently reflect curative efficacy of treatment and reflected a poor predictor of prognosis in HCC patients.
Collapse
Affiliation(s)
- Atsushi Nanashima
- Division of Surgical Oncology and Department of Surgery, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, 8528501, Japan.
| | | | | | | | | | | | | |
Collapse
|
|
23
|
Kim K, Chie EK, Kim W, Kim YJ, Yoon JH, Lee HS, Ha SW. Absence of Symptom and Intact Liver Function Are Positive Prognosticators for Patients Undergoing Radiotherapy for Lymph Node Metastasis From Hepatocellular Carcinoma. Int J Radiat Oncol Biol Phys 2010; 78:729-34. [DOI: 10.1016/j.ijrobp.2009.08.047] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2009] [Revised: 08/21/2009] [Accepted: 08/26/2009] [Indexed: 12/12/2022]
|
|
24
|
Benson AB, Abrams TA, Ben-Josef E, Bloomston PM, Botha JF, Clary BM, Covey A, Curley SA, D'Angelica MI, Davila R, Ensminger WD, Gibbs JF, Laheru D, Malafa MP, Marrero J, Meranze SG, Mulvihill SJ, Park JO, Posey JA, Sachdev J, Salem R, Sigurdson ER, Sofocleous C, Vauthey JN, Venook AP, Goff LW, Yen Y, Zhu AX. NCCN clinical practice guidelines in oncology: hepatobiliary cancers. J Natl Compr Canc Netw 2009; 7:350-91. [PMID: 19406039 PMCID: PMC4461147 DOI: 10.6004/jnccn.2009.0027] [Citation(s) in RCA: 411] [Impact Index Per Article: 25.7] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Al B Benson
- Robert H. Lurie Comprehensive Cancer Center of Northwestern University, USA
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
25
|
Chen CH, Hu FC, Huang GT, Lee PH, Tsang YM, Cheng AL, Chen DS, Wang JD, Sheu JC. Applicability of staging systems for patients with hepatocellular carcinoma is dependent on treatment method--analysis of 2010 Taiwanese patients. Eur J Cancer 2009; 45:1630-9. [PMID: 19157858 DOI: 10.1016/j.ejca.2008.12.025] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2008] [Accepted: 12/18/2008] [Indexed: 11/15/2022]
Abstract
The aim of this study was to compare six prognostic staging systems (Okuda stage, TNM stage, CLIP score, BCLC stage, JIS score and Tokyo score) in predicting survival in patients with hepatocellular carcinoma (HCC). A total of 2010 Taiwanese HCC patients were included. Demographic, laboratory and tumour characteristics were determined at diagnosis. Predictors of survival included serum levels of albumin, total bilirubin, alkaline phosphatase, alpha-fetoprotein, ascites, tumour size and portal vein invasion. The Tokyo score was the most informative one for predicting the survival of HCC patients as a whole, receiving surgical resection, or receiving transarterial chemoembolisation. CLIP score was the best fit system for HCC patients receiving chemotherapy or supportive care. Each staging system showed a significant difference in predicting the probability of survival across different stages. The applicability of staging systems for patients with HCC was dependent on treatment methods.
Collapse
Affiliation(s)
- Chien-Hung Chen
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, 7, Chung-Shan South Road, Taipei 10016, Taiwan
| | | | | | | | | | | | | | | | | |
Collapse
|
|
26
|
Nanashima A, Sumida Y, Abo T, Tobinaga S, Takeshita H, Hidaka S, Yasutake T, Nagayasu T, Mine M, Sawai T. A modified grading system for post-hepatectomy metastatic liver cancer originating from colorectal carcinoma. J Surg Oncol 2008; 98:363-70. [DOI: 10.1002/jso.21114] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
|
|
27
|
Nanashima A, Nakayama T, Sumida Y, Abo T, Takeshita H, Shibata K, Hidaka S, Sawai T, Yasutake T, Nagayasu T. Relationship between microvessel count and post-hepatectomy survival in patients with hepatocellular carcinoma. World J Gastroenterol 2008; 14:4915-22. [PMID: 18756600 PMCID: PMC2739945 DOI: 10.3748/wjg.14.4915] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To elucidate the relationship between the microvessel count (MVC) by CD34 analyzed by immunohistochemical method and prognosis in hepatocellular carcinoma (HCC) patients who underwent hepatectomy based on our preliminary study.
METHODS: We examined relationships between MVC and clinicopathological factors in 128 HCC patients. The modified Japan Integrated Staging score (mJIS) was applied to examine subsets of HCC patients.
RESULTS: Median MVC was 178/mm2, which was used as a cut-off value. MVC was not significantly associated with any clinicopathologic factors or postoperative recurrent rate. Lower MVC was associated with poor disease-free and overall survivals by univariate analysis (P = 0.039 and P = 0.087, respectively) and lower MVC represented an independent poor prognostic factor in disease-free survival by Cox’s multivariate analysis (risk ratio, 1.64; P = 0.024), in addition to tumor size, vascular invasion, macroscopic finding and hepatic dysfunction. Significant differences in disease-free and overall survivals by MVC were observed in HCC patients with mJIS 2 (P = 0.046 and P = 0.0014, respectively), but not in those with other scores.
CONCLUSION: Tumor MVC appears to offer a useful prognostic marker of HCC patient survival, particularly in HCC patients with mJIS 2.
Collapse
|
|
28
|
Luo KZ, Itamoto T, Amano H, Oshita A, Ushitora Y, Tanimoto Y, Ohdan H, Tashiro H, Asahara T. Comparative study of the Japan Integrated Stage (JIS) and modified JIS score as a predictor of survival after hepatectomy for hepatocellular carcinoma. J Gastroenterol 2008; 43:369-77. [PMID: 18592155 DOI: 10.1007/s00535-008-2164-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2007] [Accepted: 01/23/2008] [Indexed: 02/04/2023]
Abstract
BACKGROUND The purpose of the study was to compare the abilities of the JIS and modified JIS (m-JIS) scores to predict survival after hepatectomy for hepatocellular carcinoma (HCC). METHODS Data for patients who underwent hepatectomy for HCC at Hiroshima University Hospital between 1986 and 2006 were included. The overall survival and disease-free survival were calculated by the Kaplan-Meier method, and differences between groups were tested by the log-rank test. The statistics of the Akaike information criterion (AIC) were used to show the more appropriate model. RESULTS A total of 626 patients were included (male/female, 468/158; mean age, 63.4+/-9.6 years; Child-Pugh class A/B, 524/102; liver damage grade A/B/C, 356/261/9). Mean survival and disease-free survival were 8.04+/-0.39 and 4.69+/-0.32 years, respectively. There was a significant difference in the overall survival rate between JIS scores 1 and 2, and 2 and 3 (P<0.05), but not between scores 0 and 1, or 3 and 4 (P>0.05). Except between m-JIS scores 0 and 1, there was excellent discriminatory ability in overall survival rate between other consecutive groups. Concerning disease-free survival, a significant difference was found only between JIS scores 1 and 2. However, the disease-free survival rate could be well differentiated between m-JIS scores 1 and 2, and 3 and 4. The m-JIS score had a higher discriminatory ability, indicated by a linear trend analysis, and a higher homogeneity likelihood ratio, and lower AIC statistics, than the original JIS score in predicting both overall and disease-free survival. CONCLUSIONS The modified-JIS scoring system using liver damage grade is better than the original JIS scoring system in predicting survival after hepatectomy for HCC in Japan.
Collapse
Affiliation(s)
- Kai-Zhong Luo
- Department of Surgery, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan
| | | | | | | | | | | | | | | | | |
Collapse
|
|
29
|
Nanashima A, Masuda J, Miuma S, Sumida Y, Nonaka T, Tanaka K, Hidaka S, Sawai T, Nagayasu T. Selection of treatment modality for hepatocellular carcinoma according to the modified Japan Integrated Staging score. World J Gastroenterol 2008; 14:58-63. [PMID: 18176962 PMCID: PMC2673392 DOI: 10.3748/wjg.14.58] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To compare the prognosis of patients who underwent hepatectomy and ablation using the modified Japan Integrated Staging score (mJIS).
METHODS: We examined the clinicopathologic records and patient outcomes in 278 HCC patients including 226 undergoing hepatectomy and 52 undergoing ablation therapy.
RESULTS: Cirrhosis was more frequent in the ablation group. Tumor size, number and presence of vascular invasion were significantly higher in the operation group compared to the ablation group. The local recurrence rate adjacent to treated lesions was significantly higher in the ablation group compared to the operation group (P < 0.05). The 3- and 5-year survival rates in the ablation and the operation group were 66% and 78%, and 50% and 63%, respectively, but not significantly different. Over 50% survival rates were observed in patients with a mJIS score of 0-2 in both groups. However, survival rates with a score of 3-5 in both groups were significantly lower.
CONCLUSION: According to the mJIS system, both local treatments could be selected for patients with a score of 0-2. However, for patients with a score more than 3, liver transplantation might be a better option in patients with HCC.
Collapse
|
|
30
|
|