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Gu XY, Huo JL, Yu ZY, Jiang JC, Xu YX, Zhao LJ. Immunotherapy in hepatocellular carcinoma: an overview of immune checkpoint inhibitors, drug resistance, and adverse effects. ONCOLOGIE 2024; 26:9-25. [DOI: 10.1515/oncologie-2023-0412] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Abstract
Hepatocellular carcinoma (HCC) is a concerning liver cancer with rising incidence and mortality rates worldwide. The effectiveness of traditional therapies in managing advanced HCC is limited, necessitating the development of new therapeutic strategies. Immune checkpoint inhibitors (ICIs) have emerged as a promising strategy for HCC management. By preventing tumor cells from evading immune surveillance through immunological checkpoints, ICIs can restore the immune system’s ability to target and eliminate tumors. While ICIs show promise in enhancing the immune response against malignancies, challenges such as drug resistance and adverse reactions hinder their efficacy. To address these challenges, developing individualized ICI treatment strategies is critical. Combining targeted therapy and immunotherapy holds the potential for comprehensive therapeutic effects. Additionally, biomarker-based individualized ICI treatment strategies offer promise in predicting treatment response and guiding personalized patient care. Future research should explore emerging ICI treatment methods to optimize HCC immunotherapy. This review provides an overview of ICIs as a new treatment for HCC, demonstrating some success in promoting the tumor immune response. However, drug resistance and adverse reactions remain important considerations that must be addressed. As tailored treatment plans evolve, the prospect of immunotherapy for HCC is expected to grow, offering new opportunities for improved patient outcomes.
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Affiliation(s)
- Xuan-Yu Gu
- Department of General Surgery , Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University , Zunyi , China
| | - Jin-Long Huo
- Department of General Surgery , Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University , Zunyi , China
| | - Zhi-Yong Yu
- Department of General Surgery , Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University , Zunyi , China
| | - Ji-Chang Jiang
- Department of General Surgery , Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University , Zunyi , China
| | - Ya-Xuan Xu
- Department of General Surgery , Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University , Zunyi , China
| | - Li-Jin Zhao
- Department of General Surgery , Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University , Zunyi , China
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Omar A, Kaseb A, Elbaz T, El-Kassas M, El Fouly A, Hanno AF, El Dorry A, Hosni A, Helmy A, Saad AS, Alolayan A, Eysa BE, Hamada E, Azim H, Khattab H, Elghazaly H, Tawfik H, Ayoub H, Khaled H, Saadeldin I, Waked I, Barakat EMF, El Meteini M, Hamed Shaaban M, EzzElarab M, Fathy M, Shaker M, Sobhi M, Shaker MK, ElGharib M, Abdullah M, Mokhtar M, Elshazli M, Heikal OMK, Hetta O, ElWakil RM, Abdel Wahab S, Eid SS, Rostom Y. Egyptian Society of Liver Cancer Recommendation Guidelines for the Management of Hepatocellular Carcinoma. J Hepatocell Carcinoma 2023; 10:1547-1571. [PMID: 37744303 PMCID: PMC10516190 DOI: 10.2147/jhc.s404424] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Accepted: 09/01/2023] [Indexed: 09/26/2023] Open
Abstract
Globally, hepatocellular carcinoma (HCC) is the fourth most common cause of death from cancer. The prevalence of this pathology, which has been on the rise in the last 30 years, has been predicted to continue increasing. HCC is the most common cause of cancer-related morbidity and mortality in Egypt and is also the most common cancer in males. Chronic liver diseases, including chronic hepatitis C, which is a primary health concern in Egypt, are considered major risk factors for HCC. However, HCC surveillance is recommended for patients with chronic hepatitis B virus (HBV) and liver cirrhosis; those above 40 with HBV but without cirrhosis; individuals with hepatitis D co-infection or a family history of HCC; and Nonalcoholic fatty liver disease (NAFLD) patients exhibiting significant fibrosis or cirrhosis. Several international guidelines aid physicians in the management of HCC. However, the availability and cost of diagnostic modalities and treatment options vary from one country to another. Therefore, the current guidelines aim to standardize the management of HCC in Egypt. The recommendations presented in this report represent the current management strategy at HCC treatment centers in Egypt. Recommendations were developed by an expert panel consisting of hepatologists, oncologists, gastroenterologists, surgeons, pathologists, and radiologists working under the umbrella of the Egyptian Society of Liver Cancer. The recommendations, which are based on the currently available local diagnostic aids and treatments in the country, include recommendations for future prospects.
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Affiliation(s)
- Ashraf Omar
- Department of Gastroenterology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed Kaseb
- Department of Gastrointestinal Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Tamer Elbaz
- Department of Gastroenterology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed El-Kassas
- Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Amr El Fouly
- Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Abdel Fatah Hanno
- Department of Gastroenterology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Ahmed El Dorry
- Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Ahmed Hosni
- Department of Interventional Radiology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Amr Helmy
- Department of Surgery, National Liver Institute Menoufia University, Menoufia, Egypt
| | - Amr S Saad
- Department of Oncology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Ashwaq Alolayan
- Department of Oncology, National Guard Hospital, Riyadh, Saudi Arabia
| | - Basem Elsayed Eysa
- Department of Gastroenterology, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Emad Hamada
- Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Hamdy Azim
- Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Hany Khattab
- Department of Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Hesham Elghazaly
- Department of Oncology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Hesham Tawfik
- Department of Oncology, Faculty of Medicine, Tanta University, TantaEgypt
| | - Hisham Ayoub
- Department of Gastroenterology, Military Medical Academy, Cairo, Egypt
| | - Hussein Khaled
- Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ibtessam Saadeldin
- Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Imam Waked
- Department of Gastroenterology, Menoufia Liver Institute, Menoufia, Egypt
| | - Eman M F Barakat
- Department of Gastroenterology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mahmoud El Meteini
- Department of Surgery, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohamed Hamed Shaaban
- Department of Interventional Radiology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed EzzElarab
- Department of Gastroenterology, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Mohamed Fathy
- Department of Surgery, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohamed Shaker
- Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohamed Sobhi
- Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohamed Kamal Shaker
- Department of Gastroenterology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohamed ElGharib
- Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohammed Abdullah
- Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohesn Mokhtar
- Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mostafa Elshazli
- Department of Surgery, Faculty of Medicine, Cairo University, Cairo, Egypt
| | | | - Osama Hetta
- Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Reda Mahmoud ElWakil
- Department of Gastroenterology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Sameh Abdel Wahab
- Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Samir Shehata Eid
- Department of Oncology, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Yousri Rostom
- Department of Oncology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - On behalf of the Egyptian Liver Cancer Committee Study Group
- Department of Gastroenterology, Faculty of Medicine, Cairo University, Cairo, Egypt
- Department of Gastrointestinal Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo, Egypt
- Department of Gastroenterology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
- Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
- Department of Interventional Radiology, Faculty of Medicine, Cairo University, Cairo, Egypt
- Department of Surgery, National Liver Institute Menoufia University, Menoufia, Egypt
- Department of Oncology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
- Department of Oncology, National Guard Hospital, Riyadh, Saudi Arabia
- Department of Gastroenterology, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
- Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt
- Department of Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt
- Department of Oncology, Faculty of Medicine, Tanta University, TantaEgypt
- Department of Gastroenterology, Military Medical Academy, Cairo, Egypt
- Department of Gastroenterology, Menoufia Liver Institute, Menoufia, Egypt
- Department of Gastroenterology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
- Department of Surgery, Faculty of Medicine, Ain Shams University, Cairo, Egypt
- Department of Surgery, Faculty of Medicine, Cairo University, Cairo, Egypt
- Department of Oncology, Faculty of Medicine, Assiut University, Assiut, Egypt
- Department of Oncology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
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2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma. JOURNAL OF LIVER CANCER 2023; 23:1-120. [PMID: 37384024 PMCID: PMC10202234 DOI: 10.17998/jlc.2022.11.07] [Citation(s) in RCA: 68] [Impact Index Per Article: 34.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Accepted: 11/07/2022] [Indexed: 06/30/2023]
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
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Affiliation(s)
- Korean Liver Cancer Association (KLCA) and National Cancer Center (NCC) Korea
- Corresponding author: KLCA-NCC Korea Practice Guideline Revision Committee (KPGRC) (Committee Chair: Joong-Won Park) Center for Liver and Pancreatobiliary Cancer, Division of Gastroenterology, Department of Internal Medicine, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 10408, Korea Tel. +82-31-920-1605, Fax: +82-31-920-1520, E-mail:
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2022 KLCA-NCC Korea Practice Guidelines for the Management of Hepatocellular Carcinoma. Korean J Radiol 2022; 23:1126-1240. [PMID: 36447411 PMCID: PMC9747269 DOI: 10.3348/kjr.2022.0822] [Citation(s) in RCA: 74] [Impact Index Per Article: 24.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 10/28/2022] [Indexed: 11/18/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
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2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma. Clin Mol Hepatol 2022; 28:583-705. [PMID: 36263666 PMCID: PMC9597235 DOI: 10.3350/cmh.2022.0294] [Citation(s) in RCA: 169] [Impact Index Per Article: 56.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 09/23/2022] [Indexed: 01/27/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
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Cisneros-Garza LE, González-Huezo MS, Moctezuma-Velázquez C, Ladrón de Guevara-Cetina L, Vilatobá M, García-Juárez I, Alvarado-Reyes R, Álvarez-Treviño GA, Allende-Pérez S, Bornstein-Quevedo L, Calderillo-Ruiz G, Carrillo-Martínez MA, Castillo-Barradas M, Cerda-Reyes E, Félix-Leyva JA, Gabutti-Thomas JA, Guerrero-Ixtlahuac J, Higuera-de la Tijera F, Huitzil-Melendez D, Kimura-Hayama E, López-Hernández PA, Malé-Velázquez R, Méndez-Sánchez N, Morales-Ruiz MA, Ruíz-García E, Sánchez-Ávila JF, Torrecillas-Torres L. The second Mexican consensus on hepatocellular carcinoma. Part II: Treatment. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2022; 87:362-379. [PMID: 35778341 DOI: 10.1016/j.rgmx.2022.01.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Accepted: 01/20/2022] [Indexed: 01/03/2025]
Abstract
Hepatocellular carcinoma (HCC) is more frequently manifesting as one of the main complications of cirrhosis of the liver, its principal risk factor. There have been modifications in its incidence over the past decade, related to an epidemiologic transition in the etiology of cirrhosis, with a decrease in the prevalence of hepatitis C and an increase in nonalcoholic fatty liver disease (NAFLD) as a cause, as well as the development of HCC in the non-cirrhotic liver due to NAFLD. Genetic markers associated with the disease have been identified, and surveillance and diagnosis have improved. Regarding treatment, surgical techniques, in both resection and transplantation, have advanced and radiologic techniques, at the curative stage of the disease, have enhanced survival in those patients. And finally, there have been radical changes in the systemic approach, with much more optimistic expectations, when compared with the options available a decade ago. Therefore, the Asociación Mexicana de Hepatología decided to carry out the Second Mexican Consensus on Hepatocellular Carcinoma, which is an updated review of the available national and international evidence on the epidemiology, risk factors, surveillance, diagnosis, and treatment of the disease, to offer the Mexican physician current information on the different topics regarding hepatocellular carcinoma. In this second part of the document, the topics related to the treatment of HCC are presented.
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Affiliation(s)
- L E Cisneros-Garza
- Hospital Christus Muguerza Alta Especialidad, Monterrey, Nuevo León, Mexico.
| | | | | | | | - M Vilatobá
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, CDMX, Mexico
| | - I García-Juárez
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, CDMX, Mexico
| | | | | | | | - L Bornstein-Quevedo
- InmunoQ, Laboratorio de Patología, Inmunohistoquímica y Biología Molecular, CDMX, Mexico
| | | | | | | | | | | | - J A Gabutti-Thomas
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, CDMX, Mexico
| | | | | | - D Huitzil-Melendez
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, CDMX, Mexico
| | | | | | - R Malé-Velázquez
- Instituto de Salud Digestiva y Hepática SA de CV, Guadalajara, Jalisco, Mexico
| | | | - M A Morales-Ruiz
- Centro Oncológico Estatal Issemym, Toluca, Estado de México, Mexico
| | | | - J F Sánchez-Ávila
- Escuela de Medicina y Ciencias de la Salud, Tecnológico de Monterrey, Monterrey, Nuevo León, Mexico
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Cisneros-Garza L, González-Huezo M, Moctezuma-Velázquez C, Ladrón de Guevara-Cetina L, Vilatobá M, García-Juárez I, Alvarado-Reyes R, Álvarez-Treviño G, Allende-Pérez S, Bornstein-Quevedo L, Calderillo-Ruiz G, Carrillo-Martínez M, Castillo-Barradas M, Cerda-Reyes E, Félix-Leyva J, Gabutti-Thomas J, Guerrero-Ixtlahuac J, Higuera-de la Tijera F, Huitzil-Melendez D, Kimura-Hayama E, López-Hernández P, Malé-Velázquez R, Méndez-Sánchez N, Morales-Ruiz M, Ruíz-García E, Sánchez-Ávila J, Torrecillas-Torres L. The second Mexican consensus on hepatocellular carcinoma. Part II: Treatment. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2022; 87:362-379. [DOI: 10.1016/j.rgmxen.2022.01.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Accepted: 01/20/2022] [Indexed: 10/25/2022] Open
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Samant H, Amiri HS, Zibari GB. Addressing the worldwide hepatocellular carcinoma: epidemiology, prevention and management. J Gastrointest Oncol 2021; 12:S361-S373. [PMID: 34422400 PMCID: PMC8343080 DOI: 10.21037/jgo.2020.02.08] [Citation(s) in RCA: 84] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2019] [Accepted: 01/22/2020] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world with rising incidence. Globally, there has been substantial variation in prevalence of risk factors for HCC over years, like control of viral hepatitis in developing countries but growing epidemic of fatty liver disease in developed world. Changing epidemiology of HCC is related to trends in these risk factors. HCC remains asymptomatic until it is very advanced which makes early detection by surveillance important in reducing HCC related mortality. Management of HCC. depends on stage of the tumor and severity of underlying liver disease. At present, resection and transplant are still the best curative options for small HCC, but recent advances in locoregional therapy and molecular targeted systemic therapy has changed the management for HCC at intermediate and advanced stages. This review is overview of global epidemiology, prevention, surveillance and emerging therapies for hepatocellular carcinoma.
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Affiliation(s)
- Hrishikesh Samant
- Division of Gastroenterology and Hepatology, LSU Health Science Center, Shreveport, LA, USA
| | - Hosein Shokouh Amiri
- John C McDonald Transplant Center, Willis Knighton Health System, Shreveport, LA, USA
| | - Gazi B. Zibari
- John C McDonald Transplant Center, Willis Knighton Health System, Shreveport, LA, USA
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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: 405] [Impact Index Per Article: 101.3] [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.
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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
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Kamarajah SK, Bundred JR, Littler P, Reeves H, Manas DM, White SA. Treatment strategies for early stage hepatocellular carcinoma: a systematic review and network meta-analysis of randomised clinical trials. HPB (Oxford) 2021; 23:495-505. [PMID: 33309569 DOI: 10.1016/j.hpb.2020.10.031] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Revised: 10/13/2020] [Accepted: 10/14/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Several treatment strategies for early stage hepatocellular cancers (HCC) have been evaluated in randomised controlled trials (RCTs). This network meta-analysis (NMA) aimed to explore the relative effectiveness of these different approaches on their impact on overall (OS) and recurrence-free survival (RFS). METHODS A systematic review was conducted to identify RCT's reported up to 23rd January 2020. Indirect comparisons of all regimens were simultaneously compared using random-effects NMA. RESULTS Twenty-eight RCT's, involving 3,618 patients, reporting 13 different treatment strategies for early stage HCC were identified. Median follow-up, reported in 22 studies, ranged from 12-93 months. In this NMA, RFA in combination with iodine-125 was ranked first for both RFS (HR: 0.50, 95% CI: 0.19-1.31) and OS (HR: 0.41, 95% CI: 0.19-0.94). In subgroup with solitary HCC, lack of studies reporting RFS precluded reliable analysis. However, RFA in combination with iodine-125 was associated with markedly better OS (HR: 0.21, 95% CI: 0.05-0.93). CONCLUSION This NMA identified RFA in combination with iodine-125 as a treatment delivering better RFS and OS, in patients with early stage HCC, especially for those with solitary HCC. This technique warrants further evaluation in both Asia and Western regions.
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Affiliation(s)
- Sivesh K Kamarajah
- Department of HPB and Transplant Surgery, The Freeman Hospital, Newcastle upon Tyne, Tyne and Wear, UK; Institute of Cellular Medicine, University of Newcastle, Newcastle upon Tyne, Tyne and Wear, UK; Department of Surgery, Queen Elizabeth Hospital Birmingham, University Hospital Birmingham NHS Trust, Birmingham, UK.
| | - James R Bundred
- Leeds Teaching Hospitals NHS Trust Research and Innovation Department, Leeds, UK
| | - Peter Littler
- Department of Interventional Radiology, The Freeman Hospital, Newcastle upon Tyne, UK
| | - Helen Reeves
- Newcastle University Centre for Cancer, Newcastle University Medical School, Newcastle upon Tyne, UK; Hepatopancreatobiliary Multidisciplinary Team, Newcastle upon Tyne NHS Foundation Trust, The Freeman Hospital, Newcastle upon Tyne, UK
| | - Derek M Manas
- Department of HPB and Transplant Surgery, The Freeman Hospital, Newcastle upon Tyne, Tyne and Wear, UK
| | - Steven A White
- Department of HPB and Transplant Surgery, The Freeman Hospital, Newcastle upon Tyne, Tyne and Wear, UK; Institute of Cellular Medicine, University of Newcastle, Newcastle upon Tyne, Tyne and Wear, UK
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11
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Jiang G, Ling S, Zhan Q, Zhuang L, Xu X. Downstaging treatment for patients with hepatocelluar carcinoma before transplantation. Transplant Rev (Orlando) 2021; 35:100606. [PMID: 33636480 DOI: 10.1016/j.trre.2021.100606] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Revised: 01/30/2021] [Accepted: 01/31/2021] [Indexed: 12/13/2022]
Abstract
Liver transplantation (LT), one of the radical methods of treating liver cancer, has brought new hope for the treatment of unresectable liver cancer. Currently, patients who meet transplant criteria can achieve a favorable prognosis, but those who exceed transplant criteria tend not to have very satisfactory outcomes. For patients whose tumor burden exceeds the transplant criteria, downstaging treatment is a promising method to reduce tumor burden to within the transplant criteria that may lead to good posttransplant survival. Multiple treatments, such as transcatheter arterial chemoembolization (TACE), transarterial radioembolization (TARE), percutaneous ethanol injection (PEI), and radiofrequency ablation (RFA), have been used as downstaging treatments. However, there are still some issues that limit the effectiveness of downstaging treatments, such as the inclusion criteria for downstaging, which the choice of downstaging treatment method, and the endpoint of downstaging, all of which are worthy of further discussion. Based on the published literature, this review discusses these issues.
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Affiliation(s)
- Guangjiang Jiang
- Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China
| | - Sunbin Ling
- Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China
| | - Qifan Zhan
- Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China
| | - Li Zhuang
- Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou 310003, China.
| | - Xiao Xu
- Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China.
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12
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Zeng Z, Dong J, Li Y, Dong Z, Liu Z, Huang J, Wang Y, Zhen Y, Lu Y. The expression level and diagnostic value of microRNA-22 in HCC patients. ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY 2021; 48:683-686. [PMID: 32088997 DOI: 10.1080/21691401.2019.1703723] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Background: Involvements of microRNA-22 (miR-22) in cancer have attracted much attention, but its role in diagnosis of hepatocellular carcinoma (HCC) is still largely unknown. Therefore, the aim of this study was to investigate the expression level and the prognostic value of miR-22 in HCC patients.Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to evaluate serum level of miR-22 in 108 HCC patients and 67 healthy controls. The relationship between miR-22 expression level and clinicopathologic characteristics was analysed via chi-square test. Receiver operating characteristic (ROC) curve was built to estimate the diagnostic value of serum miR-22 in HCC.Results: miR-22 expression was significantly down-regulated in HCC compared to that in healthy controls (p < .05). And the low miR-22 expression was significantly associated with vein invasion (p = .002), TNM stage (p = .013) and high serum levels of AFP (α-fetoprotein), ALT (alanine aminotransferase), AST (aspartate aminotransferase) and ALP (alkaline phosphatase. miR-22 had a high diagnostic value with area under the curve of 0.866 corresponding with a sensitivity of 89.3% and a specificity of 68.9%, respectively.Conclusion: miR-22 expression was down-regulated in HCC patients. Serum miR-22 might be a novel diagnostic marker in HCC.
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Affiliation(s)
- Zhen Zeng
- Comprehensive Liver Cancer Center, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Jinghui Dong
- Radiology Department, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Yinyin Li
- Comprehensive Liver Cancer Center, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Zheng Dong
- Comprehensive Liver Cancer Center, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Ze Liu
- Comprehensive Liver Cancer Center, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Jiagan Huang
- Comprehensive Liver Cancer Center, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Yonggang Wang
- The Institute of Intensive Care Unit, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Yunhuan Zhen
- General Surgery Department, Guizhou Medical University, Guiyang, China
| | - Yinying Lu
- Comprehensive Liver Cancer Center, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
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13
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Donisi C, Puzzoni M, Ziranu P, Lai E, Mariani S, Saba G, Impera V, Dubois M, Persano M, Migliari M, Pretta A, Liscia N, Astara G, Scartozzi M. Immune Checkpoint Inhibitors in the Treatment of HCC. Front Oncol 2021; 10:601240. [PMID: 33585218 PMCID: PMC7874239 DOI: 10.3389/fonc.2020.601240] [Citation(s) in RCA: 82] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Accepted: 11/11/2020] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the typical inflammation-induced neoplasia. It often prospers where a chronic liver disease persists, thus leading a strong rationale for immune therapy. Several immune-based treatments, including immune checkpoint inhibitors (ICI), cytokines, adoptive cell transfer, and vaccines, have been tested in the treatment of HCC. In this review, we summarize the role of the ICI in HCC patients in various sets of treatment. As for advanced HCC, the anti-Programmed cell Death protein 1 (PD1) antibodies and the anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) antibodies have been examined in patients with enthusiastic results in phase I-II-III studies. Overall, this led the Food and Drug Administration (FDA) to approve pembrolizumab, nivolumab, and nivolumab + ipilimumab in the second-line setting. The anti- Programmed Death-Ligand 1 (PDL-1) antibodies have also been evaluated. Thanks to the results obtained from phase III IMbrave study, atezolizumab + bevacizumab is now the standard of care in the first-line advanced setting of HCC. As for localized HCC, the putative immunological effect of locoregional therapies led to evaluate the combination strategy with ICI. This way, chemoembolization, ablation with radiofrequency, and radioembolization combined with ICI are currently under study. Likewise, the study of adjuvant immunotherapy following surgical resection is underway. In addition, the different ICI has been studied in combination with other ICI as well as with multikinase inhibitors and anti-angiogenesis monoclonal antibody. The evidence available suggests that combining systemic therapies and locoregional treatments with ICI may represent an effective strategy in this context.
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Affiliation(s)
- Clelia Donisi
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
| | - Marco Puzzoni
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
| | - Pina Ziranu
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
| | - Eleonora Lai
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
| | - Stefano Mariani
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
| | - Giorgio Saba
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
| | - Valentino Impera
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
- Medical Oncology Unit, Sapienza University of Rome, Rome, Italy
| | - Marco Dubois
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
| | - Mara Persano
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
| | - Marco Migliari
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
| | - Andrea Pretta
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
- Medical Oncology Unit, Sapienza University of Rome, Rome, Italy
| | - Nicole Liscia
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
- Medical Oncology Unit, Sapienza University of Rome, Rome, Italy
| | - Giorgio Astara
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
| | - Mario Scartozzi
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
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14
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Cardarelli-Leite L, Hadjivassiliou A, Klass D, Chung J, Ho SGF, Lim HJ, Kim PTW, Mujoomdar A, Liu DM. Current locoregional therapies and treatment strategies in hepatocellular carcinoma. ACTA ACUST UNITED AC 2020; 27:S144-S151. [PMID: 33343208 DOI: 10.3747/co.27.7171] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Locoregional therapies (lrts) play an important role in the treatment of hepatocellular carcinoma (hcc), with the aim of increasing overall survival while preserving liver function. Various forms of lrt are available, and choosing the best one depends on technical aspects, liver morphology, tumour biology, and the patient's symptoms. The purpose of the present review article is to provide an overview of the current evidence relating to the use of percutaneous ablation, transarterial chemoembolization, and transarterial radioembolization for the curative or palliative treatment of hcc. Special situations are also reviewed, including the combined use of systemic therapy and lrt, indications and techniques for bridging to transplant and downstaging, and the use of lrt to treat patients with hcc and macrovascular invasion.
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Affiliation(s)
| | - A Hadjivassiliou
- Department of Radiology, University of British Columbia, Vancouver, BC
| | - D Klass
- Department of Radiology, University of British Columbia, Vancouver, BC
| | - J Chung
- Department of Radiology, University of British Columbia, Vancouver, BC
| | - S G F Ho
- Department of Radiology, University of British Columbia, Vancouver, BC
| | - H J Lim
- Department of Medical Oncology, BC Cancer-Vancouver Centre, Vancouver, BC
| | - P T W Kim
- Department of Surgery, University of British Columbia, Vancouver, BC
| | - A Mujoomdar
- Department of Medical Imaging, Western University, London, ON
| | - D M Liu
- Department of Radiology, University of British Columbia, Vancouver, BC
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15
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Population-based matching comparison between radiofrequency ablation and percutaneous ethanol or acetic acid injection for hepatocellular carcinoma. Eur J Surg Oncol 2020; 46:1703-1710. [PMID: 32475629 DOI: 10.1016/j.ejso.2020.04.039] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Revised: 03/23/2020] [Accepted: 04/06/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Loco-regional therapies are evolving for hepatocellular carcinoma (HCC) treatment. Radiofrequency ablation (RFA) has changed the landscape in treating HCC; however, percutaneous ethanol or acetic acid injection (PEI/PAI) remains a widely used and easily performed technique by experienced clinicians. Nevertheless, the effectiveness of RFA compared to that of PEI/PAI remains unclear. METHODS Records of 73,136 patients with newly diagnosed HCC between 2007 and 2013 were drawn from the Taiwan Cancer Registry. The primary outcome measures were the overall survival and local recurrence-free survival. Propensity score matching (PSM) was performed to compare the effectiveness of RFA and PEI. Median follow-up time was 61.6 months (36-120 months). RESULTS After PSM, 4496 patients diagnosed with stage I-III HCC, who were initially treated with RFA (3372 patients) or PEI/PAI (1124 patients), were assessed. Compared to PEI/PAI, patients treated with RFA had better 5- and 9-year overall survival, cancer-specific survival, disease-free survival, and local recurrence-free survival. Median overall survival and recurrence-free survival of patients treated with RFA vs PEI/PAI were 61.5 vs 41.9 months and 72.1 vs 45.2 months, respectively. Multivariate Cox model analysis revealed that, except for patients with high cell grade or advanced stage, RFA resulted in better overall survival (HR: 0.74, 95% CI 0.68-0.81, P < 0.001) and local recurrence-free survival (HR: 0.69, 95% CI 0.63-0.75, P < 0.001) than PEI/PAI. CONCLUSIONS RFA provides advantages over conventional PEI/PAI for HCC. Considering technological advances in instruments, loco-regional therapies for HCC can be employed in carefully selected patients.
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16
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Dendy MS, Ludwig JM, Stein SM, Kim HS. Locoregional Therapy, Immunotherapy and the Combination in Hepatocellular Carcinoma: Future Directions. Liver Cancer 2019; 8:326-340. [PMID: 31768343 PMCID: PMC6873025 DOI: 10.1159/000494843] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2018] [Accepted: 10/23/2018] [Indexed: 02/04/2023] Open
Abstract
Image-guided locoregional therapies (LRTs) have long been a vital part of treatment regimens for hepatocellular carcinoma (HCC). Ablation, chemoembolization, and radioembolization are examples of commonly used treatment techniques for HCC. This review describes the various methods utilized to treat HCC in the field of interventional oncology and also focuses on new and novel treatment concepts being developed in the field including the use of novel immunotherapy agents and combination therapy of LRTs with immunotherapy.
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Affiliation(s)
- Meaghan S. Dendy
- Division of Interventional Radiology, Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut, USA
| | - Johannes M. Ludwig
- Division of Interventional Radiology, Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut, USA,Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Stacey M. Stein
- Division of Medical Oncology, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA,Yale Cancer Center, Yale School of Medicine, New Haven, Connecticut, USA
| | - Hyun S. Kim
- Division of Interventional Radiology, Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut, USA,Division of Medical Oncology, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA,Yale Cancer Center, Yale School of Medicine, New Haven, Connecticut, USA,*Hyun S. Kim, MD, Yale Cancer Center, Yale School of Medicine, 330 Cedar Street, TE 2-224, New Haven, CT 06510 (USA), E-Mail
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17
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2018 Korean Liver Cancer Association-National Cancer Center Korea Practice Guidelines for the Management of Hepatocellular Carcinoma. Korean J Radiol 2019; 20:1042-1113. [PMID: 31270974 PMCID: PMC6609431 DOI: 10.3348/kjr.2019.0140] [Citation(s) in RCA: 191] [Impact Index Per Article: 31.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Accepted: 02/24/2019] [Indexed: 01/10/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer globally and the fourth most common cancer in men in Korea, where the prevalence of chronic hepatitis B infection is high in middle-aged and elderly patients. These practice guidelines will provide useful and constructive advice for the clinical management of patients with HCC. A total of 44 experts in hepatology, oncology, surgery, radiology, and radiation oncology in the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2014 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions.
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18
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2018 Korean Liver Cancer Association-National Cancer Center Korea Practice Guidelines for the Management of Hepatocellular Carcinoma. Gut Liver 2019; 13:227-299. [PMID: 31060120 PMCID: PMC6529163 DOI: 10.5009/gnl19024] [Citation(s) in RCA: 240] [Impact Index Per Article: 40.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2019] [Accepted: 01/24/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer globally and the fourth most common cancer in men in Korea, where the prevalence of chronic hepatitis B infection is high in middle-aged and elderly patients. These practice guidelines will provide useful and constructive advice for the clinical management of patients with HCC. A total of 44 experts in hepatology, oncology, surgery, radiology and radiation oncology in the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2014 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions.
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19
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Lin Y, Wen Q, Guo L, Wang H, Sui G, Sun Z. A network meta-analysis on the efficacy and prognosis of different interventional therapies for early-stage hepatocellular carcinoma. Int J Hyperthermia 2018; 35:450-462. [PMID: 30354777 DOI: 10.1080/02656736.2018.1507047] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Revised: 06/29/2018] [Accepted: 07/29/2018] [Indexed: 02/07/2023] Open
Abstract
PURPOSE It is unclear which kind of interventional therapies is the best when treating early-stage hepatocellular carcinoma (HCC). We conducted Bayesian network meta-analyses to compare local tumor progression (LTP), total tumor recurrence and survival rates and to rank the best intervention arm. MATERIALS AND METHODS A literature search of Pubmed, Embase, Cochrane library and Clinicaltrials.gov was conducted and randomized controlled trials (RCTs) comparing the outcomes of interventional therapies on early-stage HCC were enrolled. The quality assessment was conducted using Cochrane Collaboration's tool, while the outcome synthesis of the network meta-analysis was conducted using R-3.3.4 software. RESULTS A total of 35 RCTs were enrolled for further analysis. Using network meta-analysis, it was demonstrated that radiofrequency ablation (RFA) plus adjuvant therapies achieved the best performance in decreasing the LTP rate in early-stage HCC, while hepatic resection ranked as the best arm among all the interventional techniques for LTP at 3 years. Meanwhile, hepatic resection and RFA plus adjuvant therapies were the top two best arms in decreasing total recurrence. Furthermore, RFA plus adjuvant therapeutics ranked the best in achieving overall survival outcome, followed by hepatic resection. For disease-free survival, hepatic resection was the best, while for LTP-free survival, the difference among the included treatments was not significant. CONCLUSIONS Our network meta-analysis showed that RFA-based adjuvant therapies might be the most effective interventions in achieving the best outcomes, while hepatic resection exhibited the best performance in several situations in treating early-stage HCC. More RCTs are needed to draw more solid conclusions.
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Affiliation(s)
- Yuanqiang Lin
- a Department of Ultrasonography , China-Japan Union Hospital of Jilin University , Changchun , Jilin Province , China
| | - Qiang Wen
- b Department of Nuclear Medicine , China-Japan Union Hospital of Jilin University , Changchun , Jilin Province , China
| | - Li Guo
- c Department of Material Supply , China-Japan Union Hospital of Jilin University , Changchun , Jilin Province , China
| | - Hui Wang
- a Department of Ultrasonography , China-Japan Union Hospital of Jilin University , Changchun , Jilin Province , China
| | - Guoqing Sui
- a Department of Ultrasonography , China-Japan Union Hospital of Jilin University , Changchun , Jilin Province , China
| | - Zhixia Sun
- a Department of Ultrasonography , China-Japan Union Hospital of Jilin University , Changchun , Jilin Province , China
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20
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Tang C, Feng W, Qin L, Bao Y. Chinese Herbal Medicine, Jian Pi Li Gan Decoction, Improved Survival of Nonresectable Hepatocellular Cancer After Radiofrequency Ablation: A Retrospective Study. Integr Cancer Ther 2018; 17:431-436. [PMID: 28745082 PMCID: PMC6041913 DOI: 10.1177/1534735417722223] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2016] [Revised: 05/22/2017] [Accepted: 06/14/2017] [Indexed: 12/20/2022] Open
Abstract
OBJECTIVE To observe the effect of Jian Pi Li Gan Decoction (JPLGD) on long-term survival of nonresectable hepatocellular cancer (HCC) after radiofrequency ablation (RFA). METHODS Between January 2010 and February 2013, 95 patients with nonresectable HCC treated by RFA in our hospital were enrolled, of whom 47 patients received JPLGD accompanying RFA (JPLGD group), and 48 patients received RFA alone (control group). Medical records of these patients were retrospectively analyzed. Long-term survival, complication, and treatment event were compared. RESULTS Baseline characteristics did not differ between the 2 groups. No significant adverse effects or toxicities related to herbal medicine were found. The JPLGD group had significantly less liver failure (3/47 vs 10/48, P = .0405) and a higher treatment success rate than the control group (44/47 vs 37/48, P = .0230). The 3-year overall survival probability was significantly higher in the JPLGD group ( P = .0175). CONCLUSION JPLGD has the potential to effectively and safely improve long-term survival of nonresectable HCC by increasing treatment success of RFA.
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Affiliation(s)
- Chengwu Tang
- First People’s Hospital Affiliated to Huzhou Normal College, Huzhou, Zhejiang Province, People’s Republic of China
| | - Wenming Feng
- First People’s Hospital Affiliated to Huzhou Normal College, Huzhou, Zhejiang Province, People’s Republic of China
| | - Lianjin Qin
- First People’s Hospital Affiliated to Huzhou Normal College, Huzhou, Zhejiang Province, People’s Republic of China
| | - Ying Bao
- First People’s Hospital Affiliated to Huzhou Normal College, Huzhou, Zhejiang Province, People’s Republic of China
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21
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Nazzal M, Gadani S, Said A, Rice M, Okoye O, Taha A, Lentine KL. Liver targeted therapies for hepatocellular carcinoma prior to transplant: contemporary management strategies. GLOBAL SURGERY (LONDON) 2018; 4. [PMID: 29782618 DOI: 10.15761/gos.1000171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Hepatocellular carcinoma (HCC) is an aggressive neoplastic disease that has been rapidly increasing in incidence. It usually occurs in the background of liver disease, and cirrhosis. Definitive therapy requires surgical resection. However, in majority of cases surgical resection is not tolerated, especially in the presence of portal hypertension and cirrhosis. Orthotopic liver transplant (OLT) in well selected candidates has been accepted as a viable option. Due to a relative scarcity of donors compared to the number of listed recipients, long waiting times are anticipated. To prevent patients with HCC from dropping out from the transplant list due to progression of their disease, most centers utilize loco-regional therapies. These loco-regional therapies(LRT) include minimally invasive treatments like percutaneous thermal ablation, trans-arterial chemoembolization, trans-arterial radio-embolization or a combination thereof. The type of therapy or combination used is determined by the size and location of the HCC and Barcelona Clinic Liver Cancer (BCLC) classification. The data regarding the efficacy of LRT in reducing post-transplant recurrence or disease-free survival is limited. This article reviews the available therapies, their strengths, limitations, and current use in the management of patients with hepatocellular carcinoma awaiting transplant.
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Affiliation(s)
- Mustafa Nazzal
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA
| | - Sameer Gadani
- Interventional Radiology, Department of Radiology, St. Louis University Hospital, USA
| | - Abdullah Said
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA
| | - Mandy Rice
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA
| | - Obi Okoye
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA
| | - Ahmad Taha
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA
| | - Krista L Lentine
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA.,Division of Nephrology, Department of Medicine, St Louis University Hospital, USA
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22
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Berger NG, Tanious MN, Hammad AY, Miura JT, Mogal H, Clarke CN, Christians KK, Tsai S, Gamblin TC. External radiation or ablation for solitary hepatocellular carcinoma: A survival analysis of the SEER database. J Surg Oncol 2017; 116:307-312. [PMID: 28464313 DOI: 10.1002/jso.24661] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2017] [Accepted: 04/02/2017] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND OBJECTIVES Hepatocellular carcinoma (HCC) patients are often not candidates for resection. This study hypothesized that external beam radiation (XRT) could be equally effective compared to ablation therapy (AT) for selected HCC patients. METHODS The Surveillance, Epidemiology, and End Results (SEER) database was used to identify HCC patients (2004-2012) undergoing XRT or AT for solitary HCC lesions. Propensity score modeling was utilized to adjust for baseline characteristics. RESULTS Propensity matching identified 784 patients: 157 (20%) XRT and 627 (80%) AT. Median OS for XRT and AT was 22, and 32 months (P < 0.001), respectively. AT demonstrated improved OS for tumors 3-5 cm (30 vs 16 m, P < 0.001) and >5 cm (25 vs 9 m, P < 0.001). Similar survival was found in patients with tumor size <3 cm (37 vs 47 m P = 0.508). Following multivariate analyses, XRT was associated with an increased hazard ratio (HR = 1.64, P < 0.001). Elevated AFP at diagnosis (HR = 1.54, P = 0.001) and tumor size >3 were identified as negative predictors of survival. CONCLUSIONS Similar survival for solitary HCC lesions <3 cm exists between XRT and AT. However, AT demonstrates improved survival rates compared to XRT for lesions >3 cm. This 3 cm reference point may serve as a valuable metric to guide treatment decisions and future investigations.
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Affiliation(s)
- Nicholas G Berger
- Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Michael N Tanious
- Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Abdulrahman Y Hammad
- Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - John T Miura
- Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Harveshp Mogal
- Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Callisia N Clarke
- Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Kathleen K Christians
- Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Susan Tsai
- Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - T Clark Gamblin
- Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin
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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.
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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
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Facciorusso A, Serviddio G, Muscatiello N. Local ablative treatments for hepatocellular carcinoma: An updated review. World J Gastrointest Pharmacol Ther 2016; 7:477-489. [PMID: 27867681 PMCID: PMC5095567 DOI: 10.4292/wjgpt.v7.i4.477] [Citation(s) in RCA: 97] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2016] [Revised: 07/06/2016] [Accepted: 08/18/2016] [Indexed: 02/06/2023] Open
Abstract
Ablative treatments currently represent the first-line option for the treatment of early stage unresectable hepatocellular carcinoma (HCC). Furthermore, they are effective as bridging/downstaging therapies before orthotopic liver transplantation. Contraindications based on size, number, and location of nodules are quite variable in literature and strictly dependent on local expertise. Among ablative therapies, radiofrequency ablation (RFA) has gained a pivotal role due to its efficacy, with a reported 5-year survival rate of 40%-70%, and safety. Although survival outcomes are similar to percutaneous ethanol injection, the lower local recurrence rate stands for a wider application of RFA in hepato-oncology. Moreover, RFA seems to be even more cost-effective than liver resection for very early HCC (single nodule ≤ 2 cm) and in the presence of two or three nodules ≤ 3 cm. There is increasing evidence that combining RFA to transarterial chemoembolization may increase the therapeutic benefit in larger HCCs without increasing the major complication rate, but more robust prospective data is still needed to validate these pivotal findings. Among other thermal treatments, microwave ablation (MWA) uses high frequency electromagnetic energy to induce tissue death via coagulation necrosis. In comparison to RFA, MWA has several theoretical advantages such as a broader zone of active heating, higher temperatures within the targeted area in a shorter treatment time and the lack of heat-sink effect. The safety concerns raised on the risks of this procedure, due to the broader and less predictable necrosis areas, have been recently overcome. However, whether MWA ability to generate a larger ablation zone will translate into a survival gain remains unknown. Other treatments, such as high-intensity focused ultrasound ablation, laser ablation, and cryoablation, are less investigated but showed promising results in early HCC patients and could be a valuable therapeutic option in the next future.
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Li Z, Zhang K, Lin SM, Mi DH, Cao N, Wen ZZ, Li ZX. Radiofrequency ablation combined with percutaneous ethanol injection for hepatocellular carcinoma: a systematic review and meta-analysis. Int J Hyperthermia 2016; 33:237-246. [PMID: 27701918 DOI: 10.1080/02656736.2016.1237681] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Affiliation(s)
- Zheng Li
- Department of General Surgery, First Clinical Medical College of Lanzhou University, Lanzhou, Gansu Province, PR China
- Department of Oncology, Second People's Hospital of Gansu Province, Lanzhou, Gansu Province, PR China
| | - Kai Zhang
- Department of Infectious Disease, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, PR China
| | - Shu-Mei Lin
- Department of Infectious Disease, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, PR China
| | - Deng-Hai Mi
- Department of General Surgery, First Clinical Medical College of Lanzhou University, Lanzhou, Gansu Province, PR China
- Department of Oncology, Second People's Hospital of Gansu Province, Lanzhou, Gansu Province, PR China
| | - Nong Cao
- Department of General Surgery, First Clinical Medical College of Lanzhou University, Lanzhou, Gansu Province, PR China
| | - Zhi-Zhen Wen
- Department of Oncology, Second People's Hospital of Gansu Province, Lanzhou, Gansu Province, PR China
| | - Zhong-Xin Li
- Department of Oncology, Second People's Hospital of Gansu Province, Lanzhou, Gansu Province, PR China
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Frenk NE, Sebastianes F, Lerario AM, Fragoso MCBV, Mendonca BB, de Menezes MR. Long-term Results after CT-Guided Percutaneous Ethanol Ablation for the Treatment of Hyperfunctioning Adrenal Disorders. Clinics (Sao Paulo) 2016; 71:600-605. [PMID: 27759849 PMCID: PMC5054768 DOI: 10.6061/clinics/2016(10)08] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2016] [Accepted: 07/27/2016] [Indexed: 12/20/2022] Open
Abstract
OBJECTIVES: To evaluate the safety and long-term efficacy of computed tomography-guided percutaneous ethanol ablation for benign primary and secondary hyperfunctioning adrenal disorders. METHOD: We retrospectively evaluated the long-term results of nine patients treated with computed tomography-guided percutaneous ethanol ablation: eight subjects who presented with primary adrenal disorders, such as pheochromocytoma, primary macronodular adrenal hyperplasia and aldosterone-producing adenoma, and one subject with Cushing disease refractory to conventional treatment. Eleven sessions were performed for the nine patients. The patient data were reviewed for the clinical outcome and procedure-related complications over ten years. RESULTS: Patients with aldosterone-producing adenoma had clinical improvement: symptoms recurred in one case 96 months after ethanol ablation, and the other patient was still in remission 110 months later. All patients with pheochromocytoma had clinical improvement but were eventually submitted to surgery for complete remission. No significant clinical improvement was seen in patients with hypercortisolism due to primary macronodular adrenal hyperplasia or Cushing disease. Major complications were seen in five of the eleven procedures and included cardiovascular instability and myocardial infarction. Minor complications attributed to sedation were seen in two patients. CONCLUSION: Computed tomography-guided ethanol ablation does not appear to be suitable for the long-term treatment of hyperfunctioning adrenal disorders and is not without risks.
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Affiliation(s)
- Nathan Elie Frenk
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Instituto de Radiologia, Serviço de Intervenção Guiada por Imagem, São Paulo/SP, Brazil
| | - Fernando Sebastianes
- Faculdade de Medicina da Universidade de São Paulo, Disciplina de Endocrinologia, Departamento de Medicina Interna, São Paulo/SP, Brazil
| | - Antonio Marcondes Lerario
- Faculdade de Medicina da Universidade de São Paulo, Disciplina de Endocrinologia, Departamento de Medicina Interna, São Paulo/SP, Brazil
| | | | - Berenice Bilharinho Mendonca
- Faculdade de Medicina da Universidade de São Paulo, Disciplina de Endocrinologia, Departamento de Medicina Interna, São Paulo/SP, Brazil
| | - Marcos Roberto de Menezes
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Instituto de Radiologia, Serviço de Intervenção Guiada por Imagem, São Paulo/SP, Brazil
- Instituto do Câncer do Estado de São Paulo, Serviço de Radiologia e Intervenção Guiada por Imagem, São Paulo/SP, Brazil
- E-mail:
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27
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Assessment of Early Treatment Response With DWI After CT-Guided Radiofrequency Ablation of Functioning Adrenal Adenomas. AJR Am J Roentgenol 2016; 207:804-810. [DOI: 10.2214/ajr.16.16207] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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Qi X, Zhao Y, Li H, Guo X, Han G. Management of hepatocellular carcinoma: an overview of major findings from meta-analyses. Oncotarget 2016; 7:34703-51. [PMID: 27167195 PMCID: PMC5085185 DOI: 10.18632/oncotarget.9157] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2016] [Accepted: 04/11/2016] [Indexed: 02/07/2023] Open
Abstract
This paper aims to systematically review the major findings from meta-analyses comparing different treatment options for hepatocellular carcinoma (HCC). A total of 153 relevant papers were searched via the PubMed, EMBASE, and Cochrane library databases. They were classified according to the mainstay treatment modalities (i.e., liver transplantation, surgical resection, radiofrequency ablation, transarterial embolization or chemoembolization, sorafenib, and others). The primary outcome data, such as overall survival, diseases-free survival or recurrence-free survival, progression-free survival, and safety, were summarized. The recommendations and uncertainties regarding the treatment of HCC were also proposed.
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Affiliation(s)
- Xingshun Qi
- 1 Department of Gastroenterology and Meta-analysis Study Interest Group, General Hospital of Shenyang Military Area, Shenyang, 110840 China
- 2 Department of Liver Diseases and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032 China
| | - Yan Zhao
- 2 Department of Liver Diseases and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032 China
- 3 Department of Gastroenterology, First Affiliated Hospital of the Medical College, Xi'an Jiaotong University, Xi'an, 710000 China
| | - Hongyu Li
- 1 Department of Gastroenterology and Meta-analysis Study Interest Group, General Hospital of Shenyang Military Area, Shenyang, 110840 China
| | - Xiaozhong Guo
- 1 Department of Gastroenterology and Meta-analysis Study Interest Group, General Hospital of Shenyang Military Area, Shenyang, 110840 China
| | - Guohong Han
- 2 Department of Liver Diseases and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032 China
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29
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Shi Y, Zhai B. A Recent Advance in Image-Guided Locoregional Therapy for Hepatocellular Carcinoma. Gastrointest Tumors 2016; 3:90-102. [PMID: 27904861 DOI: 10.1159/000445888] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2016] [Accepted: 03/22/2016] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third most common cause of cancer-related deaths. Hepatic resection and liver transplantation are considered to be the preferred treatment for HCC. However, as novel therapeutic options such as image-guided locoregional therapies have emerged and been refined, the manner in which HCC is treated has changed dramatically compared with what it was considered just 2 decades earlier. SUMMARY This study reviews the current results of various image-guided locoregional therapies for treating HCC, especially focusing on thermal ablative and transarterial techniques. KEY MESSAGE Advances in image-guided locoregional therapies, including local ablative therapy and transarterial therapy, have led to a major breakthrough in the management of HCC. Both survival rates and cure rates of patients with HCC have improved markedly since the introduction of these techniques. PRACTICAL IMPLICATIONS Radiofrequency ablation is currently considered as an alternative to surgical resection for patients with early-stage HCC. A newer technique of ablation such as microwave ablation is increasingly being used, especially for large HCC. Transarterial chemoembolization has become a standard care for asymptomatic patients with multinodular tumors in intermediate-stage disease, and transarterial radioembolization has become the method of choice in HCC cases with portal vein thrombosis. Moreover, combination treatment modalities, such as thermal-based ablation combined with transarterial chemoembolization or 125I seed implant brachytherapy, may further broaden their clinical indications for HCC. Moreover, use of localized radiation in combination with thermal ablation has been reported to improve tumor control and long-term survival.
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Affiliation(s)
- Yaoping Shi
- Department of Interventional Oncology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Bo Zhai
- Department of Interventional Oncology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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Mauer K, O'Kelley R, Podda N, Flanagan S, Gadani S. New treatment modalities for hepatocellular cancer. Curr Gastroenterol Rep 2015; 17:442. [PMID: 25869473 DOI: 10.1007/s11894-015-0442-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Heptatocellular (HCC) is a rapidly progressive fatal malignancy often presenting at an advanced stage at the time of initial diagnosis. Loco-regional therapies for early-stage HCC including surgical options (surgical resection and liver transplant) and percutaneous ablations could be potentially curative. Recent technological advances in percutaneous image-guided ablations have provided clinicians with a range of options which have proven to be equal to or better than surgical resection. For intermediate- and advanced-stage HCC, palliative therapies are available which significantly increase overall and progression-free survival. These palliative therapies include intra-arterial chemo- or radioembolization as monotherapy or in combination with percutaneous ablation or antiangiogenic drugs. Availability of a multitude of treatment options for various stages of HCC as well as conflicting data comparing their safety and efficacy presented in the several randomized controlled trials poses a significant challenge to hepatologists, surgeons, and interventional radiologists in selecting optimal therapy for their patients. The aim of this article is to review and discuss currently available therapies at each stage of HCC along with presenting clinical data published in most recent and relevant randomized controlled trials.
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Affiliation(s)
- Kurt Mauer
- Division of Interventional Radiology, Department of Radiology, Saint Louis University School of Medicine, 3635 Vista Ave at Grand Blvd, St Louis, MO, 63110, USA,
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Sacco R, Antonucci M, Bresci G, Corti A, Giacomelli L, Mismas V, Rainieri M, Romano A, Eggenhoffner R, Tumino E, Cabibbo G. Curative therapies for hepatocellular carcinoma: an update and perspectives. Expert Rev Anticancer Ther 2015; 16:169-175. [PMID: 26588992 DOI: 10.1586/14737140.2016.1123625] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Curative treatments, including liver transplantation, surgical resection and percutaneous treatments, are the recommended therapies in BCLC-0 (Barcelona Clinic of Liver Cancer) or BCLC-A hepatocellular carcinoma (HCC). This review provides an overview of some issues of clinical importance concerning curative treatments in HCC.
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Affiliation(s)
- Rodolfo Sacco
- a Department of Gastroenterology , Pisa University Hospital , Pisa , Italy
| | - Michela Antonucci
- b Section of Radiology - Di.Bi.Me.F. , University of Palermo , Palermo , Italy
| | - Giampaolo Bresci
- a Department of Gastroenterology , Pisa University Hospital , Pisa , Italy
| | | | - Luca Giacomelli
- d Department of Surgical Sciences and Integrated Diagnostics, School of Medicine , Genova University , Genoa , Italy
| | - Valeria Mismas
- a Department of Gastroenterology , Pisa University Hospital , Pisa , Italy
| | - Maurizio Rainieri
- e Section of Gastroenterology - Di.Bi.M.I.S. , University of Palermo , Palermo , Italy
| | - Antonio Romano
- a Department of Gastroenterology , Pisa University Hospital , Pisa , Italy
| | - Roberto Eggenhoffner
- d Department of Surgical Sciences and Integrated Diagnostics, School of Medicine , Genova University , Genoa , Italy
| | - Emanuele Tumino
- a Department of Gastroenterology , Pisa University Hospital , Pisa , Italy
| | - Giuseppe Cabibbo
- e Section of Gastroenterology - Di.Bi.M.I.S. , University of Palermo , Palermo , Italy
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XU ZONGQUAN, YU CHEN, WANG SHUFANG, XU GUOHUI. Transcatheter arterial chemoembolization as an examination method for hepatocellular carcinoma undetected by B-mode ultrasound, computed tomography and digital subtratcion angiography: A case report. Oncol Lett 2015; 10:1759-1762. [PMID: 26622746 PMCID: PMC4533667 DOI: 10.3892/ol.2015.3446] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2014] [Accepted: 04/14/2015] [Indexed: 01/04/2023] Open
Abstract
Transcatheter arterial chemoembolization (TACE) is the conventional treatment for patients with unresectable hepatocellular carcinoma (HCC), but few studies to date have demonstrated the use of TACE as an examination method for uneasily detected HCC. The present study describes an unusual case of HCC with TACE as an examination method. A 41-year-old male presented with an elevated α-fetoprotein level (AFP) of 3,635 ng/ml, however, no tumor lesions were detected by B-mode ultrasound, computed tomography (CT) or digital subtraction angiography. During TACE treatment, two tumor lesions of ~0.5 and 0.8 cm were revealed in the right liver lobe, with no tumors in the left liver lobe. A month after TACE, a liver CT scan found 11 lesions (8 in the right liver lobe and 3 in the left liver lobe). The HCC patient's AFP levels decreased to an almost normal level following the TACE treatment. This study provokes consideration of the application of TACE in the diagnosis and treatment of HCC patients with liver lesions that are hard to detect by conventional means.
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Affiliation(s)
- ZONGQUAN XU
- Department of Hepatic Oncology, Jiangxi Province Cancer Hospital, Nanchang, Jiangxi 330029, P.R. China
| | - CHEN YU
- Department of Bone Oncology, Jiangxi Province Cancer Hospital, Nanchang, Jiangxi 330029, P.R. China
| | - SHUFANG WANG
- Department of Hepatic Oncology, Jiangxi Province Cancer Hospital, Nanchang, Jiangxi 330029, P.R. China
| | - GUOHUI XU
- Department of Hepatic Oncology, Jiangxi Province Cancer Hospital, Nanchang, Jiangxi 330029, P.R. China
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Waghray A, Murali AR, Menon KVN. Hepatocellular carcinoma: From diagnosis to treatment. World J Hepatol 2015; 7:1020-1029. [PMID: 26052391 PMCID: PMC4450179 DOI: 10.4254/wjh.v7.i8.1020] [Citation(s) in RCA: 113] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2014] [Revised: 01/15/2015] [Accepted: 02/12/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the sixth most prevalent malignancy worldwide and is a rising cause of cancer related mortality. Risk factors for HCC are well documented and effective surveillance and early diagnosis allow for curative therapies. The majority of HCC appears to be caused by cirrhosis from chronic hepatitis B and hepatitis C virus. Preventive strategies include vaccination programs and anti-viral treatments. Surveillance with ultrasonography detects early stage disease and improves survival rates. Many treatment options exist for individuals with HCC and are determined by stage of presentation. Liver transplantation is offered to patients who are within the Milan criteria and are not candidates for hepatic resection. In patients with advanced stage disease, sorafenib shows some survival benefit.
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Gomaa AI, Waked I. Recent advances in multidisciplinary management of hepatocellular carcinoma. World J Hepatol 2015; 7:673-87. [PMID: 25866604 PMCID: PMC4388995 DOI: 10.4254/wjh.v7.i4.673] [Citation(s) in RCA: 64] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2014] [Revised: 12/17/2014] [Accepted: 01/15/2015] [Indexed: 02/06/2023] Open
Abstract
The incidence of hepatocellular carcinoma (HCC) is increasing, and it is currently the second leading cause of cancer-related death worldwide. Potentially curative treatment options for HCC include resection, transplantation, and percutaneous ablation, whereas palliative treatments include trans-arterial chemoembolization (TACE), radioembolization, and systemic treatments. Due to the diversity of available treatment options and patients' presentations, a multidisciplinary team should decide clinical management of HCC, according to tumor characteristics and stage of liver disease. Potentially curative treatments are suitable for very-early- and early-stage HCC. However, the vast majority of HCC patients are diagnosed in later stages, where the tumor characteristics or progress of liver disease prevent curative interventions. For patients with intermediate-stage HCC, TACE and radioembolization improve survival and are being evaluated in addition to potentially curative therapies or with systemic targeted therapy. There is currently no effective systemic chemotherapy, immunologic, or hormonal therapy for HCC, and sorafenib is the only approved molecular-targeted treatment for advanced HCC. Other targeted agents are under investigation; trials comparing new agents in combination with sorafenib are ongoing. Combinations of systemic targeted therapies with local treatments are being evaluated for further improvements in HCC patient outcomes. This article provides an updated and comprehensive overview of the current standards and trends in the treatment of HCC.
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Affiliation(s)
- Asmaa I Gomaa
- Asmaa I Gomaa, Imam Waked, Hepatology Department, National Liver Institute, Menoufiya University, Shebeen El-Kom 35111, Egypt
| | - Imam Waked
- Asmaa I Gomaa, Imam Waked, Hepatology Department, National Liver Institute, Menoufiya University, Shebeen El-Kom 35111, Egypt
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Yang B, Zan RY, Wang SY, Li XL, Wei ML, Guo WH, You X, Li J, Liao ZY. Radiofrequency ablation versus percutaneous ethanol injection for hepatocellular carcinoma: a meta-analysis of randomized controlled trials. World J Surg Oncol 2015; 13:96. [PMID: 25889181 PMCID: PMC4355988 DOI: 10.1186/s12957-015-0516-7] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2014] [Accepted: 02/14/2015] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Radiofrequency ablation (RFA) and percutaneous ethanol injection (PEI) are treatment methods for patients with early-stage hepatocellular carcinoma (HCC) who are not suitable for surgery. Although some reports indicate that RFA is better than PEI, results from previous reviews and analyses are inconsistent. Therefore, this meta-analysis was performed to more thoroughly evaluate the effects of these treatments in patients with HCC. METHODS A literature search was conducted using the Excerpta Medica dataBASE, PubMed, the Cochrane Library, the American Society of Clinical Oncology database, the China National Knowledge Infrastructure database, the Wanfang database, the Chinese Biomedical Literature Database, and the Chongqing VIP database without language limitations. The primary outcome evaluated was overall survival, and secondary outcomes included complete response and local recurrence. Comparisons were made between Asian and European studies. RESULTS Total pooled and subgroup analyses of Asian studies that included selection biases revealed that RFA is superior to PEI with respect to overall survival (hazard ratio (HR), 0.54; 95% confidence interval (CI), 0.37 to 0.80; P < 0.01) and complete response (relative risk (RR), 1.10; 95% CI 1.03 to 1.18; P < 0.01). However, no significant difference was observed between RFA and PEI in the European studies. In Asian studies, RFA was associated with a lower local recurrence rate than PEI at 1 year (RR, 0.44; 95% CI 0.20 to 0.95; P < 0.05) and 3 years (RR, 0.35; 95% CI 0.22 to 0.55; P < 0.01). However, local recurrence was significantly lower after only 3 years in European studies (RR, 0.50; 95% CI 0.32 to 0.78; P < 0.05). CONCLUSIONS RFA was only superior to PEI in Asian studies that included selection bias. Thus, there is insufficient evidence to support the idea that RFA is superior to PEI for patients with cirrhotic HCC. Additional large-scale, multicenter, randomized controlled trials that control for selection bias are needed to fully elucidate the optimal treatment method for HCC.
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Affiliation(s)
- Biao Yang
- Department of Abdominal Oncology, West China Hospital, West China Medical School, Sichuan University, No. 17 Renming Road, Chengdu, 610000, People's Republic of China.
| | - Rui-yu Zan
- Department of Abdominal Oncology, West China Hospital, West China Medical School, Sichuan University, No. 17 Renming Road, Chengdu, 610000, People's Republic of China.
| | - Shi-yu Wang
- Department of Radiology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
| | - Xiang-lian Li
- Chinese Evidence-Based Medicine Centre, West China Hospital, West China Medical School, Sichuan University, No. 17 Renming Road, Chengdu, 610000, China.
| | - Mao-ling Wei
- Chinese Evidence-Based Medicine Centre, West China Hospital, West China Medical School, Sichuan University, No. 17 Renming Road, Chengdu, 610000, China.
| | - Wen-hao Guo
- Department of Abdominal Oncology, West China Hospital, West China Medical School, Sichuan University, No. 17 Renming Road, Chengdu, 610000, People's Republic of China.
| | - Xin You
- Department of Abdominal Oncology, West China Hospital, West China Medical School, Sichuan University, No. 17 Renming Road, Chengdu, 610000, People's Republic of China.
| | - Jing Li
- Chinese Evidence-Based Medicine Centre, West China Hospital, West China Medical School, Sichuan University, No. 17 Renming Road, Chengdu, 610000, China.
| | - Zheng-yin Liao
- Department of Abdominal Oncology, West China Hospital, West China Medical School, Sichuan University, No. 17 Renming Road, Chengdu, 610000, People's Republic of China.
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Willatt J, Hannawa KK, Ruma JA, Frankel TL, Owen D, Barman PM. Image-guided therapies in the treatment of hepatocellular carcinoma: A multidisciplinary perspective. World J Hepatol 2015; 7:235-244. [PMID: 25729478 PMCID: PMC4342605 DOI: 10.4254/wjh.v7.i2.235] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2014] [Revised: 10/26/2014] [Accepted: 11/19/2014] [Indexed: 02/06/2023] Open
Abstract
A multidisciplinary approach to the treatment of patients with unresectable hepatocellular carcinoma (HCC) has led to improvements in screening, detection, and treatments. Interventional techniques include thermal ablation, transarterial chemoembolization, and radioembolization whilst stereotactic body radiation therapy also uses imaging to target the radiation. Both survival rates and cure rates have improved markedly since the introduction of these techniques. This review article describes the image guided techniques used for the treatment of HCC.
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Yang W, Yan K, Wu GX, Wu W, Fu Y, Lee JC, Zhang ZY, Wang S, Chen MH. Radiofrequency ablation of hepatocellular carcinoma in difficult locations: Strategies and long-term outcomes. World J Gastroenterol 2015; 21:1554-1566. [PMID: 25663774 PMCID: PMC4316097 DOI: 10.3748/wjg.v21.i5.1554] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2014] [Revised: 07/29/2014] [Accepted: 09/19/2014] [Indexed: 02/07/2023] Open
Abstract
AIM: To investigate the treatment strategies and long-term outcomes of radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) in difficult locations and to compare the results with non-difficult HCC.
METHODS: From 2004 to 2012, a total of 470 HCC patients underwent ultrasound-guided percutaneous RFA. Among these HCC patients, 382 with tumors located ≤ 5 mm from a major vessel/bile duct (n = 87), from peripheral important structures (n = 232) or from the liver capsule (n = 63) were regarded as difficult cases. There were 331 male patients and 51 female patients, with an average age of 55.3 ± 10.1 years old. A total of 235 and 147 patients had Child-Pugh class A and class B liver function, respectively. The average tumor size was 3.4 ± 1.2 cm. Individual treatment strategies were developed to treat these difficult cases. During the same period, 88 HCC patients with tumors that were not in difficult locations served as the control group. In the control group, 74 patients were male, and 14 patients were female, with an average age of 57.4 ± 11.8 years old. Of these, 62 patients and 26 patients had Child-Pugh class A and class B liver function, respectively. Regular follow-up after RFA was performed to assess treatment efficacy. Survival results were generated from Kaplan-Meier estimates, and multivariate analysis was performed using the Cox regression model.
RESULTS: Early tumor necrosis rate in the difficult group was similar to that in the control group (97.6% vs 94.3%, P = 0.080). The complication rate in the difficult group was significantly higher than that in the control group (4.9% vs 0.8%, P = 0.041). The follow-up period ranged from 6 to 116 mo, with an average of 28 ± 22.4 mo. Local progression rate in the difficult group was significantly higher than that in the control group (12.7% vs 7.1%, P = 0.046). However, the 1-, 3-, 5-, and 7-year overall survival rates in the difficult group were not significantly different from those in the control group (84.3%, 54.4%, 41.2%, and 29.9% vs 92.5%, 60.3%, 43.2%, and 32.8%, respectively, P = 0.371). Additionally, a multivariate analysis revealed that tumor location was not a significant risk factor for survival.
CONCLUSION: There was no significant difference in long-term overall survival between the two groups even though the local progression rate was higher in the difficult group.
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Cabibbo G, Antonucci M, Sacco R, Sciarrino E. Ultrasound-guided ablation for hepatocellular carcinoma: time for a reappraisal? Expert Rev Anticancer Ther 2015; 15:147-150. [DOI: 10.1586/14737140.2015.1001374] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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Xu RH, Gao W, Wang C, Guo DK, Tang L, Zhang H, Wang CJ. Systematic evaluation of percutaneous radiofrequency ablation versus percutaneous ethanol injection for the treatment of small hepatocellular carcinoma: a meta-analysis. Eur J Med Res 2014; 19:39. [PMID: 25141776 PMCID: PMC4237813 DOI: 10.1186/2047-783x-19-39] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2014] [Accepted: 06/24/2014] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND Radiofrequency ablation (RFA) and percutaneous ethanol injection (PEI) have been used for patients with hepatocellular carcinoma (HCC). However, which therapy is superior remains to be further elucidated. We aimed to conduct a systematic review to assess survival and local tumor recurrence rate with RFA compared with PEI therapy for HCC. METHODS We conducted systematic review and meta-analysis of randomized controlled trials (RCTs) published up to 2014 in PubMed, MEDLINE, EMBASE, EBSCO, Springer, Ovid and the Cochrane library. Only RCTs that evaluated survival rate and occurrence of HCC between RFA and PEI therapy were included. The OR (odds ratio) with a 95% confidence interval (CI) was calculated by the Revman 5.0 software. RESULTS A total of six studies including 983 HCC patients were eligible for this analysis. The survival rate showed a significant benefit under RFA therapy over PEI at 1-year (P = 0.02, OR = 1.88, 95% CI: 1.09 to 3.22), 2-years (P = 0.0003, OR = 2.06, 95% CI: 1.39 to 3.05) and 3-years (P = 0.0007, OR = 1.68, 95% CI: 1.25 to 2.27). Likewise, RFA achieved significantly lower rates of local tumor recurrence over PEI at 1-year (P = 0.002, OR = 0.43, 95% CI: 0.26 to 0.73), 2-year (P = 0.03, OR = 0.33, 95% CI: 0.12 to 0.88) and 3-year (P = 0.003, OR = 0.61, 95% CI: 0.43 to 0.84). CONCLUSIONS The current evidence suggests that RFA is superior to PEI in better survival and local disease control for small HCCs <5 cm in diameter and that RFA is worthy of promotion in clinical applications.
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Affiliation(s)
| | | | | | | | | | - Hui Zhang
- Department of Hepatobiliary and Pancreatic Diseases, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Pudong New District, Shanghai 200120, China.
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Preoperative transcatheter arterial chemoembolization for resectable hepatocellular carcinoma: a single center analysis. Ann Hepatol 2014. [DOI: 10.1016/s1665-2681(19)30846-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/12/2023]
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Zhang QC, Pan GZ, Li GQ, Yuan QZ, Xu JB, Kong Y, Wang LM. DC-CIK cell therapy combined with transcatheter arterial chemoembolization and radiofrequency ablation for treatment of small hepatocellular carcinoma. Shijie Huaren Xiaohua Zazhi 2014; 22:2237-2242. [DOI: 10.11569/wcjd.v22.i16.2237] [Citation(s) in RCA: 5] [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 evaluate the efficacy of dendritic and cytokine-induced killer cell therapy (DC-CIK) after transcatheter arterial chemoembolization combined with radiofrequency ablation in patients with small hepatocellular carcinoma (SHCC) and to investigate the changes in immunologic indexes in patients with SHCC.
METHODS: Eighty-five patients with SHCC treated at our hospital from April 2008 to April 2012 were recruited and divided into two groups after transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA): a study group and a control group. The study group (n = 41) received DC-CIK therapy 6 times 7 days after TACE and RFA, and the number of DC-CIK cells was above 1.0×1010. The control group (n = 44) only received TACE and RFA.
RESULTS: AFP differed significantly between before and after treatment in both the control group (494.5 mg/L ± 51.3 mg/L vs 226.5 mg/L ± 39.4 mg/L, P < 0.05) and the study group (486.4 mg/L ± 54.8 mg/L vs 168.7 mg/L ± 49.5 mg/L, P < 0.01). ALT and AST differed significantly between before and after treatment in the study group (66 U/L ± 6.3 U/L vs 31 U/L ± 5.9 U/L, 68 U/L ± 7.7 U/L vs 45 U/L ± 3.7 U/L, P < 0.05 for both), but showed no significant differences in the control group (67 U/L ± 7.4 U/L vs 65 U/L ± 6.2 U/L, 63 U/L ± 4.5 U/L vs 61 U/L ± 5.2 U/L, P > 0.05 for both). The efficacy evaluated by imaging examination in the study group was better than that in the control group (87.80% vs 79.54%, P < 0.05). The 1-, 2- and 3-year survival rates were significantly better in the study group than in the control group (95.1% vs 90.9%, 71.6% vs 65.9%, 68.3% vs 59.1%, P < 0.05 for all). The percentages of CD3+ and CD16+CD56+ cells and the ratio of CD4+/CD8+ cells were significantly increased after DC-CIK therapy (P < 0.05 for all), while the percentage of CD8+ cells was decreased in the study group (P < 0.05).
CONCLUSION: Sequential DC-CIK therapy after TACE and RFA can improve hepatic function and immune function of patients with SHCC, and may play an important role in reducing recurrence of SHCC and prolonging the survival time.
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Combining radiofrequency ablation and ethanol injection may achieve comparable long-term outcomes in larger hepatocellular carcinoma (3.1-4 cm) and in high-risk locations. Kaohsiung J Med Sci 2014; 30:396-401. [PMID: 25002377 DOI: 10.1016/j.kjms.2014.04.006] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2014] [Revised: 04/08/2014] [Accepted: 04/23/2014] [Indexed: 01/20/2023] Open
Abstract
Radiofrequency ablation (RFA) is more effective for hepatocellular carcinoma (HCC) < 3 cm. Combining percutaneous ethanol injection and RFA for HCC can increase ablation; however, the long-term outcome remains unknown. The aim of this study was to compare long-term outcomes between patients with HCC of 2-3 cm versus 3.1-4 cm and in high-risk versus non-high-risk locations after combination therapy. The primary endpoint was overall survival and the secondary endpoint was local tumor progression (LTP). Fifty-four consecutive patients with 72 tumors were enrolled. Twenty-two (30.6%) tumors and 60 (83.3%) tumors were of 3.1-4 cm and in high-risk locations, respectively. Primary technique effectiveness was comparable between HCC of 2-3 cm versus 3.1-4 cm (98% vs. 95.5%, p = 0.521), and HCC in non-high risk and high-risk locations (100% vs. 96.7%, p = 1.000). The cumulative survival rates at 1 year, 3 years, and 5 years were 90.3%, 78.9%, and 60.3%, respectively, in patients with HCC of 2-3 cm; 95.0%, 84.4%, and 69.3% in HCC of 3.1-4.0 cm (p = 0.397); 90.0%, 71.1%, and 71.1% in patients with HCC in non-high-risk locations; and 92.7%, 81.6%, and 65.4% in high-risk locations (p = 0.979). The cumulative LTP rates at 1 year, 3 years, and 5 years were 10.2%, 32.6%, and 32.6%, respectively, in all HCCs; 12.6%, 33.9%, and 33.9% in HCC of 2-3 cm; 4.8%, 29.5%, and 29.5% in HCC of 3.1-4 cm (p = 0.616); 16.7%, 50.0%, and 50.0% in patients with HCC in non-high-risk locations; and 8.8%, 29.9%, and 29.9% in patients with HCC in high-risk locations (p = 0.283). The cumulative survival and LTP rates were not significantly different among the various subgroups. Combining RFA and percutaneous ethanol injection achieved comparable long-term outcomes in HCCs of 2-3 cm versus 3.1-4.0 cm and in high-risk versus non-high-risk locations. A randomized controlled or cohort studies with larger sample size are warranted.
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Zhang Z, Zheng W, Hai J. MicroRNA-148b expression is decreased in hepatocellular carcinoma and associated with prognosis. Med Oncol 2014; 31:984. [PMID: 24805877 DOI: 10.1007/s12032-014-0984-6] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2014] [Accepted: 04/25/2014] [Indexed: 02/06/2023]
Abstract
MicroRNAs are small non-coding RNA molecules that have been shown to regulate the expression of genes linked to cancer. MicroRNA-148a (miR-148a) has recently been found to be involved in many critical processes in human malignancies. The present study is to clarify the expression pattern and prognostic role of miR-148b in human hepatocellular carcinoma (HCC). The expression of miR-148b was detected in 156 cases of HCC and 36 cases of normal control specimens by real-time PCR. Results showed that miR-148b expression was significantly decreased in HCC compared with that in normal control. It was also demonstrated that aberrant miR-148b expression was associated with vein invasion and TNM stage of HCC. Kaplan-Meier analysis showed that decreased miR-148b expression was associated with poor overall survival of patients. A multivariate survival analysis also indicated that miR-148b could be an independent prognostic marker. These results proved that miR-148b expression was decreased in HCC and associated with tumor invasion and progression. The present study also provides the first evidence that miR-148b could be an independent prognostic factor for patients with HCC, indicating the potential role of miR-148b as a prognostic marker in clinical practice, and the inhibition of miR-148b may even become a new therapeutic method for the treatment of HCC.
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Affiliation(s)
- Zhiyong Zhang
- Department of Hepatobiliary Surgery, Shaanxi Provincial People's Hospital, Youyi Xi Road 256#, Xi'an, 710068, Shaanxi, China,
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Raza A, Sood GK. Hepatocellular carcinoma review: current treatment, and evidence-based medicine. World J Gastroenterol 2014; 20:4115-27. [PMID: 24764650 PMCID: PMC3989948 DOI: 10.3748/wjg.v20.i15.4115] [Citation(s) in RCA: 334] [Impact Index Per Article: 30.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2013] [Revised: 12/06/2013] [Accepted: 03/06/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common tumor worldwide. Multiple treatment options are available for HCC including curative resection, liver transplantation, radiofrequency ablation, trans-arterial chemoembolization, radioembolization and systemic targeted agent like sorafenib. The treatment of HCC depends on the tumor stage, patient performance status and liver function reserve and requires a multidisciplinary approach. In the past few years with significant advances in surgical treatments and locoregional therapies, the short-term survival of HCC has improved but the recurrent disease remains a big problem. The pathogenesis of HCC is a multistep and complex process, wherein angiogenesis plays an important role. For patients with advanced disease, sorafenib is the only approved therapy, but novel systemic molecular targeted agents and their combinations are emerging. This article provides an overview of treatment of early and advanced stage HCC based on our extensive review of relevant literature.
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