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Zhong BY, Fan W, Guan JJ, Peng Z, Jia Z, Jin H, Jin ZC, Chen JJ, Zhu HD, Teng GJ. Combination locoregional and systemic therapies in hepatocellular carcinoma. Lancet Gastroenterol Hepatol 2025; 10:369-386. [PMID: 39993404 DOI: 10.1016/s2468-1253(24)00247-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2024] [Revised: 07/20/2024] [Accepted: 07/25/2024] [Indexed: 02/26/2025]
Abstract
Locoregional therapies play a fundamental role in the treatment of patients with early and intermediate and locally advanced hepatocellular carcinomas. With encouraging recent advances in immunotherapy-based systemic therapies, locoregional therapies are being both promoted and challenged by new systemic therapy options. Combined locoregional and systemic therapies might enhance treatment outcomes compared with either option alone. This Series paper summarises the existing data on locoregional and systemic therapies for hepatocellular carcinoma, and discusses evidence from studies investigating their combination with a focus on their synergistic efficacy and safety.
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Affiliation(s)
- Bin-Yan Zhong
- Center of Interventional Radiology and Vascular Surgery, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China; Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Wenzhe Fan
- Department of Interventional Oncology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Justin J Guan
- Division of Interventional Radiology, Department of Radiology, Cleveland Clinic, Cleveland, OH, USA
| | - Zhenwei Peng
- Department of Radiation Oncology, Cancer Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China; Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Zhongzhi Jia
- Department of Interventional and Vascular Surgery, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, China
| | - Haojie Jin
- Shanghai Cancer Institute, State Key Laboratory of Systems Medicine for Cancer, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhi-Cheng Jin
- Center of Interventional Radiology and Vascular Surgery, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Jian-Jian Chen
- Center of Interventional Radiology and Vascular Surgery, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Hai-Dong Zhu
- Center of Interventional Radiology and Vascular Surgery, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Gao-Jun Teng
- Center of Interventional Radiology and Vascular Surgery, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China.
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Tombesi P, Cutini A, Grasso V, Di Vece F, Politti U, Capatti E, Labb F, Petaccia S, Sartori S. Past, present, and future perspectives of ultrasound-guided ablation of liver tumors: Where could artificial intelligence lead interventional oncology? Artif Intell Cancer 2024; 5:96690. [DOI: 10.35713/aic.v5.i1.96690] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Revised: 06/26/2024] [Accepted: 07/10/2024] [Indexed: 07/17/2024] Open
Abstract
The first ablation procedures for small hepatocellular carcinomas were percutaneous ethanol injection under ultrasound (US) guidance. Later, radiofrequency ablation was shown to achieve larger coagulation areas than percutaneous ethanol injection and became the most used ablation technique worldwide. In the past decade, microwave ablation systems have achieved larger ablation areas than radiofrequency ablation, suggesting that the 3-cm barrier could be broken in the treatment of liver tumors. Likewise, US techniques to guide percutaneous ablation have seen important progress. Contrast-enhanced US (CEUS) can define and target the tumor better than US and can assess the size of the ablation area after the procedure, which allows immediate retreatment of the residual tumor foci. Furthermore, fusion imaging fuses real-time US images with computed tomography or magnetic resonance imaging with significant improvements in detecting and targeting lesions with low conspicuity on CEUS. Recently, software powered by artificial intelligence has been developed to allow three-dimensional segmentation and reconstruction of the anatomical structures, aiding in procedure planning, assessing ablation completeness, and targeting the residual viable foci with greater precision than CEUS. Hopefully, this could lead to the ablation of tumors up to 5-7 cm in size.
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Affiliation(s)
- Paola Tombesi
- Department of Internal Medicine, Section of Interventional Ultrasound, St. Anna Hospital, Ferrara 44100, Italy
| | - Andrea Cutini
- Department of Internal Medicine, Section of Interventional Ultrasound, St. Anna Hospital, Ferrara 44100, Italy
| | - Valentina Grasso
- Department of Internal Medicine, Section of Interventional Ultrasound, St. Anna Hospital, Ferrara 44100, Italy
| | - Francesca Di Vece
- Department of Internal Medicine, Section of Interventional Ultrasound, St. Anna Hospital, Ferrara 44100, Italy
| | - Ugo Politti
- Department of Internal Medicine, Section of Interventional Ultrasound, St. Anna Hospital, Ferrara 44100, Italy
| | - Eleonora Capatti
- Department of Internal Medicine, Section of Interventional Ultrasound, St. Anna Hospital, Ferrara 44100, Italy
| | | | | | - Sergio Sartori
- Department of Internal Medicine, Section of Interventional Ultrasound, St. Anna Hospital, Ferrara 44100, Italy
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Nakla T, Chow JJ, Pham K, Abi-Jaoudeh N. Non-Thermal Liver Ablation: Existing and New Technology. Semin Intervent Radiol 2023; 40:497-504. [PMID: 38274216 PMCID: PMC10807968 DOI: 10.1055/s-0043-1777844] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2024]
Abstract
Cancer has and continues to be a complex health crisis plaguing millions around the world. Alcohol ablation was one of the initial methods used for the treatment of liver lesions. It was surpassed by thermal ablation which has played a big role in the therapeutic arsenal for primary and metastatic liver tumors. However, thermal ablation has several shortcomings and limitations that prompted the development of alternative technologies including electroporation and histotripsy. Percutaneous alcohol injection in the liver lesion leads to dehydration and coagulative necrosis. This technology is limited to the lesion with relative sparing of the surrounding tissue, making it safe to use adjacent to sensitive structures. Electroporation utilizes short high-voltage pulses to permeabilize the cell membrane and can result in cell death dependent on the threshold reached. It can effectively target the tumor margins and has lower damage rates to surrounding structures due to the short pulse duration. Histotripsy is a novel technology, and although the first human trial was just completed, its results are encouraging, given the sharp demarcation of the targeted tissue, lack of thermal damage, and potential for immunomodulation of the tumor microenvironment. Herein, we discuss these techniques, their uses, and overall clinical benefit.
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Affiliation(s)
- Tiffany Nakla
- College of Osteopathic Medicine, Touro University Nevada, Henderson, Nevada
| | - Jacqueline J. Chow
- School of Medicine, University of California, Irvine, Irvine, California
| | - Kathleen Pham
- Department of Radiological Sciences, University of California, Irvine, Irvine, California
| | - Nadine Abi-Jaoudeh
- Department of Radiological Sciences, University of California, Irvine, Irvine, California
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4
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Roldan GA, Blomker J, Aby ES. Hepatocellular Carcinoma from a Hepatologist's Perspective. Semin Intervent Radiol 2023; 40:524-535. [PMID: 38274218 PMCID: PMC10807972 DOI: 10.1055/s-0043-1777846] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2024]
Abstract
Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, represents a growing health challenge worldwide. The incidence of HCC is rising, which, in turn, has led to a corresponding increase in the associated number of deaths. HCC will become the third leading cause of cancer-related deaths in the United States by 2030. HCC usually develops in the setting of chronic liver disease. Individuals at increased risk of HCC are recommended to undergo surveillance with ultrasound every 6 months along with serum α-fetoprotein testing. Computed tomography (CT) and magnetic resonance imaging (MRI) are considered alternatives based on specific patient factors. Lesions suspicious for HCC are recommended to undergo a diagnostic testing, which includes contrast-enhanced multiphase CT or MRI and liver biopsy when findings are indeterminate. The Barcelona Clinic Liver Cancer prognosis and treatment strategy is the most used assessment for patients with HCC ( Fig. 2 ). Curative therapies include resection, liver transplantation, and ablation. Locoregional therapies, such as transarterial chemoembolization and radioembolization, can be used for patients with intermediate-stage HCC. For patients with advanced-stage HCC, systemic therapy is often used. This review aims to provide an overview of HCC from a hepatologist's perspective, including epidemiology, screening, surveillance, diagnosis, and management.
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Affiliation(s)
- Giovanni A. Roldan
- Department of Gastroenterology and Hepatology, University of Minnesota, Minneapolis, Minnesota
| | - Jacquelin Blomker
- Department of Medicine, University of Minnesota, Minneapolis, Minnesota
| | - Elizabeth S. Aby
- Department of Gastroenterology and Hepatology, University of Minnesota, Minneapolis, Minnesota
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5
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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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6
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Wang L, Liu BX, Long HY. Ablative strategies for recurrent hepatocellular carcinoma. World J Hepatol 2023; 15:515-524. [PMID: 37206650 PMCID: PMC10190693 DOI: 10.4254/wjh.v15.i4.515] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Revised: 02/14/2023] [Accepted: 03/29/2023] [Indexed: 04/20/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is the fifth leading cause of cancer death worldwide and the third leading cause of all diseases worldwide. Liver transplantation, surgical resection and ablation are the three main curative treatments for HCC. Liver transplantation is the optimal treatment option for HCC, but its usage is limited by the shortage of liver sources. Surgical resection is considered the first choice for early-stage HCC, but it does not apply to patients with poor liver function. Therefore, more and more doctors choose ablation for HCC. However, intrahepatic recurrence occurs in up to 70% patients within 5 years after initial treatment. For patients with oligo recurrence after primary treatment, repeated resection and local ablation are both alternative. Only 20% patients with recurrent HCC (rHCC) indicate repeated surgical resection because of limitations in liver function, tumor location and intraperitoneal adhesions. Local ablation has become an option for the waiting period when liver transplantation is unavailable. For patients with intrahepatic recurrence after liver transplantation, local ablation can reduce the tumor burden and prepare them for liver transplantation. This review systematically describes the various ablation treatments for rHCC, including radiofrequency ablation, microwave ablation, laser ablation, high-intensity focused ultrasound ablation, cryablation, irreversible electroporation, percutaneous ethanol injection, and the combination of ablation and other treatment modalities.
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Affiliation(s)
- Lin Wang
- Department of Medical Ultrasound, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
| | - Bao-Xian Liu
- Department of Medical Ultrasound, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
| | - Hai-Yi Long
- Department of Medical Ultrasound, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
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7
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Chami P, Jarnagin W, Abou-Alfa GK, Harding J, Kim N, Lin H, El Homsi M, Crane C, Hajj C. Non-Surgical Locoregional Therapies Alone or in Combination with Systemic Therapy in Patients with Hepatocellular Carcinoma. Cancers (Basel) 2023; 15:1748. [PMID: 36980634 PMCID: PMC10046599 DOI: 10.3390/cancers15061748] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 03/09/2023] [Accepted: 03/11/2023] [Indexed: 03/16/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer, representing the third-leading cause of cancer-related deaths worldwide. Curative intent treatment options for patients with HCC include liver transplantation, resection and ablation of small lesions. Other potentially curative therapies include cryoablation, microwave ablation and percutaneous alcohol injection. For locally advanced disease, different arterially directed therapies including transarterial chemoembolization and selective internal radiation therapy, plus external beam radiation including three-dimensional conformal radiation therapy, intensity-modulated radiation therapy, stereotactic body radiation therapy and proton beam therapy, are available or studied. Systemic therapies based on checkpoint inhibitors and tyrosine kinase inhibitors are available for the management of metastatic HCC and sometimes for locally advanced disease. Combinations of locoregional therapies with systemic drugs are currently the subject of several clinical trials.
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Affiliation(s)
- Perla Chami
- Department of Biology, Faculty of Arts and Sciences, American University of Beirut, Beirut 1107, Lebanon
| | - William Jarnagin
- Memorial Sloan Kettering Cancer Center, New York, NY 10027, USA
- Department of Surgery, Weill Medical College at Cornell University, New York, NY 10021, USA
| | - Ghassan K. Abou-Alfa
- Memorial Sloan Kettering Cancer Center, New York, NY 10027, USA
- Department of Medicine, Weill Medical College at Cornell University, New York, NY 10021, USA
| | - James Harding
- Memorial Sloan Kettering Cancer Center, New York, NY 10027, USA
- Department of Medicine, Weill Medical College at Cornell University, New York, NY 10021, USA
| | - Neal Kim
- Memorial Sloan Kettering Cancer Center, New York, NY 10027, USA
| | - Haibo Lin
- New York Proton Center, New York, NY 10035, USA
| | - Maria El Homsi
- Memorial Sloan Kettering Cancer Center, New York, NY 10027, USA
| | | | - Carla Hajj
- Memorial Sloan Kettering Cancer Center, New York, NY 10027, USA
- New York Proton Center, New York, NY 10035, USA
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Knavel Koepsel EM, Smolock AR, Pinchot JW, Kim CY, Ahmed O, Chamarthy MRK, Hecht EM, Hwang GL, Kaplan DE, Luh JY, Marrero JA, Monroe EJ, Poultsides GA, Scheidt MJ, Hohenwalter EJ. ACR Appropriateness Criteria® Management of Liver Cancer: 2022 Update. J Am Coll Radiol 2022; 19:S390-S408. [PMID: 36436965 DOI: 10.1016/j.jacr.2022.09.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Accepted: 09/01/2022] [Indexed: 11/27/2022]
Abstract
The treatment and management of hepatic malignancies can be complex because it encompasses a variety of primary and metastatic malignancies and an assortment of local and systemic treatment options. When to use each of these treatments is critical to ensure the most appropriate care for patients. Interventional radiologists have a key role to play in the delivery of a variety of liver directed treatments including percutaneous ablation, transarterial embolization with bland embolic particles alone, transarterial chemoembolization (TACE) with injection of a chemotherapeutic emulsion, and transarterial radioembolization (TARE). Based on 9 clinical variants, the appropriateness of each treatment is described in this document. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances in which peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.
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Affiliation(s)
| | - Amanda R Smolock
- Froedtert & The Medical College of Wisconsin, Milwaukee, Wisconsin
| | | | - Charles Y Kim
- Panel Vice-Chair, Duke University Medical Center, Durham, North Carolina
| | - Osmanuddin Ahmed
- Vice-Chair of Wellness, Director of Venous Interventions, University of Chicago, Chicago, Illinois
| | - Murthy R K Chamarthy
- Vascular Institute of North Texas, Dallas, Texas; Commission on Nuclear Medicine and Molecular Imaging
| | - Elizabeth M Hecht
- Vice-Chair of Academic Affairs, Professor of Radiology, Weill Cornell Medicine, New York, New York; RADS Committee; Member of Appropriateness Subcommittees on Hepatobiliary Topics; Member of LI-RADS
| | - Gloria L Hwang
- Associate Chair of Clinical Performance Improvement, Stanford Radiology, Stanford Medical Center, Stanford, California
| | - David E Kaplan
- Section Chief of Hepatology at the University of Pennsylvania Division of Gastroenterology and Hepatology, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania; American Association for the Study of Liver Diseases
| | - Join Y Luh
- Providence Health Radiation Oncology Focus Group Chair, Providence St. Joseph Health, Eureka, California; Commission on Radiation Oncology; ACR CARROS President; ACR Council Steering Committee; California Radiological Society Councilor to ACR
| | - Jorge A Marrero
- University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; American Gastroenterological Association
| | | | - George A Poultsides
- Chief of Surgical Oncology and Professor of Surgery, Stanford University School of Medicine, Stanford, California; Society of Surgical Oncology
| | - Matthew J Scheidt
- Program Director of Independent IR Residency, Froedtert & The Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Eric J Hohenwalter
- Specialty Chair; Chief, MCW VIR, Froedtert & The Medical College of Wisconsin, Milwaukee, Wisconsin
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9
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Hung TH, Tsai CC, Lee HF. The role of hepatic reserve in the mortality of cirrhotic patients with small hepatocellular carcinoma receiving radiofrequency ablation. Medicine (Baltimore) 2022; 101:e30918. [PMID: 36221339 PMCID: PMC9542574 DOI: 10.1097/md.0000000000030918] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Although radiofrequency ablation (RFA) is considered a curative treatment for early stage small hepatocellular carcinoma (HCC), the long-term prognosis is suboptimal. The major complications in cirrhotic patients are usually related to poor prognosis and include esophageal variceal bleeding, ascites, and hepatic encephalopathy. This study aimed to evaluate the role of liver reserve on mortality after RFA for early stage HCC among cirrhotic patients, according to the presence of the number of complications. The Taiwan National Health Insurance Database was used to identify 2389 cirrhotic patients with treatment-naïve HCC (<3 cm) undergoing RFA hospitalized between January 1, 2010 and December 31, 2013. Of these, 594 patients had concurrent or a history of cirrhotic-related complications. The 1-year and 3-year survival rates in the cirrhotic patients with complications were 78.5% and 39.8%, respectively, and those in the patients without complications were 92.7% and 65.9% (P < .001), respectively. Age (hazard ratio [HR] 1.03, 95% confidence interval [CI] 1.02-1.04, P < .001) and cirrhotic-related complications (HR 2.65, 95% CI 2.22-3.16, P < .001) significantly increased 3-year mortality. The HR of mortality in patients with 1, 2, or 3 complications compared to those without complications were 2.35 (95% CI 1.92-2.88), 3.27 (95% CI 2.48-4.30), and 4.63 (95% CI 2.82-7.62), respectively (all P < .001). In cirrhotic patients with early stage HCC undergoing RFA, poor liver reserve correlates with poor outcome. The presence or history of three cirrhotic-related complications increased 3-year mortality 4-fold.
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Affiliation(s)
- Tsung-Hsing Hung
- Division of Gastroenterology, Department of Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
- School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Chih-Chun Tsai
- Department of Mathematics, Tamkang University, Tamsui, Taiwan
| | - Hsing-Feng Lee
- Division of Gastroenterology, Department of Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
- School of Medicine, Tzu Chi University, Hualien, Taiwan
- *Correspondence: Hsing-Feng Lee, Division of Gastroenterology, Department of Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 2, Minsheng Rd., Dalin Township, Chiayi County 62247, Taiwan (e-mail: )
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10
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Tang MJ, Eslick GD, Lubel JS, Majeed A, Majumdar A, Kemp W, Roberts SK. Outcomes of microwave versus radiofrequency ablation for hepatocellular carcinoma: A systematic review and meta-analysis. World J Meta-Anal 2022; 10:220-237. [DOI: 10.13105/wjma.v10.i4.220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Revised: 07/01/2022] [Accepted: 08/11/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Studies to date comparing outcomes of microwave ablation (MWA) with radiofrequency ablation (RFA) on patients with hepatocellular carcinoma have yielded conflicting results, with no clear superiority of one technique over the other. The aim of this systematic review and meta-analysis was to compare the efficacy and safety of MWA with RFA.
AIM To perform a systematic review and meta-analysis comparing the efficacy and safety of MWA with RFA.
METHODS A systematic literature search was performed using Ovid Medline, Embase, PubMed, Reference Citation Analysis, Cochrane Central and Cochrane Systematic Review databases, and Web of Science. Abstracts and full manuscripts were screened for inclusion utilising predefined inclusion and exclusion criteria comparing outcomes of MWA and RFA. A random-effects model was used for each outcome. Meta-regression analysis was performed to adjust for the difference in follow-up period between the studies. Primary outcome measures included complete ablation (CA) rate, local recurrence rate (LRR), survival [local recurrence-free survival (LRFS), overall survival (OS)] and adverse events.
RESULTS A total of 42 published studies [34 cohort and 8 randomised controlled trials (RCT)] with 6719 patients fulfilled the selection criteria. There was no significant difference in tumour size between the treatment groups. CA rates between MWA and RFA groups were similar in prospective cohort studies [odds ratio (OR) 0.95, 95% confidence interval (CI) 0.28–3.23] and RCTs (OR 1.18, 95%CI 0.64–2.18). However, retrospective studies reported higher rates with MWA (OR 1.29, 95%CI 1.06–1.57). Retrospective cohort studies reported higher OS (OR 1.54, 95%CI 1.15–2.05 and lower LRR (OR 0.67, 95%CI 0.51–0.87). No difference in terms of LRFS or 30-d mortality was observed between both arms. MWA had an increased rate of adverse respiratory events when compared to RFA (OR 1.99, 95%CI 1.07–3.71, P = 0.03).
CONCLUSION MWA achieves similar CA rates and as good or better longer-term outcomes in relation to LRR and OS compared to RFA. Apart from an increased rate of respiratory events post procedure, MWA is as safe as RFA.
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Affiliation(s)
- Myo Jin Tang
- Department of Gastroenterology, Alfred Hospital, Melbourne 3004, Victoria, Australia
- Monash Medical School, Monash University, Melbourne 3004, Victoria, Australia
| | - Guy D Eslick
- Department of Statistics, Clued Pty Ltd, Sydney 2006, New South Wales, Australia
| | - John S Lubel
- Department of Gastroenterology, Alfred Hospital, Melbourne 3004, Victoria, Australia
- Central Clinical School, Monash University, Melbourne 3004, Victoria, Australia
| | - Ammar Majeed
- Department of Gastroenterology, Alfred Hospital, Melbourne 3004, Victoria, Australia
- Central Clinical School, Monash University, Melbourne 3004, Victoria, Australia
| | - Avik Majumdar
- Department of Gastroenterology, Austin Hospital, Heidelberg 3084, Victoria, Australia
- Department of Medicine, Austin Campus, University of Medicine, Melbourne 3084, Victoria, Australia
| | - William Kemp
- Department of Gastroenterology, Alfred Hospital, Melbourne 3004, Victoria, Australia
- Central Clinical School, Monash University, Melbourne 3004, Victoria, Australia
| | - Stuart K Roberts
- Department of Gastroenterology, Alfred Hospital, Melbourne 3004, Victoria, Australia
- Central Clinical School, Monash University, Melbourne 3004, Victoria, Australia
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11
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Chen L, Zhang W, Sun T, Ren Y, Sun B, Zhu L, Zhao H, Zheng C. Effect of Transarterial Chemoembolization Plus Percutaneous Ethanol Injection or Radiofrequency Ablation for Liver Tumors. J Hepatocell Carcinoma 2022; 9:783-797. [PMID: 35983562 PMCID: PMC9380831 DOI: 10.2147/jhc.s370486] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Accepted: 07/30/2022] [Indexed: 12/03/2022] Open
Abstract
Background The efficacy of the transarterial chemoembolization (TACE) process combined with percutaneous ethanol injection (PEI, TACE-P) or the radiofrequency ablation (RFA, TACE-R) process was found to be good when used for the treatment of patients suffering from early or intermediate hepatocellular carcinoma (eiHCC). The study was conducted to compare the efficacy and safety of the TACE-P with TACE-A processes followed during the treatment of patients with eiHCC. Methods A total of 241 patients suffering from eiHCC, subjected to TACE-P (147 patients) or TACE-R (94 patients) processes from January 1, 2014, to December 31, 2018, were retrospectively reviewed and included. The propensity score matching (PSM) method was used to reduce selection bias. Results The median overall survival (mOS) and progression-free survival (mPFS) of the TACE-P group were similar to those recorded for the TACE-R group (P>0.05) before using the PSM technique. Similar results were obtained post the use of the PSM technique. In the subgroup analysis after PSM, patients with single tumor (dimension: ≤5 cm), who were subjected to TACE-P-based treatment methods, exhibited worse tumor response than patients subjected to TACE-R-based methods (HR: 1.804, 95% CI: 1.083–3.005, P=0.023). Seven adverse events were reported. A statistically significant difference for all grades of adverse events (and grade III or IV adverse events) between the two groups (all P>0.05) was not reported. Conclusion The benefits and advantages of using the TACE-P based method was similar was those obtained using the TACE-R in patients with eiHCC, especially for patients with a single large tumor or multiple tumors.
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Affiliation(s)
- Lei Chen
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.,Hubei Province Key Laboratory of Molecular Imaging, Wuhan, People's Republic of China.,Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Weihua Zhang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.,Hubei Province Key Laboratory of Molecular Imaging, Wuhan, People's Republic of China.,Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Tao Sun
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.,Hubei Province Key Laboratory of Molecular Imaging, Wuhan, People's Republic of China.,Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Yanqiao Ren
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.,Hubei Province Key Laboratory of Molecular Imaging, Wuhan, People's Republic of China.,Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Bo Sun
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.,Hubei Province Key Laboratory of Molecular Imaging, Wuhan, People's Republic of China.,Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Licheng Zhu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.,Hubei Province Key Laboratory of Molecular Imaging, Wuhan, People's Republic of China.,Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Huangxuan Zhao
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.,Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Chuansheng Zheng
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.,Hubei Province Key Laboratory of Molecular Imaging, Wuhan, People's Republic of China.,Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
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12
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Luerken L, Haimerl M, Doppler M, Uller W, Beyer LP, Stroszczynski C, Einspieler I. Update on Percutaneous Local Ablative Procedures for the Treatment of Hepatocellular Carcinoma. ROFO-FORTSCHR RONTG 2022; 194:1075-1086. [PMID: 35545102 DOI: 10.1055/a-1768-0954] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the fifth most common tumor worldwide. Because many hepatocellular carcinomas are already unresectable at the time of initial diagnosis, percutaneous tumor ablation has become established in recent decades as a curative therapeutic approach for very early (BCLC 0) and early (BCLC A) HCC. The aim of this paper is to provide a concise overview of the percutaneous local ablative procedures currently in use, based on their technical characteristics as well as clinical relevance, taking into account the current body of studies. MATERIALS AND METHODS The literature search included all original papers, reviews, and meta-analyses available via MEDLINE and Pubmed on the respective percutaneous ablation procedures; the primary focus was on randomized controlled trials and publications from the last 10 years. RESULTS AND CONCLUSIONS Radiofrequency ablation (RFA) and microwave ablation (MWA) are well-established procedures that are considered equal to surgical resection in the treatment of stage BCLC 0 and A HCC with a diameter up to 3 cm due to their strong evidence in international and national guidelines. For tumors with a diameter between 3 and 5 cm, the current S3 guidelines recommend a combination of transarterial chemoembolization (TACE) and thermal ablation using RFA or MWA as combination therapy is superior to thermal ablation alone in tumors of this size and shows comparable results to surgical resection in terms of overall survival. Alternative, less frequently employed thermal procedures include cryotherapy (CT) and laser ablation (LA). Non-thermal procedures include irreversible electroporation (IRE), interstitial brachytherapy (IBT), and most recently, electrochemotherapy (ECT). Due to insufficient evidence, these have only been used in individual cases and within the framework of studies. However, the nonthermal methods are a reasonable alternative for ablation of tumors adjacent to large blood vessels and bile ducts because they cause significantly less damage to these structures than thermal ablation methods. With advances in the technology of the respective procedures, increasingly good evidence, and advancements in supportive techniques such as navigation devices and fusion imaging, percutaneous ablation procedures may expand their indications for the treatment of larger and more advanced tumors in the coming years. KEY POINTS · RFA and MWA are considered equal to surgical resection as a first-line therapy for the curative treatment of stage BCLC 0 and A HCCs with a diameter of up to 3 cm.. · For HCCs with a diameter between 3 and 5 cm, a combination of TACE and RFA or MWA is recommended. This combination therapy yields results comparable to those of surgical resection in terms of overall survival.. · Due to insufficient evidence, alternative ablation methods have only been used in individual cases and within the framework of studies. However, nonthermal methods, such as IRE, IBT, and, most recently, ECT, are a reasonable alternative for ablation of HCCs adjacent to large blood vessels and bile ducts because they cause significantly less damage to these structures than thermal ablation methods.. CITATION FORMAT · Luerken L, Haimerl M, Doppler M et al. Update on Percutaneous Local Ablative Procedures for the Treatment of Hepatocellular Carcinoma. Fortschr Röntgenstr 2022; DOI: 10.1055/a-1768-0954.
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Affiliation(s)
- Lukas Luerken
- Department of Radiology, University Hospital Regensburg, Germany
| | - Michael Haimerl
- Institut für Röntgendiagnostik, University Hospital Regensburg, Germany
| | - Michael Doppler
- Department of Radiology, University Hospital Freiburg Department of Radiology, Freiburg, Germany
| | - Wibke Uller
- Department of Radiology, University Hospital Freiburg Department of Radiology, Freiburg, Germany
| | - Lukas Philipp Beyer
- Institut für Röntgendiagnostik, University Hospital Regensburg, Germany.,Diagnostische und Interventionelle Radiologie, Klinikum Ernst von Bergmann gGmbH, Potsdam, Germany
| | | | - Ingo Einspieler
- Department of Radiology, University Hospital Regensburg, Germany
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Gosavi A, Puranik AD, Shah S, Agrawal A, Purandare NC, Shetty N, Gala K, Kulkarni S, Patkar S, Goel M, Shrikhande S, Ramaswamy A, Ostwal V, Rangarajan V. Prognostic value of lung shunt fraction in hepatocellular carcinoma and unresectable liver dominant metastatic colorectal cancer undergoing transarterial radioembolisation. Nucl Med Commun 2022; 43:24-31. [PMID: 34887368 DOI: 10.1097/mnm.0000000000001492] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
AIM To assess the overall survival and determine whether pre-TARE shunt fraction, tumor volume and tumor marker impact the outcome. METHODS This is a retrospective study of 75 patients who were referred for 90Y-glass microsphere radioembolisation by a joint clinic decision between 1 January 2010 and 31 December 2014. All patients underwent pre-TARE CECT and 99mTc-MAA lung shunt fraction (LSF) imaging. RESULTS Overall survival was 19 months for hepatocellular carcinoma (HCC) and 24 months for metastatic colorectal carcinoma. For hepatocellular carcinoma-LSF higher than 6.51 % was predictive of significantly decreased survival (P value 0.00). A progressive disease in survival was observed as LSF increased from less than 6.51 % to more than 20%. Tumor volume and tumor marker did show correlation with patient outcomes. For metastatic colorectal carcinoma-LSF and tumor marker did not show significant correlation with survival and tumor volume showed significant correlation with survival with P value of 0.049.
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Affiliation(s)
- Atul Gosavi
- Department of Nuclear Medicine and Molecular Imaging
| | | | - Sneha Shah
- Department of Nuclear Medicine and Molecular Imaging
| | - Archi Agrawal
- Department of Nuclear Medicine and Molecular Imaging
| | | | | | | | | | | | | | | | - Anant Ramaswamy
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India
| | - Vikas Ostwal
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India
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14
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Piñero F, Tanno M, Aballay Soteras G, Tisi Baña M, Dirchwolf M, Fassio E, Ruf A, Mengarelli S, Borzi S, Fernández N, Ridruejo E, Descalzi V, Anders M, Mazzolini G, Reggiardo V, Marciano S, Perazzo F, Spina JC, McCormack L, Maraschio M, Lagues C, Gadano A, Villamil F, Silva M, Cairo F, Ameigeiras B. Argentinian clinical practice guideline for surveillance, diagnosis, staging and treatment of hepatocellular carcinoma. Ann Hepatol 2021; 19:546-569. [PMID: 32593747 DOI: 10.1016/j.aohep.2020.06.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2020] [Revised: 06/05/2020] [Accepted: 06/10/2020] [Indexed: 02/08/2023]
Abstract
The A.A.E.E.H has developed this guideline for the best care of patients with hepatocellular carcinoma (HCC) from Argentina. It was done from May 2018 to March 2020. Specific clinical research questions were systematically searched. The quality of evidence and level of recommendations were organized according to GRADE. HCC surveillance is strongly recommended with abdominal ultrasound (US) every six months in the population at risk for HCC (cirrhosis, hepatitis B or hepatitis C); it is suggested to add alpha-feto protein (AFP) levels in case of inexeperienced sonographers. Imaging diagnosis in patients at risk for HCC has high specificity and tumor biopsy is not mandatory. The Barcelona Clinic Liver Cancer algorithm is strongly recommended for HCC staging and treatment-decision processes. Liver resection is strongly recommended for patients without portal hypertension and preserved liver function. Composite models are suggested for liver transplant selection criteria. Therapies for HCC with robust clinical evidence include transarterial chemoembolization (TACE) and first to second line systemic treatment options (sorafenib, lenvatinib, regorafenib, cabozantinib and ramucirumab). Immunotherapy with nivolumab and pembrolizumab has failed to show statistical benefit but the novel combination of atezolizumab plus bevacizumab has recently shown survival benefit over sorafenib in frontline.
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Affiliation(s)
- Federico Piñero
- Hepatology and Liver Unit, Hospital Universitario Austral, School of Medicine, Austral University, B1629HJ Buenos Aires, Argentina.
| | - Mario Tanno
- Hospital Centenario de Rosario, Santa Fe, Argentina
| | | | - Matías Tisi Baña
- Internal Medicine and Epidemiology Department, Hospital Universitario Austral, School of Medicine, Austral University, B1629HJ Buenos Aires, Argentina
| | | | | | - Andrés Ruf
- Hospital Privado de Rosario, Santa Fe, Argentina
| | | | - Silvia Borzi
- Instituto Rossi, La Plata, Buenos Aires, Argentina
| | | | - Ezequiel Ridruejo
- Hepatology and Liver Unit, Hospital Universitario Austral, School of Medicine, Austral University, B1629HJ Buenos Aires, Argentina; Centro de Educación Médica e Investigaciones Clínicas (CEMIC), Ciudad de Buenos Aires, Argentina
| | | | | | - Guillermo Mazzolini
- Hepatology and Liver Unit, Hospital Universitario Austral, School of Medicine, Austral University, B1629HJ Buenos Aires, Argentina
| | | | | | | | | | | | | | - Cecilia Lagues
- Hepatology and Liver Unit, Hospital Universitario Austral, School of Medicine, Austral University, B1629HJ Buenos Aires, Argentina
| | | | | | - Marcelo Silva
- Hepatology and Liver Unit, Hospital Universitario Austral, School of Medicine, Austral University, B1629HJ Buenos Aires, Argentina
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15
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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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Öcal O, Rössler D, Ricke J, Seidensticker M. Advances in Diagnostic and Interventional Radiology in Hepatocellular Carcinoma. Dig Dis 2021; 40:458-467. [PMID: 34348282 DOI: 10.1159/000518101] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Accepted: 06/25/2021] [Indexed: 02/02/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths, and radiological imaging and locoregional therapies are essential for the management of patients with HCC. SUMMARY In cirrhotic patients, a characteristic imaging pattern establishes the noninvasive diagnosis of HCC with acceptable sensitivity and high specificity. In addition to diagnosis, imaging is used in the staging of patients and treatment allocation. Multiparametric MRI with hepatospecific contrast agents improves lesion detection, characterization, and treatment allocation; recently described imaging criteria allow identification of precursor lesions. Radiofrequency ablation (RFA) and transarterial chemoembolization (TACE) have been established in the treatment of patients with HCC at the early and intermediate stages, respectively. Microwave ablation has been described as an alternative to RFA in selected cases. Imaging-guided brachytherapy, a catheter-based radiotherapy technique, offers advantages to overcome some limitations of the aforementioned therapies, including the tumor location and size. Currently, no adjuvant therapy is recommended after RFA or TACE, but several new drugs are under evaluation. Furthermore, although the exact role of selective internal radiation therapy (SIRT) in HCC still needs to be defined, it is an alternative to systemic agents in patients with intolerance, and additional benefit has been shown in selected subgroups. Additionally, SIRT offers an alternate to TACE with higher objective response rates in patients who needs bridging before transplantation. KEY MESSAGES New imaging criteria improved lesion detection in patients at a risk for HCC, and advances in interventional therapies expanded the range of patients eligible for locoregional treatments.
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Affiliation(s)
- Osman Öcal
- Department of Radiology, University Hospital, LMU Munich, Munich, Germany
| | - Daniel Rössler
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
| | - Jens Ricke
- Department of Radiology, University Hospital, LMU Munich, Munich, Germany
| | - Max Seidensticker
- Department of Radiology, University Hospital, LMU Munich, Munich, Germany
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17
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Reig M, Forner A, Ávila MA, Ayuso C, Mínguez B, Varela M, Bilbao I, Bilbao JI, Burrel M, Bustamante J, Ferrer J, Gómez MÁ, Llovet JM, De la Mata M, Matilla A, Pardo F, Pastrana MA, Rodríguez-Perálvarez M, Tabernero J, Urbano J, Vera R, Sangro B, Bruix J. Diagnosis and treatment of hepatocellular carcinoma. Update of the consensus document of the AEEH, AEC, SEOM, SERAM, SERVEI, and SETH. Med Clin (Barc) 2021; 156:463.e1-463.e30. [PMID: 33461840 DOI: 10.1016/j.medcli.2020.09.022] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Revised: 09/12/2020] [Accepted: 09/15/2020] [Indexed: 12/12/2022]
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver neoplasm and one of the most common causes of death in patients with cirrhosis of the liver. In parallel, with recognition of the clinical relevance of this cancer, major new developments have recently appeared in its diagnosis, prognostic assessment and in particular, in its treatment. Therefore, the Spanish Association for the Study of the Liver (AEEH) has driven the need to update the clinical practice guidelines, once again inviting all the societies involved in the diagnosis and treatment of this disease to participate in the drafting and approval of the document: Spanish Society for Liver Transplantation (SETH), Spanish Society of Diagnostic Radiology (SERAM), Spanish Society of Vascular and Interventional Radiology (SERVEI), Spanish Association of Surgeons (AEC) and Spanish Society of Medical Oncology (SEOM). The clinical practice guidelines published in 2016 and accepted as National Health System Clinical Practice Guidelines were taken as the reference documents, incorporating the most important recent advances. The scientific evidence and the strength of the recommendation is based on the GRADE system.
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Affiliation(s)
- María Reig
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Hepatología, Hospital Clínic, IDIBAPS, Universidad de Barcelona, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España
| | - Alejandro Forner
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Hepatología, Hospital Clínic, IDIBAPS, Universidad de Barcelona, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España
| | - Matías A Ávila
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Programa de Hepatología, Centro de Investigación Médica Aplicada, Universidad de Navarra-IDISNA, Pamplona, España
| | - Carmen Ayuso
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Servicio de Radiodiagnóstico, Hospital Clínic Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España
| | - Beatriz Mínguez
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Servicio de Hepatología, Hospital Universitario Vall d́Hebron, Grupo de Investigación en Enfermedades Hepáticas (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universidad Autónoma de Barcelona. Barcelona, España
| | - María Varela
- Sección de Hepatología, Servicio de Aparato Digestivo, Hospital Universitario Central de Asturias. Oviedo, España
| | - Itxarone Bilbao
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Servicio de Cirugía Hepatobiliopancreática y Trasplantes Digestivos, Hospital Universitario Vall d'Hebron, Universidad Autónoma de Barcelona. Barcelona, España
| | - José Ignacio Bilbao
- Unidad de Radiología Vascular e Intervencionista, Departamento de Radiodiagnóstico, Clínica Universidad de Navarra, Pamplona, España
| | - Marta Burrel
- Servicio de Radiodiagnóstico, Hospital Clínic Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España
| | - Javier Bustamante
- Servicio de Gastroenterología y Hepatología, Sección de Hepatología y Trasplante, Hospital Universitario de Cruces, Baracaldo, España
| | - Joana Ferrer
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Cirugía Hepatobiliopancreática, Hospital Clínic, IDIBAPS, Universidad de Barcelona, Barcelona, España
| | - Miguel Ángel Gómez
- Unidad de Cirugía Hepatobiliopancreática y Trasplantes, Hospital Universitario Virgen del Rocío, Sevilla, España
| | - Josep María Llovet
- Grupo de Investigación Traslacional en Oncología Hepática, Servicio de Hepatología, Hospital Clínic, IDIBAPS, Universidad de Barcelona, Barcelona, España
| | - Manuel De la Mata
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Unidad Clínica de Aparato Digestivo, Hospital Universitario Reina Sofía, Córdoba, España
| | - Ana Matilla
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Sección de Hepatología, Servicio de Aparato Digestivo, Hospital General Universitario Gregorio Marañón, Madrid, España
| | - Fernando Pardo
- Servicio de Cirugía Hepatobiliopancreática y Trasplante, Clínica Universidad de Navarra, Pamplona, España
| | - Miguel A Pastrana
- Servicio de Radiodiagnóstico, Hospital Universitario Puerta de Hierro, Universidad Autónoma de Madrid, Madrid, España
| | - Manuel Rodríguez-Perálvarez
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Unidad Clínica de Aparato Digestivo, Hospital Universitario Reina Sofía, Córdoba, España
| | - Josep Tabernero
- Servicio de Oncología Médica, Hospital Universitario Vall d'Hebron, Universidad Autónoma de Barcelona, Barcelona, España
| | - José Urbano
- Unidad de Radiología Vascular e Intervencionista, Servicio de Radiodiagnóstico, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Madrid, España
| | - Ruth Vera
- Servicio de Oncología Médica, Complejo hospitalario de Navarra, Navarrabiomed-IDISNA, Pamplona, España
| | - Bruno Sangro
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Unidad de Hepatología y Área de Oncología HBP, Clínica Universidad de Navarra-IDISNA, Pamplona, España.
| | - Jordi Bruix
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Hepatología, Hospital Clínic, IDIBAPS, Universidad de Barcelona, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España.
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18
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Llovet JM, De Baere T, Kulik L, Haber PK, Greten TF, Meyer T, Lencioni R. Locoregional therapies in the era of molecular and immune treatments for hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol 2021; 18:293-313. [PMID: 33510460 DOI: 10.1038/s41575-020-00395-0] [Citation(s) in RCA: 522] [Impact Index Per Article: 130.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/25/2020] [Indexed: 12/14/2022]
Abstract
Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related mortality and has an increasing incidence worldwide. Locoregional therapies, defined as imaging-guided liver tumour-directed procedures, play a leading part in the management of 50-60% of HCCs. Radiofrequency is the mainstay for local ablation at early stages and transarterial chemoembolization (TACE) remains the standard treatment for intermediate-stage HCC. Other local ablative techniques (microwave ablation, cryoablation and irreversible electroporation) or locoregional therapies (for example, radioembolization and sterotactic body radiation therapy) have been explored, but have not yet modified the standard therapies established decades ago. This understanding is currently changing, and several drugs have been approved for the management of advanced HCC. Molecular therapies dominate the adjuvant trials after curative therapies and combination strategies with TACE for intermediate stages. The rationale for these combinations is sound. Local therapies induce antigen and proinflammatory cytokine release, whereas VEGF inhibitors and tyrosine kinase inhibitors boost immunity and prime tumours for checkpoint inhibition. In this Review, we analyse data from randomized and uncontrolled studies reported with ablative and locoregional techniques and examine the expected effects of combinations with systemic treatments. We also discuss trial design and benchmarks to be used as a reference for future investigations in the dawn of a promising new era for HCC treatment.
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Affiliation(s)
- Josep M Llovet
- Mount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. .,Translational Research in Hepatic Oncology, Liver Unit, IDIBAPS, Hospital Clinic, University of Barcelona, Catalonia, Spain. .,Institució Catalana d'Estudis Avançats (ICREA), Barcelona, Catalonia, Spain.
| | - Thierry De Baere
- Radiology Department Gustave Roussy Cancer Center, Vilejuif, France.,University Paris-Saclay, Saint-Aubin, France
| | - Laura Kulik
- Division of Gastroenterology and Hepatology, Surgery and Interventional Radiology in Northwestern University, Chicago, IL, USA
| | - Philipp K Haber
- Mount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Tim F Greten
- Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Tim Meyer
- Deptartment of Oncology, University College London Cancer Institute, London, UK.,Deptartment of Oncology, Royal Free Hospital, London, UK
| | - Riccardo Lencioni
- Department of Radiology, University of Pisa School of Medicine, Pisa, Italy.,Miami Cancer Institute, Miami, FL, USA
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19
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Chen L, Liu ZX, Bi QC, Zhao J, Liang QR, Tang Q. Ultrasound-Guided Percutaneous Ethanol-Paclitaxel Combined Therapy for Rabbit VX2 Liver Tumors. J Hepatocell Carcinoma 2021; 8:263-270. [PMID: 33907696 PMCID: PMC8068506 DOI: 10.2147/jhc.s301083] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Accepted: 03/31/2021] [Indexed: 11/23/2022] Open
Abstract
Background It is difficult to achieve whole tumor ablation using percutaneous ethanol ablation therapy (PEAT) due to the limited diffusion of ethanol. Purpose To determine whether chemotherapy can be an adjuvant therapy to benefit PEAT, we investigated ultrasound-guided percutaneous ethanol-paclitaxel combined therapy (PEPCT) of VX2 carcinoma, a rabbit liver cancer model. Materials and Methods A six-arm study was designed to quantify the correlation between paclitaxel (PTX) dose and tumor necrosis or cell proliferation, including sham group (2 mL saline, n=6), incremented dose of PTX (0, 12.5, 25, 37.5 mg) in 2.0 mL ethanol (n=6) and a conventional PEAT group (n=6) as comparison. The test was followed by contrast-enhanced ultrasonic (CEUS) before 7-day sacrifice, tumor harvest, and sectioning. Tumor necrosis ratio was radiologically and histologically quantified; modified proliferation index (m-PI) was proposed to quantify the PTX's pharmacological effects. A linear regression model was set to correlate the PTX dose with tumor necrosis ratio or cell proliferation index. The difference of radiological, histological necrosis ratio (HNR) and modified PI in six groups was analyzed via Kruskal-Wallis H-test, Welch analysis of variance and one-way ANOVA. Results Incremental increases of PTX (0, 12.5, 25, 37.5 mg) correlated with greater fraction of tumor necrosis (R2 = 0.946, P<0.001 for radiological necrosis ratio [RNR], R2 = 0.843, P<0.001 forHNR), indicating that one week after procedure PTX's anti-proliferation and ethanol's dehydration co-induced severe tumor necrosis. Correlation analysis further testified a significant association between PTX dose and m-PI (R2 = 0.860, P<0.001). Conclusion These results suggest a clear role for PTX-induced cytotoxicity and support the use of chemotherapeutic drugs in ablation therapy.
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Affiliation(s)
- Li Chen
- Department of Ultrasonic Radiology, The First Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China
| | - Zhi-Xing Liu
- Department of Ultrasonic Radiology, The First Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China
| | - Qiu-Chen Bi
- Institute for Advanced Study, Nanchang University, Nanchang, People's Republic of China
| | - Jun Zhao
- Jiangxi Provincial Key Laboratory of Preventive Medicine, School of Public Health, Nanchang University, Nanchang, People's Republic of China
| | - Qing-Rong Liang
- Institute for Advanced Study, Nanchang University, Nanchang, People's Republic of China
| | - Qun Tang
- Institute for Advanced Study, Nanchang University, Nanchang, People's Republic of China.,Jiangxi Provincial Key Laboratory of Preventive Medicine, School of Public Health, Nanchang University, Nanchang, People's Republic of China.,Jiangxi Province Key Laboratory of Laboratory Animal, Nanchang, People's Republic of China
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20
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Cheung TT, Ma KW, She WH. A review on radiofrequency, microwave and high-intensity focused ultrasound ablations for hepatocellular carcinoma with cirrhosis. Hepatobiliary Surg Nutr 2021; 10:193-209. [PMID: 33898560 DOI: 10.21037/hbsn.2020.03.11] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Importance Hepatocellular carcinoma (HCC) is usually accompanied by liver cirrhosis, which makes treatment of this disease challenging. Liver transplantation theoretically provides an ultimate solution to the disease, but the maximal surgical stress and the scarcity of liver graft make this treatment option impossible for some patients. In an ideal situation, a treatment that is safe and effective should provide a better outcome for patients with the dilemma. Objective This article aims to give a comprehensive review of various types of loco-ablative treatment for HCC. Evidence Review Loco-ablative treatment bridges the gap between surgical resection and transarterial chemotherapy. Various types of ablative therapy have their unique ability, and evidence-based outcome analysis is the most important key to assisting clinicians to choose the most suitable treatment modality for their patients. Findings Radiofrequency ablation (RFA) has a relatively longer history and more evidence to support its effectiveness. Microwave ablation (MWA) is gaining momentum because of its shorter ablation time and consistent ablation zone. High-intensity focused ultrasound (HIFU) ablation is a relatively new technology that provides non-invasive treatment for patients with HCC. It has been carried out at centers of excellence and it is a safe and effective treatment option for selected patients with HCC and liver cirrhosis. Conclusion and Relevance Selective use of different loco-ablative therapies will enhance clinicians' treatment options for treatment of HCC.
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Affiliation(s)
- Tan To Cheung
- Department of Surgery, The University of Hong Kong, 102 Pok Fu Lam Road, Hong Kong, China
| | - Ka Wing Ma
- Department of Surgery, The University of Hong Kong, 102 Pok Fu Lam Road, Hong Kong, China
| | - Wong Hoi She
- Department of Surgery, The University of Hong Kong, 102 Pok Fu Lam Road, Hong Kong, China
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21
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Advanced Techniques in the Percutaneous Ablation of Liver Tumours. Diagnostics (Basel) 2021; 11:diagnostics11040585. [PMID: 33805107 PMCID: PMC8064108 DOI: 10.3390/diagnostics11040585] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 03/20/2021] [Accepted: 03/21/2021] [Indexed: 02/07/2023] Open
Abstract
Percutaneous ablation is an accepted treatment modality for primary hepatocellular carcinoma (HCC) and liver metastases. The goal of curative ablation is to cause the necrosis of all tumour cells with an adequate margin, akin to surgical resection, while minimising local damage to non-target tissue. Aside from the ablative modality, the proceduralist must decide the most appropriate imaging modality for visualising the tumour and monitoring the ablation zone. The proceduralist may also employ protective measures to minimise injury to non-target organs. This review article discusses the important considerations an interventionalist needs to consider when performing the percutaneous ablation of liver tumours. It covers the different ablative modalities, image guidance, and protective techniques, with an emphasis on new and advanced ablative modalities and adjunctive techniques to optimise results and achieve satisfactory ablation margins.
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22
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Alqahtani SA, Sanai FM, Alolayan A, Abaalkhail F, Alsuhaibani H, Hassanain M, Alhazzani W, Alsuhaibani A, Algarni A, Forner A, Finn RS, Al-hamoudi WK. Saudi Association for the Study of Liver diseases and Transplantation practice guidelines on the diagnosis and management of hepatocellular carcinoma. Saudi J Gastroenterol 2020; 26:S1-S40. [PMID: 33078723 PMCID: PMC7768980 DOI: 10.4103/sjg.sjg_477_20] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Accepted: 09/10/2020] [Indexed: 01/27/2023] Open
Affiliation(s)
- Saleh A. Alqahtani
- Liver Transplant Centre, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
- Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, Maryland, United States
| | - Faisal M. Sanai
- Liver Disease Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia
- Department of Medicine, Gastroenterology Unit, King Abdulaziz Medical City, Jeddah, Saudi Arabia
| | - Ashwaq Alolayan
- Adult Medical Oncology, King Abdulaziz Medical City, Riyadh, Saudi Arabia
| | - Faisal Abaalkhail
- Department of Medicine, Gastroenterology Section, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
- College of Medicine, Al Faisal University, Riyadh, Saudi Arabia
| | - Hamad Alsuhaibani
- Department of Radiology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Mazen Hassanain
- Department of Surgery, College of Medicine, King Saud University, Riyadh, Saudi Arabia
- Department of Pediatrics, Baylor College of Medicine, Houston, Texas, United States
| | - Waleed Alhazzani
- Department of Medicine, McMaster University, Hamilton, ON, Canada
| | - Abdullah Alsuhaibani
- Department of Radiology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Abdullah Algarni
- Department of Oncology, King Abdulaziz Medical City, Riyadh, Saudi Arabia
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Alejandro Forner
- Barcelona Clinic Liver Cancer Group, Liver Unit, Hospital Clinic Barcelona, IDIBAPS, CIBEREHD, University of Barcelona, Barcelona, Spain
| | - Richard S Finn
- Division of Hematology and Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California,United States
| | - Waleed K. Al-hamoudi
- Liver Transplant Centre, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
- Liver Disease Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia
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23
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O'Leary C, Mahler M, Soulen MC. Curative-Intent Therapies in Localized Hepatocellular Carcinoma. Curr Treat Options Oncol 2020; 21:31. [PMID: 32193784 DOI: 10.1007/s11864-020-0725-3] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
PURPOSE OF REVIEW The high mortality rate for hepatocellular carcinoma (HCC) relative to its prevalence underscores the need for curative-intent therapies. Image-guided therapies such as ablation and embolization have an established role as primary or neoadjuvants preparing patients for curative treatment. RECENT FINDINGS For HCC < 3 cm, percutaneous thermal ablation provides oncologic outcomes similar to surgical resection and is now a recommended first-line therapy in the EASL guidelines. Both ablation and embolization are recommended as bridging therapies for HCC patients awaiting liver transplantation. T3 HCC can be downstaged by embolization to T2, allowing liver transplantation with similar outcomes to patients transplanted within Milan criteria. New and evolving techniques such as SBRT, radiation segmentectomy and lobectomy, and combination therapies show promise but require further prospective data before they can be integrated into treatment algorithms. Combinations of embolic, ablative, and extirpative therapies can increase access to curative-intent treatment of HCC. Multidisciplinary treatment decisions are required to craft optimal treatment strategies considering tumor size, location, and underlying liver cirrhosis.
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Affiliation(s)
- Cathal O'Leary
- Department of Radiology, 3400 Spruce St, Philadelphia, PA, 19104, USA
| | - Mary Mahler
- University of Toronto, 500 University Avenue, Suite 602, Toronto, Ontario, M5G1V7, Canada
| | - Michael C Soulen
- Department of Radiology, 3400 Spruce St, Philadelphia, PA, 19104, USA.
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24
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Chagas AL, Mattos AAD, Carrilho FJ, Bittencourt PL, Vezozzo DCP, Horvat N, Rocha MDS, Alves VAF, Coral GP, Alvares-DA-Silva MR, Barros FMDR, Menezes MR, Monsignore LM, Coelho FF, Silva RFD, Silva RDCMA, Boin IDFSF, D Albuquerque LAC, Garcia JHP, Felga GEG, Moreira AM, Braghiroli MIFM, Hoff PMG, Mello VBD, Dottori MF, Branco TP, Schiavon LDL, Costa TDFA. BRAZILIAN SOCIETY OF HEPATOLOGY UPDATED RECOMMENDATIONS FOR DIAGNOSIS AND TREATMENT OF HEPATOCELLULAR CARCINOMA. ARQUIVOS DE GASTROENTEROLOGIA 2020; 57:1-20. [PMID: 32294682 DOI: 10.1590/s0004-2803.202000000-20] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Accepted: 12/19/2019] [Indexed: 02/06/2023]
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. The Brazilian Society of Hepatology (SBH) published in 2015 its first recommendations about the management of HCC. Since then, new data have emerged in the literature, prompting the governing board of SBH to sponsor a single-topic meeting in August 2018 in São Paulo. All the invited experts were asked to make a systematic review of the literature reviewing the management of HCC in subjects with cirrhosis. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of updated recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present manuscript is the final version of the reviewed manuscript containing the recommendations of SBH.
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Affiliation(s)
- Aline Lopes Chagas
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil.,Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil
| | - Angelo Alves de Mattos
- Universidade Federal de Ciências da Saúde de Porto Alegre e Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, RS, Brasil
| | - Flair José Carrilho
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil.,Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil
| | | | | | | | - Natally Horvat
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil.,Hospital Sírio-Libanês, São Paulo, SP, Brasil
| | - Manoel de Souza Rocha
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil
| | - Venâncio Avancini Ferreira Alves
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil.,Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil
| | - Gabriela Perdomo Coral
- Universidade Federal de Ciências da Saúde de Porto Alegre e Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, RS, Brasil
| | | | | | - Marcos Roberto Menezes
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil.,Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil.,Hospital Sírio-Libanês, São Paulo, SP, Brasil
| | - Lucas Moretti Monsignore
- Universidade de São Paulo, Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, São Paulo, SP, Brasil
| | | | - Renato Ferreira da Silva
- Faculdade de Medicina de São José do Rio Preto (FAMERP) e Hospital de Base de São José do Rio Preto (FUNFARME), São José do Rio Preto, SP, Brasil
| | - Rita de Cássia Martins Alves Silva
- Faculdade de Medicina de São José do Rio Preto (FAMERP) e Hospital de Base de São José do Rio Preto (FUNFARME), São José do Rio Preto, SP, Brasil
| | | | | | | | | | - Airton Mota Moreira
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil.,Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil
| | | | - Paulo Marcelo Gehm Hoff
- Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil
| | | | | | - Tiago Pugliese Branco
- Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil
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25
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Lee J, Gangi A. Regional Therapies in Hepatocellular Carcinoma and Cholangiocarcinoma. CANCER REGIONAL THERAPY 2020:311-322. [DOI: 10.1007/978-3-030-28891-4_26] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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26
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McMillan RR, Agopian VG. The Management of Hepatocellular Carcinoma. THE CRITICALLY ILL CIRRHOTIC PATIENT 2020:237-271. [DOI: 10.1007/978-3-030-24490-3_13] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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27
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Inchingolo R, Posa A, Mariappan M, Spiliopoulos S. Locoregional treatments for hepatocellular carcinoma: Current evidence and future directions. World J Gastroenterol 2019; 25:4614-4628. [PMID: 31528090 PMCID: PMC6718039 DOI: 10.3748/wjg.v25.i32.4614] [Citation(s) in RCA: 57] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2019] [Revised: 07/12/2019] [Accepted: 07/19/2019] [Indexed: 02/06/2023] Open
Abstract
Liver cancers are the second most frequent cause of global cancer-related mortality of which 90% are attributable to hepatocellular carcinoma (HCC). Despite the advent of screening programmes for patients with known risk factors, a substantial number of patients are ineligible for curative surgery at presentation with limited outcomes achievable with systemic chemotherapy/external radiotherapy. This has led to the advent of numerous minimally invasive options including but not limited to trans-arterial chemoembolization, radiofrequency/microwave ablation and more recently selective internal radiation therapy many of which are often the first-line treatment for select stages of HCC or serve as a conduit to liver transplant. The authors aim to provide a comprehensive overview of these various image guided minimally invasive therapies with a brief focus on the technical aspects accompanied by a critical analysis of the literature to assess the most up-to-date evidence from comparative systematic reviews and meta-analyses finishing with an assessment of novel combination regimens and future directions of travel.
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Affiliation(s)
- Riccardo Inchingolo
- Division of Interventional Radiology, Department of Radiology, Madonna delle Grazie Hospital, Matera 75100, Italy
- Department of Radiology, King´s College Hospital, London SE5 9RS, United Kingdom
| | - Alessandro Posa
- Department of Radiology, IRCSS Fatebenefratelli Hospital, Roma 00186, Italy
| | - Martin Mariappan
- Interventional Radiology Department, Aberdeen Royal Infirmary Hospital, Aberdeen AB25 2ZN, United Kingdom
| | - Stavros Spiliopoulos
- 2nd Radiology Department, School of Medicine; National and Kapodistrian University of Athens, Chaidari Athens 12461, Greece
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28
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Schiavon LDL, Ejima FH, Menezes MRD, Bittencourt PL, Moreira AM, Farias AQ, Chagas AL, Assis AMD, Mattos ÂZD, Salomão BC, Terra C, Martins FPB, Carnevale FC, Rezende GFDM, Paulo GAD, Pereira GHS, Leal Filho JMDM, Meneses JD, Costa LSND, Carneiro MDV, Álvares-DA-Silva MR, Soares MVA, Pereira OI, Ximenes RO, Durante RFS, Ferreira VA, Lima VMD. RECOMMENDATIONS FOR INVASIVE PROCEDURES IN PATIENTS WITH DISEASES OF THE LIVER AND BILIARY TRACT: REPORT OF A JOINT MEETING OF THE BRAZILIAN SOCIETY OF HEPATOLOGY (SBH), BRAZILIAN SOCIETY OF DIGESTIVE ENDOSCOPY (SOBED) AND BRAZILIAN SOCIETY OF INTERVENTIONAL RADIOLOGY AND ENDOVASCULAR SURGERY (SOBRICE). ARQUIVOS DE GASTROENTEROLOGIA 2019; 56:213-231. [PMID: 31460590 DOI: 10.1590/s0004-2803.201900000-42] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/08/2019] [Accepted: 04/12/2019] [Indexed: 12/12/2022]
Abstract
Liver and biliary tract diseases are common causes of morbidity and mortality worldwide. Invasive procedures are usually performed in those patients with hepatobiliary diseases for both diagnostic and therapeutic purposes. Defining proper indications and restraints of commonly used techniques is crucial for proper patient selection, maximizing positive results and limiting complications. In 2018, the Brazilian Society of Hepato-logy (SBH) in cooperation with the Brazilian Society of Interventional Radiology and Endovascular surgery (SOBRICE) and the Brazilian Society of Digestive Endoscopy (SOBED) sponsored a joint single-topic meeting on invasive procedures in patients with hepatobiliary diseases. This paper summarizes the proceedings of the aforementioned meeting. It is intended to guide clinicians, gastroenterologists, hepatologists, radiologists, and endoscopists for the proper use of invasive procedures for management of patients with hepatobiliary diseases.
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Affiliation(s)
- Leonardo de Lucca Schiavon
- Universidade Federal de Santa Catarina, Faculdade de Medicina, Departamento de Clínica Médica, Florianópolis, SC, Brasil
| | | | - Marcos Roberto de Menezes
- Instituto do Câncer do Estado de São Paulo, Setor de Diagnóstico por Imagem, São Paulo, SP, Brasil.,Instituto do Câncer do Estado de São Paulo da Faculdade de Medicina da Universidade de São Paulo, Serviço de Radiologia Intervencionista, São Paulo, SP, Brasil
| | | | | | - Aírton Mota Moreira
- Universidade de São Paulo, Faculdade de Medicina, Serviço de Radiologia Intervencionista do Instituto de Radiologia, São Paulo, SP, Brasil
| | - Alberto Queiroz Farias
- Universidade de São Paulo, Faculdade de Medicina, Departamento de Gastroenterologia, São Paulo, SP, Brasil
| | - Aline Lopes Chagas
- Universidade de São Paulo, Faculdade de Medicina, Departamento de Gastroenterologia, São Paulo, SP, Brasil
| | - André Moreira de Assis
- Universidade de São Paulo, Faculdade de Medicina, Serviço de Radiologia Intervencionista do Instituto de Radiologia, São Paulo, SP, Brasil.,Hospital Sírio-Libanês, São Paulo, SP, Brasil
| | - Ângelo Zambam de Mattos
- Universidade Federal de Ciências da Saúde de Porto Alegre, Programa de Pós-Graduação em Medicina: Hepatologia, RS, Brasil
| | | | - Carlos Terra
- Universidade do Estado do Rio de Janeiro, Faculdade de Medicina, Departamento de Gastroenterologia, RJ, Brasil.,Hospital Federal de Lagoa, Departamento de Gastroenterologia, Rio de Janeiro, RJ, Brasil
| | | | - Francisco Cesar Carnevale
- Instituto de Radiologia da Faculdade de Medicina da Universidade de São Paulo, Serviço de Radiologia Intervencionista, São Paulo, SP, Brasil
| | | | | | | | - Joaquim Maurício da Motta Leal Filho
- Instituto do Câncer do Estado de São Paulo da Faculdade de Medicina da Universidade de São Paulo, Serviço de Radiologia Intervencionista, São Paulo, SP, Brasil
| | - Juliana de Meneses
- Instituto Hospital de Base do Distrito Federal, Brasília, DF, Brasil.,Instituto Nacional do Câncer, Brasília, DF, Brasil
| | - Lucas Santana Nova da Costa
- Instituto Hospital de Base do Distrito Federal, Brasília, DF, Brasil.,Hospital Sírio-Libanês Unidade Brasília, Brasília, DF, Brasil
| | - Marcos de Vasconcelos Carneiro
- Hospital das Forças Armadas, Brasília, DF, Brasil.,Universidade Católica de Brasília, Curso de Medicina, Brasília, DF, Brasil
| | - Mário Reis Álvares-DA-Silva
- Universidade Federal do Rio Grande do Sul, Faculdade de Medicina, Departamento de Medicina Interna, Rio Grande do Sul, RS, Brasil
| | - Mayra Veloso Ayrimoraes Soares
- Hospital Sírio-Libanês Unidade Brasília, Brasília, DF, Brasil.,Universidade de Brasília, Serviço de Radiologia, Brasília, DF, Brasil
| | - Osvaldo Ignácio Pereira
- Instituto de Radiologia da Faculdade de Medicina da Universidade de São Paulo, Serviço de Radiologia Intervencionista, São Paulo, SP, Brasil
| | - Rafael Oliveira Ximenes
- Hospital das Clínicas da Universidade Federal de Goiás, Serviço de Gastroenterologia e Hepatologia, Goiás, GO, Brasil
| | | | - Valério Alves Ferreira
- Instituto Hospital de Base do Distrito Federal, Brasília, DF, Brasil.,Hospital Santa Marta, Brasília, DF, Brasil
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Rochigneux P, Nault JC, Mallet F, Chretien AS, Barget N, Garcia AJ, Del Pozo L, Bourcier V, Blaise L, Grando-Lemaire V, N’Kontchou G, Nahon P, Seror O, Ziol M, Ganne-Carrié N, Olive D. Dynamic of systemic immunity and its impact on tumor recurrence after radiofrequency ablation of hepatocellular carcinoma. Oncoimmunology 2019; 8:1615818. [PMID: 31413924 PMCID: PMC6682367 DOI: 10.1080/2162402x.2019.1615818] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2019] [Revised: 04/30/2019] [Accepted: 05/01/2019] [Indexed: 02/08/2023] Open
Abstract
Background: Percutaneous radiofrequency ablation (RFA) is one of the main treatments of small hepatocellular carcinoma (HCC). However, it remains unclear whether this local treatment can induce systemic immune variations. Methods: We conducted a prospective study in a tertiary center including consecutive cirrhotic patients with unifocal HCC<5 cm treated by a first RFA between 2010 and 2014. Peripheral blood mononuclear cells were isolated on the day before (D0), day after (D1) and month after RFA (M1). Frequencies and phenotypes of myeloid cells, T cells, and NK cells were compared between timepoints. Overall recurrence and associated variables were estimated using Kaplan-Meier, log-rank and Cox proportional-hazards models. Results: 80 patients were included (69% male, median age: 67 years old). Main aetiologies of HCC were alcohol (51%), hepatitis C virus (45%), non-alcoholic steatohepatitis (36%) and hepatitis B virus (9%). Median overall survival was 55 months (M); median progression-free survival was 29.5M. Among innate immune populations, we observed variations between D0, D1 and M1 in NKp30+ NK cells (p < .0001) and in plasmacytoid dendritic cells (pDC, p < .01). Concerning adaptive immunity, we observed variations in CD8 Central Memory (p < .05) and CD28+ CD8 Central Memory (p < .01). An early dynamic (D0/D1) of activated NKp30+ NK cells was associated with a decreased overall recurrence (log-rank, p = .016, median delay 25.1 vs 40.6 months). In contrast, a late dynamic (D1/M1) of immature NK cells (CD56bright) and altered myeloid DC (PDL1+) was associated with an increased overall recurrence (log-rank, p = .011 and p = .0044, respectively). In multivariate analysis, variation of immature NK cells predicts tumor recurrence independently of classical clinical prognostic features (HR = 2.41, 95% CI: 1.15-5.057), p = .019). Conclusions: Percutaneous RFA of small HCC leads to systemic modifications of innate and adaptive immunity closely linked with overall tumor recurrence.
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Affiliation(s)
- Philippe Rochigneux
- Medical Oncology Department, Paoli-Calmettes Institute, Marseille, France
- Team Immunity and Cancer, Centre de Recherche en Cancérologie de Marseille (CRCM), Inserm, U1068, CNRS, UMR7258, Institut Paoli-Calmettes, Aix-Marseille University, Marseille, France
| | - Jean-Charles Nault
- Inserm UMR 1162, Génomique fonctionnelle des Tumeurs solides, Université Paris Descartes, Université Paris Diderot, Université Paris 13, Labex Immuno-Oncology, Paris, France
- Liver Unit, Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, APHP, Bondy, Unité de Formation et de Recherche Santé Médecine et Biologie humaine, Université Paris 13, Communauté d’Universités et Etablissements Sorbonne Paris Cité, Paris, France
| | - Françoise Mallet
- Immunomonitoring Platform, Institut Paoli-Calmettes, Marseille, France
| | - Anne-Sophie Chretien
- Team Immunity and Cancer, Centre de Recherche en Cancérologie de Marseille (CRCM), Inserm, U1068, CNRS, UMR7258, Institut Paoli-Calmettes, Aix-Marseille University, Marseille, France
- Immunomonitoring Platform, Institut Paoli-Calmettes, Marseille, France
| | - Nathalie Barget
- Tumor Biobank, Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, APHP, Bondy, France
| | - Alejandro J. Garcia
- Core Cytometry Laboratory, University of California at Los Angeles, Los Angeles, USA
| | - Lucie Del Pozo
- Liver Unit, Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, APHP, Bondy, Unité de Formation et de Recherche Santé Médecine et Biologie humaine, Université Paris 13, Communauté d’Universités et Etablissements Sorbonne Paris Cité, Paris, France
| | - Valérie Bourcier
- Liver Unit, Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, APHP, Bondy, Unité de Formation et de Recherche Santé Médecine et Biologie humaine, Université Paris 13, Communauté d’Universités et Etablissements Sorbonne Paris Cité, Paris, France
| | - Lorraine Blaise
- Liver Unit, Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, APHP, Bondy, Unité de Formation et de Recherche Santé Médecine et Biologie humaine, Université Paris 13, Communauté d’Universités et Etablissements Sorbonne Paris Cité, Paris, France
| | - Véronique Grando-Lemaire
- Liver Unit, Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, APHP, Bondy, Unité de Formation et de Recherche Santé Médecine et Biologie humaine, Université Paris 13, Communauté d’Universités et Etablissements Sorbonne Paris Cité, Paris, France
| | - Gisèle N’Kontchou
- Liver Unit, Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, APHP, Bondy, Unité de Formation et de Recherche Santé Médecine et Biologie humaine, Université Paris 13, Communauté d’Universités et Etablissements Sorbonne Paris Cité, Paris, France
| | - Pierre Nahon
- Inserm UMR 1162, Génomique fonctionnelle des Tumeurs solides, Université Paris Descartes, Université Paris Diderot, Université Paris 13, Labex Immuno-Oncology, Paris, France
- Liver Unit, Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, APHP, Bondy, Unité de Formation et de Recherche Santé Médecine et Biologie humaine, Université Paris 13, Communauté d’Universités et Etablissements Sorbonne Paris Cité, Paris, France
| | - Olivier Seror
- Inserm UMR 1162, Génomique fonctionnelle des Tumeurs solides, Université Paris Descartes, Université Paris Diderot, Université Paris 13, Labex Immuno-Oncology, Paris, France
- Radiology Department, Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, APHP, Bondy, France
| | - Marianne Ziol
- Inserm UMR 1162, Génomique fonctionnelle des Tumeurs solides, Université Paris Descartes, Université Paris Diderot, Université Paris 13, Labex Immuno-Oncology, Paris, France
- Pathology Department, Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, APHP, Bondy, Unité de Formation et de Recherche Santé Médecine et Biologie humaine, Université Paris 13, Communauté d’Universités et Etablissements Sorbonne Paris Cité, Paris, France
| | - Nathalie Ganne-Carrié
- Inserm UMR 1162, Génomique fonctionnelle des Tumeurs solides, Université Paris Descartes, Université Paris Diderot, Université Paris 13, Labex Immuno-Oncology, Paris, France
- Liver Unit, Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, APHP, Bondy, Unité de Formation et de Recherche Santé Médecine et Biologie humaine, Université Paris 13, Communauté d’Universités et Etablissements Sorbonne Paris Cité, Paris, France
| | - Daniel Olive
- Team Immunity and Cancer, Centre de Recherche en Cancérologie de Marseille (CRCM), Inserm, U1068, CNRS, UMR7258, Institut Paoli-Calmettes, Aix-Marseille University, Marseille, France
- Immunomonitoring Platform, Institut Paoli-Calmettes, Marseille, France
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Hepatocellular Carcinoma: Essentials Interventional Radiologists Need to Know. Cardiovasc Intervent Radiol 2019; 42:1262-1270. [PMID: 31069465 DOI: 10.1007/s00270-019-02221-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2018] [Accepted: 04/10/2019] [Indexed: 02/08/2023]
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31
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Murad HY, Yu H, Luo D, Bortz EP, Halliburton GM, Sholl AB, Khismatullin DB. Mechanochemical Disruption Suppresses Metastatic Phenotype and Pushes Prostate Cancer Cells toward Apoptosis. Mol Cancer Res 2019; 17:1087-1101. [PMID: 30617107 DOI: 10.1158/1541-7786.mcr-18-0782] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2018] [Revised: 10/22/2018] [Accepted: 01/03/2019] [Indexed: 12/30/2022]
Abstract
Chemical-based medicine that targets specific oncogenes or proteins often leads to cancer recurrence due to tumor heterogeneity and development of chemoresistance. This challenge can be overcome by mechanochemical disruption of cancer cells via focused ultrasound (FUS) and sensitizing chemical agents such as ethanol. We demonstrate that this disruptive therapy decreases the viability, proliferation rate, tumorigenicity, endothelial adhesion, and migratory ability of prostate cancer cells in vitro. It sensitized the cells to TNFR1-- and Fas--mediated apoptosis and reduced the expression of metastatic markers CD44 and CD29. Using a prostate cancer xenograft model, we observed that the mechanochemical disruption led to complete tumor regression in vivo. This switch to a nonaggressive cell phenotype was caused by ROS and Hsp70 overproduction and subsequent impairment of NFκB signaling. FUS induces mechanical perturbations of diverse cancer cell populations, and its combination with agents that amplify and guide remedial cellular responses can stop lethal cancer progression. IMPLICATIONS: Mechanochemical disruption therapy in which FUS is combined with ethanol can be curative for locally aggressive and castration-resistant prostate cancer.
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Affiliation(s)
- Hakm Y Murad
- Department of Biomedical Engineering, Tulane University, New Orleans, Louisiana.,Tulane Institute for Integrative Engineering for Health and Medicine, Tulane University, New Orleans, Louisiana
| | - Heng Yu
- Department of Biomedical Engineering, Tulane University, New Orleans, Louisiana.,Tulane Institute for Integrative Engineering for Health and Medicine, Tulane University, New Orleans, Louisiana
| | - Daishen Luo
- Department of Biomedical Engineering, Tulane University, New Orleans, Louisiana.,Tulane Institute for Integrative Engineering for Health and Medicine, Tulane University, New Orleans, Louisiana
| | - Emma P Bortz
- Department of Biomedical Engineering, Tulane University, New Orleans, Louisiana.,Tulane Institute for Integrative Engineering for Health and Medicine, Tulane University, New Orleans, Louisiana
| | - Gray M Halliburton
- Department of Biomedical Engineering, Tulane University, New Orleans, Louisiana.,Tulane Institute for Integrative Engineering for Health and Medicine, Tulane University, New Orleans, Louisiana
| | - Andrew B Sholl
- Department of Pathology and Laboratory Medicine, Tulane University, New Orleans, Louisiana
| | - Damir B Khismatullin
- Department of Biomedical Engineering, Tulane University, New Orleans, Louisiana. .,Tulane Institute for Integrative Engineering for Health and Medicine, Tulane University, New Orleans, Louisiana.,Tulane Cancer Center, Tulane University, New Orleans, Louisiana
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32
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Krishan S, Dhiman RK, Kalra N, Sharma R, Baijal SS, Arora A, Gulati A, Eapan A, Verma A, Keshava S, Mukund A, Deva S, Chaudhary R, Ganesan K, Taneja S, Gorsi U, Gamanagatti S, Madhusudan KS, Puri P, Shalimar, Govil S, Wadhavan M, Saigal S, Kumar A, Thapar S, Duseja A, Saraf N, Khandelwal A, Mukhopadyay S, Gulati A, Shetty N, Verma N. Joint Consensus Statement of the Indian National Association for Study of the Liver and Indian Radiological and Imaging Association for the Diagnosis and Imaging of Hepatocellular Carcinoma Incorporating Liver Imaging Reporting and Data System. J Clin Exp Hepatol 2019; 9:625-651. [PMID: 31695253 PMCID: PMC6823668 DOI: 10.1016/j.jceh.2019.07.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2019] [Accepted: 07/12/2019] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the 6th most common cancer and the second most common cause of cancer-related mortality worldwide. There are currently no universally accepted practice guidelines for the diagnosis of HCC on imaging owing to the regional differences in epidemiology, target population, diagnostic imaging modalities, and staging and transplant eligibility. Currently available regional and national guidelines include those from the American Association for the Study of Liver Disease (AASLD), the European Association for the Study of the Liver (EASL), the Asian Pacific Association for the Study of the Liver, the Japan Society of Hepatology, the Korean Liver Cancer Study Group, Hong Kong, and the National Comprehensive Cancer Network in the United States. India with its large population and a diverse health infrastructure faces challenges unique to its population in diagnosing HCC. Recently, American Association have introduced a Liver Imaging Reporting and Data System (LIRADS, version 2017, 2018) as an attempt to standardize the acquisition, interpretation, and reporting of liver lesions on imaging and hence improve the coherence between radiologists and clinicians and provide guidance for the management of HCC. The aim of the present consensus was to find a common ground in reporting and interpreting liver lesions pertaining to HCC on imaging keeping LIRADSv2018 in mind.
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Affiliation(s)
- Sonal Krishan
- Department of Radiology, Medanta Hospital, Gurgaon, India
| | - Radha K. Dhiman
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India,Address for correspondence: Radha Krishan Dhiman, MD, DM, FACG, FRCP, FAASLD, Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
| | - Navin Kalra
- Department of Radiology, Postgraduate Institute Of Medical Education and Research, Chandigarh, India
| | - Raju Sharma
- Department of Radiology, All India Institute of Medical Sciences, New Delhi, India
| | - Sanjay S. Baijal
- Department of Diagnostic and Intervention Radiology, Medanta Hospital, Gurgaon, India
| | - Anil Arora
- Institute Of Liver Gastroenterology & Pancreatico Biliary Sciences, Sir Gangaram Hospital, New Delhi, India
| | - Ajay Gulati
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Anu Eapan
- Department of Radiology, Christian Medical College, Vellore, India
| | - Ashish Verma
- Department of Radiology, Banaras Hindu University, Varanasi, India
| | - Shyam Keshava
- Department of Radiology, Christian Medical College, Vellore, India
| | - Amar Mukund
- Department of Intervention Radiology, Institute of liver and biliary Sciences, New Delhi, India
| | - S. Deva
- Department of Radiology, All India Institute of Medical Sciences, New Delhi, India
| | - Ravi Chaudhary
- Department of Radiology, Medanta Hospital, Gurgaon, India
| | | | - Sunil Taneja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Ujjwal Gorsi
- Department of Radiology, Postgraduate Institute Of Medical Education and Research, Chandigarh, India
| | | | - Kumble S. Madhusudan
- Department of Radiology, All India Institute of Medical Sciences, New Delhi, India
| | - Pankaj Puri
- Institute Of Liver Gastroenterology & Pancreatico Biliary Sciences, Sir Gangaram Hospital, New Delhi, India
| | - Shalimar
- Department of GastroEnterology, All India Institute of Medical Sciences, New Delhi, India
| | | | - Manav Wadhavan
- Institute of Digestive and Liver Diseases, BLK Hospital, Delhi, India
| | - Sanjiv Saigal
- Department of Hepatology, Medanta Hospital, Gurgaon, India
| | - Ashish Kumar
- Institute Of Liver Gastroenterology & Pancreatico Biliary Sciences, Sir Gangaram Hospital, New Delhi, India
| | - Shallini Thapar
- Department of Radiology, Institute of liver and biliary Sciences, New Delhi, India
| | - Ajay Duseja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Neeraj Saraf
- Department of Hepatology, Medanta Hospital, Gurgaon, India
| | | | | | - Ajay Gulati
- Department of Radiology, Postgraduate Institute Of Medical Education and Research, Chandigarh, India
| | - Nitin Shetty
- Department of Radiology, Tata Memorial Hospital, Kolkata, India
| | - Nipun Verma
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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33
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Galle PR, Forner A, Llovet JM, Mazzaferro V, Piscaglia F, Raoul JL, Schirmacher P, Vilgrain V. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol 2018; 69:182-236. [PMID: 29628281 DOI: 10.1016/j.jhep.2018.03.019] [Citation(s) in RCA: 5778] [Impact Index Per Article: 825.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2018] [Accepted: 03/20/2018] [Indexed: 02/06/2023]
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Kis B, El-Haddad G, Sheth RA, Parikh NS, Ganguli S, Shyn PB, Choi J, Brown KT. Liver-Directed Therapies for Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma. Cancer Control 2018; 24:1073274817729244. [PMID: 28975829 PMCID: PMC5937250 DOI: 10.1177/1073274817729244] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (IHC) are primary liver cancers where all or most of the tumor burden is usually confined to the liver. Therefore, locoregional liver-directed therapies can provide an opportunity to control intrahepatic disease with minimal systemic side effects. The English medical literature and clinical trials were reviewed to provide a synopsis on the available liver-directed percutaneous therapies for HCC and IHC. Locoregional liver-directed therapies provide survival benefit for patients with HCC and IHC compared to best medical treatment and have lower comorbid risks compared to surgical resection. These treatment options should be considered, especially in patients with unresectable disease.
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Affiliation(s)
- Bela Kis
- 1 Department of Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Ghassan El-Haddad
- 1 Department of Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Rahul A Sheth
- 2 Department of Interventional Radiology, MD Anderson Cancer Center, Houston, TX, USA
| | - Nainesh S Parikh
- 1 Department of Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Suvranu Ganguli
- 3 Center for Image Guided Cancer Therapy, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Paul B Shyn
- 4 Department of Radiology, Abdominal Imaging and Intervention, Brigham and Women's, Boston, MA, USA
| | - Junsung Choi
- 1 Department of Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Karen T Brown
- 5 Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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Cressman ENK, Guo C. Feasibility study using tissue as reagent for cancer therapy: endovascular ablation via thermochemistry. CONVERGENT SCIENCE PHYSICAL ONCOLOGY 2018. [DOI: 10.1088/2057-1739/aab905] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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36
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Morisco F, Camera S, Guarino M, Tortora R, Cossiga V, Vitiello A, Cordone G, Caporaso N, Di Costanzo GG. Laser ablation is superior to TACE in large-sized hepatocellular carcinoma: a pilot case-control study. Oncotarget 2018; 9:17483-17490. [PMID: 29707122 PMCID: PMC5915130 DOI: 10.18632/oncotarget.24756] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2017] [Accepted: 02/27/2018] [Indexed: 12/25/2022] Open
Abstract
Background Limited therapies are available for large (≥40 mm) unresectable hepatocellular carcinoma (HCC). Currently, the standard treatment with transarterial chemoembolisation (TACE) is unsatisfactory with high recurrence rate and limited effect on survival. Laser Ablation (LA) has emerged as a relatively new technique characterized by high efficacy and good safety. This study is aimed to evaluate the efficacy of LA in comparison to TACE in patients with large HCC. Methods Eighty-two patients with a single HCC nodule ≥40 mm (BCLC stage A or B) were enrolled in this case-control study. Forty-one patients were treated with LA and 41 patients were treated with TACE. Response to therapy was evaluated according to the mRECIST criteria. Survival was calculated with Kaplan-Meier from the time of cancer diagnosis to death with values censored at the date of the last follow-up. Results Twenty-six (63.4%) and 8 (19.5%) patients had a complete response after LA and TACE, respectively (p < 0.001). Subsequently we stratified the HCCs in 3 categories according to the nodule size: 40–50 mm, 51–60 mm, and >60 mm. LA resulted superior to TACE especially in nodules ranging between 51 and 60 mm in diameter, with a complete response rate post-LA and post-TACE of 75% and 14.3%, respectively (p = 0.0133). The 36 months cumulative survival rate in patients treated with LA and TACE was 55.4% and 48.8%, respectively. The disease recurrence rates after LA and TACE were 19.5% and 75.0%, respectively. Conclusions LA is a more effective therapeutic option than TACE in patients with solitary large HCC.
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Affiliation(s)
- Filomena Morisco
- Gastroenterology Unit, Department of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy
| | - Silvia Camera
- Gastroenterology Unit, Department of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy
| | - Maria Guarino
- Gastroenterology Unit, Department of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy
| | | | - Valentina Cossiga
- Gastroenterology Unit, Department of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy
| | - Anna Vitiello
- Gastroenterology Unit, Department of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy
| | | | - Nicola Caporaso
- Gastroenterology Unit, Department of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy
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Nault JC, Sutter O, Nahon P, Ganne-Carrié N, Séror O. Percutaneous treatment of hepatocellular carcinoma: State of the art and innovations. J Hepatol 2018; 68:783-797. [PMID: 29031662 DOI: 10.1016/j.jhep.2017.10.004] [Citation(s) in RCA: 275] [Impact Index Per Article: 39.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2017] [Revised: 10/01/2017] [Accepted: 10/06/2017] [Indexed: 02/06/2023]
Abstract
Percutaneous treatment of hepatocellular carcinoma (HCC) encompasses a vast range of techniques, including monopolar radiofrequency ablation (RFA), multibipolar RFA, microwave ablation, cryoablation and irreversible electroporation. RFA is considered one of the main curative treatments for HCC of less than 5 cm developing on cirrhotic liver, together with surgical resection and liver transplantation. However, controversies exist concerning the respective roles of ablation and liver resection for HCC of less than 3 to 5 cm on cirrhotic liver. In line with the therapeutic algorithm of early HCC, percutaneous ablation could also be used as a bridge to liver transplantation or in a sequence of upfront percutaneous treatment, followed by transplantation if the patient relapses. Moreover, several innovations in ablation methods may help to efficiently treat early HCC, initially considered as "non-ablatable", and might, in some cases, extend ablation criteria beyond early HCC, enabling treatment of more patients with a curative approach.
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Affiliation(s)
- Jean-Charles Nault
- Liver Unit, Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bondy, France; Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Communauté d'Universités et Etablissements Sorbonne Paris Cité, Paris, France; Unité Mixte de Recherche 1162, Génomique fonctionnelle des tumeurs solides, Institut National de la Santé et de la Recherche Médicale, Paris, France.
| | - Olivier Sutter
- Department of Radiology, Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bondy, France
| | - Pierre Nahon
- Liver Unit, Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bondy, France; Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Communauté d'Universités et Etablissements Sorbonne Paris Cité, Paris, France; Unité Mixte de Recherche 1162, Génomique fonctionnelle des tumeurs solides, Institut National de la Santé et de la Recherche Médicale, Paris, France
| | - Nathalie Ganne-Carrié
- Liver Unit, Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bondy, France; Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Communauté d'Universités et Etablissements Sorbonne Paris Cité, Paris, France; Unité Mixte de Recherche 1162, Génomique fonctionnelle des tumeurs solides, Institut National de la Santé et de la Recherche Médicale, Paris, France
| | - Olivier Séror
- Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Communauté d'Universités et Etablissements Sorbonne Paris Cité, Paris, France; Unité Mixte de Recherche 1162, Génomique fonctionnelle des tumeurs solides, Institut National de la Santé et de la Recherche Médicale, Paris, France; Department of Radiology, Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bondy, France.
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Cheung TTT, Kwok PCH, Chan S, Cheung CC, Lee AS, Lee V, Cheng HC, Chia NH, Chong CC, Lai TW, Law AL, Luk MY, Tong CC, Yau TC. Hong Kong Consensus Statements for the Management of Unresectable Hepatocellular Carcinoma. Liver Cancer 2018; 7:40-54. [PMID: 29662832 PMCID: PMC5892367 DOI: 10.1159/000485984] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2017] [Accepted: 12/04/2017] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is highly prevalent in Hong Kong due to the high prevalence of chronic hepatitis B infection. Liver cancer is the fourth most common cancer and the third most common cause of cancer death. Due to the high case load, there is a high level of local expertise in treating HCC, and the full spectrum of treatment modalities is available. This document summarizes how these modalities should be used based on the latest evidence. SUMMARY In 2 meetings held in early 2017, a multidisciplinary group of Hong Kong clinicians, including liver surgeons, interventional radiologists, clinical oncologists, and medical oncologists, met to update local consensus statements for management of HCC. These statements are based on the latest evidence and give detailed guidance on how to deploy these modalities, in particular for cases of HCC which are not suited to surgical resection. KEY MESSAGES These statements give detailed information on how to decide if a patient is a candidate for resection, methods to improve candidacy for resection, and guidance for use of various nonsurgical interventions to manage patients ineligible for resection.
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Affiliation(s)
- Tom Tan-To Cheung
- Department of Surgery, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
| | | | - Stephen Chan
- Department of Clinical Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
| | | | - Ann-Shing Lee
- Department of Clinical Oncology, Tuen Mun Hospital, Hong Kong, China
| | - Victor Lee
- Department of Clinical Oncology, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
| | - Hoi-Ching Cheng
- Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong, China
| | - Nam-Hung Chia
- Department of Surgery, Queen Elizabeth Hospital, Hong Kong, China
| | - Charing C.N. Chong
- Department of Surgery, The Chinese University of Hong Kong, Hong Kong, China
| | - Tak-Wing Lai
- Department of Surgery, Princess Margaret Hospital, Hong Kong, China
| | - Ada L.Y. Law
- Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, Hong Kong, China
| | - Mai-Yee Luk
- Department of Clinical Oncology, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
| | - Chi Chung Tong
- Department of Clinical Oncology, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
| | - Thomas C.C. Yau
- Department of Medicine and Surgery, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
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Prenner S, Kulik L. Hepatocellular Carcinoma. ZAKIM AND BOYER'S HEPATOLOGY 2018:668-692.e9. [DOI: 10.1016/b978-0-323-37591-7.00046-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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40
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Benson AB, D'Angelica MI, Abbott DE, Abrams TA, Alberts SR, Saenz DA, Are C, Brown DB, Chang DT, Covey AM, Hawkins W, Iyer R, Jacob R, Karachristos A, Kelley RK, Kim R, Palta M, Park JO, Sahai V, Schefter T, Schmidt C, Sicklick JK, Singh G, Sohal D, Stein S, Tian GG, Vauthey JN, Venook AP, Zhu AX, Hoffmann KG, Darlow S. NCCN Guidelines Insights: Hepatobiliary Cancers, Version 1.2017. J Natl Compr Canc Netw 2017; 15:563-573. [PMID: 28476736 DOI: 10.6004/jnccn.2017.0059] [Citation(s) in RCA: 245] [Impact Index Per Article: 30.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The NCCN Guidelines for Hepatobiliary Cancers provide treatment recommendations for cancers of the liver, gallbladder, and bile ducts. The NCCN Hepatobiliary Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding locoregional therapy for treatment of patients with hepatocellular carcinoma.
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Affiliation(s)
- Al B Benson
- Robert H. Lurie Comprehensive Cancer Center of Northwestern University
| | | | | | | | | | | | | | | | | | | | - William Hawkins
- Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
| | | | - Rojymon Jacob
- University of Alabama at Birmingham Comprehensive Cancer Center
| | | | - R Kate Kelley
- UCSF Helen Diller Family Comprehensive Cancer Center
| | - Robin Kim
- Huntsman Cancer Institute at the University of Utah
| | | | - James O Park
- Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance
| | | | | | - Carl Schmidt
- The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute
| | | | | | - Davendra Sohal
- Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute
| | | | - G Gary Tian
- St. Jude Children’s Research Hospital/The University of Tennessee Health Science Center
| | | | - Alan P Venook
- UCSF Helen Diller Family Comprehensive Cancer Center
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Armengol C, Sarrias MR, Sala M. Hepatocellular carcinoma: Present and future. Med Clin (Barc) 2017; 150:390-397. [PMID: 29096967 DOI: 10.1016/j.medcli.2017.08.010] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2017] [Revised: 08/17/2017] [Accepted: 08/21/2017] [Indexed: 12/19/2022]
Abstract
Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide with over 740,000 new cases per year and the third leading cause of cancer-related death, with a growing incidence in recent years. This tumor usually arises in patients with an underlying chronic liver disease. The management of this tumor has improved over the past 2 decades: patients at risk are included in a surveillance program, a prognostic staging system has been created and, finally, new treatments particularly aimed at patients with advanced HCC have been developed. This fact has resulted in a greater interest in this tumor and several scientific societies have developed clinical practice guidelines for the management of patients with this disease. In this article, we review the current and future prospects of this tumor.
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Affiliation(s)
- Carolina Armengol
- Unidad de Hepatología, Servicio de Aparato Digestivo, Institut de Recerca Germans Trias i Pujol (IGTP), Hospital Germans Trias i Pujol, Badalona, Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Badalona, Barcelona, España; Childhood Liver Oncology group (c-LOG), Program of Predictive and Personalized Medicine of Cancer (PMPPC), Institut de Recerca Germans Trias i Pujol (IGTP), Badalona, Barcelona, España
| | - Maria Rosa Sarrias
- Unidad de Hepatología, Servicio de Aparato Digestivo, Institut de Recerca Germans Trias i Pujol (IGTP), Hospital Germans Trias i Pujol, Badalona, Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Badalona, Barcelona, España; Innate Immunity Group, Germans Trias i Pujol Health Sciences Institute (IGTP), Badalona, Barcelona, España
| | - Margarita Sala
- Unidad de Hepatología, Servicio de Aparato Digestivo, Institut de Recerca Germans Trias i Pujol (IGTP), Hospital Germans Trias i Pujol, Badalona, Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Badalona, Barcelona, España.
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Sim HW, Knox J, Dawson LA. An Update on Randomized Clinical Trials in Hepatocellular Carcinoma. Surg Oncol Clin N Am 2017; 26:647-666. [PMID: 28923223 DOI: 10.1016/j.soc.2017.05.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Hepatocellular carcinoma is a common malignancy that typically occurs in the setting of comorbid liver disease. Optimal management is challenging, especially given the assortment of available treatment modalities. This article reviews the randomized clinical trials that have formed the basis of contemporary hepatocellular carcinoma management.
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Affiliation(s)
- Hao-Wen Sim
- Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada
| | - Jennifer Knox
- Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada
| | - Laura A Dawson
- Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada.
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Kollmann D, Selzner N, Selzner M. Bridging to liver transplantation in HCC patients. Langenbecks Arch Surg 2017; 402:863-871. [PMID: 28755240 DOI: 10.1007/s00423-017-1609-2] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2017] [Accepted: 07/19/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND Liver transplantation (LT) is the only cure for patients diagnosed with unresectable hepatocellular carcinoma (HCC), and HCC has become the leading indication for LT in the USA. The shortage of liver grafts results in a significant waiting time for LT with the risk of tumour progression. Treating HCCs during the waiting time prior to transplantation (bridging therapy) is an attractive strategy to reduce the risk of exceeding the tumour criteria for transplantation. Studies on bridging therapy are heterogenous and due to ethical issues, mostly of retrospective design. PURPOSE We summarize the main studies and methods that have been reported on bridging therapies for patients with HCC waiting for a LT. CONCLUSION During the waiting period for LT, patients with HCC at risk for tumour progression and therefore bridging therapy is recommended for patients with an estimated waiting time of ≥6 months. Bridging therapy for patients with HCC prior to LT mainly include locoregional therapies (LRTs), with transarterial chemoembolization (TACE) being the most common, followed by radio frequency ablation (RFA). Because of a continuous enhancement of therapy options, including a more precise adjustment of external radiotherapy, further possibilities for an individualized bridging therapy for patients with HCC have been developed. Patients with compensated liver cirrhosis and small tumour size are preferably treated with RFA, whereas patients with larger tumour size but compensated liver function are treated with TACE/TARE. Patients with uncompensated liver cirrhosis and larger tumour size can nowadays be successfully bridged to LT with external radiotherapy without increasing the risk for further deterioration of liver function.
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Affiliation(s)
- Dagmar Kollmann
- Multi Organ Transplant Program, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Canada
| | - Nazia Selzner
- Department of Medicine, Toronto General Hospital, University Health Network, Toronto, Canada
| | - Markus Selzner
- Multi Organ Transplant Program, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Canada. .,General Surgery and Multi-Organ Transplant Program, Toronto General Hospital, University Health Network, University of Toronto, 585 University Avenue, 11 PMB 178, Toronto, ON, M5G 2N2, Canada.
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Giorgio A, Merola MG, Montesarchio L, Merola F, Gatti P, Coppola C, Giorgio V, Calisti G. Percutaneous radiofrequency ablation of hepatocellular carcinoma in cirrhosis: analysis of complications in a single centre over 20 years. Br J Radiol 2017; 90:20160804. [PMID: 28402124 DOI: 10.1259/bjr.20160804] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
OBJECTIVE To report on our 20 years' experience on complications after radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) in patients with cirrhosis. METHODS From 1994 to 2014, 1787 RFA procedures were performed percutaneously in 1162 patients with cirrhosis (852 Child A and 310 Child B) with HCC nodules (1.2-7 cm), prothrombin time >50%, platelet count of 50.000 mm3 and total bilirubin ranging from 0.80 to 4.5 mg dl-1. In 67 patients, RFA was performed on both intraparenchymal HCC nodule and tumour thrombus extended in the main portal vein and/or its branches. RESULTS Four patients (0.3%) died after RFA. 39 patients (3.2%) changed in Child's class: 26 out of 28 Child A patients with cirrhosis changed to Child B and 2 changed to Child C class; 11 Child B patients changed to Child C class. On multivariate analysis, the total bilirubin pre-RFA was the only independent risk factor for impairment of liver function and death. Complications were hemoperitoneum, abscess and intrahepatic haematoma. CONCLUSION RFA of HCC in patients with cirrhosis is safe, even in case of invasion of the portal venous system. Functional liver reserve should be strictly monitored, mainly when pre-RFA total bilirubin value is >2.5 mg dl-1. The study was approved by our institutional review board. Advances in knowledge: The total bilirubin value >2.5 mg dl-1 represents the main marker of functional liver reserve that predicts decompensation of liver cirrhosis in patients undergoing RFA for HCC.
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Affiliation(s)
- Antonio Giorgio
- 1 Interventional Ultrasound Unit, D Cotugno Hospital, Naples, Italy.,2 Interventional Ultrasound Unit, Tortorella Clinical Institute, Salerno, Italy
| | - Maria G Merola
- 2 Interventional Ultrasound Unit, Tortorella Clinical Institute, Salerno, Italy
| | - Luca Montesarchio
- 2 Interventional Ultrasound Unit, Tortorella Clinical Institute, Salerno, Italy
| | - Francesca Merola
- 2 Interventional Ultrasound Unit, Tortorella Clinical Institute, Salerno, Italy
| | - Pietro Gatti
- 2 Interventional Ultrasound Unit, Tortorella Clinical Institute, Salerno, Italy
| | - Carmine Coppola
- 2 Interventional Ultrasound Unit, Tortorella Clinical Institute, Salerno, Italy
| | - Valentina Giorgio
- 2 Interventional Ultrasound Unit, Tortorella Clinical Institute, Salerno, Italy
| | - Giorgio Calisti
- 2 Interventional Ultrasound Unit, Tortorella Clinical Institute, Salerno, Italy
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A Review and Update of Treatment Options and Controversies in the Management of Hepatocellular Carcinoma. Ann Surg 2017; 263:1112-25. [PMID: 26813914 DOI: 10.1097/sla.0000000000001556] [Citation(s) in RCA: 216] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To review the current management, outline recent advances and address controversies in the management of hepatocellular carcinoma (HCC). SUMMARY OF BACKGROUND DATA The treatment of HCC is multidisciplinary involving hepatologists, surgeons, medical oncologists, radiation oncologists, radiologists, interventional radiologists, and other disciplines. Each of these disciplines brings its unique perspective and differing opinions that add to controversies in the management of HCC. METHODS A focused literature review was performed to identify recent studies on the management of HCC and thereby summarize relevant information on the various therapeutic modalities and controversies involved in the treatment of HCC. RESULTS The main treatment algorithms continue to rely on hepatic resection or transplantation with controversies involving patients harboring early stage disease and borderline hepatic function. The other treatment strategies include locoregional therapies, radiation, and systemic therapy used alone or in combination with other treatment modalities. Recent advances in locoregional therapies, radiation, and systemic therapies have provided better therapeutic options with curative intent potential for some locoregional therapies. Further refinements in combination therapies such as algorithms consisting of locoregional therapies and systemic or radiation therapies are likely to add additional options and improve survival. CONCLUSIONS The management of HCC has witnessed significant strides with advances in existing options and introduction of several new treatment modalities of various combinations. Further refinements in these treatment options combined with enrollment in clinical trials are essential to improve the management and outcomes of patients with HCC.
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Prior JO, Gillessen S, Wirth M, Dale W, Aapro M, Oyen WJ. Radiopharmaceuticals in the elderly cancer patient: Practical considerations, with a focus on prostate cancer therapy. Eur J Cancer 2017; 77:127-139. [DOI: 10.1016/j.ejca.2017.01.030] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2016] [Revised: 01/12/2017] [Accepted: 01/29/2017] [Indexed: 11/24/2022]
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Bridging locoregional therapy: Longitudinal trends and outcomes in patients with hepatocellular carcinoma. Transplant Rev (Orlando) 2017; 31:136-143. [PMID: 28214240 DOI: 10.1016/j.trre.2017.01.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2016] [Accepted: 01/28/2017] [Indexed: 12/19/2022]
Abstract
The purpose of this article is to analyze longitudinal trends in locoregional therapy (LRT) use and review locoregional therapy's role in the management of hepatocellular carcinoma prior to orthotropic liver transplantation Porrett et al. (2006) . LRT has a role in both bridge to transplantation and downstaging of patients not initially meeting Milan or UCSF Criteria. Due to the lack of randomized controlled trials, no specific bridging LRT modality is recommended over another for treating patients on the waiting list, however each modality has unique and patient-specific advantages. Pre-transplant LRT use in the United States has increased dramatically over the last two decades with more than 50% of the currently listed patients receiving LRT Freeman et al. (2008) . Despite these national trends, significant differences in LRT utilization, referral patterns, recurrence rates and survival have been observed among UNOS regions, socioeconomic levels and races. The use of LRT as a biologic selection tool based on response to treatment has shown promising results in its ability to predict successful post-transplant outcomes.
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Kouri BE, Abrams RA, Al-Refaie WB, Azad N, Farrell J, Gaba RC, Gervais DA, Gipson MG, Kolbeck KJ, Marshalleck FE, Pinchot JW, Small W, Ray CE, Hohenwalter EJ. ACR Appropriateness Criteria Radiologic Management of Hepatic Malignancy. J Am Coll Radiol 2016; 13:265-73. [PMID: 26944037 DOI: 10.1016/j.jacr.2015.12.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2015] [Accepted: 12/04/2015] [Indexed: 12/18/2022]
Abstract
Management of primary and secondary hepatic malignancy is a complex problem. Achieving optimal care for this challenging population often requires the involvement of multiple medical and surgical disciplines. Because of the wide variety of potential therapies, treatment protocols for various malignancies continue to evolve. Consequently, development of appropriate therapeutic algorithms necessitates consideration of medical options, such as systemic chemotherapy; surgical options, such as resection or transplantation; and loco-regional therapies, such as thermal ablation and transarterial embolization techniques. This article provides a review of treatment strategies for the three most common subtypes of hepatic malignancy treated with loco-regional therapies: hepatocellular carcinoma, neuroendocrine metastases, and colorectal metastases. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every three years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
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Affiliation(s)
- Brian E Kouri
- Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina.
| | | | - Waddah B Al-Refaie
- Georgetown University Hospital, Washington, District of Columbia, American College of Surgeons
| | - Nilofer Azad
- Sidney Kimmel Cancer Center at Johns Hopkins University, Baltimore, Maryland, American Society of Clinical Oncology
| | - James Farrell
- Interventional Endoscopy and Pancreatic Diseases, New Haven, Connecticut, American Gastroenterological Association
| | - Ron C Gaba
- University of Illinois Hospital, Chicago, Illinois
| | | | - Matthew G Gipson
- University of Colorado, Anschutz Medical Campus, Aurora, Colorado
| | | | | | | | - William Small
- Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois
| | - Charles E Ray
- University of Illinois Hospital and Health Science System, Chicago, Illinois
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Delicque J, Boulin M, Guiu B, Pelage JP, Escal L, Schembri V, Assenat E, Fohlen A. Interventional oncology for hepatocellular carcinoma. Clin Res Hepatol Gastroenterol 2016; 40:530-537. [PMID: 27055387 DOI: 10.1016/j.clinre.2016.01.007] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2016] [Accepted: 01/17/2016] [Indexed: 02/04/2023]
Abstract
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and is increasing in incidence. The overall prognosis of patients with liver cancer is poor. The Barcelona Clinic Liver Cancer (BCLC) classification in 5 stages is endorsed by European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Disease (AASLD). This classification is recommended for treatment allocation. Because a small proportion of patients are suitable for curative surgical treatment, various locoregional therapies are widely used to manage patients with HCC. The image-guided therapies, also called interventional radiology or interventional oncology (IO) techniques consisted in percutaneous or endovascular approach. This article reviews the different IO treatments available in HCC patients and the strength of the data.
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Affiliation(s)
- Julien Delicque
- St-Eloi University Hospital, Department of Radiology, 34000 Montpellier, France
| | - Mathieu Boulin
- Dijon University Hospital, Department of Pharmacy, 21000 Dijon, France
| | - Boris Guiu
- St-Eloi University Hospital, Department of Radiology, 34000 Montpellier, France.
| | - Jean-Pierre Pelage
- St-Eloi University Hospital, Department of Radiology, 34000 Montpellier, France
| | - Laure Escal
- St-Eloi University Hospital, Department of Radiology, 34000 Montpellier, France
| | - Valentina Schembri
- St-Eloi University Hospital, Department of Radiology, 34000 Montpellier, France
| | - Eric Assenat
- St-Eloi University Hospital, Department of Oncology, 34000 Montpellier, France
| | - Audrey Fohlen
- University and Medical Center of Caen, 14033 Caen cedex, France.
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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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