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Domini J, Makary MS. Single-center analysis of percutaneous ablation in the treatment of hepatocellular carcinoma: long-term outcomes of a 7-year experience. Abdom Radiol (NY) 2023; 48:1173-1180. [PMID: 36717404 DOI: 10.1007/s00261-023-03819-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2022] [Revised: 01/15/2023] [Accepted: 01/16/2023] [Indexed: 02/01/2023]
Abstract
PURPOSE The objective of this study is to examine the safety and efficacy of ablative therapy for hepatocellular carcinoma (HCC). METHODS A retrospective review of 419 consecutive patients diagnosed with HCC, treated with percutaneous ablation at a tertiary academic medical center from June 2015 to June 2022, was conducted. Data evaluated included demographics, disease and tumor burden scores, and functional status. Procedural outcomes included procedural course, complication rates, biochemical and radiologic response, survival, and functional status. RESULTS A total of 419 patients, including 313 males (74.7%) and 106 females (25.3%) with a mean age of 63.8 ± 6.64 years, made up the study cohort. 120 patients (28.6%) presented with solitary lesions and 299 patients (71.4%) had multifocal involvement, with a mean tumor size of 2.3 ± 0.92 cm. A majority of the interventions performed were microwave ablations (n = 413, 98.3%), with 6 radiofrequency ablations (1.4%). Treatment response was radiographically assessed up to 6 months post-ablation and graded as complete response (96.2%), partial response (2.6%), stable disease (0%), and progressive disease (1.2%). 97 (23.2%) of the treated patients went on to receive liver transplant. The average progression-free survival in the study population was 24 months with a survival of 85.9% (n = 360), 67.8% (n = 284), and 63.2% (n = 265) at 1 year, 3 years, and 5 years respectively. Functional outcomes, as defined by ECOG scores, were maintained or improved in 383 patients (91.4%) and 349 patients (83.3%) at 6 months and 12 months respectively. CONCLUSIONS This large institutional experience demonstrated safety and efficacy of ablation therapies for treatment of HCC with promising tumor response rates and enduring clinical outcomes including prolonged survival and preserved functional status.
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Affiliation(s)
- John Domini
- Department of Radiology, The Ohio State University Wexner Medical Center, 395 W 12Th Ave, 4Th Floor Faculty Office Tower, Columbus, OH, 43210, USA
| | - Mina S Makary
- Department of Radiology, The Ohio State University Wexner Medical Center, 395 W 12Th Ave, 4Th Floor Faculty Office Tower, Columbus, OH, 43210, USA.
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2
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Zou YW, Ren ZG, Sun Y, Liu ZG, Hu XB, Wang HY, Yu ZJ. The latest research progress on minimally invasive treatments for hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int 2023; 22:54-63. [PMID: 36041973 DOI: 10.1016/j.hbpd.2022.08.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Accepted: 08/09/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide. Due to the high prevalence of hepatitis B virus (HBV) infection in China, the incidence of HCC in China is high, and liver cirrhosis caused by chronic hepatitis also brings great challenges to treatment. This paper reviewed the latest research progress on minimally invasive treatments for HCC, including percutaneous thermal ablation and new nonthermal ablation techniques, and introduced the principles, advantages, and clinical applications of various therapeutic methods in detail. DATA SOURCES The data of treatments for HCC were systematically collected from the PubMed, ScienceDirect, American Chemical Society and Web of Science databases published in English, using "minimally invasive" and "hepatocellular carcinoma" or "liver cancer" as the keywords. RESULTS Percutaneous thermal ablation is still a first-line strategy for the minimally invasive treatment of HCC. The effect of microwave ablation (MWA) on downgrading treatment before liver transplantation is better than that of radiofrequency ablation (RFA), while RFA is more widely used in the clinical practice. High-intensity focused ultrasound (HIFU) is mainly used for the palliative treatment of advanced liver cancer. Electrochemotherapy (ECT) delivers chemotherapeutic drugs to the target cells while reducing the blood supply around HCC. Irreversible electroporation (IRE) uses a microsecond-pulsed electric field that induces apoptosis and necrosis and triggers a systemic immune response. The nanosecond pulsed electric field (nsPEF) has achieved a good response in the ablation of mice with HCC, but it has not been reported in China for the treatment of human HCC. CONCLUSIONS A variety of minimally invasive treatments provide a sufficient survival advantage for HCC patients. Nonthermal ablation will lead to a new wave with its unique advantage of antitumor recurrence and metastasis.
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Affiliation(s)
- Ya-Wen Zou
- Department of Infectious Diseases, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Key Laboratory of Pulsed Power Translational Medicine of Zhejiang Province, 2959 Yuhangtang Road, Hangzhou 310000, China; Gene Hospital of Henan Province; Precision Medicine Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Zhi-Gang Ren
- Department of Infectious Diseases, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Key Laboratory of Pulsed Power Translational Medicine of Zhejiang Province, 2959 Yuhangtang Road, Hangzhou 310000, China; Gene Hospital of Henan Province; Precision Medicine Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Ying Sun
- Department of Infectious Diseases, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Key Laboratory of Pulsed Power Translational Medicine of Zhejiang Province, 2959 Yuhangtang Road, Hangzhou 310000, China; Gene Hospital of Henan Province; Precision Medicine Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Zhen-Guo Liu
- Department of Infectious Diseases, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Key Laboratory of Pulsed Power Translational Medicine of Zhejiang Province, 2959 Yuhangtang Road, Hangzhou 310000, China; Gene Hospital of Henan Province; Precision Medicine Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Xiao-Bo Hu
- Department of Infectious Diseases, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Gene Hospital of Henan Province; Precision Medicine Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Hai-Yu Wang
- Department of Infectious Diseases, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Gene Hospital of Henan Province; Precision Medicine Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Zu-Jiang Yu
- Department of Infectious Diseases, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Gene Hospital of Henan Province; Precision Medicine Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
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Minici R, Siciliano MA, Ammendola M, Santoro RC, Barbieri V, Ranieri G, Laganà D. Prognostic Role of Neutrophil-to-Lymphocyte Ratio (NLR), Lymphocyte-to-Monocyte Ratio (LMR), Platelet-to-Lymphocyte Ratio (PLR) and Lymphocyte-to-C Reactive Protein Ratio (LCR) in Patients with Hepatocellular Carcinoma (HCC) undergoing Chemoembolizations (TACE) of the Liver: The Unexplored Corner Linking Tumor Microenvironment, Biomarkers and Interventional Radiology. Cancers (Basel) 2022; 15:257. [PMID: 36612251 PMCID: PMC9818978 DOI: 10.3390/cancers15010257] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 12/04/2022] [Accepted: 12/27/2022] [Indexed: 01/03/2023] Open
Abstract
TACE plays a pivotal role in hepatocellular carcinoma, from disease control to downstaging and bridging to liver transplant. Response to TACE is a surrogate marker of tumor aggressive biology, with manifold practical implications such as survival, the need for more aggressive treatments in the intermediate stage, the selection of patients on the transplant waiting list, the dropout rate from the transplant list and the post-transplant recurrence rate. Inflammation-based scores are biomarkers of the relationship between the tumor stromal microenvironment and the immune response. Investigating the connection among the tumor stromal microenvironment, biomarkers, and the response to TACE is crucial to recognize TACE refractoriness/failure, thus providing patients with tailored therapeutics. This review aims to provide a comprehensive overview of the prognostic roles of the neutrophil-to-lymphocyte ratio (NLR), the lymphocyte-to-monocyte ratio (LMR), the platelet-to-lymphocyte ratio (PLR), and the lymphocyte-to-C reactive protein ratio (LCR) in patients with HCC undergoing chemoembolization of the liver. Inflammation-based scores may be convenient, easily obtained, low-cost, and reliable biomarkers with prognostic significance for HCC undergoing TACE. Baseline cut-off values differ between various studies, thus increasing confusion about using of inflammation-based scores in clinical practice. Further investigations should be conducted to establish the optimal cut-off values for inflammation-based scores, consolidating their use in clinical practice.
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Affiliation(s)
- Roberto Minici
- Radiology Division, Pugliese-Ciaccio Hospital, 88100 Catanzaro, Italy
| | | | - Michele Ammendola
- Digestive Surgery Unit, Science of Health Department, Magna Graecia University, 88100 Catanzaro, Italy
| | - Rita Carlotta Santoro
- Haemophilia and Thrombosis Center, Pugliese-Ciaccio Hospital, 88100 Catanzaro, Italy
| | - Vito Barbieri
- Oncology Division, Pugliese-Ciaccio Hospital, 88100 Catanzaro, Italy
| | - Girolamo Ranieri
- Interventional and Medical Oncology Unit, IRCCS Istituto Tumori “Giovanni Paolo II”, 70124 Bari, Italy
| | - Domenico Laganà
- Radiology Unit, Department of Experimental and Clinical Medicine, Magna Graecia University, 88100 Catanzaro, Italy
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Yin Z, Chen D, Liang S, Li X. Neoadjuvant Therapy for Hepatocellular Carcinoma. J Hepatocell Carcinoma 2022; 9:929-946. [PMID: 36068876 PMCID: PMC9441170 DOI: 10.2147/jhc.s357313] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2022] [Accepted: 06/15/2022] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is characterized by low resection and high postoperative recurrence rates, and conventional treatment strategies have failed to meet clinical needs. Neoadjuvant therapy (NAT) is widely employed in the routine management of several solid tumors because it increases resectability and reduces the rate of postoperative recurrence. However, a consensus has not been reached regarding the effects of NAT on HCC. As systemic therapy, particularly targeted therapy and immunotherapy, is given for HCC treatment, accumulating evidence shows that the "spring" of NAT for HCC is imminent. In the future, HCC researchers should focus on identifying biomarkers for treatment response, explore the mechanisms of resistance, and standardize the endpoints of NAT.
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Affiliation(s)
- Zongyi Yin
- Department of Hepatobiliary Surgery, Shenzhen University General Hospital, Shenzhen University, Shenzhen, 518055, People’s Republic of China
- Guangdong Provincial Key Laboratory of Regional Immunity and Diseases & Carson International Cancer, Shenzhen University, Shenzhen, 518055, People’s Republic of China
- Shenzhen University Clinical Medical Academy Center, Shenzhen University, Shenzhen, 518055, People’s Republic of China
| | - Dongying Chen
- Shenzhen University Clinical Medical Academy Center, Shenzhen University, Shenzhen, 518055, People’s Republic of China
- Department of Anesthesiology, Shenzhen University General Hospital, Shenzhen University, Shenzhen, 518055, People’s Republic of China
| | - Shuang Liang
- Department of Hepatobiliary Surgery, Shenzhen University General Hospital, Shenzhen University, Shenzhen, 518055, People’s Republic of China
| | - Xiaowu Li
- Department of Hepatobiliary Surgery, Shenzhen University General Hospital, Shenzhen University, Shenzhen, 518055, People’s Republic of China
- Guangdong Provincial Key Laboratory of Regional Immunity and Diseases & Carson International Cancer, Shenzhen University, Shenzhen, 518055, People’s Republic of China
- Shenzhen University Clinical Medical Academy Center, Shenzhen University, Shenzhen, 518055, People’s Republic of China
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5
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Deng Q, He M, Fu C, Feng K, Ma K, Zhang L. Radiofrequency ablation in the treatment of hepatocellular carcinoma. Int J Hyperthermia 2022; 39:1052-1063. [PMID: 35944905 DOI: 10.1080/02656736.2022.2059581] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVE The purpose of this article is to discuss the use, comparative efficacy, and research progress of radiofrequency ablation (RFA), alone or in combination with other therapies, for the treatment of hepatocellular carcinoma (HCC). METHOD To search and summarize the basic and clinical studies of RFA in recent years. RESULTS RFA is one of the radical treatment methods listed in the guidelines for the diagnosis and treatment of HCC. It has the characteristics of being minimally invasive and safe and can obtain good local tumor control, and it can improve the local immune ability, improve the tumor microenvironment and enhance the efficacy of chemotherapy drugs. It is commonly used for HCC treatment before liver transplantation and combined ALPPS and hepatectomy for HCC. In addition, the technology of RFA is constantly developing. The birth of noninvasive, no-touch RFA technology and equipment and the precise RFA concept have improved the therapeutic effect of RFA. CONCLUSION RFA has good local tumor control ability, is minimally invasive, is safe and has other beneficial characteristics. It plays an increasingly important role in the comprehensive treatment strategy of HCC. Whether RFA alone or combined with other technologies expands the surgical indications of patients with HCC and provides more benefits for HCC patients needs to be determined.
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Affiliation(s)
- Qingsong Deng
- Army Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Minglian He
- Department of Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Chunchuan Fu
- Department of Hepatobiliary Surgery, Xuanhan County People's Hospital, Xuanhan, China
| | - Kai Feng
- Army Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Kuansheng Ma
- Army Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Leida Zhang
- Army Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
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Hendriquez R, Keihanian T, Goyal J, Abraham RR, Mishra R, Girotra M. Radiofrequency ablation in the management of primary hepatic and biliary tumors. World J Gastrointest Oncol 2022; 14:203-215. [PMID: 35116111 PMCID: PMC8790419 DOI: 10.4251/wjgo.v14.i1.203] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Revised: 06/15/2021] [Accepted: 12/07/2021] [Indexed: 02/06/2023] Open
Abstract
In the United States, 80%-90% of primary hepatic tumors are hepatocellular carcinomas and 10%-15% are cholangiocarcinomas (CCA), both with high mortality rate, particularly CCA, which portends a worse prognosis. Traditional management with surgery has good outcomes in appropriately selected patients; however, novel ablative treatment options have emerged, such as radiofrequency ablation (RFA), which can improve the prognosis of both hepatic and biliary tumors. RFA is aimed to generate an area of necrosis within the targeted tissue by applying thermal therapy via an electrode, with a goal to completely eradicate the tumor while preserving surrounding healthy tissue. Role of RFA in management of hepatic and biliary tumors forms the focus of our current mini-review article.
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Affiliation(s)
- Richard Hendriquez
- Department of Internal Medicine, University of Central Florida, Orlando, FL 32816, United States
| | - Tara Keihanian
- Department of Gastroenterology and Hepatology, University of Miami, Miami, FL 33136, United States
| | - Jatinder Goyal
- Department of Gastroenterology and Hepatology, Wellspan Digestive Health - York Hospital, York, PA 17403, United States
| | - Rtika R Abraham
- Department of Endocrinology, Swedish Medical Center, Seattle, WA 98104, United States
| | - Rajnish Mishra
- Digestive Health Institute, Section of Gastroenterology and Interventional Endoscopy, Swedish Medical Center, Seattle, WA 98104, United States
| | - Mohit Girotra
- Digestive Health Institute, Section of Gastroenterology and Interventional Endoscopy, Swedish Medical Center, Seattle, WA 98104, United States
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Role of Pretransplant Treatments for Patients with Hepatocellular Carcinoma Waiting for Liver Transplantation. Cancers (Basel) 2022; 14:cancers14020396. [PMID: 35053558 PMCID: PMC8773674 DOI: 10.3390/cancers14020396] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 01/09/2022] [Accepted: 01/12/2022] [Indexed: 02/01/2023] Open
Abstract
Simple Summary Hepatocellular carcinoma (HCC) is the fifth most common cancer in men worldwide and the second leading cause of cancer death. Liver transplantation (LT) is one of the treatment options for patients with HCC. Recently, there have been many reports of the usefulness of locoregional therapy, such as transarterial chemoembolization and radiofrequency ablation, for HCC as pretreatment before LT. In Western countries, locoregional therapy is used to bridge until transplantation to prevent drop-outs from the waiting list or for downstaging to treat patients with advanced HCC who initially exceed the criteria for LT. With the progress of locoregional therapy, new reports on the effects of bridging and downstaging locoregional therapy as pretransplant treatment are increasing in number. Abstract Recently, there have been many reports of the usefulness of locoregional therapy such as transarterial chemoembolization and radiofrequency ablation for hepatocellular carcinoma (HCC) as pretreatment before liver transplantation (LT). Locoregional therapy is performed with curative intent in Japan, where living donor LT constitutes the majority of LT due to the critical shortage of deceased donors. However, in Western countries, where deceased donor LT is the main procedure, LT is indicated for early-stage HCC regardless of liver functional reserve, and locoregional therapy is used for bridging until transplantation to prevent drop-outs from the waiting list or for downstaging to treat patients with advanced HCC who initially exceed the criteria for LT. There are many reports of the effect of bridging and downstaging locoregional therapy before LT, and its indications and efficacy are becoming clear. Responses to locoregional therapy, such as changes in tumor markers, the avidity of FDG-PET, etc., are considered useful for successful bridging and downstaging. In this review, the effects of bridging and downstaging locoregional therapy as a pretransplant treatment on the results of transplantation are clarified, focusing on recent reports.
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Quantification of contrast agent uptake in the hepatobiliary phase helps to differentiate hepatocellular carcinoma grade. Sci Rep 2021; 11:22991. [PMID: 34837039 PMCID: PMC8626433 DOI: 10.1038/s41598-021-02499-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Accepted: 11/10/2021] [Indexed: 12/02/2022] Open
Abstract
This study aimed to assess the degree of differentiation of hepatocellular carcinoma (HCC) using Gd-EOB-DTPA-assisted magnetic resonance imaging (MRI) with T1 relaxometry. Thirty-three solitary HCC lesions were included in this retrospective study. This study's inclusion criteria were preoperative Gd-EOB-DTPA-assisted MRI of the liver and a histopathological evaluation after hepatic tumor resection. T1 maps of the liver were evaluated to determine the T1 relaxation time and reduction rate between the native phase and hepatobiliary phase (HBP) in liver lesions. These findings were correlated with the histopathologically determined degree of HCC differentiation (G1, well-differentiated; G2, moderately differentiated; G3, poorly differentiated). There was no significant difference between well-differentiated (950.2 ± 140.2 ms) and moderately/poorly differentiated (1009.4 ± 202.0 ms) HCCs in the native T1 maps. After contrast medium administration, a significant difference (p ≤ 0.001) in the mean T1 relaxation time in the HBP was found between well-differentiated (555.4 ± 140.2 ms) and moderately/poorly differentiated (750.9 ± 146.4 ms) HCCs. For well-differentiated HCCs, the reduction rate in the T1 time was significantly higher at 0.40 ± 0.15 than for moderately/poorly differentiated HCCs (0.25 ± 0.07; p = 0.006). In conclusion this study suggests that the uptake of Gd-EOB-DTPA in HCCs is correlated with tumor grade. Thus, Gd-EOB-DTPA-assisted T1 relaxometry can help to further differentiation of HCC.
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Crocetti L, Bozzi E, Scalise P, Bargellini I, Lorenzoni G, Ghinolfi D, Campani D, Balzano E, De Simone P, Cioni R. Locoregional Treatments for Bridging and Downstaging HCC to Liver Transplantation. Cancers (Basel) 2021; 13:5558. [PMID: 34771720 PMCID: PMC8583584 DOI: 10.3390/cancers13215558] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Revised: 10/27/2021] [Accepted: 11/03/2021] [Indexed: 02/08/2023] Open
Abstract
Liver transplantation (LT) is the first-line treatment for patients diagnosed with unresectable early-stage hepatocellular carcinoma (HCC) in the setting of cirrhosis. It is well known that HCC patients within the Milan criteria (solitary tumour ≤ 5 cm or ≤3 tumours, each <3 cm) could undergo LT with excellent results. However, there is a growing tendency to enlarge inclusion criteria since the Milan criteria are nowadays considered too restrictive and may exclude patients who would benefit from LT. On the other hand, there is a persistent shortage of donor organs. In this scenario, there is consensus about the role of loco-regional therapy (LRT) during the waiting list to select patients who would benefit more from LT, reducing the risk of drop off from the waiting list as well as decreasing tumour dimension to meet acceptable criteria for LT. In this review, current evidence on the safety, efficacy and utility of LRTs as neoadjuvant therapies before LT are summarized.
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Affiliation(s)
- Laura Crocetti
- Division of Interventional Radiology, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy; (E.B.); (P.S.); (I.B.); (G.L.); (R.C.)
- Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, 56126 Pisa, Italy; (D.C.); (P.D.S.)
| | - Elena Bozzi
- Division of Interventional Radiology, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy; (E.B.); (P.S.); (I.B.); (G.L.); (R.C.)
| | - Paola Scalise
- Division of Interventional Radiology, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy; (E.B.); (P.S.); (I.B.); (G.L.); (R.C.)
| | - Irene Bargellini
- Division of Interventional Radiology, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy; (E.B.); (P.S.); (I.B.); (G.L.); (R.C.)
| | - Giulia Lorenzoni
- Division of Interventional Radiology, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy; (E.B.); (P.S.); (I.B.); (G.L.); (R.C.)
| | - Davide Ghinolfi
- Division of Hepatobiliary Surgery and Liver Transplantation, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy; (D.G.); (E.B.)
| | - Daniela Campani
- Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, 56126 Pisa, Italy; (D.C.); (P.D.S.)
- Division of Pathology, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy
| | - Emanuele Balzano
- Division of Hepatobiliary Surgery and Liver Transplantation, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy; (D.G.); (E.B.)
| | - Paolo De Simone
- Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, 56126 Pisa, Italy; (D.C.); (P.D.S.)
- Division of Hepatobiliary Surgery and Liver Transplantation, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy; (D.G.); (E.B.)
| | - Roberto Cioni
- Division of Interventional Radiology, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy; (E.B.); (P.S.); (I.B.); (G.L.); (R.C.)
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10
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Hetzer B, Vogel GF, Entenmann A, Heil M, Schullian P, Putzer D, Meister B, Crazzolara R, Kropshofer G, Salvador C, Straub S, Karall D, Niederwanger C, Cortina G, Janecke A, Freund-Unsinn K, Maurer K, Schweigmann G, Oberhuber G, Renz O, Schneeberger S, Müller T, Bale R. Stereotactic radiofrequency ablation of a variety of liver masses in children. Int J Hyperthermia 2021; 37:1074-1081. [PMID: 32954876 DOI: 10.1080/02656736.2020.1822549] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND AND AIMS Surgical resection is currently the cornerstone of liver tumor treatment in children. In adults radiofrequency ablation (RFA) is an established minimally invasive treatment option for small focal liver tumors. Multiprobe stereotactic RFA (SRFA) with intraoperative image fusion to confirm ablation margins allows treatment for large lesions. We describe our experience with SRFA in children with liver masses. METHODS SRFA was performed in 10 patients with a median age of 14 years (range 0.5-17.0 years) suffering from liver adenoma (n = 3), hepatocellular carcinoma (n = 1), hepatoblastoma (n = 2), myofibroblastic tumor (n = 1), hepatic metastases of extrahepatic tumors (n = 2) and infiltrative hepatic cysts associated with alveolar echinococcosis (n = 1). Overall, 15 lesions with a mean lesion size of 2.6 cm (range 0.7-9.5 cm) were treated in 11 sessions. RESULTS The technical success rate was 100%, as was the survival rate. No transient adverse effects higher than grade II (Clavien and Dindo) were encountered after interventions. The median hospital stay was 5 d (range 2-33 d). In two patients who subsequently underwent transplant hepatectomy complete ablation was histologically confirmed. Follow-up imaging studies (median 55 months, range 18-129 months) revealed no local or distant recurrence of disease in any patient. CONCLUSIONS SRFA is an effective minimal-invasive treatment option in pediatric patients with liver tumors of different etiologies.
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Affiliation(s)
- Benjamin Hetzer
- Department of Pediatrics I, Medical University of Innsbruck, Innsbruck, Austria
| | | | - Andreas Entenmann
- Department of Pediatrics I, Medical University of Innsbruck, Innsbruck, Austria
| | - Michel Heil
- Department of Radiology, Interventional Oncology-Microinvasive Therapy (SIP), Medical University of Innsbruck, Innsbruck, Austria
| | - Peter Schullian
- Department of Radiology, Interventional Oncology-Microinvasive Therapy (SIP), Medical University of Innsbruck, Innsbruck, Austria
| | - Daniel Putzer
- Department of Radiology, Interventional Oncology-Microinvasive Therapy (SIP), Medical University of Innsbruck, Innsbruck, Austria
| | - Bernhard Meister
- Department of Pediatrics I, Medical University of Innsbruck, Innsbruck, Austria
| | - Roman Crazzolara
- Department of Pediatrics I, Medical University of Innsbruck, Innsbruck, Austria
| | - Gabriele Kropshofer
- Department of Pediatrics I, Medical University of Innsbruck, Innsbruck, Austria
| | - Christina Salvador
- Department of Pediatrics I, Medical University of Innsbruck, Innsbruck, Austria
| | - Simon Straub
- Department of Pediatrics I, Medical University of Innsbruck, Innsbruck, Austria
| | - Daniela Karall
- Department of Pediatrics I, Medical University of Innsbruck, Innsbruck, Austria
| | | | - Gérard Cortina
- Department of Pediatrics I, Medical University of Innsbruck, Innsbruck, Austria
| | - Andreas Janecke
- Department of Pediatrics I, Medical University of Innsbruck, Innsbruck, Austria
| | - Karin Freund-Unsinn
- Department of Radiology, Interventional Oncology-Microinvasive Therapy (SIP), Medical University of Innsbruck, Innsbruck, Austria
| | - Kathrin Maurer
- Department of Radiology, Interventional Oncology-Microinvasive Therapy (SIP), Medical University of Innsbruck, Innsbruck, Austria
| | - Gisela Schweigmann
- Department of Radiology, Interventional Oncology-Microinvasive Therapy (SIP), Medical University of Innsbruck, Innsbruck, Austria
| | - Georg Oberhuber
- INNPATH, Institute of Pathology, Tirol Kliniken Innsbruck, Innsbruck, Austria
| | - Oliver Renz
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Stefan Schneeberger
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Thomas Müller
- Department of Pediatrics I, Medical University of Innsbruck, Innsbruck, Austria
| | - Reto Bale
- Department of Radiology, Interventional Oncology-Microinvasive Therapy (SIP), Medical University of Innsbruck, Innsbruck, Austria
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11
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Minici R, Ammendola M, Manti F, Siciliano MA, Giglio E, Minici M, Melina M, Currò G, Laganà D. Safety and Efficacy of Degradable Starch Microspheres Transcatheter Arterial Chemoembolization as a Bridging Therapy in Patients with Early Stage Hepatocellular Carcinoma and Child-Pugh Stage B Eligible for Liver Transplant. Front Pharmacol 2021; 12:634084. [PMID: 33897421 PMCID: PMC8062923 DOI: 10.3389/fphar.2021.634084] [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: 11/27/2020] [Accepted: 02/19/2021] [Indexed: 12/12/2022] Open
Abstract
In patients with early-stage hepatocellular carcinoma, awaiting liver transplantation, current guidelines by AASLD and ESMO recommend a bridging therapy with a loco-regional treatment to prevent progression outside transplantation criteria. The standard of care in delaying disease progression has been recognized to be the transarterial chemoembolization. Permanent occlusion of tumor feeding vessels has effects on tumour stromal microenvironment by inducing intra- and intercellular signaling processes counteracting hypoxia, such as the release of vascular endothelial growth factor, a promoter of neoangiogenesis, tumour proliferation and metastatic growth. Among chemoembolization interventions, TACE with degradable starch microspheres represents an alternative to conventional cTACE and DEB-TACE and it minimizes detrimental effects on tumour stromal microenvironment, guaranteeing a transient occlusion of tumour feeding arteries and avoiding VEGF overexpression.Between January 2015 and September 2020, 54 consecutive patients with early-stage hepatocellular carcinoma and Child-Pugh stage B, who had undergone DSM-TACE as a bridging therapy while awaiting liver transplantation, were eligible for the study. A total of 154 DSM-TACE was performed, with a mean number of 2.85 procedures per patient. 18 patients (33.3%) succeeded in achieving liver transplantation, with a mean waiting time-to-transplantation of 11.7 months. The cumulative rates of patients still active on the WL at 6 months were about 91 and 93% when considering overall drop-out and tumour-specific drop-out respectively. Overall survival was about 96% at 6 months and 92% at 12 months. 17 patients experienced adverse events after the chemoembolizations. For patients with HCC in the transplant waiting list and within the Child-Pugh B stage, life expectancy may be dominated by the liver dysfunction, rather than by the tumour progression itself. In this population subset, the choice of LRT is critical because LRT itself could become a dangerous tool that is likely to precipitate liver dysfunction to an extent that survival is shortened rather than prolonged. Hence, the current study demonstrates that DSM-TACE is not far from being an ideal LRT, because it has an excellent safety profile, maintaining an efficacy that guarantees a clear advantage on the dropout rate with respect to the non-operative strategy, thus justifying its use.
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Affiliation(s)
- Roberto Minici
- Radiology Unit, Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy
| | - Michele Ammendola
- Digestive Surgery Unit, Science of Health Department, Magna Graecia University, Catanzaro, Italy
| | - Francesco Manti
- Radiology Unit, Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy
| | - Maria Anna Siciliano
- Medical Oncology Unit, Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy
| | - Enrica Giglio
- Medical Oncology Unit, University Hospital-Marche Polytechnic University, Ancona, Italy
| | - Marco Minici
- National Research Council (Cnr), Institute for High Performance Computing and Networking (ICAR), Rende, Italy
| | - Marica Melina
- Department of Medical and Surgical Sciences, Sant’Orsola Malpighi Hospital, Alma Mater Studiorum University of Bologna, Bologna, Italy
| | - Giuseppe Currò
- General Surgery Unit, Science of Health Department, Magna Graecia University, Catanzaro, Italy
| | - Domenico Laganà
- Radiology Unit, Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy
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12
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Jiang G, Ling S, Zhan Q, Zhuang L, Xu X. Downstaging treatment for patients with hepatocelluar carcinoma before transplantation. Transplant Rev (Orlando) 2021; 35:100606. [PMID: 33636480 DOI: 10.1016/j.trre.2021.100606] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Revised: 01/30/2021] [Accepted: 01/31/2021] [Indexed: 12/13/2022]
Abstract
Liver transplantation (LT), one of the radical methods of treating liver cancer, has brought new hope for the treatment of unresectable liver cancer. Currently, patients who meet transplant criteria can achieve a favorable prognosis, but those who exceed transplant criteria tend not to have very satisfactory outcomes. For patients whose tumor burden exceeds the transplant criteria, downstaging treatment is a promising method to reduce tumor burden to within the transplant criteria that may lead to good posttransplant survival. Multiple treatments, such as transcatheter arterial chemoembolization (TACE), transarterial radioembolization (TARE), percutaneous ethanol injection (PEI), and radiofrequency ablation (RFA), have been used as downstaging treatments. However, there are still some issues that limit the effectiveness of downstaging treatments, such as the inclusion criteria for downstaging, which the choice of downstaging treatment method, and the endpoint of downstaging, all of which are worthy of further discussion. Based on the published literature, this review discusses these issues.
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Affiliation(s)
- Guangjiang Jiang
- Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China
| | - Sunbin Ling
- Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China
| | - Qifan Zhan
- Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China
| | - Li Zhuang
- Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou 310003, China.
| | - Xiao Xu
- Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China.
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13
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Histological Correlation for Radiofrequency and Microwave Ablation in the Local Control of Hepatocellular Carcinoma (HCC) before Liver Transplantation: A Comprehensive Review. Cancers (Basel) 2020; 13:cancers13010104. [PMID: 33396289 PMCID: PMC7795634 DOI: 10.3390/cancers13010104] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 12/24/2020] [Accepted: 12/28/2020] [Indexed: 02/06/2023] Open
Abstract
Simple Summary Liver cancer is a growing problem around the world. Drugs for liver cancer have limited effect, there are not enough donors for liver transplants and many patients are not candidates for surgery to remove the tumor. In many of these cases, hyperthermia can destroy the tumor in situ with minimally invasive methods such as radiofrequency or microwave ablation. In this paper we review the literature evaluating success rates for complete ablation as judged by actual examination of treated tumors that were removed when patients received a liver transplant. While notable successes can be achieved with ablation, the published studies indicate both that complete treatment is not as common as thought and that imaging methods such as computed tomography and magnetic resonance scans do not completely identify residual cancer. There is therefore an important opportunity for improvement in the treatment of this disease. Abstract Radiofrequency ablation (RFA) and microwave ablation (MWA) are the most widely studied and applied ablation techniques for treating primary and secondary liver tumors. These techniques are considered curative for small hepatic tumors, with post-ablation outcomes most commonly assessed by an imaging follow up. However, there is increasing evidence of a discrepancy between radiological and pathological findings when ablated lesions are evaluated following liver resection or liver transplantation. A comprehensive review of the available literature reporting the complete pathological response (cPR) following RFA and MWA was performed to estimate the success rate and identify the factors associated with treatment failure. Following RFA, cPR is reported in 26–96% of tumors compared to 57–95% with MWA. Larger tumor size and vessels larger than 3 mm adjacent to the treated tumor are the most important factors identified by previous studies associated with viable residual tumors after RFA. Correlating post-ablation radiological studies with pathological findings shows that computed tomography (CT) and magnetic resonance imaging (MRI) have low sensitivity but high specificity for detecting residual viable or recurrent hepatocellular carcinoma (HCC) tumors. There are promising recent reports combining multiprobe ablation techniques with three-dimensional treatment planning software and stereotactic-aiming instrumentation to achieve more than 90% cPR in both small and large HCC tumors. In conclusion, the reported success for achieving cPR in HCC following RFA and MWA is highly variable in different studies and decreases with increasing lesion size and unfavorable tumor characteristics. Very few studies have reported a high rate of cPR. As these studies are single-center and retrospective, they need to be further validated and reproduced in other clinical settings.
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14
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Differential Survival Impact of Diabetes Mellitus on Hepatocellular Carcinoma: Role of Staging Determinants. Dig Dis Sci 2020; 65:3389-3402. [PMID: 31955286 DOI: 10.1007/s10620-020-06053-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Accepted: 01/06/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Diabetes mellitus (DM) is common in patients with hepatocellular carcinoma (HCC) and may impact survival. Very few studies focused on the influence of DM in different clinical scenarios. We evaluated the prognostic impact of DM on HCC patients stratified by liver dysfunction, Milan criteria, and performance status defined in the Barcelona Clínic Liver Cancer staging parameters. METHODS A prospective dataset of 3573 HCC patients between 2002 and 2016 was retrospectively analyzed. The multivariate Cox proportional hazards model was used to identify independent prognostic predictors. The Kaplan-Meier method with a log-rank test was applied to compare the survival distributions between different patient groups. RESULTS Among all, DM was not an independent prognostic predictor in the Cox multivariate analysis (p = 0.1044). In the subgroup analysis, DM was not a significant prognostic predictor in Child-Turcotte-Pugh class A or class B/C patients. However, DM was associated with a decreased survival in patients within the Milan criteria (hazard ratio [HR] 1.36, 95% confidence interval [CI] 1.155-1.601, p = 0.0002) and in those with the performance status 0 (HR 1.213, 95% CI 1.055-1.394, p = 0.0067) in the multivariate Cox analysis, but not in those beyond the Milan criteria and poor performance status. CONCLUSIONS DM is highly prevalent in HCC patients and has a distinct survival impact. DM is an independent survival predictor among patients within the Milan criteria and good performance status. These high-risk patients should be closely monitored, and aggressive anticancer treatment should be considered.
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15
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Victor DW, Monsour HP, Boktour M, Lunsford K, Balogh J, Graviss EA, Nguyen DT, McFadden R, Divatia MK, Heyne K, Ankoma-Sey V, Egwim C, Galati J, Duchini A, Saharia A, Mobley C, Gaber AO, Ghobrial RM. Outcomes of Liver Transplantation for Hepatocellular Carcinoma Beyond the University of California San Francisco Criteria: A Single-center Experience. Transplantation 2020; 104:113-121. [PMID: 31233480 DOI: 10.1097/tp.0000000000002835] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor. Currently, liver transplantation may be the optimal treatment for HCC in cirrhotic patients. Patient selection is currently based on tumor size. We developed a program to offer liver transplantation to selected patients with HCC outside of traditional criteria. METHODS Retrospective review for patients transplanted with HCC between April 2008 and June 2017. Patients were grouped by tumor size according to Milan, University of California San Francisco (UCSF), and outside UCSF criteria. Patient demographics, laboratory values, and outcomes were compared. Patients radiographically outside Milan criteria were selected based on tumor control with locoregional therapy (LRT) and 9 months of stability from LRT. α-fetoprotein values were not exclusionary. RESULTS Two hundred twenty HCC patients were transplanted, 138 inside Milan, 23 inside UCSF, and 59 beyond UCSF criteria. Patient survival was equivalent at 1, 3, or 5 years despite pathologic tumor size. Waiting time to transplantation was not significantly different at an average of 344 days. In patients outside UCSF, tumor recurrence was equivalent to Milan and UCSF criteria recipients who waited >9 months from LRT. Although tumor recurrence was more likely in outside of UCSF patients (3% versus 9% versus 15%; P = 0.02), recurrence-free survival only trended toward significance among the groups (P = 0.053). CONCLUSIONS Selective patients outside of traditional size criteria can be effectively transplanted with equivalent survival to patients with smaller tumors, even when pathologic tumor burden is considered. Tumor stability over time can be used to help select patients for transplantation.
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Affiliation(s)
- David W Victor
- Houston Methodist Hospital, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston, TX
| | - Howard P Monsour
- Houston Methodist Hospital, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston, TX
| | - Maha Boktour
- Houston Methodist Hospital, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston, TX
| | - Keri Lunsford
- Houston Methodist Hospital, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston, TX
| | - Julius Balogh
- Department of Anesthesia, University of Texas Health Science Center at Houston, Houston, TX
| | | | - Duc T Nguyen
- Department of Anesthesia, University of Texas Health Science Center at Houston, Houston, TX
| | - Robert McFadden
- Houston Methodist Hospital, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston, TX
| | | | - Kirk Heyne
- The Methodist Hospital Research Institute, Houston, TX
| | - Victor Ankoma-Sey
- Houston Methodist Hospital, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston, TX
| | - Chukwuma Egwim
- Houston Methodist Hospital, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston, TX
| | - Joseph Galati
- Houston Methodist Hospital, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston, TX
| | - Andrea Duchini
- Houston Methodist Hospital, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston, TX
| | - Ashish Saharia
- Houston Methodist Hospital, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston, TX
| | - Constance Mobley
- Houston Methodist Hospital, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston, TX
| | - A Osama Gaber
- Houston Methodist Hospital, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston, TX
| | - R Mark Ghobrial
- Houston Methodist Hospital, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston, TX
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16
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Garg R, Foley K, Movahedi B, Masciocchi MJ, Bledsoe JR, Ding L, Rava P, Fitzgerald TJ, Sioshansi S. Outcomes After Stereotactic Body Radiation Therapy as a Bridging Modality to Liver Transplantation for Hepatocellular Carcinoma. Adv Radiat Oncol 2020; 6:100559. [PMID: 33665482 PMCID: PMC7897771 DOI: 10.1016/j.adro.2020.08.016] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Revised: 08/23/2020] [Accepted: 08/31/2020] [Indexed: 01/04/2023] Open
Abstract
Purpose For patients with hepatocellular carcinoma awaiting liver transplantation (LT), stereotactic body radiation therapy (SBRT) has emerged as a bridging treatment to ensure patients maintain priority status and eligibility per Milan criteria. In this study, we aimed to determine the efficacy and safety of SBRT in such situations. Methods and Materials A retrospective analysis was conducted of the outcomes of 27 patients treated with SBRT who were listed for LT at 1 institution. Among these, 20 patients with 26 tumors went on to LT and were the focus of this study. Operative reports and postoperative charts were evaluated for potential radiation-related complications. The explant pathology findings were correlated with equivalent dose in 2 Gy fractions and tumor size. Results Median pretreatment tumor size was 3.05 cm. Median total dose of radiation was 50 Gy delivered in 5 fractions. Pathologic complete response (pCR) was achieved in 16 tumors (62%). Median interval from end of SBRT to transplant was 287 days. Of the 21 tumors imaged before transplant, 16 or 76% demonstrated a clinical complete response based on modified Response Evaluation Criteria in Solid Tumors criteria. There was no significant correlation between pCR rate and increasing tumor size (odds ratio [OR], 0.95; 95% confidence interval, 0.595-1.53) or pCR rate and equivalent dose in 2 Gy fractions (OR, 1.03; 95% confidence interval, 0.984-1.07.) No patients experienced radiation-related operative or postoperative complications. Of the 27 patients who were listed for transplant, the dropout rate was 22%. Two of the 5 patients with Child-Pugh score 10 died of liver failure. Conclusions These data demonstrate that SBRT as a bridging modality is a feasible option, with a pCR rate comparable to that of other bridging modalities and no additional radiation-related operative or postoperative complications. There was no dose dependence nor size dependence for pCR rate, which may indicate that for the tumor sizes in this study, the radiation doses delivered were sufficiently high.
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Affiliation(s)
- Rashi Garg
- Department of Radiation Oncology, Tufts Medical Center and Tufts University School of Medicine, Boston, Massachusetts
| | - Kimberly Foley
- Department of Transplant Surgery, University of Massachusetts Memorial Medical Center, Worcester, Massachusetts
| | - Babak Movahedi
- Department of Transplant Surgery, University of Massachusetts Memorial Medical Center, Worcester, Massachusetts
| | - Mark J Masciocchi
- Department of Radiology, University of Massachusetts Memorial Medical Center, Worcester, Massachusetts
| | - Jacob R Bledsoe
- Department of Pathology, University of Massachusetts Memorial Medical Center, Worcester, Massachusetts
| | - Linda Ding
- Department of Radiation Oncology, University of Massachusetts Memorial Medical Center, Worcester, Massachusetts
| | - Paul Rava
- Department of Radiation Oncology, University of Massachusetts Memorial Medical Center, Worcester, Massachusetts
| | - Thomas J Fitzgerald
- Department of Radiation Oncology, University of Massachusetts Memorial Medical Center, Worcester, Massachusetts
| | - Shirin Sioshansi
- Department of Radiation Oncology, University of Massachusetts Memorial Medical Center, Worcester, Massachusetts
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Satiya J, Schwartz I, Tabibian JH, Kumar V, Girotra M. Ablative therapies for hepatic and biliary tumors: endohepatology coming of age. Transl Gastroenterol Hepatol 2020; 5:15. [PMID: 32258519 PMCID: PMC7063520 DOI: 10.21037/tgh.2019.10.17] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2019] [Accepted: 10/23/2019] [Indexed: 12/12/2022] Open
Abstract
Ablative therapies refer to minimally invasive procedures performed to destroy abnormal tissue that may arise with many conditions, and can be achieved clinically using chemical, thermal, and other techniques. In this review article, we explore the different ablative therapies used in the management of hepatic and biliary malignancies, namely hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), with a particular focus on radiofrequency ablation (RFA) and photodynamic therapy (PDT) techniques.
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Affiliation(s)
- Jinendra Satiya
- Internal Medicine, University of Miami/JFK Medical Center Palm Beach Regional GME Consortium, West Palm Beach, FL, USA
| | - Ingrid Schwartz
- Internal Medicine, University of Miami Miller School of Medicine/Jackson Memorial Hospital, Miami, FL, USA
| | - James H. Tabibian
- Geffen School of Medicine, University of California, Los Angeles, CA, USA
- Division of Gastroenterology, Department of Medicine, Olive View-UCLA Medical Center, Sylmar, CA, USA
| | - Vivek Kumar
- Gastroenterology and Hepatology, UPMC Susquehanna, Williamsport, PA, USA
| | - Mohit Girotra
- Division of Gastroenterology and Hepatology, University of Miami Miller School of Medicine, Miami, FL, USA
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18
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Evolution of etiology, presentation, management and prognostic tool in hepatocellular carcinoma. Sci Rep 2020; 10:3925. [PMID: 32127619 PMCID: PMC7054529 DOI: 10.1038/s41598-020-61028-9] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2019] [Accepted: 02/06/2020] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide, but its current status is unclear. We aimed to investigate the evolution of etiology, presentation, management and prognostic tool in HCC over the past 12 years. A total of 3349 newly diagnosed HCC patients were enrolled and retrospectively analyzed. The comparison of survival was performed by the Kaplan-Meier method with the log-rank test. Hepatitis B and C virus infection in HCC were continuously declining over the three time periods (2004–2007, 2008–2011, 2012–2015; p < 0.001). At diagnosis, single tumor detection rate increased to 73% (p < 0.001), whereas vascular invasion gradually decreased to 20% in 2012–2015 (p < 0.001). Early stage HCC gradually increased from 2004–2007 to 2012–2015 (p < 0.001). The probability of patients receiving curative treatment and long-term survival increased from 2004–2007 to 2012–2015 (p < 0.001). The Cancer of Liver Italian Program (CLIP) and Taipei Integrated Scoring (TIS) system were two more accurate staging systems among all. In conclusion, the clinical presentations of HCC have significantly changed over the past 12 years. Hepatitis B and C virus-associated HCC became less common, and more patients were diagnosed at early cancer stage. Patient survival increased due to early cancer detection that results in increased probability to undergo curative therapies.
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19
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Ho SY, Liu PH, Hsu CY, Hsia CY, Huang YH, Su CW, Lei HJ, Lee RC, Hou MC, Huo TI. A New Prognostic Model Based on Albumin-Bilirubin Grade for Hepatocellular Carcinoma Beyond the Milan Criteria. Dig Dis Sci 2020; 65:658-667. [PMID: 31659612 DOI: 10.1007/s10620-019-05813-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Accepted: 08/20/2019] [Indexed: 12/26/2022]
Abstract
BACKGROUND The survival of patients with advanced hepatocellular carcinoma (HCC) is highly variable due to heterogeneous tumoral characteristics. We proposed and validated an albumin-bilirubin (ALBI)-based model for HCC beyond Milan criteria, the ALBI-HOME, for these patients. METHODS A total of 2186 patients were enrolled and randomly assigned to the derivation cohort (n = 1093) and validation cohort (n = 1093). Multivariate Cox proportional hazards model was used to determine significant prognostic factors in the derivation cohort. The performance of ALBI-HOME was evaluated in the validation cohort. RESULTS In the Cox model, six factors were identified as independent predictors of poor survival: ALBI grade 2 [hazard ratio (HR) 1.848, 95% confidence incidence (CI) 1.556-2.195, p < 0.001], ALBI grade 3 (HR 3.266, 95% CI 2.531-4.215, p < 0.001), serum AFP ≥ 100 ng/ml (HR 1.482, 95% CI 1.279-1.717, p < 0.001), total tumor volume ≥ 250 cm3 (HR 1.503, 95% CI 1.294-1.746, p < 0.001), ascites (HR 1.400, 95% CI 1.187-1.561, p < 0.001), performance status 0-1 (HR 1.756, 95% CI 1.485-2.076 p < 0.001), and vascular invasion or metastasis (HR 2.110, 95% CI 1.809-2.0, p < 0.001). The ALBI-HOME is based on these six parameters, and the score ranges from 0 to 7. This model was associated with the best prognostic ability among different HCC staging systems to predict survival in patients beyond Milan criteria; its ability remained consistently stable in different treatment subgroups and viral etiologies. CONCLUSIONS The proposed ALBI-HOME is a simple and feasible predictive model for HCC beyond Milan criteria. It demonstrates superior prognostic performance among the currently used staging systems and may help identify at-risk patients to undergo more aggressive treatments.
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Affiliation(s)
- Shu-Yein Ho
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Po-Hong Liu
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Chia-Yang Hsu
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA
| | - Cheng-Yuan Hsia
- Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Yi-Hsiang Huang
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
- Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Chien-Wei Su
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Hao-Jan Lei
- Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Rheun-Chuan Lee
- Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Ming-Chih Hou
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Teh-Ia Huo
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
- Department of Medical Research, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd., Taipei, 11217, Taiwan.
- Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan.
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Kwon J, Chun KS, Song IS, Kim SH, Han S. Long-term outcome of intraoperative radiofrequency ablation for hepatocellular carcinoma and its efficacy as a primary treatment. Ann Hepatobiliary Pancreat Surg 2020; 24:24-32. [PMID: 32181425 PMCID: PMC7061039 DOI: 10.14701/ahbps.2020.24.1.24] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2019] [Revised: 10/10/2019] [Accepted: 10/23/2019] [Indexed: 12/26/2022] Open
Abstract
BACKGROUNDS/AIMS We conducted this study to identify long-term outcomes following intraoperative radiofrequency ablation (IO-RFA) for hepatocellular carcinoma (HCC) and to reveal independent prognostic factors for survival. METHODS From December 1998 to February 2019, 183 patients underwent IO-RFA for HCC. These patients were divided into two groups according to whether RFA was done as a first-line (1-RFA group, n=106) or secondary-line (2-RFA group, n=77) treatment. Furthermore, we compared the survival outcomes between the 1-RFA and 2-RFA groups. RESULTS There were no significant differences in type of surgical approaches between the two groups (p=0.079). The number of tumors and largest tumor size were not significantly different between the two groups. Overall recurrence rate was 53%, and the 2-RFA group showed a higher recurrence rate (46.2% in 1-RFA group versus 62.3% in 2-RFA group; p=0.031). The 5-year overall survival (OS) and disease-free survival (DFS) rates of all the patients were 75.2% and 27.9%, respectively. The OS and DFS rates were significantly higher in the 1-RFA group. The 5-year OS rates were 83.6% and 64.9% in the 1-RFA and 2-RFA groups, respectively (p=0.010), whereas the 5-year DFS rates were 32.2% and 21.6%, respectively (p=0.012). On multivariate analysis, HBV-LC, 2-RFA, recurrence, and postoperative complications were independent predictive factors for survival. CONCLUSIONS Therapeutic outcomes of IO-RFA were comparable to those of surgical resection. Additionally, 1-RFA might be an alternative treatment for naïve HCC in patients with uncompensated liver function and severe comorbidities.
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Affiliation(s)
- Jongduk Kwon
- Department of Surgery, Chungnam National University Hospital, Daejeon, Korea
| | - Kwang-Sik Chun
- Department of Surgery, Chungnam National University Hospital, Daejeon, Korea
| | - In-Sang Song
- Department of Surgery, Chungnam National University Hospital, Daejeon, Korea
| | - Seok-Hwan Kim
- Department of Surgery, Chungnam National University Hospital, Daejeon, Korea
| | - Sunjong Han
- Department of Surgery, Chungnam National University Hospital, Daejeon, Korea
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21
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Bale R, Schullian P, Eberle G, Putzer D, Zoller H, Schneeberger S, Manzl C, Moser P, Oberhuber G. Stereotactic Radiofrequency Ablation of Hepatocellular Carcinoma: a Histopathological Study in Explanted Livers. Hepatology 2019; 70:840-850. [PMID: 30520063 PMCID: PMC6766867 DOI: 10.1002/hep.30406] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2018] [Accepted: 11/25/2018] [Indexed: 12/23/2022]
Abstract
This retrospective study was performed to evaluate the efficacy of three-dimensional (3D)-navigated multiprobe radiofrequency ablation (RFA) with intraprocedural image fusion for treatment of hepatocellular carcinoma (HCC) by histopathological examination. From 2009 to 2018, 97 patients (84 men, 13 women; median age, 60 years; range, 1-71) were transplanted after bridging therapy of 195 HCCs by stereotactic RFA (SRFA). The median interval between the first SRFA and transplantation was 6.8 months (range, 0-71). The rate of residual vital tissue (RVT) could be assessed in 188 of 195 lesions in 96 of 97 patients by histological examination of the explanted livers using hematoxylin and eosin (H&E) and Tdt-mediated UTP nick-end labeling (TUNEL) stains. Histopathological results were compared with the findings of the last computed tomography (CT) imaging before liver transplantation (LT). Median number and size of treated tumors were 1 (range, 1-8) and 2.5 cm (range, 1-8). Complete radiological response was achieved in 186 of 188 nodules (98.9%) and 94 of 96 patients (97.9%) and complete pathological response in the explanted liver specimen in 183 of 188 nodules (97.3%) and 91 of 96 patients (94.8%), respectively. In lesions ≥3 cm, complete tumor cell death was achieved in 50 of 52 nodules (96.2%). Residual tumor did not correlate with tumor size (P = 0.5). Conclusion: Multiprobe SRFA with intraprocedural image fusion represents an efficient, minimally invasive therapy for HCC, even with tumor sizes larger than 3 cm, and without the need of a combination with additional treatments. The results seem to justify the additional efforts related to the stereotactic approach.
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Affiliation(s)
- Reto Bale
- Department of Radiology, Section of Interventional Oncology ‐ Microinvasive TherapyMedical University InnsbruckInnsbruckAustria
| | - Peter Schullian
- Department of Radiology, Section of Interventional Oncology ‐ Microinvasive TherapyMedical University InnsbruckInnsbruckAustria
| | - Gernot Eberle
- Department of Radiology, Section of Interventional Oncology ‐ Microinvasive TherapyMedical University InnsbruckInnsbruckAustria
| | - Daniel Putzer
- Department of Radiology, Section of Interventional Oncology ‐ Microinvasive TherapyMedical University InnsbruckInnsbruckAustria
| | - Heinz Zoller
- Departments of Medicine II Gastroenterology and HepatologyMedical University InnsbruckInnsbruckAustria
| | | | - Claudia Manzl
- PathologyMedical University InnsbruckInnsbruckAustria
| | - Patrizia Moser
- INNPATH, Institute of Pathology, Tirol Kliniken InnsbruckInnsbruckAustria
| | - Georg Oberhuber
- INNPATH, Institute of Pathology, Tirol Kliniken InnsbruckInnsbruckAustria
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22
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Akateh C, Black SM, Conteh L, Miller ED, Noonan A, Elliott E, Pawlik TM, Tsung A, Cloyd JM. Neoadjuvant and adjuvant treatment strategies for hepatocellular carcinoma. World J Gastroenterol 2019; 25:3704-3721. [PMID: 31391767 PMCID: PMC6676544 DOI: 10.3748/wjg.v25.i28.3704] [Citation(s) in RCA: 109] [Impact Index Per Article: 18.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Revised: 06/13/2019] [Accepted: 06/22/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common liver malignancy worldwide and a major cause of cancer-related mortality for which liver resection is an important curative-intent treatment option. However, many patients present with advanced disease and with underlying chronic liver disease and/or cirrhosis, limiting the proportion of patients who are surgical candidates. In addition, the development of recurrent or de novo cancers following surgical resection is common. These issues have led investigators to evaluate the benefit of neoadjuvant and adjuvant treatment strategies aimed at improving resectability rates and decreasing recurrence rates. While high-level evidence to guide treatment decision making is lacking, recent advances in locoregional and systemic therapies, including antiviral treatment and immunotherapy, raise the prospect of novel approaches that may improve the outcomes of patients with HCC. In this review, we evaluate the evidence for various neoadjuvant and adjuvant therapies and discuss opportunities for future clinical and translational research.
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Affiliation(s)
- Clifford Akateh
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Sylvester M Black
- Division of Transplant Surgery, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Lanla Conteh
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Eric D Miller
- Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Anne Noonan
- Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Eric Elliott
- Division of Diagnostic Radiology, Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Timothy M Pawlik
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Allan Tsung
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Jordan M Cloyd
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
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23
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Serra C, Cucchetti A, Felicani C, Mosconi C, De Cinque A, Golfieri R, Andreone P, Ercolani G, Maroni L, Ravaioli M, D'Errico A, Pinna AD, Cescon M. Assessment of Radiofrequency Ablation Efficacy for Hepatocellular Carcinoma by Histology and Pretransplant Radiology. Liver Transpl 2019; 25:88-97. [PMID: 30415500 DOI: 10.1002/lt.25381] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2018] [Accepted: 10/19/2018] [Indexed: 12/12/2022]
Abstract
Radiofrequency ablation (RFA) represents a potentially curative option for early-stage hepatocellular carcinoma (HCC). This study aims at evaluating the histologic response after RFA of small HCCs arising in cirrhosis. Data were reviewed from 78 patients with de novo HCCs who were treated with RFA and subsequently transplanted. The last radiological assessment before liver transplantation (LT) was used for comparison between modified Response Evaluation Criteria in Solid Tumors (mRECIST) and histological findings. A total of 125 de novo HCCs (median diameter, 20 mm) were treated with RFA only in 92 sessions. There were 98 nodules that did not show local recurrence during follow-up (78.4%), and the remaining were retreated, except 1 because of subsequent LT. On explanted livers, complete pathological response (CPR) was observed in 61.6%, being 76.9% when <2 cm, 55.0% when 2-3 cm, and 30.8% when >3 cm. Tumors near hepatic vessels had CPR in 50% of patients versus 69.3% for tumors distant from vessels (P = 0.039). Of the 125 HCCs, 114 had available radiological assessment within a median of 3 months before LT. Complete radiological response, according to mRECIST, was observed in 77.2% of nodules before LT. The Cohen κ was 0.48 (moderate agreement). The overall accuracy was 78.1%. A total of 18 complications were recorded with only 1 graded as major. In conclusion, RFA can provide high CPR for HCC, especially in smaller tumors distant from hepatic veins or portal branches. The agreement between mRECIST and histology is only moderate. Further refinements in radiological assessment are essential to accurately assess the true effectiveness of RFA.
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Affiliation(s)
- Carla Serra
- Department of Organ Insufficiency and Transplantation, S. Orsola-Malpighi Hospital, Bologna, Italy
| | - Alessandro Cucchetti
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy
- Morgagni-Pierantoni Hospital, Forlì, Italy
| | - Cristina Felicani
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - Cristina Mosconi
- Radiology Unit, Department of Diagnostic Medicine and Prevention, S. Orsola-Malpighi Hospital, Bologna, Italy
| | - Antonio De Cinque
- Department of Organ Insufficiency and Transplantation, S. Orsola-Malpighi Hospital, Bologna, Italy
| | - Rita Golfieri
- Radiology Unit, Department of Diagnostic Medicine and Prevention, S. Orsola-Malpighi Hospital, Bologna, Italy
| | - Pietro Andreone
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - Giorgio Ercolani
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy
- Morgagni-Pierantoni Hospital, Forlì, Italy
| | - Lorenzo Maroni
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - Matteo Ravaioli
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - Antonia D'Errico
- Department of Organ Insufficiency and Transplantation, S. Orsola-Malpighi Hospital, Bologna, Italy
| | - Antonio Daniele Pinna
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - Matteo Cescon
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy
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24
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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: 279] [Impact Index Per Article: 39.9] [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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25
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Pommergaard HC, Rostved AA, Adam R, Thygesen LC, Salizzoni M, Gómez Bravo MA, Cherqui D, De Simone P, Boudjema K, Mazzaferro V, Soubrane O, García-Valdecasas JC, Fabregat Prous J, Pinna AD, O'Grady J, Karam V, Duvoux C, Rasmussen A. Locoregional treatments before liver transplantation for hepatocellular carcinoma: a study from the European Liver Transplant Registry. Transpl Int 2018; 31:531-539. [PMID: 29380442 DOI: 10.1111/tri.13123] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2017] [Revised: 11/20/2017] [Accepted: 01/23/2018] [Indexed: 12/15/2022]
Abstract
Locoregional treatment while on the waiting list for liver transplantation (Ltx) for hepatocellular carcinoma (HCC) has been shown to improve survival. However, the effect of treatment type has not been investigated. We investigate the effect of locoregional treatment type on survival after Ltx for HCC. We investigated patients registered in the European Liver Transplant Registry database using multivariate Cox regression survival analysis. Information on locoregional therapy was registered for 4978 of 23 124 patients and was associated with improved overall survival [hazard ratio (HR) 0.84 (0.73-0.96)] and HCC-specific survival [HR 0.76 (0.59-0.98)]. Radiofrequency ablation (RFA) was the one monotherapy associated with improved overall survival [HR 0.51 (0.40-0.65)]. In addition, the combination of RFA and transarterial chemoembolization also improved survival [HR 0.74 (0.55-0.99)]. Adjusting for factors related to prognosis, disease severity, and tumor aggressiveness, RFA was highly beneficial for overall and HCC-specific survival. The effect may represent a selection of patients with favorable tumor biology; however, the treatment may be effective per se by halting tumor progression. Clinicaltrials.gov number: NCT02995096.
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Affiliation(s)
- Hans-Christian Pommergaard
- Department of Surgical Gastroenterology and Transplantation, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Andreas Arendtsen Rostved
- Department of Surgical Gastroenterology and Transplantation, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - René Adam
- Department of Hepatobiliary Surgery, Cancer and Transplantation, AP-HP, Hôpital Universitaire Paul Brousse, Inserm U 935, University Paris-Sud, Villejuif, France
| | - Lau Caspar Thygesen
- National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark
| | - Mauro Salizzoni
- Liver Transplant Center and General Surgery, A.O.U. Città della Salute e della Scienza di Torino, Molinette Hospital, Turin, Italy
| | | | - Daniel Cherqui
- Department of Hepatobiliary Surgery, Cancer and Transplantation, AP-HP, Hôpital Universitaire Paul Brousse, Inserm U 935, University Paris-Sud, Villejuif, France
| | - Paolo De Simone
- Liver Transplantation Unit, Hepatobiliary Surgery, University of Pisa Medical School Hospital, Pisa, Italy
| | - Karim Boudjema
- Service de Chirurgie Hépatobiliaire et Digestive, Hôpital Pontchaillou, Centre Hospitalier Université de Rennes 1, Rennes, France.,INSERM, UMR991, Foie, Métabolisme et Cancer, Université de Rennes 1, Rennes, France
| | - Vincenzo Mazzaferro
- Division of Gastrointestinal Surgery and Liver Transplantation, Istituto Nazionale Tumori, Fondazione IRCCS, University of Milan, Milan, Italy
| | - Olivier Soubrane
- Department of HPB Surgery and Liver Transplant, Beaujon Hospital, Clichy, University Denis Diderot, Paris, France
| | | | - Joan Fabregat Prous
- Unitat de Cirurgia Hepato-Bilio-Pancreàtica, Hospital Universitari de Bellvitge, Barcelona, Spain
| | - Antonio D Pinna
- General Surgery and Transplant Division, S. Orsola Hospital, University of Bologna, Bologna, Italy
| | - John O'Grady
- Institute of Liver Studies, King's College Hospital, London, UK
| | - Vincent Karam
- Department of Hepatobiliary Surgery, Cancer and Transplantation, AP-HP, Hôpital Universitaire Paul Brousse, Inserm U 935, University Paris-Sud, Villejuif, France
| | - Christophe Duvoux
- Liver Transplant Unit, Department of Hepatology, Henri Mondor Hospital, Paris Est University (UPEC), Créteil, France
| | - Allan Rasmussen
- Department of Surgical Gastroenterology and Transplantation, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
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26
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Prognostic Performance of Ten Liver Function Models in Patients with Hepatocellular Carcinoma Undergoing Radiofrequency Ablation. Sci Rep 2018; 8:843. [PMID: 29339752 PMCID: PMC5770426 DOI: 10.1038/s41598-018-19251-y] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2017] [Accepted: 12/20/2017] [Indexed: 02/06/2023] Open
Abstract
Liver functional capacity is a crucial survival determinant for hepatocellular carcinoma (HCC). Noninvasive models were proposed to assess hepatic reserve, but their performance in outcome prediction is unclear. We aimed to investigate 10 currently used liver function models in HCC patients undergoing radiofrequency ablation (RFA). A total 499 HCC patients were prospectively identified. Homogeneity and corrected Akaike information criteria (AICc) were compared. Cox proportional hazards model was used to identify independent survival predictors. Significance survival differences were found across 10 noninvasive models (all p < 0.001) except for GUCI and APRI grade 2 vs 3, and King’s score grade 1 vs 2. Among these models, ALBI grade showed the highest homogeneity and lowest AICs value, indicating a better prognostic performance. Within Child-Turcotte-Pugh (CTP) score 5 group, significant survival difference was demonstrated between ALBI grade 1 and 2 (p < 0.001); for those with CTP score 6 or higher, only ALBI grade 2 and 3 showed survival difference (p < 0.001). Cox analysis disclosed that ALBI grade, tumor size and performance status were independent prognostic predictors. There was significant correlation between CTP score and other 9 models. We conclude that ALBI grade may serve as objective and feasible surrogate for prognostic prediction in HCC patients undergoing RFA.
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27
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Rubinstein MM, Kaubisch A, Kinkhabwala M, Reinus J, Liu Q, Chuy JW. Bridging therapy effectiveness in the treatment of hepatocellular carcinoma prior to orthotopic liver transplantation. J Gastrointest Oncol 2017; 8:1051-1055. [PMID: 29299366 DOI: 10.21037/jgo.2017.08.11] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Background Orthotopic liver transplantation (OLT) is the most effective treatment for hepatocellular carcinoma (HCC) in patients with underlying cirrhosis and portal hypertension. Availability of OLT is limited by donor-organ shortages, which increase patient waiting time until OLT. A variety of bridging therapies (BT) have been used to halt tumor progression in patients on the OLT waiting list. Despite complete radiologic responses following BT, viable tumor is often present in explants. Methods Treatment outcomes were evaluated in 50 patients who had a total of 125 BT for treatment of 93 nodules. Success of BT was assessed by radiologic response compared to histopathological examination of explanted livers. Results Pre-transplant treatments included: transcatheter arterial chemoembolization (TACE), alcohol ablation (ETOH), radiofrequency ablation (RFA), microwave ablation (MWA), selective internal radiation therapy (SIRT) and stereotactic body radiation therapy (SBRT). Fifty-nine (64%) nodules had a complete radiographic response to therapy; however, only 28 nodules (30%) had complete tumor necrosis (CTN) on explant examination. Ten nodules with CTN were treated with TACE alone. Seven of the 28 nodules with CTN were treated with TACE and RFA. Three of seven nodules treated with TACE and SIRT had CTN. Patients underwent a mean of 2.5 BTs. Six of 50 patients (12%) had no residual HCC in their explants. Five of those six patients (83%) had complete response (CR) on pre-transplant imaging. Conclusions Although favorable radiologic responses are seen following BT, viable HCC is seen in the majority of liver explants and radiographic imaging cannot always accurately predict pathological response. This underscores the need for aggressive treatment of patients who otherwise may not be eligible for OLT.
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Affiliation(s)
| | | | - Milan Kinkhabwala
- Montefiore-Einstein Center for Transplantation, Bronx, New York, USA
| | - John Reinus
- Montefiore-Einstein Center for Transplantation, Bronx, New York, USA
| | - Qiang Liu
- Montefiore Medical Center, Bronx, New York, USA
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28
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Györi GP, Felsenreich DM, Silberhumer GR, Soliman T, Berlakovich GA. Multimodality locoregional treatment strategies for bridging HCC patients before liver transplantation. Eur Surg 2017; 49:236-243. [PMID: 29104589 PMCID: PMC5653748 DOI: 10.1007/s10353-017-0487-8] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2017] [Accepted: 07/24/2017] [Indexed: 12/14/2022]
Abstract
BACKGROUND It is current practice that patients with hepatocellular carcinoma (HCC) listed for liver transplantation should receive locoregional treatment if the suspected waiting time for transplantation is longer than 6 months, even in the absence of prospective randomized data. Aim of this study was the comparison of single versus multimodality locoregional treatment strategies on outcomes after liver transplantation. METHODS This is a retrospective analysis of 150 HCC patients listed for liver transplantation at our center between 2004 and 2011. Outcomes were analyzed according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) in relation to intention-to-treat and overall survival after liver transplantation. RESULTS Overall, 92 patients (63%) were transplanted in this cohort. The intention-to-treat 1‑, 3‑, 5‑year waiting list survival was 80, 59, and 50% respectively. In RFA-(radiofrequency ablative) and TACE-(transarterial chemoembolisation)-based regimens, rates of transplanted patients were comparable (69 vs. 58%, p = ns). No difference was seen in overall survival after liver transplantation when comparing TACE- and RFA-based regimens. Patients receiving multimodality locoregional therapy had lower overall survival after transplantation (p = 0.05). CONCLUSION TACE- and RFA-based regimens showed equal outcomes in terms of transplantation rate, tumor response, and post-transplant survival. Patients in need of more than one treatment modality might identify a cohort with poorer post-transplant survival. POINTS OF NOVELTY Direct comparison of TACE and RFA in a multimodality setting, analysis according to mRECIST.
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Affiliation(s)
- Georg P. Györi
- Department of Surgery, Division of Transplantation, Medical University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, Austria
| | - D. Moritz Felsenreich
- Department of Surgery, Division of Transplantation, Medical University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, Austria
| | - Gerd R. Silberhumer
- Department of Surgery, Division of Transplantation, Medical University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, Austria
| | - Thomas Soliman
- Department of Surgery, Division of Transplantation, Medical University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, Austria
| | - Gabriela A. Berlakovich
- Department of Surgery, Division of Transplantation, Medical University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, Austria
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29
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Lee MW, Raman SS, Asvadi NH, Siripongsakun S, Hicks RM, Chen J, Worakitsitisatorn A, McWilliams J, Tong MJ, Finn RS, Agopian VG, Busuttil RW, Lu DSK. Radiofrequency ablation of hepatocellular carcinoma as bridge therapy to liver transplantation: A 10-year intention-to-treat analysis. Hepatology 2017; 65:1979-1990. [PMID: 28170115 DOI: 10.1002/hep.29098] [Citation(s) in RCA: 75] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2016] [Revised: 01/26/2017] [Accepted: 01/30/2017] [Indexed: 12/14/2022]
Abstract
UNLABELLED In a long-term (10-year) study of radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) as bridging therapy in patients listed for orthotopic liver transplantation (LT), we evaluated the impact of RFA on waiting list dropout rate, post-LT tumor recurrence, and long-term intention-to-treat, disease-specific survival (DSS). From March 2004 to October 2014, RFA was performed as the initial stand-alone bridge therapy to LT for 121 patients (men/women ratio, 83:38; mean age, 60.0 years) with 156 de novo HCCs (mean size, 2.4 cm). Follow-up period from initial RFA ranged from 1.3 to 128.0 months (median, 42.9 months). We assessed the overall and tumor-specific waiting list dropout rates, post-LT tumor recurrence, and 10-year post-LT and intention-to-treat survival rates. Dropout from the waiting list due to tumor progression occurred in 7.4% of patients. HCC recurrence after LT occurred in 5.6% of patients. The post-LT overall survival (OS) rate at 5 and 10 years was 75.8% and 42.2%, respectively, and the recurrence-free survival (RFS) rate was 71.1% and 39.6%, respectively. Intention-to-treat OS, RFS, and DSS rates for the entire study population at 5 and 10 years were 63.5% and 41.2%, 60.8% and 37.7%, and 89.5% and 89.5%, respectively. CONCLUSION RFA as a first-line stand-alone bridge therapy to LT achieves excellent long-term overall and tumor-specific survivals, with a low dropout rate from tumor progression despite long wait list times and a sustained low tumor recurrence rate upon post-LT follow-up of up to 10 years. (Hepatology 2017;65:1979-1990).
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Affiliation(s)
- Min Woo Lee
- Department of Radiological Sciences, David Geffen School of Medicine at UCLA, 757 Westwood Plaza, Los Angeles, CA.,Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Steven S Raman
- Department of Radiological Sciences, David Geffen School of Medicine at UCLA, 757 Westwood Plaza, Los Angeles, CA
| | - Nazanin H Asvadi
- Department of Radiological Sciences, David Geffen School of Medicine at UCLA, 757 Westwood Plaza, Los Angeles, CA
| | - Surachate Siripongsakun
- Department of Radiological Sciences, David Geffen School of Medicine at UCLA, 757 Westwood Plaza, Los Angeles, CA.,Department of Radiology, Chulabhorn Hospital, Bangkok, Thailand
| | - Robert M Hicks
- Department of Radiological Sciences, David Geffen School of Medicine at UCLA, 757 Westwood Plaza, Los Angeles, CA
| | - Jeffrey Chen
- Department of Radiological Sciences, David Geffen School of Medicine at UCLA, 757 Westwood Plaza, Los Angeles, CA
| | - Akeanong Worakitsitisatorn
- Department of Radiological Sciences, David Geffen School of Medicine at UCLA, 757 Westwood Plaza, Los Angeles, CA.,Department of Radiology, Chulabhorn Hospital, Bangkok, Thailand
| | - Justin McWilliams
- Department of Radiological Sciences, David Geffen School of Medicine at UCLA, 757 Westwood Plaza, Los Angeles, CA
| | - Myron J Tong
- Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, CA
| | - Richard S Finn
- Department of Medicine, Division of Hematology/Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA
| | - Vatche G Agopian
- Department of Surgery, Dumont-UCLA Transplant and Liver Cancer Centers, Los Angeles, CA
| | - Ronald W Busuttil
- Department of Surgery, Dumont-UCLA Transplant and Liver Cancer Centers, Los Angeles, CA
| | - David S K Lu
- Department of Radiological Sciences, David Geffen School of Medicine at UCLA, 757 Westwood Plaza, Los Angeles, CA
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Treatment Options in Patients Awaiting Liver Transplantation with Hepatocellular Carcinoma and Cholangiocarcinoma. Clin Liver Dis 2017; 21:231-251. [PMID: 28364811 DOI: 10.1016/j.cld.2016.12.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Liver transplantation (LT) provides a good chance of cure for selected patients with hepatocellular carcinoma (HCC) and perihilar cholangiocarcinoma (pCCA). Patients with HCC on a waiting list for LT are at risk for tumor progression and dropout. Treatment of HCC with locoregional therapies may lessen dropout due to tumor progression. Strict selection and adherence to the LT criteria for patients with pCCA before and after neoadjuvant chemotherapy are critical for optimal outcome with LT. This article reviews the existing data for the various treatment strategies used for patients with HCC and pCCA awaiting LT.
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Radiofrequency ablation for HCC patients with multifocal tumours meeting the Milan criteria: A single-centre experience. Dig Liver Dis 2016; 48:1485-1491. [PMID: 27495779 DOI: 10.1016/j.dld.2016.07.018] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2015] [Revised: 07/05/2016] [Accepted: 07/19/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND Radiofrequency ablation (RFA) has been recommended as a curative treatment for patients with single early-stage unifocal hepatocellular carcinomas (HCCs) for years; however, the effect of this treatment on multifocal tumours has remained uncertain. AIMS We conducted a retrospective study to evaluate the overall survival (OS) and recurrence-free survival (RFS) rates of early HCC patients with multiple tumours subjected to different RFA modalities. METHODS One hundred fifty-four HCC patients with multifocal tumours who met the Milan criteria and underwent RFA were enrolled in this study. We divided the patients into 3 groups according to the surgical approach utilised (percutaneous, laparoscopic and open RFA; selection was based on the locations of the tumours for whether they were adhered to the subhepatic inferior vena cava or the gastrointestinal tract) and into 2 subgroups according to the tumour numbers and locations. RESULTS No deaths occurred in the 30-day post-operation period, and there were no significant differences in the complication, OS or RFS rates between the 3 groups. The 1-, 3- and 5-year OS rates were 88.9%, 75.5% and 50.9% in the subgroup with 2 tumours, respectively, versus 91.3%, 56.3% and 17.5% in the subgroup with 3 tumours, respectively (P=0.001). The corresponding values were 93.2%, 77.4% and 50.8% in the subgroup with tumours in the same segment and 82.4%, 54.8% and 23.0% in the subgroup with tumours in different segments (P=0.001). CONCLUSION RFA was proven to be an effective and safe method for the treatment of multifocal HCCs. Among the patients with 2 tumours within the same segment, RFA achieved better long-term outcomes in terms of both overall and recurrence-free survival.
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Current Treatment Approaches to HCC with a Special Consideration to Transplantation. J Transplant 2016; 2016:7926264. [PMID: 27413539 PMCID: PMC4931061 DOI: 10.1155/2016/7926264] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2016] [Accepted: 05/19/2016] [Indexed: 12/13/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide. The mainstay of treatment of HCC has been both resectional and transplantation surgery. It is well known that, in selected, optimized patients, hepatectomy for HCC may be an option, even in patients with underlying cirrhosis. Resectable patients with early HCC and underlying liver disease are however increasingly being considered for transplantation because of potential for better disease-free survival and resolution of underlying liver disease, although this approach is limited by the availability of donor livers, especially in resectable patients. Outcomes following liver transplantation improved dramatically for patients with HCC following the implementation of the Milan criteria in the late 1990s. Ever since, the rather restrictive nature of the Milan criteria has been challenged with good outcomes. There has also been an increase in the donor pool with marginal donors including organs retrieved following cardiac death being used. Even so, patients still continue to die while waiting for a liver transplant. In order to reduce this attrition, bridging techniques and methods for downstaging disease have evolved. Additionally new techniques for organ preservation have increased the prospect of this potentially curative procedure being available for a greater number of patients.
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She WH, Cheung TT. Bridging and downstaging therapy in patients suffering from hepatocellular carcinoma waiting on the list of liver transplantation. Transl Gastroenterol Hepatol 2016; 1:34. [PMID: 28138601 DOI: 10.21037/tgh.2016.03.04] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2015] [Accepted: 01/04/2016] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a common primary malignancy worldwide especially in the patients with the background of chronic liver disease. Liver transplantation (LT) is the only curative treatment effective for both malignancy as well as the cirrhosis and portal hypertension. Unfortunately, living donor is not always possible and the deceased graft is scarce. Neoadjuvant therapies, therefore, have been developed as a downstaging treatment to try to downstage the tumor within the transplant criteria, or as a bridging therapy to control the tumor growth in patients while waiting in the transplant list. This paper reviewed the common modalities used as bridging and downstaging therapies for patients suffering from HCC before undergoing LT.
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Affiliation(s)
- Wong Hoi She
- Division of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Department of Surgery, the University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Tan To Cheung
- Division of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Department of Surgery, the University of Hong Kong, Queen Mary Hospital, Hong Kong
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Xu DW, Wan P, Xia Q. Liver transplantation for hepatocellular carcinoma beyond the Milan criteria: A review. World J Gastroenterol 2016; 22:3325-34. [PMID: 27022214 PMCID: PMC4806190 DOI: 10.3748/wjg.v22.i12.3325] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2015] [Revised: 12/14/2015] [Accepted: 01/30/2016] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation (LT) has been accepted as an effective therapy for hepatocellular carcinoma (HCC). The Milan criteria (MC) are widely used across the world to select LT candidates in HCC patients. However, the MC may be too strict because a substantial subset of patients who have HCC exceed the MC and who would benefit from LT may be unnecessarily excluded from the waiting list. In recent years, many extended criteria beyond the MC were raised, which were proved to be able to yield similar outcomes compared with those patients meeting the MC. Because the simple use of tumor size and number was insufficient to indicate HCC biological features and to predict the risk of tumor recurrence, some biological markers such as Alpha-fetoprotein, Des-Gamma-carboxy prothrombin and the neutrophil-to-lymphocyte ratio were useful in selecting LT candidates in HCC patients beyond the MC. For patients with advanced HCC, downstaging therapy is an effective way to reduce the tumor stage to fulfill the MC by using liver-directed therapy such as transarterial chemoembolization, radiofrequency ablation and percutaneous ethanol injection. This article reviews the recent advances in LT for HCC beyond the MC.
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Sheth RA, Patel MS, Koottappillil B, Shah JA, Oklu R, Mueller P, Vagefi PA, Ganguli S. Role of Locoregional Therapy and Predictors for Dropout in Patients with Hepatocellular Carcinoma Listed for Liver Transplantation. J Vasc Interv Radiol 2015; 26:1761-8; quiz 1768. [DOI: 10.1016/j.jvir.2015.08.015] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2015] [Revised: 08/13/2015] [Accepted: 08/13/2015] [Indexed: 12/20/2022] Open
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Fahrner R, Dondorf F, Ardelt M, Dittmar Y, Settmacher U, Rauchfuß F. Liver transplantation for hepatocellular carcinoma - factors influencing outcome and disease-free survival. World J Gastroenterol 2015; 21:12071-12082. [PMID: 26576092 PMCID: PMC4641125 DOI: 10.3748/wjg.v21.i42.12071] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Revised: 08/04/2015] [Accepted: 09/14/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma is one of the leading causes of cancer-related death worldwide. Liver transplantation can be a curative treatment in selected patients. However, there are several factors that influence disease-free survival after transplantation. This review addresses the pre-, intra- and postoperative factors that influence the risk of tumor recurrence after liver transplantation.
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Hinshaw JL, Lubner MG, Ziemlewicz TJ, Lee FT, Brace CL. Percutaneous tumor ablation tools: microwave, radiofrequency, or cryoablation--what should you use and why? Radiographics 2015; 10:47-57. [PMID: 25208284 DOI: 10.1053/j.tvir.2007.08.005] [Citation(s) in RCA: 80] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Image-guided thermal ablation is an evolving and growing treatment option for patients with malignant disease of multiple organ systems. Treatment indications have been expanding to include benign tumors as well. Specifically, the most prevalent indications to date have been in the liver (primary and metastatic disease, as well as benign tumors such as hemangiomas and adenomas), kidney (primarily renal cell carcinoma, but also benign tumors such as angiomyolipomas and oncocytomas), lung (primary and metastatic disease), and soft tissue and/or bone (primarily metastatic disease and osteoid osteomas). Each organ system has different underlying tissue characteristics, which can have profound effects on the resulting thermal changes and ablation zone. Understanding these issues is important for optimizing clinical results. In addition, thermal ablation technology has evolved rapidly during the past several decades, with substantial technical and procedural improvements that can help improve clinical outcomes and safety profiles. Staying up to date on these developments is challenging but critical because the physical properties underlying the different ablation modalities and the appropriate use of adjuncts will have a tremendous effect on treatment results. Ultimately, combining an understanding of the physical properties of the ablation modalities with an understanding of the thermal kinetics in tissue and using the most appropriate ablation modality for each patient are key to optimizing clinical outcomes. Suggested algorithms are described that will help physicians choose among the various ablation modalities for individual patients.
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Affiliation(s)
- J Louis Hinshaw
- From the Departments of Radiology (J.L.H., M.G.L., T.J.Z., F.T.L., C.L.B.), Biomedical Engineering (C.L.B.), and Medical Physics (C.L.B.), University of Wisconsin, 600 Highland Ave, E3 366, Madison, WI 53792-3252
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Gonzalez-Beicos A, Venkat S, Songrug T, Poveda J, Garcia-Buitrago M, Poozhikunnath Mohan P, Narayanan G. Irreversible Electroporation of Hepatic and Pancreatic Malignancies: Radiologic-Pathologic Correlation. Tech Vasc Interv Radiol 2015; 18:176-82. [PMID: 26365548 DOI: 10.1053/j.tvir.2015.06.009] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Irreversible electroporation (IRE) is a novel therapy that has shown to be a feasible and promising alternative to conventional ablative techniques when treating tumors near vital structures or blood vessels. The clinical efficacy of IRE has been evaluated using established imaging criteria. This study evaluates the histologic and imaging response of hepatic and pancreatic malignancies that were surgically resected after IRE. In total, 12 lesions ablated with IRE were included, including 3 pancreatic carcinomas, 5 primary tumors of the liver, and 4 metastatic tumors of the liver. The rate of complete response to IRE was 25% based on the histologic evaluation of the resected tumors. Although treatment-related vessel wall changes were noted in several cases in histologic findings, there was no evidence of vascular luminal narrowing or obliteration in any of the specimens. The imaging response to IRE before surgical resection usually resulted in underestimation of disease burden when compared with the histologic response seen on the resected specimens.
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Affiliation(s)
- Aldo Gonzalez-Beicos
- Interventional Radiology, Department of Radiology, University of Miami, Miller School of Medicine, Miami, FL.
| | - Shree Venkat
- Interventional Radiology, Department of Radiology, University of Miami, Miller School of Medicine, Miami, FL
| | - Tanakorn Songrug
- Interventional Radiology, Department of Radiology, University of Miami, Miller School of Medicine, Miami, FL
| | - Julio Poveda
- Gastrointestinal Pathology, Department of Pathology, University of Miami, Miller School of Medicine, Miami, FL
| | - Monica Garcia-Buitrago
- Gastrointestinal Pathology, Department of Pathology, University of Miami, Miller School of Medicine, Miami, FL
| | - Prasoon Poozhikunnath Mohan
- Interventional Radiology, Department of Radiology, University of Miami, Miller School of Medicine, Miami, FL
| | - Govindarajan Narayanan
- Interventional Radiology, Department of Radiology, University of Miami, Miller School of Medicine, Miami, FL
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Waghray A, Murali AR, Menon KVN. Hepatocellular carcinoma: From diagnosis to treatment. World J Hepatol 2015; 7:1020-1029. [PMID: 26052391 PMCID: PMC4450179 DOI: 10.4254/wjh.v7.i8.1020] [Citation(s) in RCA: 113] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2014] [Revised: 01/15/2015] [Accepted: 02/12/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the sixth most prevalent malignancy worldwide and is a rising cause of cancer related mortality. Risk factors for HCC are well documented and effective surveillance and early diagnosis allow for curative therapies. The majority of HCC appears to be caused by cirrhosis from chronic hepatitis B and hepatitis C virus. Preventive strategies include vaccination programs and anti-viral treatments. Surveillance with ultrasonography detects early stage disease and improves survival rates. Many treatment options exist for individuals with HCC and are determined by stage of presentation. Liver transplantation is offered to patients who are within the Milan criteria and are not candidates for hepatic resection. In patients with advanced stage disease, sorafenib shows some survival benefit.
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Chen CF, Liu PH, Lee YH, Tsai YJ, Hsu CY, Huang YH, Chiou YY, Huo TI. Impact of renal insufficiency on patients with hepatocellular carcinoma undergoing radiofrequency ablation. J Gastroenterol Hepatol 2015; 30:192-8. [PMID: 25039567 DOI: 10.1111/jgh.12669] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/18/2014] [Indexed: 12/25/2022]
Abstract
BACKGROUND AND AIM Renal insufficiency (RI) is commonly seen in patients with hepatocellular carcinoma (HCC). We aimed to investigate the impact of RI on the long-term survival of HCC patients undergoing radiofrequency ablation (RFA) and to determine the optimal staging strategy for these patients. METHODS RI was defined as an estimated glomerular filtration rate < 60 mL/min/1.73 m(2) . A total of 123 and 344 patients with and without RI undergoing RFA, respectively, were enrolled. A one-to-one propensity score matching analysis with preset caliper width was performed. The prognostic ability of four currently used staging systems was compared by the Akaike information criterion (AIC). RESULTS HCC patients with RI undergoing RFA were older (P < 0.001) and had significantly different baseline characteristics. Of all patients, RI was significantly associated with a decreased long-term survival (P = 0.03). After matching in the propensity model, the baseline characteristics were similar between patients with (n = 92) and without (n = 92) RI. In the propensity model, RI was not significantly associated with a shortened survival (P = 0.273). In the Cox multivariate analysis, Child-Turcotte-Pugh class B or C was identified as the only independent predictor of poor prognosis. Among patients with RI undergoing RFA, the Taipei Integrated Scoring (TIS) system provided the highest homogeneity and lowest AIC value among the currently used staging systems. CONCLUSIONS The long-term survival of HCC patients undergoing RFA is not affected by RI. The TIS staging system may provide a better prognostic prediction for HCC patients with RI undergoing RFA.
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Affiliation(s)
- Chuan-Fu Chen
- Division of Gastroenterology, Wei Gong Memorial Hospital, Miaoli, Taiwan
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41
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Liu PH, Hsu CY, Lee YH, Hsia CY, Huang YH, Su CW, Chiou YY, Lin HC, Huo TI. Uncompromised treatment efficacy in elderly patients with hepatocellular carcinoma: a propensity score analysis. Medicine (Baltimore) 2014; 93:e264. [PMID: 25526453 PMCID: PMC4603105 DOI: 10.1097/md.0000000000000264] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
The number of elderly hepatocellular carcinoma (HCC) patients is expected to rise. We analyzed the impact of age on clinical presentations, treatment allocation, and long-term survival between elderly (≥75 years) and younger (<75 years) HCC patients. In this study, a total of 812 elderly and 2270 younger HCC patients were evaluated. The baseline information and long-term survival were compared in the entire population and in different treatment groups. A propensity score matching analysis with preset caliper width was utilized to compare survival differences in different patient subgroups. Elderly HCC patients had discrete characteristics compared with younger HCC patients. Elderly patients received surgical resection (SR) less frequently, while more elderly patients underwent radiofrequency ablation (RFA) and transarterial chemoembolization (TACE). Younger patients had significantly better long-term survival than the elderly patients in all patients and in patients receiving SR (both P<0.05). However, of the entire cohort, age was not an independent predictor of poor prognosis in the Cox multivariate model. The long-term survival was similar between 2 age groups in patients receiving RFA and TACE. In the propensity model, there were no significant survival differences among patients receiving SR, RFA, or TACE (all P>0.05). Among the elderly, the Cancer of the Liver Italian Program (CLIP) score provided the lowest Akaike information criterion value. In conclusion, advanced age is not associated with inferior treatment result in HCC patients receiving different therapeutic modalities. Elderly HCC patients should be encouraged for active treatment when indicated. The CLIP is an optimal prognostic model for outcome assessment.
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Affiliation(s)
- Po-Hong Liu
- From the Faculty of Medicine (PHL, CYH, YHL, CYH, CWS, YYC, HCL, TIH); Institute of Clinical Medicine (YHH); Institute of Pharmacology (TIH), National Yang-Ming University School of Medicine, Taipei, Taiwan; Department of Medicine (PHL, CYH, YHL, YHH, CWS, HCL, TIH); Department of Surgery (CYH); Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan (YYC); and Department of Biostatistics, UCLA, Los Angeles, CA, USA (CYH)
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Bhoori S, Mazzaferro V. Current challenges in liver transplantation for hepatocellular carcinoma. Best Pract Res Clin Gastroenterol 2014; 28:867-79. [PMID: 25260314 DOI: 10.1016/j.bpg.2014.08.001] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2014] [Accepted: 08/14/2014] [Indexed: 01/31/2023]
Abstract
Liver transplantation (LT) is the best option of cure for hepatocellular carcinoma (HCC). Notwithstanding several alternatives, Milan Criteria remain the cornerstone for patient selection. Currently, expanded criteria patients are unsuitable for LT without taking downstaging approaches and response to therapies into consideration. Relative weight of HCC as indication to LT is increasing and that generates competition with MELD-described non-cancer indications. Allocation policies should be adjusted accordingly, considering principles of urgency and utility in the management of the waiting list and including transplant benefit to craft equitable criteria to deal with the limited resource of donated grafts. Maximization of cost-effectiveness of LT in HCC can be also pursued through changes in immunosuppression policies and multimodal management of post-transplant recurrences. This review is focused on those constantly mutating challenges that have to be faced by anyone dealing with the management of HCC in the context of liver transplantation.
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Affiliation(s)
- Sherrie Bhoori
- Gastroenterology, Surgery and Liver Transplantation Unit, Fondazione Istituto Nazionale Tumori IRCCS, National Cancer Institute, Via Venezian 1, Milan 20133, Italy
| | - Vincenzo Mazzaferro
- Gastroenterology, Surgery and Liver Transplantation Unit, Fondazione Istituto Nazionale Tumori IRCCS, National Cancer Institute, Via Venezian 1, Milan 20133, Italy.
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Liu PH, Lee YH, Hsu CY, Huang YH, Chiou YY, Lin HC, Huo TI. Survival advantage of radiofrequency ablation over transarterial chemoembolization for patients with hepatocellular carcinoma and good performance status within the Milan criteria. Ann Surg Oncol 2014; 21:3835-43. [PMID: 24903236 DOI: 10.1245/s10434-014-3831-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2014] [Indexed: 12/13/2022]
Abstract
BACKGROUND Performance status is closely linked with survival in patients with hepatocellular carcinoma (HCC). We evaluated the impact of performance status on patients with small HCC receiving radiofrequency ablation (RFA) versus transarterial chemoembolization (TACE). METHODS A total of 424 and 282 patients within the Milan criteria undergoing RFA and TACE, respectively, were analyzed. Patients were classified as performance status 0 (n = 516) and performance status ≥1 (n = 190) groups. A propensity-score matching analysis with preset caliper width was used. A total of 167 and 68 matched pairs were selected from patients with a performance status of 0 and ≥1, respectively. RESULTS Radiofrequency ablation provided significantly better long-term survival than TACE for patients within the Milan criteria (p < 0.01). After being stratified by performance status and matched in the propensity model, the baseline characteristics were similar between the RFA and TACE groups for patients with a performance status of 0 or ≥1. RFA provided significantly better long-term survival than TACE in patients with a performance status of 0 in the propensity model (p < 0.05); TACE was significantly associated with 1.784-fold increased risk of mortality (95 % confidence interval 1.075-2.506) by using the Cox proportional hazards model. TACE was not a significant prognostic predictor in patients with a performance status ≥1 in the propensity model. CONCLUSIONS For HCC patients within the Milan criteria with a performance status of 0, RFA provides better long-term survival than TACE. RFA should be considered a priority treatment in inoperable HCC patients within the Milan criteria. Performance status is a feasible surrogate marker to enhance treatment allocation.
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Affiliation(s)
- Po-Hong Liu
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
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Chung H, Chapman WC. Liver transplantation for hepatocellular carcinoma: how far have we come and what is the future? Hepat Oncol 2014; 1:309-321. [DOI: 10.2217/hep.14.8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
SUMMARY: Liver transplantation is the best treatment for hepatocellular carcinoma in the setting of chronic liver disease, completely removing malignancy and underlying diseased liver tissue. Technical aspects of liver transplantation have improved over the years, along with outcomes. But challenges continue in the areas of expanding existing indications for transplant with limited organ supply, calling for optimization of patient selection and the development of alternative or adjunctive treatment options. Expansion of existing transplant criteria will help identify patients most likely to have good outcomes. Locoregional and systemic treatments showing therapeutic promise are being investigated for use in achieving acceptable oncologic effect. Improvements in post-transplant treatment and continued attempts to enlarge the donor pool will continue to provide avenues for further improvements in outcomes.
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Affiliation(s)
- Haniee Chung
- Washington University in St Louis, 660 S Euclid Avenue, St Louis, MO 63110, USA
| | - William C Chapman
- Washington University in St Louis, 660 S Euclid Avenue, St Louis, MO 63110, USA
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Feng K, Ma KS. Value of radiofrequency ablation in the treatment of hepatocellular carcinoma. World J Gastroenterol 2014; 20:5987-98. [PMID: 24876721 PMCID: PMC4033438 DOI: 10.3748/wjg.v20.i20.5987] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2013] [Revised: 02/21/2014] [Accepted: 04/01/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a malignant disease that substantially affects public health worldwide. It is especially prevalent in east Asia and sub-Saharan Africa, where the main etiology is the endemic status of chronic hepatitis B. Effective treatments with curative intent for early HCC include liver transplantation, liver resection (LR), and radiofrequency ablation (RFA). RFA has become the most widely used local thermal ablation method in recent years because of its technical ease, safety, satisfactory local tumor control, and minimally invasive nature. This technique has also emerged as an important treatment strategy for HCC in recent years. RFA, liver transplantation, and hepatectomy can be complementary to one another in the treatment of HCC, and the outcome benefits have been demonstrated by numerous clinical studies. As a pretransplantation bridge therapy, RFA extends the average waiting time without increasing the risk of dropout or death. In contrast to LR, RFA causes almost no intra-abdominal adhesion, thus producing favorable conditions for subsequent liver transplantation. Many studies have demonstrated mutual interactions between RFA and hepatectomy, effectively expanding the operative indications for patients with HCC and enhancing the efficacy of these approaches. However, treated tumor tissue remains within the body after RFA, and residual tumors or satellite nodules can limit the effectiveness of this treatment. Therefore, future research should focus on this issue.
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Pompili M, Francica G, Ponziani FR, Iezzi R, Avolio AW. Bridging and downstaging treatments for hepatocellular carcinoma in patients on the waiting list for liver transplantation. World J Gastroenterol 2013; 19:7515-7530. [PMID: 24282343 PMCID: PMC3837250 DOI: 10.3748/wjg.v19.i43.7515] [Citation(s) in RCA: 86] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2013] [Revised: 09/30/2013] [Accepted: 10/18/2013] [Indexed: 02/06/2023] Open
Abstract
Several therapeutic procedures have been proposed as bridging treatments for patients with hepatocellular carcinoma (HCC) awaiting liver transplantation (LT). The most used treatments include transarterial chemoembolization and radiofrequency ablation. Surgical resection has also been successfully used as a bridging procedure, and LT should be considered a rescue treatment in patients with previous HCC resection who experience tumor recurrence or post-treatment severe decompensation of liver function. The aims of bridging treatments include decreasing the waiting list dropout rate before transplantation, reducing HCC recurrence after transplantation, and improving post-transplant overall survival. To date, no data from prospective randomized studies are available; however, for HCC patients listed for LT within the Milan criteria, prolonging the waiting time over 6-12 mo is a risk factor for tumor spread. Bridging treatments are useful in containing tumor progression and decreasing dropout. Furthermore, the response to pre-LT treatments may represent a surrogate marker of tumor biological aggressiveness and could therefore be evaluated to prioritize HCC candidates for LT. Lastly, although a definitive conclusion can not be reached, the experiences reported to date suggest a positive impact of these treatments on both tumor recurrence and post-transplant patient survival. Advanced HCC may be downstaged to achieve and maintain the current conventional criteria for inclusion in the waiting list for LT. Recent studies have demonstrated that successfully downstaged patients can achieve a 5-year survival rate comparable to that of patients meeting the conventional criteria without requiring downstaging.
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Hanson JA, Ason R, Weinreb J, Van Dyke A, Mitchell KA. Radiology estimates of viable tumor percentage in hepatocellular carcinoma ablation cavities correlate poorly with pathology assessment. Arch Pathol Lab Med 2013; 137:392-9. [PMID: 23451750 DOI: 10.5858/arpa.2012-0126-oa] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
CONTEXT No study has evaluated radiology/pathology correlation of percentage viable tumor (PVT) estimates in ablated hepatocellular carcinoma (HCC) to examine the reliability of radiologic estimates. OBJECTIVE To determine how well interdisciplinary PVT estimates correlate and identify pathologic factors that influence this correlation. DESIGN Pathologists and radiologists established blinded PVT estimates in 22 HCC ablation cavities. Paired sample t tests examined the differences between the interdisciplinary estimates. RESULTS Fifteen cavities had pathologic viable tumor (VT) (68%) and 6 had radiographic VT (22%). Radiology's sensitivity for detecting VT was 40% and the specificity was 100%. Pathology detected significantly more VT than radiology (pathology mean = 22.3% versus radiology mean = 2.6%; P = .005). Five cavities had tumor growth in a discontinuous rim pattern, 7 in a nodular pattern, and 3 in a solid pattern. Radiology did not detect VT in cavities with a discontinuous rim pattern (sensitivity = 0%) but did detect VT in 3 cavities with a nodular pattern (sensitivity = 43%), and in all cavities with a solid pattern (sensitivity = 100%). There was no significant difference in PVT estimates in cavities 3.5 cm or larger (P = .07), but there was a significant difference in cavities smaller than 3.5 cm (P = .01). CONCLUSION This study clarifies that the risk of underestimation by imaging is greatest in small lesions (<3.5 cm), though the sensitivity of detection depends primarily on the tumor growth pattern within the cavity. This underestimation raises the question of whether basing treatment decisions on a radiologic impression of complete ablation is valid.
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Tao C, Dan L, Ling F, Peng G. In vivo and in vitro effects of QHF combined with chemotherapy on hepatocellular carcinoma. J Biomed Res 2013; 24:161-8. [PMID: 23554627 PMCID: PMC3596551 DOI: 10.1016/s1674-8301(10)60025-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2009] [Indexed: 12/21/2022] Open
Abstract
Objective To investigate the synergistic anti-tumor effect of QHF (a Chinese medicine formula with anti-tumor active ingredients, including 800 mg/kg Cinobufotalin, 14 mg/kg Ginsenoside Rg3, 5.5 mg/kg Notoginseng and 100 mg/kg Lentinan) when combined with the chemotherapy drug cisplatin (DDP). Methods Hepatocellular carcinoma H22 cells were implanted into mice and after the transplants were successfully established the animals were divided into four groups, namely a normal saline(NS) control group, QHF group, DDP group and QHF+DDP group. The tumor growth was monitored and the survival time determined. In vitro studies employing H22 cells used the first three groups, and determined the effects of QHF and DDP on tumor cell cycle distribution, apoptosis and morphologic changes in vitro. Results QHF significantly inhibited the growth of tumors and prolonged the survival time of mice with hepatocellular carcinomas. QHF combined with DDP could attenuate DDP-induced leucopenia, spleen and thymus atrophy and other indicators of toxicity. The inhibition rate of tumor growth reached 82.54% with QHF+DDP, and QHF prolonged the life span of DDP-treated mice by 66.83%. In the in vitro experiments tumor cells showed morphological changes characteristic of apoptosis by both light and transmission electron microscopy in the QHF group, and the apoptosis rate was 33.85%. Moreover, the proportion of cells in the G0/G1 phase was increased and those in the S-phase decreased. Conclusion QHF combined with DDP could significantly inhibit tumor growth, induce the apoptosis of tumor cells and effectively attenuate DDP toxicity.
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Affiliation(s)
- Chen Tao
- Medical College of Three Gorges University, Yichang 443002, China
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The role of bridging therapy in hepatocellular carcinoma. Int J Hepatol 2013; 2013:419302. [PMID: 24455285 PMCID: PMC3880689 DOI: 10.1155/2013/419302] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2013] [Revised: 10/10/2013] [Accepted: 10/10/2013] [Indexed: 12/19/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver accounting for 7% of all cancers worldwide. Most cases of HCC develop within an established background of chronic liver disease. For that reason, liver resection is only possible in selected patients. Liver transplantation has become the treatment of choice in patients with HCC, end-stage liver disease, and significant portal hypertension. Shortage of organ donors has resulted in overall increase of waiting list time with increased risk of dropout due to tumor progression. Neoadjuvant therapies have emerged as an alternative to control tumor growth in patients while waiting. The aim of this study is to review the literature on the role of bridging therapy and downstaging prior to liver transplantation in patients with HCC. We are also presenting our single-center experience of 96 patients undergoing transplantation for HCC with and without bridging therapy.
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