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Desai J, Okeke RI, Desai R, Zhang Z, Engelhardt A, Schnitzler M, Barron J, Varma CR, Randall HB, Lentine KL, Nazzal M. Pre-transplant Loco-Regional Therapy for Hepatocellular Carcinoma and Post-transplant Outcomes: A National Study. Cureus 2024; 16:e67960. [PMID: 39328600 PMCID: PMC11427028 DOI: 10.7759/cureus.67960] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/26/2024] [Indexed: 09/28/2024] Open
Abstract
The ultimate preferred treatment for hepatocellular carcinoma (HCC) complicated with cirrhosis and portal hypertension is an orthotopic liver transplant (OLT). Loco regional therapy (LRT) has emerged to prevent tumor growth and progression of disease beyond the Milan criteria to achieve transplant. There is a paucity of data regarding safety, posttransplant survival benefits, and tumor recurrence rate achieved by these LRT modalities. We aim to assess and compare the five-year survival rate and tumor recurrence rate with or without LRT in patients after OLT with diagnosed HCC utilizing the nation's largest dataset. This is a retrospective observational study approved by Saint Louis University institutional review board. We utilized the largest dataset from the years 2003-2013 where pertaining data were gathered from Organ Procurement Transplant Network (OPTN) standard analysis and research files (STAR) through novel linkages with Medicare bills. Descriptive and comparative statistics were performed. 2412 (51.6%) patients received any form of locoregional therapy (single or combination) out of 4669 total study sample size. The overall five-year survival in the study sample was 76.1%. There was statistically no significant improvement seen in five-year posttransplant survival in the group that received one mode of LRT (adjusted hazard ratio (aHR) 0.97, P<0.64) or a combination of LRT (aHR 0.94, P<0.58) in comparison to those that received none after adjusting donor and recipient clinical characteristics. However, five-year survival trended higher among those treated with combination therapy over those treated with single LRT or none. Overall HCC recurrence was 4.8%, while no significant difference was noted when comparing above-mentioned groups. Five-year posttransplant survival and HCC recurrence rate were also found to have no difference when compared between above-mentioned groups after adjusting explant pathology. This is the largest retrospective study comparing liver transplant patients with HCC who received LRT to none. Although it did not show any statistically significant benefit of single or combination of LRT on survival or tumor recurrence after liver transplant for HCC patients, the outcomes encourage the safe and feasible use of LRT as a bridging therapy. Our study also suggests an observed pattern of improved posttransplant survival and tumor recurrence rate with combination loco-regional therapy. Larger multicenter prospective studies will be required to achieve the effect size to determine the best therapies for maximizing patient survival cost-effectively.
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Affiliation(s)
- Jay Desai
- Department of Surgery, Saint Louis University Hospital, Saint Louis, USA
| | - Raymond I Okeke
- Department of Surgery, Saint Louis University Hospital, Saint Louis, USA
| | - Roshani Desai
- Gastroenterology, Saint Louis University School of Medicine, Saint Louis, USA
| | - Zidong Zhang
- Surgery, Saint Louis University School of Medicine, Saint Louis, USA
| | | | - Mark Schnitzler
- Center for Abdominal Transplantation, Saint Louis University School of Medicine, Saint Louis, USA
| | - John Barron
- Surgery, Saint Louis University School of Medicine, Saint Louis, USA
| | - Chintalapati R Varma
- Center for Abdominal Transplantation, Saint Louis University School of Medicine, Saint Louis, USA
| | - Henry B Randall
- Center for Abdominal Transplantation, Saint Louis University School of Medicine, Saint Louis, USA
| | - Krista L Lentine
- Center for Abdominal Transplantation, Saint Louis University School of Medicine, Saint Louis, USA
| | - Mustafa Nazzal
- Center for Abdominal Transplantation, Saint Louis University School of Medicine, Saint Louis, USA
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Lee DU, Adonizio EA, Hastie DJ, Ponder R, Lee KJ, Jung D, Fan GH, Malik R. The Trends in Health Care Utilization and Costs Associated With Primary Liver Cancer: An Analysis of United States Hospitals Between 2016 and 2019. J Clin Gastroenterol 2024; 58:726-736. [PMID: 37983843 PMCID: PMC10978554 DOI: 10.1097/mcg.0000000000001927] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Accepted: 08/20/2023] [Indexed: 11/22/2023]
Abstract
BACKGROUND Primary liver cancer (PLC) has placed an increasing economic and resource burden on the health care system of the United States. We attempted to quantify its epidemiology and associated costs using a national inpatient database. METHODS Hospital discharge and insurance claims data from the National Inpatient Sample were used to conduct this analysis. Patients diagnosed with PLC (hepatocellular carcinoma or cholangiocarcinoma) were included in the study population, which was then stratified using patient demographics, comorbidities, degree of cancer spread, liver disease complications, and other descriptors. Trends were analyzed via regression curves for each of these strata from the years 2016 to 2019, with special attention to patterns in hospitalization incidence, inpatient mortality rate, total costs, and average per-capita costs. The resulting curves were evaluated using goodness-of-fit statistics and P -values. RESULTS Aggregate hospitalization incidence, inpatient mortality rates, and total costs were found to significantly increase throughout the study period ( P =0.002, 0.002, and 0.02, respectively). Relative to their demographic counterparts, males, White Americans, and those older than 65 years of age contributed the largest proportions of total costs. These population segments also experienced significant increases in total expenditure ( P =0.04, 0.03, and 0.02, respectively). Admissions deemed to have multiple comorbidities were associated with progressively higher total costs throughout the study period ( P =0.01). Of the categorized underlying liver diseases, only admissions diagnosed with alcoholic liver disease or nonalcoholic fatty liver disease saw significantly increasing total costs ( P =0.006 and 0.01), although hepatitis C was found to be the largest contributor to total expenses. CONCLUSIONS From 2016 to 2019, total costs, admission incidence, and inpatient mortality rates associated with PLC hospitalization increased. Strata-specific findings may be reflective of demographic shifts in the PLC patient populations, as well as changes in underlying chronic liver disease etiologies.
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Affiliation(s)
- David Uihwan Lee
- Division of Gastroenterology and Hepatology, University of Maryland, 22 S. Greene St, Baltimore, MD 21201, USA
| | - Elyse Ann Adonizio
- Department of Medicine, Tufts University School of Medicine, Washington St, Boston, MA 02111, USA
| | - David Jeffrey Hastie
- Department of Medicine, Tufts University School of Medicine, Washington St, Boston, MA 02111, USA
| | - Reid Ponder
- Department of Medicine, Tufts University School of Medicine, Washington St, Boston, MA 02111, USA
| | - Ki Jung Lee
- Department of Medicine, Tufts University School of Medicine, Washington St, Boston, MA 02111, USA
| | - Daniel Jung
- Department of Medicine, University of Missouri–Kansas City School of Medicine, 2411 Holmes St, Kansas City, MO 64108
| | - Gregory Hongyuan Fan
- Department of Medicine, Tufts University School of Medicine, Washington St, Boston, MA 02111, USA
| | - Raza Malik
- Liver Center, Division of Gastroenterology, Albany Medical Center, 43 New Scotland Ave, Albany, NY 12208, USA
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Suddle A, Reeves H, Hubner R, Marshall A, Rowe I, Tiniakos D, Hubscher S, Callaway M, Sharma D, See TC, Hawkins M, Ford-Dunn S, Selemani S, Meyer T. British Society of Gastroenterology guidelines for the management of hepatocellular carcinoma in adults. Gut 2024; 73:1235-1268. [PMID: 38627031 PMCID: PMC11287576 DOI: 10.1136/gutjnl-2023-331695] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Accepted: 03/19/2024] [Indexed: 05/01/2024]
Abstract
Deaths from the majority of cancers are falling globally, but the incidence and mortality from hepatocellular carcinoma (HCC) is increasing in the United Kingdom and in other Western countries. HCC is a highly fatal cancer, often diagnosed late, with an incidence to mortality ratio that approaches 1. Despite there being a number of treatment options, including those associated with good medium to long-term survival, 5-year survival from HCC in the UK remains below 20%. Sex, ethnicity and deprivation are important demographics for the incidence of, and/or survival from, HCC. These clinical practice guidelines will provide evidence-based advice for the assessment and management of patients with HCC. The clinical and scientific data underpinning the recommendations we make are summarised in detail. Much of the content will have broad relevance, but the treatment algorithms are based on therapies that are available in the UK and have regulatory approval for use in the National Health Service.
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Affiliation(s)
- Abid Suddle
- King's College Hospital NHS Foundation Trust, London, UK
| | - Helen Reeves
- Newcastle University Translational and Clinical Research Institute, Newcastle upon Tyne, UK
| | - Richard Hubner
- Department of Oncology, The Christie NHS Foundation Trust, Manchester, UK
| | | | - Ian Rowe
- University of Leeds, Leeds, UK
- St James's University Hospital, Leeds, UK
| | - Dina Tiniakos
- Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
| | - Stefan Hubscher
- Department of Pathology, University of Birmingham, Birmingham, UK
| | - Mark Callaway
- Division of Diagnostics and Therapies, University Hospitals Bristol NHS Trust, Bristol, UK
| | | | - Teik Choon See
- Department of Radiology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Maria Hawkins
- Department of Medical Physics and Biomedical Engineering, University College London, London, UK
| | | | - Sarah Selemani
- King's College Hospital NHS Foundation Trust, London, UK
| | - Tim Meyer
- Department of Oncology, University College, London, UK
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Njei B, Yi I, Strazzabosco M. Cost-effectiveness analysis: The missing factor in the management of HCC. Clin Liver Dis (Hoboken) 2024; 23:e0178. [PMID: 38860130 PMCID: PMC11164007 DOI: 10.1097/cld.0000000000000178] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2023] [Accepted: 03/08/2024] [Indexed: 06/12/2024] Open
Affiliation(s)
- Basile Njei
- Liver Center, Digestive Disease Section, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA
- Department of Internal Medicine, Yale Cancer Center, Yale School of Medicine, New Haven, Connecticut, USA
| | - Irvin Yi
- Liver Center, Digestive Disease Section, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA
- Department of Internal Medicine, Yale Cancer Center, Yale School of Medicine, New Haven, Connecticut, USA
| | - Mario Strazzabosco
- Liver Center, Digestive Disease Section, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA
- Department of Internal Medicine, Yale Cancer Center, Yale School of Medicine, New Haven, Connecticut, USA
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Koch DT, Yu H, Beirith I, Schirren M, Drefs M, Liu Y, Knoblauch M, Koliogiannis D, Sheng W, De Toni EN, Bazhin AV, Renz BW, Guba MO, Werner J, Ilmer M. Tigecycline causes loss of cell viability mediated by mitochondrial OXPHOS and RAC1 in hepatocellular carcinoma cells. J Transl Med 2023; 21:876. [PMID: 38041179 PMCID: PMC10693093 DOI: 10.1186/s12967-023-04615-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2023] [Accepted: 10/11/2023] [Indexed: 12/03/2023] Open
Abstract
BACKGROUND Despite recent advances in locoregional, systemic, and novel checkpoint inhibitor treatment, hepatocellular carcinoma (HCC) is still associated with poor prognosis. The feasibility of potentially curative liver resection (LR) and transplantation (LT) is limited by the underlying liver disease and a shortage of organ donors. Especially after LR, high recurrence rates present a problem and circulating tumor cells are a major cause of extrahepatic recurrence. Tigecycline, a commonly used glycylcycline antibiotic, has been shown to have antitumorigenic effects and could be used as a perioperative and adjuvant therapeutic strategy to target circulating tumor cells. We aimed to investigate the effect of tigecycline on HCC cell lines and its mechanisms of action. METHODS Huh7, HepG2, Hep3B, and immortalized hepatocytes underwent incubation with clinically relevant tigecycline concentrations, and the influence on proliferation, migration, and invasion was assessed in two- and three-dimensional in vitro assays, respectively. Bioinformatic analysis was used to identify specific targets of tigecycline. The expression of RAC1 was detected using western blot, RT-PCR and RNA sequencing. ELISA and flow cytometry were utilized to measure reactive oxygen species (ROS) generation upon tigecycline treatment and flow cytometry to detect alterations in cell cycle. Changes in mitochondrial function were detected via seahorse analysis. RNA sequencing was performed to examine involved pathways. RESULTS Tigecycline treatment resulted in a significant reduction of mitochondrial function with concomitantly preserved mitochondrial size, which preceded the observed decrease in HCC cell viability. The sensitivity of HCC cells to tigecycline treatment was higher than that of immortalized non-cancerous THLE-2 hepatocytes. Tigecycline inhibited both migratory and invasive properties. Tigecycline application led to an increase of detected ROS and an S-phase cell cycle arrest. Bioinformatic analysis identified RAC1 as a likely target for tigecycline and the expression of this molecule was increased in HCC cells as a result of tigecycline treatment. CONCLUSION Our study provides evidence for the antiproliferative effect of tigecycline in HCC. We show for the first time that this effect, likely to be mediated by reduced mitochondrial function, is associated with increased expression of RAC1. The reported effects of tigecycline with clinically relevant and achievable doses on HCC cells lay the groundwork for a conceivable use of this agent in cancer treatment.
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Affiliation(s)
- Dominik T Koch
- Department of General, Visceral and Transplantation Surgery, LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, Marchioninistr. 15, 81377, Munich, Germany
- Transplantation Center Munich, LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, Munich, Germany
- Liver Center Munich, Ludwig-Maximilians-University Munich, Munich, Germany
| | - Haochen Yu
- Department of General, Visceral and Transplantation Surgery, LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - Iris Beirith
- Department of General, Visceral and Transplantation Surgery, LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - Malte Schirren
- Department of General, Visceral and Transplantation Surgery, LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, Marchioninistr. 15, 81377, Munich, Germany
- Transplantation Center Munich, LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, Munich, Germany
- Liver Center Munich, Ludwig-Maximilians-University Munich, Munich, Germany
| | - Moritz Drefs
- Department of General, Visceral and Transplantation Surgery, LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, Marchioninistr. 15, 81377, Munich, Germany
- Transplantation Center Munich, LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, Munich, Germany
- Liver Center Munich, Ludwig-Maximilians-University Munich, Munich, Germany
| | - Yunfei Liu
- Department of General, Visceral and Transplantation Surgery, LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - Mathilda Knoblauch
- Department of General, Visceral and Transplantation Surgery, LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - Dionysios Koliogiannis
- Department of General, Visceral and Transplantation Surgery, LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, Marchioninistr. 15, 81377, Munich, Germany
- Transplantation Center Munich, LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, Munich, Germany
- Liver Center Munich, Ludwig-Maximilians-University Munich, Munich, Germany
| | - Weiwei Sheng
- Department of Gastrointestinal Surgery, The First Hospital, China Medical University, Shenyang, 110001, China
| | - Enrico N De Toni
- Liver Center Munich, Ludwig-Maximilians-University Munich, Munich, Germany
- Department of Internal Medicine II, LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, Munich, Germany
| | - Alexandr V Bazhin
- Department of General, Visceral and Transplantation Surgery, LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, Marchioninistr. 15, 81377, Munich, Germany
- German Cancer Consortium (DKTK), DKTK Partner Site Munich, Munich, Germany
- Bavarian Cancer Research Center (BZKF), Munich, Germany
| | - Bernhard W Renz
- Department of General, Visceral and Transplantation Surgery, LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, Marchioninistr. 15, 81377, Munich, Germany
- German Cancer Consortium (DKTK), DKTK Partner Site Munich, Munich, Germany
- Transplantation Center Munich, LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, Munich, Germany
- Liver Center Munich, Ludwig-Maximilians-University Munich, Munich, Germany
- Bavarian Cancer Research Center (BZKF), Munich, Germany
| | - Markus O Guba
- Department of General, Visceral and Transplantation Surgery, LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, Marchioninistr. 15, 81377, Munich, Germany
- Transplantation Center Munich, LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, Munich, Germany
- Liver Center Munich, Ludwig-Maximilians-University Munich, Munich, Germany
- Bavarian Cancer Research Center (BZKF), Munich, Germany
| | - Jens Werner
- Department of General, Visceral and Transplantation Surgery, LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, Marchioninistr. 15, 81377, Munich, Germany
- German Cancer Consortium (DKTK), DKTK Partner Site Munich, Munich, Germany
- Transplantation Center Munich, LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, Munich, Germany
- Liver Center Munich, Ludwig-Maximilians-University Munich, Munich, Germany
- Bavarian Cancer Research Center (BZKF), Munich, Germany
| | - Matthias Ilmer
- Department of General, Visceral and Transplantation Surgery, LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, Marchioninistr. 15, 81377, Munich, Germany.
- German Cancer Consortium (DKTK), DKTK Partner Site Munich, Munich, Germany.
- Transplantation Center Munich, LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, Munich, Germany.
- Liver Center Munich, Ludwig-Maximilians-University Munich, Munich, Germany.
- Bavarian Cancer Research Center (BZKF), Munich, Germany.
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Wu X, Lokken RP, Mehta N. Optimal treatment for small HCC (<3 cm): Resection, liver transplantation, or locoregional therapy? JHEP Rep 2023; 5:100781. [PMID: 37456674 PMCID: PMC10339255 DOI: 10.1016/j.jhepr.2023.100781] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Accepted: 03/30/2023] [Indexed: 07/18/2023] Open
Abstract
Hepatocellular carcinoma (HCC) remains the most common form of liver cancer, accounting for 90% of all primary liver cancers. Up to 30% of HCC cases could be small (2-3 cm in diameter) at the time of diagnosis with advances in imaging techniques and surveillance programmes. Treating patients with early-stage HCC can be complex and often requires interdisciplinary care, owing to the wide and increasing variety of treatment options, which include liver resection, liver transplantation, and various locoregional therapies offered by interventional radiology and radiation oncology. Decisions regarding the optimal management strategy for a patient involve many considerations, including patient- and tumour-specific characteristics, as well as socioeconomic factors. In this review, we aim to comprehensively summarise the commonly used therapies for single, small HCC (<3 cm), with a focus on the impact of tumour size (<2 cm vs. 2-3 cm), as well as a brief discussion on the cost-effectiveness of the different treatment options.
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Affiliation(s)
- Xiao Wu
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA
| | - Ryan Peter Lokken
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA
| | - Neil Mehta
- Department of General Hepatology and Liver Transplantation, University of California, San Francisco, CA, USA
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2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma. JOURNAL OF LIVER CANCER 2023; 23:1-120. [PMID: 37384024 PMCID: PMC10202234 DOI: 10.17998/jlc.2022.11.07] [Citation(s) in RCA: 68] [Impact Index Per Article: 34.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Accepted: 11/07/2022] [Indexed: 06/30/2023]
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
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Affiliation(s)
- Korean Liver Cancer Association (KLCA) and National Cancer Center (NCC) Korea
- Corresponding author: KLCA-NCC Korea Practice Guideline Revision Committee (KPGRC) (Committee Chair: Joong-Won Park) Center for Liver and Pancreatobiliary Cancer, Division of Gastroenterology, Department of Internal Medicine, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 10408, Korea Tel. +82-31-920-1605, Fax: +82-31-920-1520, E-mail:
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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] [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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Fang C, Luo R, Zhang Y, Wang J, Feng K, Liu S, Chen C, Yao R, Shi H, Zhong C. Hepatectomy versus transcatheter arterial chemoembolization for resectable BCLC stage A/B hepatocellular carcinoma beyond Milan criteria: A randomized clinical trial. Front Oncol 2023; 13:1101162. [PMID: 36923427 PMCID: PMC10010190 DOI: 10.3389/fonc.2023.1101162] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Accepted: 02/03/2023] [Indexed: 03/02/2023] Open
Abstract
Background Hepatectomy is the recommended option for radical treatment of BCLC stage A/B hepatocellular carcinoma (HCC) that has progressed beyond the Milan criteria. This study evaluated the efficacy and safety of preoperative neoadjuvant transcatheter arterial chemoembolization (TACE) for these patients. Methods In this prospective, randomized, open-label clinical study, BCLC stage A/B HCC patients beyond the Milan criteria were randomly assigned (1:1) to receive either neoadjuvant TACE prior to hepatectomy (NT group) or hepatectomy alone (OP group). The primary outcome was overall survival (OS), while the secondary outcomes were progression-free survival (PFS) and adverse events (AEs). Results Of 249 patients screened, 164 meeting the inclusion criteria were randomly assigned to either the NT group (n = 82) or OP group (n = 82) and completed follow-up requirements. Overall survival was significantly greater in the NT group compared to the OP group at 1 year (97.2% vs. 82.4%), two years (88.4% vs. 60.4%), and three years (71.6% vs. 45.7%) (p = 0.0011) post-treatment. Similarly, PFS was significantly longer in the NT group than the OP group at 1 year (60.1% vs. 39.9%), 2 years (53.4% vs. 24.5%), and 3 years (42.2% vs. 24.5%) (p = 0.0003). No patients reported adverse events of grade 3 or above in either group. Conclusions Neoadjuvant TACE prolongs the survival of BCLC stage A/B HCC patients beyond the Milan criteria without increasing severe adverse events frequency. Clinical trial registration https://www.chictr.org.cn/, identifier ChiCTR2200055618.
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Affiliation(s)
- Chongkai Fang
- The First Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou, China.,The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China.,Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Rui Luo
- The First Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou, China.,The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China.,Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Ying Zhang
- The First Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou, China.,The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China.,Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Jinan Wang
- The First Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou, China.,The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China.,Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Kunliang Feng
- The First Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou, China.,The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China.,Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Silin Liu
- The First Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou, China.,The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China.,Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Chuyao Chen
- The First Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou, China.,The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China.,Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Ruiwei Yao
- The First Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou, China.,The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China.,Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Hanqian Shi
- The First Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou, China.,The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China.,Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Chong Zhong
- The First Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou, China.,The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China.,Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, China
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2022 KLCA-NCC Korea Practice Guidelines for the Management of Hepatocellular Carcinoma. Korean J Radiol 2022; 23:1126-1240. [PMID: 36447411 PMCID: PMC9747269 DOI: 10.3348/kjr.2022.0822] [Citation(s) in RCA: 74] [Impact Index Per Article: 24.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 10/28/2022] [Indexed: 11/18/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
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11
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2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma. Clin Mol Hepatol 2022; 28:583-705. [PMID: 36263666 PMCID: PMC9597235 DOI: 10.3350/cmh.2022.0294] [Citation(s) in RCA: 161] [Impact Index Per Article: 53.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 09/23/2022] [Indexed: 01/27/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
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12
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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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13
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Yuen SC, Amaefule AQ, Kim HH, Owoo BV, Gorman EF, Mattingly TJ. A Systematic Review of Cost-Effectiveness Analyses for Hepatocellular Carcinoma Treatment. PHARMACOECONOMICS - OPEN 2022; 6:9-19. [PMID: 34427897 PMCID: PMC8807829 DOI: 10.1007/s41669-021-00298-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 08/08/2021] [Indexed: 05/05/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is associated with significant financial burden for patients and payers. The objective of this study was to review economic models to identify, evaluate, and compare cost-effectiveness estimates for HCC treatments. METHODS A systematic search of the PubMed, Embase, and Cochrane Library databases to identify economic evaluations was performed and studies that modeled treatments for HCC reporting costs and cost effectiveness were included. Risk of bias was assessed qualitatively, considering costing approach, reported study perspective, and funding received. Intervention costs were adjusted to 2021 US dollars for comparison. For studies reporting quality-adjusted life-years (QALYs), we conducted analyses stratified by comparison type to assess cost effectiveness at the time of the analysis. RESULTS A total of 27 studies were included. Non-curative versus non-curative therapy comparisons were used in 20 (74.1%) studies, curative versus curative comparisons were used in 5 (18.5%) studies, and curative versus non-curative comparisons were used in 2 (7.4%) studies. Therapy effectiveness was estimated using a QALY measure in 20 (74.1%) studies, while 7 (25.9%) studies only assessed life-years gained (LYG). A health sector perspective was used in 26 (96.3%) of the evaluations, with only 1 study including costs beyond this perspective. Median intervention cost was $53,954 (range $4550-$4,760,835), with a median incremental cost of $6546 (range - $72,441 to $1,279,764). In cost-utility analyses, 11 (55%) studies found the intervention cost effective using a $100,000/QALY threshold at the time of the study, with an incremental cost-effectiveness ratio (ICER) ranging from - $1,176,091 to $1,152,440 when inflated to 2021 US dollars. CONCLUSION The majority of HCC treatments were found to be cost effective, but with significant variation and with few studies considering indirect costs. Standards for value assessment for HCC treatments may help improve consistency and comparability.
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Affiliation(s)
- Sydney C Yuen
- University of Maryland School of Pharmacy, 220 Arch Street, 12th Floor, Baltimore, MD, 21201, USA
| | - Adaeze Q Amaefule
- University of Maryland School of Pharmacy, 220 Arch Street, 12th Floor, Baltimore, MD, 21201, USA
| | - Hannah H Kim
- University of Maryland School of Pharmacy, 220 Arch Street, 12th Floor, Baltimore, MD, 21201, USA
| | - Breanna-Verissa Owoo
- University of Maryland School of Pharmacy, 220 Arch Street, 12th Floor, Baltimore, MD, 21201, USA
| | - Emily F Gorman
- Health Sciences and Human Services Library, University of Maryland, Baltimore, MD, USA
| | - T Joseph Mattingly
- University of Maryland School of Pharmacy, 220 Arch Street, 12th Floor, Baltimore, MD, 21201, USA.
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14
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Xu L, Chen L, Zhang W. Neoadjuvant treatment strategies for hepatocellular carcinoma. World J Gastrointest Surg 2021; 13:1550-1566. [PMID: 35070063 PMCID: PMC8727178 DOI: 10.4240/wjgs.v13.i12.1550] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 06/27/2021] [Accepted: 11/30/2021] [Indexed: 02/06/2023] Open
Abstract
The incidence of hepatocellular carcinoma (HCC) remains high globally. Surgical treatment is the best treatment for improving the prognosis of patients with HCC. Neoadjuvant therapy plays a key role in preventing tumor progression and even downstaging HCC. The liver transplantation rate and resectability rate have increased for neoadjuvant therapy. Neoadjuvant therapy is effective in different stages of HCC. In this review, we summarized the definition, methods, effects, indications and contraindications of neoadjuvant therapy in HCC, which have significance for guiding treatment.
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Affiliation(s)
- Lei Xu
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Lin Chen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Wei Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
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15
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Biolato M, Galasso T, Marrone G, Miele L, Grieco A. Upper Limits of Downstaging for Hepatocellular Carcinoma in Liver Transplantation. Cancers (Basel) 2021; 13:cancers13246337. [PMID: 34944957 PMCID: PMC8699392 DOI: 10.3390/cancers13246337] [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: 11/08/2021] [Revised: 12/07/2021] [Accepted: 12/13/2021] [Indexed: 11/30/2022] Open
Abstract
Simple Summary Currently, most transplant centres worldwide accept patients with hepatocellular carcinoma who underwent successful downstaging. Concurrently, the effectiveness of radiological and systemic therapies used for the downstaging of hepatocellular carcinoma are increasing. It is now more frequently observed that candidates for liver transplantation have an excellent response to downstaging, even if the baseline stage was well beyond the transplantable tumour. Downstaged patients have a higher risk of dropout from the waiting list and post-transplant recurrence if not transplanted in a short time. Since an increasing number of downstaged patients affects the waitlist dynamics, the definition of upper limits of downstaging is becoming a crucial issue. In this narrative review, we summarise current evidence on the downstaging of hepatocellular carcinoma for liver transplantation, including downstaging of patients with macrovascular invasion or extrahepatic metastasis at presentation and employment of the new systemic treatments for hepatocellular carcinoma. Abstract In Europe and the United States, approximately 1100 and 1800 liver transplantations, respectively, are performed every year for hepatocellular carcinoma (HCC), compared with an annual incidence of 65,000 and 39,000 new cases, respectively. Because of organ shortages, proper patient selection is crucial, especially for those exceeding the Milan criteria. Downstaging is the reduction of the HCC burden to meet the eligibility criteria for liver transplantation. Many techniques can be used in downstaging, including ablation, chemoembolisation, radioembolisation and systemic treatments, with a reported success rate of 60–70%. In recent years, an increasing number of patient responders to downstaging procedures has been included in the waitlist, generally with a comparable five-year post-transplant survival but with a higher probability of dropout than HCC patients within the Milan criteria. While the Milan criteria are generally accepted as the endpoint of downstaging, the upper limits of tumour burden for downstaging HCC for liver transplantation are controversial. Very challenging situations involve HCC patients with large nodules, macrovascular invasion or even extrahepatic metastasis at baseline who respond to increasingly more effective downstaging procedures and who aspire to be placed on the waitlist for transplantation. This narrative review analyses the most important evidence available on cohorts subjected to “extended” downstaging, including HCC patients over the up-to-seven criteria and over the University of California San Francisco downstaging criteria. We also address surrogate markers of biological aggressiveness, such as alpha-fetoprotein and the response stability to locoregional treatments, which are very useful in selecting responders to downstaging procedures for waitlisting inclusion.
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Affiliation(s)
- Marco Biolato
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Roma, Italy; (M.B.); (G.M.); (L.M.)
- Institute of Internal Medicine, Catholic University of Sacred Hearth, 00168 Rome, Italy;
| | - Tiziano Galasso
- Institute of Internal Medicine, Catholic University of Sacred Hearth, 00168 Rome, Italy;
| | - Giuseppe Marrone
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Roma, Italy; (M.B.); (G.M.); (L.M.)
- Institute of Internal Medicine, Catholic University of Sacred Hearth, 00168 Rome, Italy;
| | - Luca Miele
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Roma, Italy; (M.B.); (G.M.); (L.M.)
- Institute of Internal Medicine, Catholic University of Sacred Hearth, 00168 Rome, Italy;
| | - Antonio Grieco
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Roma, Italy; (M.B.); (G.M.); (L.M.)
- Institute of Internal Medicine, Catholic University of Sacred Hearth, 00168 Rome, Italy;
- Correspondence:
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Guo C, Zou X, Hong Z, Sun J, Xiao W, Sun K, Li X, Shen Y, Liang T, Bai X. Preoperative transarterial chemoembolization for barcelona clinic liver cancer stage A/B hepatocellular carcinoma beyond the milan criteria: a propensity score matching analysis. HPB (Oxford) 2021; 23:1427-1438. [PMID: 33715958 DOI: 10.1016/j.hpb.2021.02.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2020] [Revised: 02/05/2021] [Accepted: 02/17/2021] [Indexed: 01/27/2023]
Abstract
BACKGROUND Debate continues about the benefits of preoperative transarterial chemoembolization (TACE) for treatment of hepatocellular carcinoma (HCC). This study aimed to assess the impact of preoperative TACE on long-term outcomes after curative resection for HCC beyond the Milan criteria. METHODS Patients who underwent HCC resection exceeding the Milan criteria without macrovascular invasion between 2015 and 2018 were identified (n = 393). Short- and long-term outcomes were compared between patients who underwent preoperative TACE and patients who did not before and after propensity score matching (PSM). Factors associated with recurrence after resection were analyzed. RESULTS 100 patients (25.4%) underwent preoperative TACE. Recurrence-free survival (RFS) and overall survival (OS) were comparable with patients who underwent primary liver resection. 7 patients (7.0%) achieved total necrosis with better RFS compared with patients who had an incomplete response to TACE (P=0.041). PSM created 73 matched patient pairs. In the PSM cohort, preoperative TACE improved RFS (P=0.002) and OS (P=0.003). The maximum preoperatively diagnosed tumor diameter (HR 3.230, 95% CI: 1.116-9.353; P=0.031) and hepatitis B infection (HR 2.905, 95%CI: 1.281-6.589; P=0.011) were independently associated with favorable RFS after HCC resection. CONCLUSION Preoperative TACE made no significant difference to perioperative complications and was correlated with an improved prognosis after surgical resection for patients with HCC beyond the Milan criteria.
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Affiliation(s)
- Chengxiang Guo
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310000, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang Province, Hangzhou, 310000, China; Clinical Medical Research Center for Hepatobiliary Pancreatic Diseases, Zhejiang Province, Hangzhou, 310000, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, 310000, China
| | - Xiuwen Zou
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310000, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang Province, Hangzhou, 310000, China; Clinical Medical Research Center for Hepatobiliary Pancreatic Diseases, Zhejiang Province, Hangzhou, 310000, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, 310000, China
| | - Zhengtao Hong
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310000, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang Province, Hangzhou, 310000, China; Clinical Medical Research Center for Hepatobiliary Pancreatic Diseases, Zhejiang Province, Hangzhou, 310000, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, 310000, China
| | - Junhui Sun
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310000, China
| | - Wenbo Xiao
- Department of Radiology, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310000, China
| | - Ke Sun
- Department of Pathology, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310000, China
| | - Xuejie Li
- Department of Pathology, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310000, China
| | - Yinan Shen
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310000, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang Province, Hangzhou, 310000, China; Clinical Medical Research Center for Hepatobiliary Pancreatic Diseases, Zhejiang Province, Hangzhou, 310000, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, 310000, China
| | - Tingbo Liang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310000, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang Province, Hangzhou, 310000, China; Clinical Medical Research Center for Hepatobiliary Pancreatic Diseases, Zhejiang Province, Hangzhou, 310000, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, 310000, China
| | - Xueli Bai
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310000, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang Province, Hangzhou, 310000, China; Clinical Medical Research Center for Hepatobiliary Pancreatic Diseases, Zhejiang Province, Hangzhou, 310000, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, 310000, China.
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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 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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Likhitsup A, Parikh ND. Economic Implications of Hepatocellular Carcinoma Surveillance and Treatment: A Guide for Clinicians. PHARMACOECONOMICS 2020; 38:5-24. [PMID: 31573053 DOI: 10.1007/s40273-019-00839-9] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
The incidence of hepatocellular carcinoma (HCC) is increasing worldwide, with significant morbidity and associated costs. Treatment allocation depends on the stage of diagnosis; however, resource utilization can be significant across all stages. We aimed to summarize the available data on the cost effectiveness of surveillance of and treatments for HCC in the context of current treatment guidelines. We performed a focused review of studies investigating the economic burden and cost effectiveness of HCC surveillance treatment modalities published between January 2000 and January 2019. The overall economic burden of HCC is increasing in the USA and in several countries worldwide due to its rising incidence and the proliferation of therapies. Liver transplantation is a cost-effective strategy for early-stage HCC treatment in selected patients. In settings where liver transplantation is not available or in patients awaiting transplant, ablative or locoregional therapies are cost effective with increases in quality-adjusted life-years. First-line therapy with sorafenib for advanced stage HCC is cost effective in the treatment of compensated cirrhosis. The cost effectiveness of recently approved systemic therapies for advanced HCC require further investigation. Existing studies have shown that guideline-recommended surveillance techniques and several available therapies for the treatment of HCC are cost effective; however, there are limitations in the literature, including reliance on suboptimal modeling with incomplete/simplified model structure or inadequate inputs. With increasing therapeutic options in patients with HCC, understanding their relative value is critical in designing HCC treatment algorithms.
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Affiliation(s)
- Alisa Likhitsup
- Division of Gastroenterology and Hepatology, University of Missouri, Kansas City, MO, USA
| | - Neehar D Parikh
- Division of Gastroenterology and Hepatology, University of Michigan, 1500 E. Medical Center Dr., Ann Arbor, MI, 48109, USA.
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19
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2018 Korean Liver Cancer Association-National Cancer Center Korea Practice Guidelines for the Management of Hepatocellular Carcinoma. Korean J Radiol 2019; 20:1042-1113. [PMID: 31270974 PMCID: PMC6609431 DOI: 10.3348/kjr.2019.0140] [Citation(s) in RCA: 191] [Impact Index Per Article: 31.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Accepted: 02/24/2019] [Indexed: 01/10/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer globally and the fourth most common cancer in men in Korea, where the prevalence of chronic hepatitis B infection is high in middle-aged and elderly patients. These practice guidelines will provide useful and constructive advice for the clinical management of patients with HCC. A total of 44 experts in hepatology, oncology, surgery, radiology, and radiation oncology in the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2014 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions.
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20
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Santopaolo F, Lenci I, Milana M, Manzia TM, Baiocchi L. Liver transplantation for hepatocellular carcinoma: Where do we stand? World J Gastroenterol 2019; 25:2591-2602. [PMID: 31210712 PMCID: PMC6558441 DOI: 10.3748/wjg.v25.i21.2591] [Citation(s) in RCA: 74] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Revised: 04/09/2019] [Accepted: 04/29/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma represents an important cause of morbidity and mortality worldwide. It is the sixth most common cancer and the fourth leading cause of cancer death. Liver transplantation is a key tool for the treatment of this disease in human therefore hepatocellular carcinoma is increasing as primary indication for grafting. Although liver transplantation represents an outstanding therapy for hepatocellular carcinoma, due to organ shortage, the careful selection and management of patients who may have a major survival benefit after grafting remains a fundamental question. In fact, only some stages of the disease seem amenable of this therapeutic option, stimulating the debate on the appropriate criteria to select candidates. In this review we focused on current criteria to select patients with hepatocellular carcinoma for liver transplantation as well as on the strategies (bridging) to avoid disease progression and exclusion from grafting during the stay on wait list. The treatments used to bring patients within acceptable criteria (down-staging), when their tumor burden exceeds the standard criteria for transplant, are also reported. Finally, we examined tumor reappearance following liver transplantation. This occurrence is estimated to be approximately 8%-20% in different studies. The possible approaches to prevent this outcome after transplant are reported with the corresponding results.
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Affiliation(s)
- Francesco Santopaolo
- Hepatology Unit, Department of Medicine, Policlinico Universitario Tor Vergata, Rome 00133, Italy
| | - Ilaria Lenci
- Hepatology Unit, Department of Medicine, Policlinico Universitario Tor Vergata, Rome 00133, Italy
| | - Martina Milana
- Hepatology Unit, Department of Medicine, Policlinico Universitario Tor Vergata, Rome 00133, Italy
| | - Tommaso Maria Manzia
- Transplant Surgery Unit, Department of Surgery, Policlinico Universitario Tor Vergata, Rome 00133, Italy
| | - Leonardo Baiocchi
- Hepatology Unit, Department of Medicine, Policlinico Universitario Tor Vergata, Rome 00133, Italy
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2018 Korean Liver Cancer Association-National Cancer Center Korea Practice Guidelines for the Management of Hepatocellular Carcinoma. Gut Liver 2019; 13:227-299. [PMID: 31060120 PMCID: PMC6529163 DOI: 10.5009/gnl19024] [Citation(s) in RCA: 239] [Impact Index Per Article: 39.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2019] [Accepted: 01/24/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer globally and the fourth most common cancer in men in Korea, where the prevalence of chronic hepatitis B infection is high in middle-aged and elderly patients. These practice guidelines will provide useful and constructive advice for the clinical management of patients with HCC. A total of 44 experts in hepatology, oncology, surgery, radiology and radiation oncology in the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2014 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions.
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22
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Affiliation(s)
- Augusto Villanueva
- From the Liver Cancer Program, Division of Liver Diseases, Department of Medicine, Tisch Cancer Institute, Graduate School of Biomedical Sciences, and the Division of Hematology and Medical Oncology, Department of Medicine, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York
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23
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Tan EK, Goh BKP, Lee SY, Krishnamoorthy TL, Tan CK, Jeyaraj PR. Liver Transplant Waitlist Outcomes and the Allocation of Hepatocellular Carcinoma Model for End-Stage Liver Disease Exception Points at a Low-Volume Center. Transplant Proc 2018; 50:3564-3570. [PMID: 30577239 DOI: 10.1016/j.transproceed.2018.08.032] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2018] [Accepted: 08/29/2018] [Indexed: 12/13/2022]
Abstract
BACKGROUND Organ scarcity continues to be the main problem limiting the number of liver transplants performed. Outcomes of patients waitlisted for an organ in an Asian country with low organ donation rate have not been well evaluated. Our current policy of allocating 15 exception points to patients with hepatocellular carcinoma (HCC) to render them competitive for a transplant also requires review. METHODS The waiting list registry and the organ transplant registry of a single institution in Asia were reviewed from December 2005 to June 2016 for all patients who underwent liver transplantation. Patient characteristics and outcomes of waitlist dropouts were evaluated. Statistical analyses were performed using SPSS version 20.0. RESULTS One hundred seventy-three patients were waitlisted for a deceased donor liver-only transplant. The most common etiology of liver disease was hepatitis B, followed by cholestatic diseases. Approximately half of the patients had HCC (45.6%). Priority listing for transplant comprised 15.6% of cases. Median Model for End-Stage Liver Disease (MELD) at listing was 15, and median waiting time to transplant was 17 weeks (interquartile range = 6.5-43.5). Overall, 89 (51.4%) patients underwent liver transplantation and 68 (39.3%) dropped out. For patients with HCC, the most common cause of dropout was progression beyond University of California San Francisco transplant criteria (62.5%). The cumulative incidence of dropout at 3 months among patients with HCC who received exception MELD scores was 11%. This was higher than those listed with physiologic MELD of 14-16 points (7%) but lower than those with 17-19 points (16%). CONCLUSIONS Hepatitis B-related liver disease and HCC comprise the majority of patients listed for liver transplant. Dropout rates are high and this is due to the lack of donor organs. The current policy of allocating 15 exception MELD points to patients with HCC within transplant criteria may underestimate the dropout risk of patients with HCC in our population.
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Affiliation(s)
- E K Tan
- Department of Hepato-pancreato-biliary and Transplant Surgery, Singapore General Hospital, Bukit Merah, Singapore.
| | - B K P Goh
- Department of Hepato-pancreato-biliary and Transplant Surgery, Singapore General Hospital, Bukit Merah, Singapore
| | - S Y Lee
- Department of Hepato-pancreato-biliary and Transplant Surgery, Singapore General Hospital, Bukit Merah, Singapore
| | - T L Krishnamoorthy
- Department of Gastroenterology & Hepatology, Singapore General Hospital, Bukit Merah, Singapore
| | - C K Tan
- Department of Gastroenterology & Hepatology, Singapore General Hospital, Bukit Merah, Singapore
| | - P R Jeyaraj
- Department of Hepato-pancreato-biliary and Transplant Surgery, Singapore General Hospital, Bukit Merah, Singapore
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A Model for Adaptive Decision Making of "Ablate-and-Wait" Versus Transplantation in Patients With Hepatocellular Carcinoma. J Clin Gastroenterol 2018; 52:655-661. [PMID: 29356782 DOI: 10.1097/mcg.0000000000000981] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND/AIMS In patients with early-stage hepatocellular carcinoma (HCC), selection of candidates for liver transplantation (LT) requires refinement based on tumor biology to maximize the outcome. We aimed to prognosticate LT candidates with HCC using a risk prediction model for post-LT recurrence. PATIENTS AND METHODS A total of 197 consecutive patients were included who underwent LT for hepatitis B-related HCC within the Milan criteria. A risk prediction model was developed for post-LT recurrence using the Cox model and was internally validated. RESULTS Among those undergoing LT as their first HCC treatment (n=70, initial LT group), poor prognosis was associated with maximal tumor size and multinodularity. The remaining 127 patients (deferred LT group) received radiofrequency ablation (n=69) and/or transarterial chemoembolization (n=98) before LT. Multinodularity, maximal tumor size, posttransarterial chemoembolization progressive disease, baseline alpha-fetoprotein, and alpha-fetoprotein difference (between baseline and pre-LT) were incorporated into a risk prediction model for the deferred LT group, which was thereby stratified into low-risk (score<5), intermediate-risk, and high-risk (score≥8) subgroups. Recurrence-free survival was significantly different among the deferred LT prognostic subgroups (P<0.001). CONCLUSIONS This risk prediction model may help refinement of "ablate-and-wait" strategy for LT candidates by avoiding LT in those with either high risk score at baseline or increasing score under repeated locoregional therapies.
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Galle PR, Forner A, Llovet JM, Mazzaferro V, Piscaglia F, Raoul JL, Schirmacher P, Vilgrain V. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol 2018; 69:182-236. [PMID: 29628281 DOI: 10.1016/j.jhep.2018.03.019] [Citation(s) in RCA: 5784] [Impact Index Per Article: 826.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2018] [Accepted: 03/20/2018] [Indexed: 02/06/2023]
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Radiofrequency and Microwave Ablation in the Treatment of Hepatocelular Carcinoma. IRANIAN JOURNAL OF RADIOLOGY 2018. [DOI: 10.5812/iranjradiol.62396] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Nazzal M, Gadani S, Said A, Rice M, Okoye O, Taha A, Lentine KL. Liver targeted therapies for hepatocellular carcinoma prior to transplant: contemporary management strategies. GLOBAL SURGERY (LONDON) 2018; 4. [PMID: 29782618 DOI: 10.15761/gos.1000171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Hepatocellular carcinoma (HCC) is an aggressive neoplastic disease that has been rapidly increasing in incidence. It usually occurs in the background of liver disease, and cirrhosis. Definitive therapy requires surgical resection. However, in majority of cases surgical resection is not tolerated, especially in the presence of portal hypertension and cirrhosis. Orthotopic liver transplant (OLT) in well selected candidates has been accepted as a viable option. Due to a relative scarcity of donors compared to the number of listed recipients, long waiting times are anticipated. To prevent patients with HCC from dropping out from the transplant list due to progression of their disease, most centers utilize loco-regional therapies. These loco-regional therapies(LRT) include minimally invasive treatments like percutaneous thermal ablation, trans-arterial chemoembolization, trans-arterial radio-embolization or a combination thereof. The type of therapy or combination used is determined by the size and location of the HCC and Barcelona Clinic Liver Cancer (BCLC) classification. The data regarding the efficacy of LRT in reducing post-transplant recurrence or disease-free survival is limited. This article reviews the available therapies, their strengths, limitations, and current use in the management of patients with hepatocellular carcinoma awaiting transplant.
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Affiliation(s)
- Mustafa Nazzal
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA
| | - Sameer Gadani
- Interventional Radiology, Department of Radiology, St. Louis University Hospital, USA
| | - Abdullah Said
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA
| | - Mandy Rice
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA
| | - Obi Okoye
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA
| | - Ahmad Taha
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA
| | - Krista L Lentine
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA.,Division of Nephrology, Department of Medicine, St Louis University Hospital, USA
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Results of 15-Year Experience in Liver Transplant for Hepatocellular Carcinoma. Transplant Proc 2018; 50:617-618. [DOI: 10.1016/j.transproceed.2017.11.050] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2017] [Revised: 10/04/2017] [Accepted: 11/11/2017] [Indexed: 01/30/2023]
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Tan CHN, Yu Y, Tan YRN, Lim BLK, Iyer SG, Madhavan K, Kow AWC. Bridging therapies to liver transplantation for hepatocellular carcinoma: A bridge to nowhere? Ann Hepatobiliary Pancreat Surg 2018. [PMID: 29536053 PMCID: PMC5845608 DOI: 10.14701/ahbps.2018.22.1.27] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Backgrounds/Aims Liver Transplantation (LT) is a recognized treatment for Hepatocellular Carcinoma (HCC). The role of Bridging Therapies (BT) remains controversial. Methods From January 2001 to October 2012, 192 patients were referred to the National University Hospital, Singapore for consideration of LT for HCC. Sixty-five patients (33.8%) were found suitable for transplant and were placed on the waitlist. Analysis was performed in these patients. Results The most common etiology of HCC was Hepatitis B (n=28, 43.1%). Thirty-six patients (55.4%) received BT. Seventeen patients (47.2%) received TACE only, while 10 patients (27.8%) received radiofrequency ablation (RFA) only. The remaining patients received a combination of transarterial chemoembolization (TACE) and RFA. Baseline tumor and patient characteristics were comparable between the two groups. The overall dropout rate was 44.4% and 31.0% in the BT and non-BT groups, respectively (p=0.269). The dropout rate due to disease progression beyond criteria was 6.9% (n=2) in the non-bridged group and 22.2% (n=8) in the bridged group (p=0.089). Thirty-nine patients (60%) underwent LT, of which all patients who underwent Living Donor LT did not receive BT (n=4, 21.1%, p=0.030). The median time to LT was 180 days (range, 20–558 days) in the non-BT group and 291 days (range, 17–844 days) in the BT group (p=0.214). There was no difference in survival or recurrence between the BT and non-BT groups (p=0.862). Conclusions BT does not influence the dropout rate or survival after LT but it should be considered in patients who are on the waitlist for more than 6 months.
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Affiliation(s)
- Chun Han Nigel Tan
- Division of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Department of Surgery, University Surgical Cluster, National University Health System, Singapore, Singapore.,National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
| | - Yue Yu
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Yan Rui Nicholas Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Boon Leng Kieron Lim
- Department of Gastroenterology and Hepatology, National University Health System, Singapore, Singapore.,National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
| | - Shridhar Ganpathi Iyer
- Division of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Department of Surgery, University Surgical Cluster, National University Health System, Singapore, Singapore.,National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
| | - Krishnakumar Madhavan
- Division of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Department of Surgery, University Surgical Cluster, National University Health System, Singapore, Singapore.,National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
| | - Alfred Wei Chieh Kow
- Division of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Department of Surgery, University Surgical Cluster, National University Health System, Singapore, Singapore.,National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
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Cohen EI, Field D, Lynskey GE, Kim AY. Technology of irreversible electroporation and review of its clinical data on liver cancers. Expert Rev Med Devices 2018; 15:99-106. [PMID: 29307242 DOI: 10.1080/17434440.2018.1425612] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Irreversible electroporation (IRE) has developed as a novel percutaneous ablative technique over the past decade and its utility in the treatment of primary and metastatic liver disease has progressed rapidly. AREAS COVERED After discussing the principles behind the technology and the practical steps in its use, this article offers a detailed analysis of the recent published work that evaluates its safety and efficacy. The strengths and weaknesses of other ablative techniques, including radiofrequency ablation, microwave ablation and cryoablation, are discussed in detail. Other aspects of IRE, including post-treatment clinical follow-up, expected imaging findings, and the most frequently encountered complications, are covered. Finally, the future of IRE is examined as it pertains to advancements in the treatment of hepatic malignancy. EXPERT COMMENTARY The characteristics of IRE that make this technology uniquely suited for the treatment of liver tumors have allowed it to gain a significant foothold in interventional oncology. Continued development of IRE will lead to further advances in the management of previously untreatable liver cancers.
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Affiliation(s)
- Emil I Cohen
- a Division of Interventional Radiology, Department of Radiology , Medstar Georgetown University Hospital , Washington , DC , USA
| | - David Field
- a Division of Interventional Radiology, Department of Radiology , Medstar Georgetown University Hospital , Washington , DC , USA
| | - George Emmett Lynskey
- a Division of Interventional Radiology, Department of Radiology , Medstar Georgetown University Hospital , Washington , DC , USA
| | - Alexander Y Kim
- a Division of Interventional Radiology, Department of Radiology , Medstar Georgetown University Hospital , Washington , DC , USA
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Abstract
Patients with hepatocellular carcinoma (HCC) may be eligible for liver transplantation. Liver transplant candidates with HCC compete for the same deceased donor organs as those without HCC. These scarce organs must be allocated fairly and justly to those who will benefit most. Unlike most other cancers, HCC is often diagnosed noninvasively by imaging without biopsy confirmation. Therefore, radiologists play an important role in diagnosing definite HCC (i.e., LR-5 category) that counts toward staging and determination of liver transplant eligibility. This review explains the conversion of LI-RADS observation categories to organ procurement and transplantation network classes, illustrates the radiologic T-staging systems, reviews selection criteria for liver transplant eligibility, and discusses prioritization of liver transplant candidates with HCC. In addition, this review summarizes imaging requirements, including contrast agents accepted, minimum specifications for dynamic CT or MRI of the liver, and modalities accepted for assessment of extrahepatic spread or metastatic disease in liver transplant candidates with HCC.
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Sá GPD, Carlotto JRM, Vicentine FPP, Romero L, Tejada DFP, Salzedas AA, Lopes GDJ, Gonzalez AM. Evaluation of the treatment of the hepatocarcinoma nodules in the patients in waiting list for liver transplant. ACTA ACUST UNITED AC 2017; 44:360-366. [PMID: 29019539 DOI: 10.1590/0100-69912017004010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2016] [Accepted: 04/28/2017] [Indexed: 11/22/2022]
Abstract
OBJECTIVE to compare the outcome of liver transplantation for hepatocarcinoma in submitted or not to locoregional treatment and downstaging regarding survival and risk of recurrence in transplant waiting list patients. METHODS retrospective study of patients with hepatocarcinoma undergoing liver transplantation in the metropolitan region of São Paulo, between January 2007 and December 2011, from a deceased donor. The sample consisted of 414 patients. Of these, 29 patients were included in the list by downstaging. The other 385 were submitted or not to locoregional treatment. RESULTS the analysis of 414 medical records showed a predominance of male patients (79.5%) with average age of 56 years. Treatment of the lesions was performed in 56.4% of patients on the waiting list for transplant. The most commonly used method was chemoembolization (79%). The locoregional patients undergoing treatment had a significant reduction in nodule size greater (p<0.001). There was no statistical difference between groups with and without locoregional treatment (p=0.744) and on mortality among patients enrolled in the Milan criteria or downstaging (p=0.494). CONCLUSION there was no difference in survival and recurrence rate associated with locoregional treatment. Patients included by downstaging process had comparable survival results to those previously classified as Milan/Brazil criteria.
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Affiliation(s)
- Gustavo Pilotto Domingues Sá
- Escola Paulista de Medicina, Universidade Federal de São Paulo, Gastroenterologia Cirúrgica, São Paulo, SP, Brasil
| | | | | | - Luiz Romero
- Escola Paulista de Medicina, Universidade Federal de São Paulo, Gastroenterologia Cirúrgica, São Paulo, SP, Brasil
| | | | - Alcides Augusto Salzedas
- Escola Paulista de Medicina, Universidade Federal de São Paulo, Gastroenterologia Cirúrgica, São Paulo, SP, Brasil
| | - Gaspar de Jesus Lopes
- Escola Paulista de Medicina, Universidade Federal de São Paulo, Gastroenterologia Cirúrgica, São Paulo, SP, Brasil
| | - Adriano Miziara Gonzalez
- Escola Paulista de Medicina, Universidade Federal de São Paulo, Gastroenterologia Cirúrgica, São Paulo, SP, Brasil
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TURRI JAO, DECIMONI TC, FERREIRA LA, DINIZ MA, HADDAD LBDP, CAMPOLINA AG. Higher MELD score increases the overall cost on the waiting list for liver transplantation: a micro-costing analysis based study. ARQUIVOS DE GASTROENTEROLOGIA 2017; 54:238-245. [DOI: 10.1590/s0004-2803.201700000-35] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/07/2017] [Accepted: 04/10/2017] [Indexed: 12/18/2022]
Abstract
ABSTRACT BACKGROUND: The pre-transplant period is complex and includes lots of procedures. The severity of liver disease predisposes to a high number of hospitalizations and high costs procedures. Economic evaluation studies are important tools to handle costs on the waiting list for liver transplantation. OBJECTIVE: The objective of the present study was to evaluate the total cost of the patient on the waiting list for liver transplantation and the main resources related to higher costs. METHODS: A cost study in a cohort of 482 patients registered on waiting list for liver transplantation was carried out. In 24 months follow-up, we evaluated all costs of materials, medicines, consultations, procedures, hospital admissions, laboratorial tests and image exams, hemocomponents replacements, and nutrition. The total amount of each resource or component used was aggregated and multiplied by the unitary cost, and thus individual cost for each patient was obtained. RESULTS: The total expenditure of the 482 patients was US$ 6,064,986.51. Outpatient and impatient costs correspond to 32.4% of total cost (US$ 1,965,045.52) and 67.6% (US$ 4,099,940.99) respectively. Main cost drivers in outpatient were: medicines (44.31%), laboratorial tests and image exams (31.68%). Main cost drivers regarding hospitalizations were: medicines (35.20%), bed use in ward and ICU (26.38%) and laboratorial tests (13.72%). Patients with MELD score between 25-30 were the most expensive on the waiting list (US$ 16,686.74 ± 16,105.02) and the less expensive were those with MELD below 17 (US$ 5,703.22 ± 9,318.68). CONCLUSION: Total costs on the waiting list for liver transplantation increased according to the patient’s severity. Individually, hospitalizations, hemocomponents reposition and hepatocellular carcinoma treatment were the main cost drivers to the patient on the waiting list. The longer the waiting time, the higher the total cost on list, causing greater impact on health systems.
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Liver transplantation for hepatocellular carcinoma: outcomes and novel surgical approaches. Nat Rev Gastroenterol Hepatol 2017; 14:203-217. [PMID: 28053342 DOI: 10.1038/nrgastro.2016.193] [Citation(s) in RCA: 312] [Impact Index Per Article: 39.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Liver transplantation for hepatocellular carcinoma (HCC) is the best treatment option for patients with early-stage tumours and accounts for ∼20-40% of all liver transplantations performed at most centres worldwide. The Milan criteria are the most common criteria to select patients with HCC for transplantation but they can be seen as too restrictive. Several proposals have been made for a moderate expansion of the criteria, which result in good outcomes but with an increase in the risk of tumour recurrence. In this Review, we provide a comprehensive overview of the outcomes after liver transplantation for HCC, focusing on tumour recurrence in terms of surveillance, prevention and treatment. Additionally, novel surgical techniques have been developed to increase the available pool of organs for liver transplantation (such as living donor liver transplantation, donation after circulatory death and split livers), but the effect of these techniques on patients with HCC is still under debate. Thus, we will describe these techniques and expose the benefits and disadvantages of each surgical approach. Finally, we will comment on the limitations of the current priority policies for liver transplantation and the need to further refine them to better serve the population.
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Clinical validity of Metroticket calculator in transplant patients undergoing prior chemoembolization for hepatocellular carcinoma. Hepatol Int 2017; 11:209-219. [PMID: 28144812 DOI: 10.1007/s12072-017-9785-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2016] [Accepted: 01/10/2017] [Indexed: 01/15/2023]
Abstract
AIM To test the predictive performance of the Metroticket calculator for survival after liver transplantation (LT) of patients with hepatocellular carcinoma (HCC) undergoing prior transarterial chemoembolization (TACE). METHODS A total of 142 patients treated with TACE and subsequent LT who had arterial enhancing HCC(s) were entered into this analysis. Tumor parameters measured by the enhancement radiological method pre-LT or by pathology post-LT were incorporated into the Metroticket analysis. The calculator was validated in terms of calibration and discrimination capacity. RESULTS Mean 3- and 5-year survival rates predicted in the radiological model for all 142 patients were 76.4 and 70.1 %, respectively, lying comfortably within the 95 % confidence interval (CI) of the observed survival rate estimates (72.8-86.2 and 68.6-83.2 %, respectively). In the pathological model incorporating microvascular invasion, the mean anticipated survival rate at 5 years of 120 patients with viable nodules on explants was 69.5 %, also lying inside the 95 % CI of the actuarial rates (67.9-83.5 %). The c-indices as measures of discriminatory power were 0.61 and 0.62, respectively, for the 3- and 5-year predictions in the radiological model, and 0.72 for the 5-year prediction in the pathological model. The corresponding findings were similar for subgroups with hepatitis B virus infection and undergoing living-donor LT. CONCLUSIONS The Metroticket calculation based on explant data accurately predicts post-LT survival of HCC patients with prior TACE. Imaging estimate-based predictions before LT appear to provide poorer discrimination than calibration.
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The evolution and outcome of surveillance of Barrett's oesophagus over four decades in a UK District General Hospital. Eur J Gastroenterol Hepatol 2016; 28:1365-1373. [PMID: 27571366 DOI: 10.1097/meg.0000000000000730] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
INTRODUCTION We present the long-term outcome of Barrett's oesophagus (BO) at a District General Hospital set against the increasing numbers of patients with gastro-oesophageal reflux disease (GORD). METHODS Data were collected prospectively over 37 years. Comparison of GORD without Barrett's (NoBO) versus BO was performed from 1/1/1977 to 31/12/2001 when the NoBO database closed and outcomes of all cases of BO diagnosed until 31/12/2011 and followed up until 31/12/2013 have been reported. RESULTS During the period 1977-2001 the number of GORD NoBO cases was 11 610, and that of BO cases was 764 (6.2% of all GORD); total number of BO cases in 1977-2011 was 1468. NoBO patients were younger than BO patients: 52.2 versus 61.6 years. There was a male predominance in both groups: NoBO 55% and BO 62% (P<0.0001). The prevalence of oesophageal adenocarcinoma (OAC) was 87/1468 (5.9%) BO cases. Its incidence was 54/1381 (3.9%); the mean interval between the diagnosis of BO and incident OAC was 9 years (range 13 months-25.4 years); there was one OAC per 192 patient-years of follow-up (0.52% per year). Mortality was significantly lower in 37 patients under endoscopic surveillance at the time OAC was diagnosed (51 vs. 88% P=0.0141) partly because of older age and comorbidity of the other 17, in whom serial endoscopy was contraindicated. A proportional hazards model to allow for age estimated that the hazard rate ratio was lower in the surveillance group; however, this difference did not reach statistical significance (0.64, 95% confidence interval 0.30-1.48, P=0.08). Excluding prevalent cancers from both groups, mortality in BO was double that in NoBO (47 vs. 24%). CONCLUSION These 37 years of observation suggest, but do not confirm, that endoscopic surveillance may reduce the risk of death from OAC. Modern technology is likely to yield better results, but larger prospective studies are needed to confirm the benefits.
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Delicque J, Boulin M, Guiu B, Pelage JP, Escal L, Schembri V, Assenat E, Fohlen A. Interventional oncology for hepatocellular carcinoma. Clin Res Hepatol Gastroenterol 2016; 40:530-537. [PMID: 27055387 DOI: 10.1016/j.clinre.2016.01.007] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2016] [Accepted: 01/17/2016] [Indexed: 02/04/2023]
Abstract
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and is increasing in incidence. The overall prognosis of patients with liver cancer is poor. The Barcelona Clinic Liver Cancer (BCLC) classification in 5 stages is endorsed by European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Disease (AASLD). This classification is recommended for treatment allocation. Because a small proportion of patients are suitable for curative surgical treatment, various locoregional therapies are widely used to manage patients with HCC. The image-guided therapies, also called interventional radiology or interventional oncology (IO) techniques consisted in percutaneous or endovascular approach. This article reviews the different IO treatments available in HCC patients and the strength of the data.
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Affiliation(s)
- Julien Delicque
- St-Eloi University Hospital, Department of Radiology, 34000 Montpellier, France
| | - Mathieu Boulin
- Dijon University Hospital, Department of Pharmacy, 21000 Dijon, France
| | - Boris Guiu
- St-Eloi University Hospital, Department of Radiology, 34000 Montpellier, France.
| | - Jean-Pierre Pelage
- St-Eloi University Hospital, Department of Radiology, 34000 Montpellier, France
| | - Laure Escal
- St-Eloi University Hospital, Department of Radiology, 34000 Montpellier, France
| | - Valentina Schembri
- St-Eloi University Hospital, Department of Radiology, 34000 Montpellier, France
| | - Eric Assenat
- St-Eloi University Hospital, Department of Oncology, 34000 Montpellier, France
| | - Audrey Fohlen
- University and Medical Center of Caen, 14033 Caen cedex, France.
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Shinozawa T, Yoshikawa HY, Takebe T. Reverse engineering liver buds through self-driven condensation and organization towards medical application. Dev Biol 2016; 420:221-229. [PMID: 27364470 DOI: 10.1016/j.ydbio.2016.06.036] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2016] [Revised: 05/24/2016] [Accepted: 06/25/2016] [Indexed: 12/15/2022]
Abstract
The self-organizing tissue-based approach coupled with induced pluripotent stem (iPS) cell technology is evolving as a promising field for designing organoids in culture and is expected to achieve valuable practical outcomes in regenerative medicine and drug development. Organoids show properties of functional organs and represent an alternative to cell models in conventional two-dimensional differentiation platforms; moreover, organoids can be used to investigate mechanisms of development and disease, drug discovery and toxicity assessment. Towards a more complex and advanced organoid model, it is essential to incorporate multiple cell lineages including developing vessels. Using a self-condensation method, we recently demonstrated self-organizing "organ buds" of diverse systems together with human mesenchymal and endothelial progenitors, proposing a new reverse engineering method to generate a more complex organoid structure. In this section, we review characters of organ bud technology based on two important principles: self-condensation and self-organization focusing on liver bud as an example, and discuss their practicality in regenerative medicine and potential as research tools for developmental biology and drug discovery.
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Affiliation(s)
- Tadahiro Shinozawa
- Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA
| | - Hiroshi Y Yoshikawa
- Department of Chemistry, Saitama University, Shimo-okubo 255, Sakura-ku, Saitama 338-8570, Japan.
| | - Takanori Takebe
- Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA; Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan; PRESTO, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.
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Strassburg CP. HCC-Associated Liver Transplantation - Where Are the Limits and What Are the New Regulations? Visc Med 2016; 32:263-271. [PMID: 27722163 DOI: 10.1159/000446385] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) represents an increasing health burden worldwide and a challenging disease both in terms of diagnosis and treatment. METHODS The literature available on PubMed for the period of 1990-2016 was reviewed with reference to liver allocation, HCC, liver transplantation (LT), and prediction, and the allocation rules of the German Transplant Act were reviewed. RESULTS Due to etiological and geographical diversity, HCC is not a homogeneous disease. In the vast majority of patients, HCC develops as a complication of chronic liver disease and cirrhosis. While most patients present with advanced HCC for which palliative strategies are the only available option, LT is the best treatment approach as it not only eliminates the diseased liver and the underlying hepatocarcinogenic mechanisms but also the cancer. The decision for LT is not an easy one to make, because outcome prediction, staging, bridging therapy, and recurrence prevention are difficult and are estimated against the background of the scarce resource of donor organs which are also competitively sought after by patients suffering from non-neoplastic terminal liver diseases, raising the issue of equality of chances in a rationed therapeutic modality. Currently, the Milan criteria are the best evaluated decision tool for LT, but many issues such as down-staging, favorable biological behavior during treatment, expansion of the morphological classification, molecular predictors, and individualized approaches are not yet satisfactorily addressed. CONCLUSION In order to provide a fair and effective approach to LT in HCC, the employed allocation rules require continuous development and scientific evaluation. Recently, the allocation rules for standard exception priority according to the German Transplant Act have been revised to improve patient selection for LT in HCC.
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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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Abstract
Hepatocellular carcinoma (HCC) is the second most common cause of cancer death worldwide. This cancer commonly arises against a background of chronic liver disease. As a result, a patient with HCC requires multidisciplinary care. Treatment options vary widely based on tumor burden and metastases. The most widely utilized staging system is the Barcelona Clinic Liver Cancer staging system, which recommends treatments based on tumor size and the underlying liver disease and functional status of the patient. Treatment options range from surgical resection or transplantation to locoregional therapies with modalities such as radiofrequency ablation and transarterial chemoembolization to systemic chemotherapies. Future care involves the development of combination therapies that afford the best tumor response, further clarification of the patients best suited for therapies and the development of new oral chemotherapeutic agents.
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Affiliation(s)
- Jennifer S Au
- Division of Gastroenterology and Hepatology, Scripps Clinic
| | - Catherine T Frenette
- Liver Transplantation, Center for Organ and Cell Transplantation, Scripps Clinic, La Jolla, CA, USA
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Forner A, Reig M, Varela M, Burrel M, Feliu J, Briceño J, Sastre J, Martí-Bonmati L, Llovet JM, Bilbao JI, Sangro B, Pardo F, Ayuso C, Bru C, Tabernero J, Bruix J. [Diagnosis and treatment of hepatocellular carcinoma. Update consensus document from the AEEH, SEOM, SERAM, SERVEI and SETH]. Med Clin (Barc) 2016; 146:511.e1-511.e22. [PMID: 26971984 DOI: 10.1016/j.medcli.2016.01.028] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2015] [Revised: 01/22/2016] [Accepted: 01/28/2016] [Indexed: 02/07/2023]
Abstract
Hepatocellular carcinoma is the most common primary malignancy of the liver and one of the most frequent causes of death in patients with liver cirrhosis. Simultaneously with the recognition of the clinical relevance of this neoplasm, in recent years there have been important developments in the diagnosis, staging and treatment of HCC. Consequently, the Asociación Española para el Estudio del Hígado has driven the need to update clinical practice guidelines, continuing to invite all the societies involved in the diagnosis and treatment of this disease to participate in the drafting and approval of the document (Sociedad Española de Trasplante Hepático, Sociedad Española de Radiología Médica, Sociedad Española de Radiología Vascular e Intervencionista y Sociedad Española de Oncología Médica). The clinical practice guidelines published in 2009 accepted as Clinical Practice Guidelines of the National Health System has been taken as reference document, incorporating the most important advances that have been made in recent years. The scientific evidence for the treatment of HCC has been evaluated according to the recommendations of the National Cancer Institute (www.cancer.gov) and the strength of recommendation is based on the GRADE system.
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Affiliation(s)
- Alejandro Forner
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Hepatología, Hospital Clínic, Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España
| | - María Reig
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Hepatología, Hospital Clínic, Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España
| | - María Varela
- Sección de Hepatología, Servicio de Aparato Digestivo, Hospital Universitario Central de Asturias (HUCA), Universidad de Oviedo, Oviedo, España
| | - Marta Burrel
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Radiodiagnóstico, Hospital Clínic, Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España
| | - Jaime Feliu
- Servicio de Oncología Médica, Hospital Universitario La Paz, Universidad Autónoma de Madrid, Sociedad Española de Oncología Médica, Madrid, España
| | - Javier Briceño
- Unidad de Trasplante Hepático, Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitario Reina Sofía, Córdoba, España
| | - Javier Sastre
- Servicio de Oncología Médica, Hospital Clínico San Carlos, Madrid, España
| | - Luis Martí-Bonmati
- Departamento de Radiología, Hospital Universitario y Politécnico La Fe, Valencia, España
| | - Josep María Llovet
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Hepatología, Hospital Clínic, Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España; Mount Sinai Liver Cancer Program, Division of Liver Diseases, Department of Medicine, Mount Sinai School of Medicine, New York, Estados Unidos
| | - José Ignacio Bilbao
- Unidad de Radiología Vascular e Intervencionista, Departamento de Radiodiagnóstico, Clínica Universidad de Navarra, Pamplona, España
| | - Bruno Sangro
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España; Unidad de Hepatología, Departamento de Medicina Interna, Clínica Universidad de Navarra, Pamplona, España
| | - Fernando Pardo
- Servicio de Cirugía Hepatobliopancreática y Trasplante, Clínica Universidad de Navarra, Pamplona, España
| | - Carmen Ayuso
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Radiodiagnóstico, Hospital Clínic, Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España
| | - Concepció Bru
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Radiodiagnóstico, Hospital Clínic, Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España
| | - Josep Tabernero
- Servicio de Oncología Médica, Hospital Universitario Vall d'Hebrón, Barcelona, Universidad Autónoma de Barcelona, Barcelona, España
| | - Jordi Bruix
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Hepatología, Hospital Clínic, Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España.
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Cillo U, Giuliani T, Polacco M, Herrero Manley LM, Crivellari G, Vitale A. Prediction of hepatocellular carcinoma biological behavior in patient selection for liver transplantation. World J Gastroenterol 2016; 22:232-252. [PMID: 26755873 PMCID: PMC4698488 DOI: 10.3748/wjg.v22.i1.232] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2015] [Revised: 08/14/2015] [Accepted: 11/09/2015] [Indexed: 02/06/2023] Open
Abstract
Morphological criteria have always been considered the benchmark for selecting hepatocellular carcinoma (HCC) patients for liver transplantation (LT). These criteria, which are often inappropriate to express the tumor’s biological behavior and aggressiveness, offer only a static view of the disease burden and are frequently unable to correctly stratify the tumor recurrence risk after LT. Alpha-fetoprotein (AFP) and its progression as well as AFP-mRNA, AFP-L3%, des-γ-carboxyprothrombin, inflammatory markers and other serological tests appear to be correlated with post-transplant outcomes. Several other markers for patient selection including functional imaging studies such as 18F-FDG-PET imaging, histological evaluation of tumor grade, tissue-specific biomarkers, and molecular signatures have been outlined in the literature. HCC growth rate and response to pre-transplant therapies can further contribute to the transplant evaluation process of HCC patients. While AFP, its progression, and HCC response to pre-transplant therapy have already been used as a part of an integrated prognostic model for selecting patients, the utility of other markers in the transplant setting is still under investigation. This article intends to review the data in the literature concerning predictors that could be included in an integrated LT selection model and to evaluate the importance of biological aggressiveness in the evaluation process of these patients.
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Tapper EB, Catana AM, Sethi N, Mansuri D, Sethi S, Vong A, Afdhal NH. Direct costs of care for hepatocellular carcinoma in patients with hepatitis C cirrhosis. Cancer 2015; 122:852-8. [PMID: 26716758 DOI: 10.1002/cncr.29855] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2015] [Revised: 09/30/2015] [Accepted: 10/15/2015] [Indexed: 01/17/2023]
Abstract
BACKGROUND Hepatitis C virus (HCV) is the commonest cause of hepatocellular carcinoma (HCC) in the United States. The benefits of HCV therapy may be measured in part by the prevention of HCC and other complications of cirrhosis. The true cost of care of the HCV patient with HCC is unknown. METHODS One hundred patients were randomly selected from a cohort of all HCC patients with HCV at a US transplant center between 2003 and 2013. Patients were categorized by the primary treatment modality, Barcelona class, and ultimate transplant status. Costs included the unit costs of procedures, imaging, hospitalizations, medications, and all subsequent care of the HCC patient until either death or the end of follow-up. Associations with survival and cost were assessed in multivariate regression models. RESULTS Overall costs included a median of $176,456 (interquartile range [IQR], $84,489-$292,192) per patient or $6279 (IQR, $4043-$9720) per patient-month of observation. The median costs per patient-month were $7492 (IQR, $5137-$11,057) for transplant patients and $4830 for nontransplant patients. The highest median monthly costs were for transplant patients with Barcelona A4 disease ($11,349) and patients who received chemoembolization whether they underwent transplantation ($10,244) or not ($8853). Transarterial chemoembolization and radiofrequency ablation were independently associated with a 28% increase and a 22% decrease in costs, respectively, with adjustments for the severity of liver disease and Barcelona class. CONCLUSIONS These data represent real-world estimates of the cost of HCC care provided at a transplant center and should inform economic studies of HCV therapy.
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Affiliation(s)
- Elliot B Tapper
- Division of Gastroenterology/Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Andreea M Catana
- Division of Gastroenterology/Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Nidhi Sethi
- Division of Gastroenterology/Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Daniel Mansuri
- Division of Gastroenterology/Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Saurabh Sethi
- Division of Gastroenterology/Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Annie Vong
- Division of Gastroenterology/Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Nezam H Afdhal
- Division of Gastroenterology/Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
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CT Appearance of Hepatocellular Carcinoma after Locoregional Treatments: A Comprehensive Review. Gastroenterol Res Pract 2015; 2015:670965. [PMID: 26798332 PMCID: PMC4700180 DOI: 10.1155/2015/670965] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2015] [Revised: 09/09/2015] [Accepted: 09/14/2015] [Indexed: 02/08/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a major health problem worldwide, affecting more than 600,000 new patients per year. Curative treatments are available in a small percentage of patients, while most of them present in stages requiring locoregional treatments such as thermoablation, transarterial chemoembolization, and/or radioembolization. These therapies
result in specific imaging features that the general radiologist has to be aware of in order to assess the response to treatment and to correctly manage the follow-up of treated patients. Multiphasic helical computed tomography has become a popular imaging modality for detecting hypervascular tumors and characterizing liver lesions. On this basis, many staging and diagnostic systems have been proposed for evaluating response to all different existing strategies. Radiofrequencies and microwaves generate thermoablation of tumors, and transarterial chemoembolization exploits the double effect of the locoregional administration of drugs and embolizing particles. Eventually radioembolization uses a beta-emitting isotope to induce necrosis. Therefore, the aim of this comprehensive review is to analyze and compare CT imaging appearance of HCC after various locoregional treatments, with regard to specific indications for all possible procedures.
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Pardo F, Pons JA, Briceño J. V Reunión de Consenso de la Sociedad Española de Trasplante Hepático sobre receptores de riesgo elevado, escenarios actuales de inmunosupresión y manejo del hepatocarcinoma en espera de trasplante. Cir Esp 2015; 93:619-37. [PMID: 26187597 DOI: 10.1016/j.ciresp.2015.04.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2015] [Accepted: 04/17/2015] [Indexed: 12/11/2022]
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V Reunión de Consenso de la Sociedad Española de Trasplante Hepático sobre receptores de riesgo elevado, escenarios actuales de inmunosupresión y manejo del hepatocarcinoma en espera de trasplante. GASTROENTEROLOGIA Y HEPATOLOGIA 2015; 38:600-18. [DOI: 10.1016/j.gastrohep.2015.06.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/15/2015] [Revised: 06/11/2015] [Accepted: 06/30/2015] [Indexed: 12/14/2022]
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Faltermeier C, Busuttil RW, Zarrinpar A. A Surgical Perspective on Targeted Therapy of Hepatocellular Carcinoma. Diseases 2015; 3:221-252. [PMID: 28943622 PMCID: PMC5548262 DOI: 10.3390/diseases3040221] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2015] [Revised: 09/15/2015] [Accepted: 09/21/2015] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC), the second leading cause of cancer deaths worldwide, is difficult to treat and highly lethal. Since HCC is predominantly diagnosed in patients with cirrhosis, treatment planning must consider both the severity of liver disease and tumor burden. To minimize the impact to the patient while treating the tumor, techniques have been developed to target HCC. Anatomical targeting by surgical resection or locoregional therapies is generally reserved for patients with preserved liver function and minimal to moderate tumor burden. Patients with decompensated cirrhosis and small tumors are optimal candidates for liver transplantation, which offers the best chance of long-term survival. Yet, only 20%-30% of patients have disease amenable to anatomical targeting. For the majority of patients with advanced HCC, chemotherapy is used to target the tumor biology. Despite these treatment options, the five-year survival of patients in the United States with HCC is only 16%. In this review we provide a comprehensive overview of current approaches to target HCC. We also discuss emerging diagnostic and prognostic biomarkers, novel therapeutic targets identified by recent genomic profiling studies, and potential applications of immunotherapy in the treatment of HCC.
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Affiliation(s)
- Claire Faltermeier
- Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
| | - Ronald W Busuttil
- Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
| | - Ali Zarrinpar
- Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
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2014 KLCSG-NCC Korea Practice Guideline for the Management of Hepatocellular Carcinoma. Gut Liver 2015; 9:267-317. [PMID: 25918260 PMCID: PMC4413964 DOI: 10.5009/gnl14460] [Citation(s) in RCA: 101] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2014] [Accepted: 03/09/2015] [Indexed: 12/23/2022] Open
Abstract
The guideline for the management of hepatocellular carcinoma (HCC) was first developed in 2003 and revised in 2009 by the Korean Liver Cancer Study Group and the National Cancer Center, Korea. Since then, many studies on HCC have been carried out in Korea and other countries. In particular, a substantial body of knowledge has been accumulated on diagnosis, staging, and treatment specific to Asian characteristics, especially Koreans, prompting the proposal of new strategies. Accordingly, the new guideline presented herein was developed on the basis of recent evidence and expert opinions. The primary targets of this guideline are patients with suspicious or newly diagnosed HCC. This guideline provides recommendations for the initial treatment of patients with newly diagnosed HCC.
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