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Dasari BVM, Line PD, Sapisochin G, Hibi T, Bhangui P, Halazun KJ, Shetty S, Shah T, Magyar CTJ, Donnelly C, Chatterjee D. Liver transplantation as a treatment for cancer: comprehensive review. BJS Open 2025; 9:zraf034. [PMID: 40380811 PMCID: PMC12084677 DOI: 10.1093/bjsopen/zraf034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Revised: 01/30/2025] [Accepted: 02/07/2025] [Indexed: 05/19/2025] Open
Abstract
BACKGROUND Liver transplantation for cancer indications has gained momentum in recent years. This review is intended to optimize the care setting of liver transplant candidates by highlighting current indications, technical aspects and barriers with available solutions to facilitate the guidance of available strategies for healthcare professionals in specialized centres. METHODS A review of the most recent relevant literature was conducted for all the cancer indications of liver transplantation including colorectal cancer liver metastases, hilar cholangiocarcinoma, intrahepatic cholangiocarcinoma, neuroendocrine tumours, hepatocellular carcinoma and hepatic epitheloid haemangioendothelioma. RESULTS Transplant benefit from the best available evidence, including SECA I, SECA II, TRANSMET studies for colorectal liver metastases, various preoperative protocols for cholangiocarcinoma patients, standard, extended selection criteria for hepatocellular carcinoma and neuroendocrine tumours, are discussed. Innovative approaches to deal with organ shortages, including machine-perfused deceased grafts, living donor liver transplantation and RAPID procedures, are also explored. CONCLUSION Cancer indications for liver transplantation are here to stay, and the selection criteria among all cancer groups are likely to evolve further with improved prognostication of tumour biology using adjuncts such as radiomics, cancer genomics, and circulating DNA and RNA status. International prospective registry-based studies could overcome the limitations of smaller patient cohorts and lack of level 1 evidence.
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Affiliation(s)
- Bobby V M Dasari
- Department of Liver Transplantation and HBP Surgery, Queen Elizabeth Hospital, Birmingham, UK
- Department of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
| | - Pal-Dag Line
- Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
| | - Gonzalo Sapisochin
- Department of Surgery, Multi-Organ Transplant Program, University Health Network, Toronto, Canada
| | - Taizo Hibi
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
| | - Prashant Bhangui
- Liver Transplantation and Hepatobiliary Surgery, Medanta Institute of Liver Transplantation and Regenerative Medicine, Medanta-The Medicity, Gurgaon (Delhi NCR), India
| | - Karim J Halazun
- Department of Liver Transplantation and Hepatobiliary Surgery, NYU Grossman School of Medicine, NYU Langone Health, New York, USA
| | - Shishir Shetty
- Department of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
- Department of Hepatology, Queen Elizabeth Hospital, Birmingham, UK
| | - Tahir Shah
- Department of Hepatology, Queen Elizabeth Hospital, Birmingham, UK
| | - Christian T J Magyar
- Department of Abdominal Transplant & HBP Surgical Oncology, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Canada
| | - Conor Donnelly
- Department of Liver Transplantation and Hepatobiliary Surgery, NYU Grossman School of Medicine, NYU Langone Health, New York, USA
| | - Dev Chatterjee
- BRC Clinical Fellow Liver Medicine, University Hospitals of Birmingham, Birmingham, UK
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Medio P, Matesanz S, Margareto M, Ostos P, Palomo C, Hernández Oliveros F, Moreno AA. Outcomes of Pediatric Hepatocellular Carcinoma: A Single-Center Experience With Resection Versus Transplantation. Pediatr Transplant 2024; 28:e14882. [PMID: 39523995 DOI: 10.1111/petr.14882] [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: 06/25/2024] [Revised: 09/05/2024] [Accepted: 10/13/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND Pediatric hepatocellular carcinoma (HCC) presents significant challenges due to its aggressive nature, with survival depending on complete resection. We aimed to assess outcomes between liver resection (LR) and liver transplantation (LT). METHODS A total of 25 patients were retrieved, four of whom were classified as palliative at diagnosis. A subanalysis comparing cirrhotic liver (n = 14) versus de novo (n = 11) HCC was performed to identify confounding variables. Further evaluation focused on the 21 children with histologically confirmed HCC who underwent LR (n = 7) versus LT (n = 14). Kaplan-Meier survival curves were constructed. RESULTS The mean age was 7.8 ± 6.1 years for patients with cirrhotic liver and 12.1 ± 3.5 years for de novo HCC. Our group observed overall total survival rates of 100%, 85%, and 77% at 12, 36, and 60 months, respectively. De novo tumors had a higher recurrence rate and a poorer prognosis (p = 0.039 and p = 0.045). The disease-free survival at 60 months in our cohort was significantly lower among the LR group compared to the LT group (14% vs. 82%; p = 0.0081). Recurrence after initial management (n = 8) showed location differences between LR and LT. Preoperative alpha-fetoprotein (AFP) was elevated in 71% of children, but did not correlate with recurrence or compromised survival. Elevated AFP 3 months post-operation affected the course negatively (p = 0.044). Tumor number and diameter exhibited a trend towards poorer outcomes. CONCLUSIONS These findings emphasize the need for comprehensive pediatric surgical guidelines for HCC. We recommend LT over LR in pediatric cases. Extrahepatic disease post-neoadjuvant chemotherapy remains the only absolute contraindication.
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Affiliation(s)
- Paula Medio
- Faculty of Medicine, Autonomous University of Madrid, Madrid, Spain
| | - Sofía Matesanz
- Faculty of Medicine, Autonomous University of Madrid, Madrid, Spain
| | - María Margareto
- Faculty of Medicine, Autonomous University of Madrid, Madrid, Spain
| | - Paula Ostos
- Faculty of Medicine, Autonomous University of Madrid, Madrid, Spain
| | - Claudia Palomo
- Faculty of Medicine, Autonomous University of Madrid, Madrid, Spain
| | - Francisco Hernández Oliveros
- Division of Abdominal Organ Transplantation and Hepatobiliary Surgery, Department of Pediatric Surgery, La Paz University Hospital, Madrid, Spain
| | - Ane Andrés Moreno
- Division of Abdominal Organ Transplantation and Hepatobiliary Surgery, Department of Pediatric Surgery, La Paz University Hospital, Madrid, Spain
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Kim J, Kim YT, Lee JG, Han DH, Joo DJ, Kim DY, Seong J. Liver-Directed Combined Radiation Therapy for Downstaging Beyond-Milan Hepatocellular Carcinoma to Liver Transplantation. Int J Radiat Oncol Biol Phys 2024; 119:1171-1178. [PMID: 38364951 DOI: 10.1016/j.ijrobp.2024.01.221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 01/15/2024] [Accepted: 01/28/2024] [Indexed: 02/18/2024]
Abstract
PURPOSE Curative surgery involving either resection or liver transplantation (LT) is indicated only for early-stage hepatocellular carcinoma (HCC). Over the years, numerous efforts have been made to downstage advanced HCC to curative surgery using various locoregional therapies. In this study, we investigated the role of liver-directed combined radiation therapy (LD-CRT) as a downstaging strategy for converting beyond-Milan advanced HCC to LT. METHODS AND MATERIALS From January 2009 to February 2022, 53 patients with HCC who were initially beyond-Milan criteria were treated with LD-CRT and subsequent LT. These patients were compared with those who underwent upfront LT for within-Milan HCCs. The primary endpoint was overall survival (OS) and the secondary endpoint recurrence-free survival (RFS). RESULTS After LD-CRT, substantial downstaging was achieved in 35 patients (66%) who were initially beyond-Milan to within-Milan. At a median follow-up period of 47.6 months (range, 6.9-151.7 months), 5-year OS and 2-year RFS of the patients who received downstaging LD-CRT followed by LT were 66.9% and 63.2%, respectively. Patients who were successfully downstaged to within-Milan after LD-CRT had improved 5-year OS compared with their counterparts (81.9% vs 74.3%, P = .219). Recurrence after transplantation was observed in 18 patients (4 intrahepatic recurrences and 14 extrahepatic metastases). CONCLUSIONS LD-CRT achieved favorable oncological outcomes as a downstaging strategy for LT in patients with beyond-Milan HCC. The findings of this study suggest that the active adoption of LD-CRT needs full consideration for patients with beyond-Milan HCC, presenting the possibility of curing patients with advanced HCC.
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Affiliation(s)
- Jina Kim
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea
| | - Yong Tae Kim
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea
| | - Jae Geun Lee
- Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Dai Hoon Han
- Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Dong Jin Joo
- Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Do Young Kim
- Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Jinsil Seong
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.
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Mehta N, Kelley RK, Yao FY. Refining the approach to down-staging of HCC prior to liver transplantation: Patient selection, loco-regional treatments, and systemic therapies. Hepatology 2024; 80:238-253. [PMID: 37183865 DOI: 10.1097/hep.0000000000000452] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Accepted: 04/20/2023] [Indexed: 05/16/2023]
Affiliation(s)
- Neil Mehta
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, California, USA
| | - R Katie Kelley
- Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California, USA
| | - Francis Y Yao
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, California, USA
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, California, USA
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Pang L, Xu LB, Wu WR. Downstaging of Hepatocellular Carcinoma Before Liver Transplantation: Current Advances in Selection Criteria and Therapeutic Options. Transplant Proc 2024; 56:1396-1405. [PMID: 39089899 DOI: 10.1016/j.transproceed.2024.05.041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2024] [Accepted: 05/07/2024] [Indexed: 08/04/2024]
Abstract
Liver transplantation (LT) is an ideal therapeutic option for selected patients with hepatocellular carcinoma (HCC). The selection criteria of HCC for LT have evolved in recent decades. Downstaging therapy is a promising strategy for patients with tumor burden beyond transplant criteria to increase the chance of receiving LT and improve posttransplant survival. Downstaging therapy is also a selection tool that refines the conventional selection criteria based on tumor morphology. Recently, the success of systemic treatment, including immune checkpoint inhibitors, antiangiogenic tyrosine kinase inhibitors, and VEGF inhibitors, in advanced HCC has prompted the discussion regarding the role of systemic therapies for HCC downstaging before transplantation. In this review, we aimed to summarize the current advances in selection criteria and therapeutic options of downstaging therapy for HCC before LT.
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Affiliation(s)
- Li Pang
- Liver Transplantation Center & Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Lei-Bo Xu
- Liver Transplantation Center & Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Wen-Rui Wu
- Liver Transplantation Center & Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
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Korean Liver Cancer Association (KLCA) and National Cancer Center (NCC) Korea. 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: 80] [Impact Index Per Article: 40.0] [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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Kim P, Littau M, Baker TB, Abdelsattar Z, Tonelli C, Bunn C, Kulshrestha S, Luchette FA, Scaglione S, Baker MS. The benefit of liver transplant beyond Milan criteria: An analysis using the National Cancer Database. Surgery 2022; 172:1823-1828. [PMID: 36096963 DOI: 10.1016/j.surg.2022.07.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 06/06/2022] [Accepted: 07/25/2022] [Indexed: 01/06/2023]
Abstract
BACKGROUND Published studies examining the efficacy of liver transplantation in patients presenting with hepatocellular cancer beyond the traditional Milan criteria for liver transplantation have primarily been single institution series with limited ability to compare outcomes to alternative methods of management. METHODS We queried the National Cancer Database to identify patients presenting between 2004 and 2016 with histologically confirmed clinical stage III and IVA hepatocellular cancer. Multivariable regression was used to identify factors associated with liver transplantation. Patients undergoing liver transplantation were 1:1 propensity score-matched for age, demographics, comorbid disease, clinical stage, and histologic resection margin to those undergoing surgical resection. The Kaplan-Meier method was used to compare overall survival profiles for matched cohorts. RESULTS Seven hundred and ninety-two patients met inclusion criteria-590 (74.5%) underwent surgical resection and 202 (25.5%) liver transplantation. On adjusted analysis, patients undergoing liver transplantation were less likely to have advanced age (>60 years; odds ratio 0.39, 95% confidence interval [0.21-0.71]) and to be of Black race (odds ratio 0.42, 95% confidence interval [0.23-0.73]) or Asian (odds ratio 0.25, 95% confidence interval [0.11-0.53]) ethnicity but were more likely to have advanced (Charlson score >2) comorbidity scores, (odds ratio 2.48, 95% confidence interval [1.58-3.90]) and more likely to have private health insurance (odds ratio 4.17, 95% confidence interval [1.31-18.66]) than those undergoing surgical resection. On Kaplan-Meier analysis of matched cohorts, patients undergoing liver transplantation demonstrated significantly better rates of 5-year overall survival (65.3% vs 26.3%, P < .0001) and longer median overall survival times than those undergoing resection (53.1 ± 2.78 vs 26.9 ± 1.20 months, P < .0001). CONCLUSION Liver transplantation offers the potential to be an effective treatment modality in select patients presenting with stage III and IVA hepatocellular cancer.
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Affiliation(s)
- Preston Kim
- Loyola University Chicago Stritch School of Medicine, Maywood, IL
| | - Michael Littau
- Loyola University Chicago Stritch School of Medicine, Maywood, IL
| | - Talia B Baker
- University of Chicago Pritzker School of Medicine, IL
| | - Zaid Abdelsattar
- Loyola University Chicago Stritch School of Medicine, Maywood, IL
| | - Celsa Tonelli
- Loyola University Chicago Stritch School of Medicine, Maywood, IL
| | - Corinne Bunn
- Loyola University Chicago Stritch School of Medicine, Maywood, IL
| | | | - Fred A Luchette
- Loyola University Chicago Stritch School of Medicine, Maywood, IL
| | - Steven Scaglione
- Loyola University Chicago Stritch School of Medicine, Maywood, IL
| | - Marshall S Baker
- Loyola University Chicago Stritch School of Medicine, Maywood, IL.
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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: 82] [Impact Index Per Article: 27.3] [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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9
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Beumer BR, van Vugt JL, Sapisochin G, Yoon P, Bongini M, Lu D, Xu X, De Simone P, Pintore L, Golse N, Nowosad M, Bennet W, Tsochatzis E, Koutli E, Abbassi F, Claasen MP, Merli M, O'Rourke J, Gambato M, Benito A, Majumdar A, Tan EK, Ebadi M, Montano‐Loza AJ, Berenguer M, Metselaar HJ, Polak WG, Mazzaferro V, IJzermans JN, Collaborators. Impact of muscle mass on survival of patients with hepatocellular carcinoma after liver transplantation beyond the Milan criteria. J Cachexia Sarcopenia Muscle 2022; 13:2373-2382. [PMID: 36622940 PMCID: PMC9530497 DOI: 10.1002/jcsm.13053] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Revised: 05/31/2022] [Accepted: 06/25/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Access to the liver transplant waitlist for patients with hepatocellular carcinoma (HCC) depends on tumour presentation, biology, and response to treatments. The Milan Criteria (MC) represent the benchmark for expanded criteria that incorporate additional prognostic factors. The purpose of this study was to determine the added value of skeletal muscle index (SMI) in HCC patients beyond the MC. METHOD Patients with HCC that were transplanted beyond the MC were included in this retrospective multicentre study. SMI was quantified using the Computed Tomography (CT) within 3 months prior to transplantation. Cox regression models were used to identify predictors of overall survival (OS). The discriminative performance of SMI extended Metroticket 2.0 and AFP models was also assessed. RESULTS Out of 889 patients transplanted outside the MC, 528 had a CT scan within 3 months prior to liver transplantation (LT), of whom 176 (33%) were classified as sarcopenic. The median time between assessment of the SMI and LT was 1.8 months (IQR: 0.77-2.67). The median follow-up period was 5.1 95% CI [4.7-5.5] years, with a total of 177 recorded deaths from any cause. In a linear regression model with SMI as the dependent variable, only male gender (8.55 95% CI [6.51-10.59], P < 0.001) and body mass index (0.74 95% CI [0.59-0.89], P < 0.001) were significant. Univariable survival analysis of patients with sarcopenia versus patients without sarcopenia showed a significant difference in OS (HR 1.44 95% CI [1.07 - 1.94], P = 0.018). Also the SMI was significant (HR 0.98 95% CI [0.96-0.99], P = 0.014). The survival difference between the lowest SMI quartile versus the highest SMI quartile was significant (log-rank: P = 0.005) with 5 year OS of 57% and 71%, respectively. Data from 423 patients, describing 139 deaths, was used for multivariate analysis. Both sarcopenia (HR 1.45 95% CI [1.02 - 2.05], P = 0.036) and SMI were (HR 0.98 95% CI [0.95-0.99], P = 0.035) significant. On the survival scale this translates to a 5 year OS difference of 11% between sarcopenia and no sarcopenia. Whereas for SMI, this translates to a survival difference of 8% between first and third quartiles for both genders. CONCLUSIONS Overall, we can conclude that higher muscle mass contributes to a better long-term survival. However, for individual patients, low muscle mass should not be considered an absolute contra-indication for LT as its discriminatory performance was limited.
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Affiliation(s)
- Berend R. Beumer
- Erasmus MC Transplant Institute, Department of Surgery, Division of HPB & Transplant SurgeryUniversity Medical Centre RotterdamRotterdamThe Netherlands
| | - Jeroen L.A. van Vugt
- Erasmus MC Transplant Institute, Department of Surgery, Division of HPB & Transplant SurgeryUniversity Medical Centre RotterdamRotterdamThe Netherlands
| | - Gonzalo Sapisochin
- Multi Organ Transplant Program, University Health NetworkUniversity of TorontoTorontoCanada
| | - Peter Yoon
- Multi Organ Transplant Program, University Health NetworkUniversity of TorontoTorontoCanada
- Department of SurgeryWestmead HospitalSydneyAustralia
| | - Marco Bongini
- Gastrointestinal Surgery and Liver Transplantation, National Cancer Institute of Milan, Department of OncologyUniversity of MilanMilanItaly
| | - Di Lu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
| | - Xiao Xu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
| | - Paolo De Simone
- Hepatobiliary Surgery and Liver TransplantationAzienda Ospedaliero‐Universitaria PisanaPisaItaly
| | - Lorenzo Pintore
- Hepatobiliary Surgery and Liver TransplantationAzienda Ospedaliero‐Universitaria PisanaPisaItaly
| | - Nicolas Golse
- Centre Hépato‐Biliaire, Hôpital Paul BrousseUniversité Paris‐SudVillejuifFrance
| | - Malgorzata Nowosad
- Department of General Transplant and Liver SurgeryMedical University of WarsawWarsawPoland
| | - William Bennet
- Transplant Institute, Sahlgrenska University HospitalSahlgrenska AcademyGothenburgSweden
| | - Emmanouil Tsochatzis
- Royal Free Sheila Sherlock Liver CentreRoyal Free Hospital and UCL Institute of Liver and Digestive HealthLondonUK
| | - Evangelia Koutli
- Royal Free Sheila Sherlock Liver CentreRoyal Free Hospital and UCL Institute of Liver and Digestive HealthLondonUK
| | - Fariba Abbassi
- Division of Digestive SurgeryUniversity Hospitals of GenevaGenèveSwitzerland
| | - Marco P.A.W. Claasen
- Erasmus MC Transplant Institute, Department of Surgery, Division of HPB & Transplant SurgeryUniversity Medical Centre RotterdamRotterdamThe Netherlands
- Multi Organ Transplant Program, University Health NetworkUniversity of TorontoTorontoCanada
| | - Manuela Merli
- Section of Gastroenterology, Department of Translational and Precision MedicineSapienza University of RomeRomeItaly
| | - Joanne O'Rourke
- The Liver UnitQueen Elizabeth Hospital BirminghamBirminghamUK
| | - Martina Gambato
- Section of Gastroenterology, Department of Surgery, Oncology and GastroenterologyUniversity of PadovaPadovaItaly
| | - Alberto Benito
- Section of RadiologyClinica Universidad de NavarraPamplonaSpain
| | - Avik Majumdar
- AW Morrow Gastroenterology and Liver CentreRoyal Prince Alfred HospitalSydneyAustralia
| | - Ek Khoon Tan
- Department of Hepatopancreatobiliary and Transplant SurgerySingapore General HospitalSingapore
| | - Maryam Ebadi
- Division of Gastroenterology and Liver Unit, Zeidler Ledcor CentreUniversity of AlbertaEdmontonCanada
| | - Aldo J. Montano‐Loza
- Division of Gastroenterology and Liver Unit, Zeidler Ledcor CentreUniversity of AlbertaEdmontonCanada
| | - Marina Berenguer
- Hepatology & Liver Transplantation Unit and Ciberehd and ISS La Fe, Hospital Universitario y Politécnico La FeUniversity of ValenciaValenciaSpain
| | - Herold J. Metselaar
- Erasmus MC Transplant Institute, Department of Gastroenterology and HepatologyUniversity Medical Centre RotterdamRotterdamThe Netherlands
| | - Wojciech G. Polak
- Erasmus MC Transplant Institute, Department of Surgery, Division of HPB & Transplant SurgeryUniversity Medical Centre RotterdamRotterdamThe Netherlands
| | - Vincenzo Mazzaferro
- Gastrointestinal Surgery and Liver Transplantation, National Cancer Institute of Milan, Department of OncologyUniversity of MilanMilanItaly
| | - Jan N.M. IJzermans
- Erasmus MC Transplant Institute, Department of Surgery, Division of HPB & Transplant SurgeryUniversity Medical Centre RotterdamRotterdamThe Netherlands
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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: 174] [Impact Index Per Article: 58.0] [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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Wong PC, She WH, Ma KW, Sin SL, Wong TCL, Dai WC, Cheung TT, Chan ACY, Lo CM. Impact of Time to Recurrence on Survival Outcome of Salvage Liver Transplantation. J Gastrointest Surg 2022; 26:813-821. [PMID: 34622351 DOI: 10.1007/s11605-021-05146-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2021] [Accepted: 08/25/2021] [Indexed: 01/31/2023]
Abstract
BACKGROUND Salvage liver transplantation (SLT) is the ideal treatment for patients with recurrent hepatocellular carcinoma (HCC) and liver cirrhosis. The optimal timing for offering SLT was controversial. This study aimed at investigating the impact of time to recurrence and other prognostic factors on survival outcome after SLT. METHODS Between May 2000 and April 2019, patients who had undergone hepatectomy or ablation for HCC and later received SLT in Queen Mary Hospital were included. Clinico-pathological data during primary treatment and SLT were retrospectively reviewed. Kaplan-Meier analysis and log-rank test were used to determine overall and disease-free survival after SLT. Prognostic factors affecting overall and disease-free survival were determined by multivariate analysis using Cox regression analysis. P-value of less than 0.05 was considered statistically significant. RESULTS Fifty-three patients were identified within the specified period including 22 patients in early recurrence group (ER group, time to recurrence within 1 year) and 31 patients in late recurrence group (LR group, time to recurrence more than 1 year). The 1-, 5-, and 10-year overall survival after primary treatment was 100%, 76.6%, and 61.1% in the ER group and 100%, 90%, and 76.4% in the LR group (p = 0.59). There were no statistical differences in overall survival (p = 0.84) and disease-free survival (p = 0.85) after SLT between ER and LR group. Pre-transplant alpha-fetoprotein > = 400 ng/mL (p = 0.007) and macrovascular invasion in explant (p = 0.002) were independent risk factors for shorter overall survival after primary treatment. CONCLUSION Time to recurrence after primary treatment of HCC did not affect survival outcome after SLT. With careful patient selection, SLT could be offered to patient with early or late tumor recurrence.
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Affiliation(s)
- Pak Chiu Wong
- Division of Liver Transplantation, Department of Surgery, The University of Hong Kong, Queen Mary Hospital, 102 Pok Fu Lam Road, Pok Fu Lam, Hong Kong
| | - Wong Hoi She
- Division of Liver Transplantation, Department of Surgery, The University of Hong Kong, Queen Mary Hospital, 102 Pok Fu Lam Road, Pok Fu Lam, Hong Kong.
| | - Ka Wing Ma
- Division of Liver Transplantation, Department of Surgery, The University of Hong Kong, Queen Mary Hospital, 102 Pok Fu Lam Road, Pok Fu Lam, Hong Kong
| | - Sui Ling Sin
- Division of Liver Transplantation, Department of Surgery, The University of Hong Kong, Queen Mary Hospital, 102 Pok Fu Lam Road, Pok Fu Lam, Hong Kong
| | - Tiffany Cho Lam Wong
- Division of Liver Transplantation, Department of Surgery, The University of Hong Kong, Queen Mary Hospital, 102 Pok Fu Lam Road, Pok Fu Lam, Hong Kong
| | - Wing Chiu Dai
- Division of Liver Transplantation, Department of Surgery, The University of Hong Kong, Queen Mary Hospital, 102 Pok Fu Lam Road, Pok Fu Lam, Hong Kong
| | - Tan To Cheung
- Division of Liver Transplantation, Department of Surgery, The University of Hong Kong, Queen Mary Hospital, 102 Pok Fu Lam Road, Pok Fu Lam, Hong Kong
| | - Albert Chi Yan Chan
- Division of Liver Transplantation, Department of Surgery, The University of Hong Kong, Queen Mary Hospital, 102 Pok Fu Lam Road, Pok Fu Lam, Hong Kong
| | - Chung Mau Lo
- Division of Liver Transplantation, Department of Surgery, The University of Hong Kong, Queen Mary Hospital, 102 Pok Fu Lam Road, Pok Fu Lam, Hong Kong
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12
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Lerut J, Foguenne M, Lai Q. Hepatocellular cancer selection systems and liver transplantation: from the tower of babel to an ideal comprehensive score. Updates Surg 2021; 73:1599-1614. [PMID: 34003479 PMCID: PMC8500859 DOI: 10.1007/s13304-021-01078-4] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Accepted: 05/03/2021] [Indexed: 12/13/2022]
Abstract
The Milan criteria (MC) remain the cornerstone for the selection of patients with hepatocellular cancer (HCC) to be listed for liver transplantation (LT). Recently, several expanded criteria have been proposed to increase the transplantability of HCC patients without compromising their (oncologic) outcome. This paper aims to systematically review the different reported HCC-LT selection systems looking thereby at their ability to increase the number of transplantable patients and the overall survival and oncological outcome. A systematic review of the literature covering the period 1993 (date of the first reported HCC-LT selection system)-2021 identified 59 different inclusion criteria of HCC for LT. Among the 59 studies reporting HCC-LT selection systems, 15 (28.3%) were exclusively based on morphological aspects of the tumor; 29 (54.7%) included biologic, seven (13.2%) radiological, and two (3.8%) only included pathological tumor features. Overall, 31% more patients could be transplanted when adhering to the new HCC-LT selection systems. Despite the increased number of LT, 5-year patient and disease-free survival rates were similar between MC-IN and MC-OUT/new HCC-LT-IN criteria. A careful extension of the inclusion criteria should allow many more patients to access a potentially curative LT without compromising their outcome. The development of a widely accepted "comprehensive" HCC-LT Score able to offer a fair chance of justified transplantation to more patients should become a priority within the liver transplant community. Further studies are needed to develop internationally accepted, expanded selection criteria for liver transplantation of HCC patients.
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Affiliation(s)
- Jan Lerut
- Institute for Experimental and Clinical Research (IREC), Université Catholique de Louvain (UCL), Avenue Hippocrates 55, 1200 Brussels, Belgium
| | - Maxime Foguenne
- University Hospitals Saint-Luc Université Catholique de Louvain (UCL), Brussels, Belgium
| | - Quirino Lai
- General Surgery and Organ Transplantation Unit, Sapienza University of Rome, Rome, Italy
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13
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Pelizzaro F, Gambato M, Gringeri E, Vitale A, Cillo U, Farinati F, Burra P, Russo FP. Management of Hepatocellular Carcinoma Recurrence after Liver Transplantation. Cancers (Basel) 2021; 13:4882. [PMID: 34638365 PMCID: PMC8508053 DOI: 10.3390/cancers13194882] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 09/19/2021] [Accepted: 09/24/2021] [Indexed: 02/06/2023] Open
Abstract
Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT), occurring in 10-15% of cases, is a major concern. A lot of work has been done in order to refine the selection of LT candidates with HCC and to improve the outcome of patients with recurrence. Despite this, the prognosis of these patients remains poor, partly due to the several areas of uncertainty in their management. Even if surveillance for HCC recurrence is crucial for early detection, there is currently no evidence to support a specific and cost-effective post-LT surveillance strategy. Concerning preventive measures, consensus on the best immunosuppressive drugs has not been reached and not enough data to support adjuvant therapy are present. Several therapeutic approaches (surgical, locoregional and systemic treatments) are available in case of recurrence, but there are still few data in the post-LT setting. Moreover, the use of immune checkpoint inhibitors is controversial in transplant recipients considered the risk of rejection. In this paper, the available evidence on the management of HCC recurrence after LT is comprehensively reviewed, considering pre- and post-transplant risk stratification, post-transplant surveillance, preventive strategies and treatment options.
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Affiliation(s)
- Filippo Pelizzaro
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
| | - Martina Gambato
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy
| | - Enrico Gringeri
- Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (E.G.); (A.V.); (U.C.)
| | - Alessandro Vitale
- Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (E.G.); (A.V.); (U.C.)
| | - Umberto Cillo
- Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (E.G.); (A.V.); (U.C.)
| | - Fabio Farinati
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
| | - Patrizia Burra
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy
| | - Francesco Paolo Russo
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy
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14
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Li H, Li XL, Cao S, Jia YN, Wang RL, Xu WL, Lang R, He Q, Zhu JQ. Decreased granzyme B +CD19 +B cells are associated with tumor progression following liver transplantation. Am J Cancer Res 2021; 11:4485-4499. [PMID: 34659900 PMCID: PMC8493381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Accepted: 07/20/2021] [Indexed: 06/13/2023] Open
Abstract
Lymphocytes play an important role in antitumor immunity following organ transplantation. However, the function of granzyme B+CD19+B cells on the hepatocellular carcinoma cells from liver transplant recipients remains largely unknown; we aimed to analyze the function and elucidate the mechanisms behind it. Blood samples and clinical data from liver transplant recipients and healthy controls at Beijing Chaoyang Hospital as well as from a validation cohort were collected and analyzed. In this study, we found decreased granzyme B+CD19+B cells were correlated with early hepatocellular carcinoma recurrence and could further identify liver transplant recipients with poor tumor differentiation, microvascular invasion, increased total tumor diameter, and tumor beyond Milan criteria. Notably, granzyme B+CD19+B cells directly inhibited the proliferation, migration, and invasion of hepatocellular carcinoma cells. Upon activation regulatory B cells from liver transplant recipients with hepatocellular carcinoma recurrence displayed a CD5+CD38+CD27+CD138+CD19+ granzyme B+ phenotype, but the increased expression of CD5, CD38, and CD138, and the decreased protein level and transcriptional level requiring JAK/STAT signaling. In an independent validation cohort, liver transplant recipients with decreased granzyme B+CD19+B cells had not only early hepatocellular carcinoma cell recurrence but also shorter survival. Our study provides comprehensive data from liver transplant recipients with hepatocellular carcinoma, indicating a critical role of granzyme B+CD19+B cells in preventing cancer progression. Our findings warrant further investigations for the design of future immunotherapies leading to immune responses and improved patient survival.
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Affiliation(s)
- Han Li
- Department of Head and Neck Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021, China
| | - Xian-Liang Li
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Medical Research Center, Beijing Organ Transplant Center, Beijing Chaoyang Hospital, Capital Medical UniversityNo.8 Gongtinan Road, Chaoyang District, Beijing 100020, China
| | - Shuang Cao
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Medical Research Center, Beijing Organ Transplant Center, Beijing Chaoyang Hospital, Capital Medical UniversityNo.8 Gongtinan Road, Chaoyang District, Beijing 100020, China
| | - Ya-Nan Jia
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Medical Research Center, Beijing Organ Transplant Center, Beijing Chaoyang Hospital, Capital Medical UniversityNo.8 Gongtinan Road, Chaoyang District, Beijing 100020, China
| | - Ruo-Lin Wang
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Medical Research Center, Beijing Organ Transplant Center, Beijing Chaoyang Hospital, Capital Medical UniversityNo.8 Gongtinan Road, Chaoyang District, Beijing 100020, China
| | - Wen-Li Xu
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Medical Research Center, Beijing Organ Transplant Center, Beijing Chaoyang Hospital, Capital Medical UniversityNo.8 Gongtinan Road, Chaoyang District, Beijing 100020, China
| | - Ren Lang
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Medical Research Center, Beijing Organ Transplant Center, Beijing Chaoyang Hospital, Capital Medical UniversityNo.8 Gongtinan Road, Chaoyang District, Beijing 100020, China
| | - Qiang He
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Medical Research Center, Beijing Organ Transplant Center, Beijing Chaoyang Hospital, Capital Medical UniversityNo.8 Gongtinan Road, Chaoyang District, Beijing 100020, China
| | - Ji-Qiao Zhu
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Medical Research Center, Beijing Organ Transplant Center, Beijing Chaoyang Hospital, Capital Medical UniversityNo.8 Gongtinan Road, Chaoyang District, Beijing 100020, China
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15
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Mehta N, Bhavsar R, Das SP. Transplantation in hepatocellular carcinoma - controversies and recommendations: A review of current literature. INTERNATIONAL JOURNAL OF ADVANCED MEDICAL AND HEALTH RESEARCH 2021. [DOI: 10.4103/ijamr.ijamr_220_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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16
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Abstract
INTRODUCTION Hepatocellular carcinoma (HCC) is an increasingly common disease with liver transplant (LT) the best long-term therapy for early stage disease. We will review the data for assessing risk and managing recurrence for patients undergoing LT for HCC. AREAS COVERED In this review, we will provide an overview of methods of patient risk stratification in the post-transplant period, the data around surveillance for HCC recurrence, and the evidence for and against post-LT adjuvant treatment strategies. Finally, we will provide data regarding treatment options for patients with HCC recurrence after LT. Using an extensive search of original papers and society guidelines, this paper provides a comprehensive review of the data for assessing risk and managing recurrence for patients undergoing LT for HCC. EXPERT OPINION The development of multiple post-transplant prognostic scoring systems have allowed for improved assessment of recurrence risk and stratification of patients. However, the ability to translate this information into surveillance and therapeutic strategies that improve patient outcomes still have to be fully demonstrated. Post-LT immunosuppression strategies have been implemented in order to attempt to reduce this risk. Evidence-based strategies for managing recurrent HCC are evolving. We expect that with further understanding of individual patient characteristics will allow for optimal therapeutic selection.
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Affiliation(s)
- Daniel Hoffman
- Department of Surgery, University of California , San Francisco, CA, USA
| | - Neil Mehta
- Division of Gastroenterology, Department of Medicine, University of California , San Francisco, CA, USA
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17
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Nebbia G, Zhang Q, Arefan D, Zhao X, Wu S. Pre-operative Microvascular Invasion Prediction Using Multi-parametric Liver MRI Radiomics. J Digit Imaging 2020; 33:1376-1386. [PMID: 32495126 PMCID: PMC7728938 DOI: 10.1007/s10278-020-00353-x] [Citation(s) in RCA: 50] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Microvascular invasion (mVI) is the most significant independent predictor of recurrence for hepatocellular carcinoma (HCC), but its pre-operative assessment is challenging. In this study, we investigate the use of multi-parametric MRI radiomics to predict mVI status before surgery. We retrospectively collected pre-operative multi-parametric liver MRI scans for 99 patients who were diagnosed with HCC. These patients received surgery and pathology-confirmed diagnosis of mVI. We extracted radiomics features from manually segmented HCC regions and built machine learning classifiers to predict mVI status. We compared the performance of such classifiers when built on five MRI sequences used both individually and combined. We investigated the effects of using features extracted from the tumor region only, the peritumoral marginal region only, and the combination of the two. We used the area under the receiver operating characteristic curve (AUC) and accuracy as performance metrics. By combining features extracted from multiple MRI sequences, AUCs are 86.69%, 84.62%, and 84.19% when features are extracted from the tumor only, the peritumoral region only, and the combination of the two, respectively. For tumor-extracted features, the T2 sequence (AUC = 80.84%) and portal venous sequence (AUC = 79.22%) outperform other MRI sequences in single-sequence-based models and their combination yields the highest AUC of 86.69% for mVI status prediction. Our results show promise in predicting mVI from pre-operative liver MRI scans and indicate that information from multi-parametric MRI sequences is complementary in identifying mVI.
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Affiliation(s)
- Giacomo Nebbia
- Intelligent Systems Program, University of Pittsburgh, 3362 Fifth Ave, Rm. 130, Pittsburgh, PA, 15213, USA
| | - Qian Zhang
- Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, China
| | - Dooman Arefan
- Department of Radiology, University of Pittsburgh, 3362 Fifth Ave, Rm. 130, Pittsburgh, PA, 15213, USA
| | - Xinxiang Zhao
- Department of Radiology, The Second Affiliated Hospital of Kunming Medical University, 374 Dianmian Road, Wuhua District, Kunming, 650101, Yunnan, China.
| | - Shandong Wu
- Intelligent Systems Program, University of Pittsburgh, 3362 Fifth Ave, Rm. 130, Pittsburgh, PA, 15213, USA.
- Department of Radiology, University of Pittsburgh, 3362 Fifth Ave, Rm. 130, Pittsburgh, PA, 15213, USA.
- Department of Bioengineering, University of Pittsburgh, 3362 Fifth Ave, Rm. 130, Pittsburgh, PA, 15213, USA.
- Department of Biomedical Informatics, University of Pittsburgh, 3362 Fifth Ave, Rm. 130, Pittsburgh, PA, 15213, USA.
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18
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Liu B, Huang G, Xie X, Zhao Q, Su L, Liu M, Li X, Long J, Kuang M, Xie X. Feasibility and outcomes of percutaneous radiofrequency ablation for intrahepatic recurrent hepatocellular carcinoma after liver transplantation: a single-center experience. Int J Hyperthermia 2020; 37:1202-1209. [PMID: 33100042 DOI: 10.1080/02656736.2020.1834154] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Affiliation(s)
- Baoxian Liu
- Division of Interventional Ultrasound, Department of Medical Ultrasound, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Guangliang Huang
- Division of Interventional Ultrasound, Department of Medical Ultrasound, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xiaohua Xie
- Division of Interventional Ultrasound, Department of Medical Ultrasound, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Qiang Zhao
- Department of Organ Transplantation, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Liya Su
- Division of Interventional Ultrasound, Department of Medical Ultrasound, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Ming Liu
- Division of Interventional Ultrasound, Department of Medical Ultrasound, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xiaoju Li
- Division of Interventional Ultrasound, Department of Medical Ultrasound, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jianting Long
- Department of Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Ming Kuang
- Division of Interventional Ultrasound, Department of Medical Ultrasound, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Department of Liver Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xiaoyan Xie
- Division of Interventional Ultrasound, Department of Medical Ultrasound, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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19
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Mehta N, Bhangui P, Yao FY, Mazzaferro V, Toso C, Akamatsu N, Durand F, Ijzermans J, Polak W, Zheng S, Roberts JP, Sapisochin G, Hibi T, Kwan NM, Ghobrial M, Soin A. Liver Transplantation for Hepatocellular Carcinoma. Working Group Report from the ILTS Transplant Oncology Consensus Conference. Transplantation 2020; 104:1136-1142. [PMID: 32217938 DOI: 10.1097/tp.0000000000003174] [Citation(s) in RCA: 154] [Impact Index Per Article: 30.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Liver transplantation (LT) offers excellent long-term outcome for certain patients with hepatocellular carcinoma (HCC), with a push to not simply rely on tumor size and number. Selection criteria should also consider tumor biology (including alpha-fetoprotein), probability of waitlist and post-LT survival (ie, transplant benefit), organ availability, and waitlist composition. These criteria may be expanded for live donor LT (LDLT) compared to deceased donor LT though this should not adversely affect the double equipoise in LDLT, namely ensuring both acceptable recipient outcomes and donor safety. HCC patients with compensated liver disease and minimal tumor burden have low urgency for LT, especially after local-regional therapy with complete response, and do not appear to derive the same benefit from LT as other waitlist candidates. These guidelines were developed to assist in selecting appropriate HCC patients for both deceased donor LT and LDLT.
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Affiliation(s)
- Neil Mehta
- Department of Medicine, University of California San Francisco, San Francisco, CA
| | - Prashant Bhangui
- Institute of Liver Transplantation and Regenerative Medicine, Medanta, The Medicity, Gurgaon, India
| | - Francis Y Yao
- Department of Medicine, University of California San Francisco, San Francisco, CA
- Department of Surgery, University of California San Francisco, San Francisco, CA
| | - Vincenzo Mazzaferro
- Department of Surgery, GI Surgery and Liver Transplantation, Istituto Nazionale Tumori, Milan, Italy
| | - Christian Toso
- Division of Abdominal Surgery, University Hospitals of Geneva, Geneva, Switzerland
| | | | - Francois Durand
- Service d'Hépatologie & Réanimation Hépatodigestive, Université Paris VII Hôpital Beaujon, Paris, France
| | - Jan Ijzermans
- Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Wojciech Polak
- Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Shusen Zheng
- Department of Surgery, First Affiliated Hospital, Zhejiang University, Hangzhou, China
| | - John P Roberts
- Department of Surgery, University of California San Francisco, San Francisco, CA
| | - Gonzalo Sapisochin
- Multi-Organ Transplant and HPB Surgical Oncology, Toronto General Hospital, University of Toronto, Toronto, Canada
| | - Taizo Hibi
- Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
| | - Nancy Man Kwan
- Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Mark Ghobrial
- J C Walter Jr Transplant Center, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Weill Cornell Medical College, Houston Methodist Hospital and Research Institute, Houston, TX
| | - Avi Soin
- Institute of Liver Transplantation and Regenerative Medicine, Medanta, The Medicity, Gurgaon, India
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20
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Ju MR, Yopp AC. Evolving thresholds for liver transplantation in hepatocellular carcinoma: A Western experience. Ann Gastroenterol Surg 2020; 4:208-215. [PMID: 32490334 PMCID: PMC7240148 DOI: 10.1002/ags3.12316] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2019] [Revised: 01/09/2020] [Accepted: 01/16/2020] [Indexed: 12/13/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. Once considered an experimental treatment with dismal survival rates, liver transplantation for HCC entered a new era with the establishment of the Milan criteria over 20 years ago. In the modern post-Milan-criteria era, 5-year survival outcomes are now upwards of 70% in select patients. Liver transplantation (LT) is now considered the optimal treatment for patients with moderate to severe cirrhosis and HCC, and the rates of transplantation in the United States are continuing to rise. Several expanded selection criteria have been proposed for determining which patients with HCC should be candidates for undergoing LT with similar overall and recurrence-free survival rates to patients within the Milan criteria. There is also a growing experience with downstaging of patients who fall outside conventional LT criteria at the time of HCC diagnosis with the goal of tumor shrinkage via locoregional therapies to become a candidate for transplantation. The aim of this review article is to characterize the various patient selection criteria for LT, discuss balancing organ stewardship with outcome measures in HCC patients, present evidence on the role of downstaging for large tumors, and explore future directions of LT for HCC.
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Affiliation(s)
- Michelle R. Ju
- Division of Surgical OncologyDepartment of SurgeryUniversity of Texas Southwestern Medical CenterDallasTexas
| | - Adam C. Yopp
- Division of Surgical OncologyDepartment of SurgeryUniversity of Texas Southwestern Medical CenterDallasTexas
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21
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McMillan RR, Agopian VG. The Management of Hepatocellular Carcinoma. THE CRITICALLY ILL CIRRHOTIC PATIENT 2020:237-271. [DOI: 10.1007/978-3-030-24490-3_13] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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22
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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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23
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Mullath A, Krishna M. Hepatocellular carcinoma - time to take the ticket. World J Gastrointest Surg 2019; 11:287-295. [PMID: 31367276 PMCID: PMC6658361 DOI: 10.4240/wjgs.v11.i6.287] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Revised: 06/13/2019] [Accepted: 06/20/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma is one of the leading malignancies worldwide. Early detection of hepatocellular carcinoma and its management in the form of liver transplantation offers an attractive treatment option. The Milan criteria, proposed by Mazzaferro et al, have been the standard for selecting patients with hepatocellular carcinoma for transplantation. Recently, several studies have shown that even patients selected outside the Milan criteria can undergo transplantation with a relatively good outcome. This article examines the currently existing criteria other than the Milan criteria and also evaluates use of alpha-fetoprotein and positron emission tomography scans to predict the chance of recurrence.
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Affiliation(s)
- Anju Mullath
- Department of Gastroenterology, Lakeshore Hospital and Research Centre, Kochi 682040, Kerala, India
| | - Murali Krishna
- Department of Surgery, Military Hospital, Palampur 176061, Himachal Pradesh, India
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24
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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: 241] [Impact Index Per Article: 40.2] [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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Costentin CE, Bababekov YJ, Zhu AX, Yeh H. Is It Time to Reconsider the Milan Criteria for Selecting Patients With Hepatocellular Carcinoma for Deceased-Donor Liver Transplantation? Hepatology 2019; 69:1324-1336. [PMID: 30229978 DOI: 10.1002/hep.30278] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2018] [Accepted: 08/31/2018] [Indexed: 12/12/2022]
Abstract
Liver transplantation (LT) is considered the optimal treatment for hepatocellular carcinoma (HCC) because it removes tumor as well as the underlying cirrhotic liver. Because of a global organ shortage, LT for patients with HCC is limited to patients with expected survival comparable to that of nonmalignant indications. Therefore, identifying patients with lower rates of HCC recurrence and higher rates of survival is critical. International guidelines have considered the Milan Criteria (MC) the standard for selecting patients with HCC for deceased-donor LT (DDLT). However, several alternative criteria have been reported in the Western world. Interestingly, the two most recent models combining α-fetoprotein level, number of nodules, and size of the largest nodule have been shown to outperform MC in identifying patients with low risk of HCC recurrence or those who will survive for 5 years after liver transplantation. In addition, new models overcome limitations of MC in improving classification of high- versus low-risk patients with HCC for DDLT. These recent scoring systems also provide clinicians with user-friendly tools to better identify patients at lower risk of recurrence. Conclusion: Although most Western countries still select patients based on MC, there is a mounting change in recent practice patterns regarding the selection of patients with HCC for DDLT. Herein, we describe how alternative criteria should lead to reconsideration of MC as it applies to selecting patients with HCC for DDLT in international guidelines.
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Affiliation(s)
| | - Yanik J Bababekov
- Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Andrew X Zhu
- Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Heidi Yeh
- Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
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Daoud A, Teeter L, Ghobrial RM, Graviss EA, Mogawer S, Sholkamy A, El-Shazli M, Gaber AO. Transplantation for Hepatocellular Carcinoma: Is There a Tumor Size Limit? Transplant Proc 2018; 50:3577-3581. [PMID: 30577241 DOI: 10.1016/j.transproceed.2018.04.038] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2018] [Accepted: 04/12/2018] [Indexed: 12/07/2022]
Abstract
BACKGROUND The advent of tumor-size-based criteria (Milan and University of California, San Francisco [UCSF]) for the transplantation of hepatocellular carcinomas (HCC) has facilitated tumor patients' access to transplantation. Recent success in transplanting patients with larger tumors (beyond UCSF) necessitates an understanding of the patient, the tumor, and biological criteria that determine successful outcomes for HCC transplantation across all size criteria. METHODS We analyzed 11,928 patients who received OLT between 2002 and 2013 from the United Network for Organ Sharing Standard Transplant Analysis and Research file. Clinical outcomes were compared by tumor size at transplant; Milan (n = 11,555), beyond Milan within UCSF (n = 291), and beyond both Milan and UCSF (n = 82). A statistical analysis was conducted to determine the factors impacting survival. RESULTS There were no statistically significant differences in the 1-, 3-, and 5-year survival rates between the 3 patient groups (within Milan 91.1%, 74.8%, and 60.3%; beyond Milan within UCSF, 92.7%, 71.1%, and 51.6%; and beyond Milan and UCSF 95.8%, 75.9%, and 58.1%). In a multivariate analysis, factors significantly affecting survival included, AA race, AFP >3000, and hepatitis C infection, while age, diabetes and largest tumor diameter had a more modest impact. Total tumor burden and time to transplantation were not significant predictors of survival. CONCLUSIONS These data indicate that, based on current clinical selection criteria, a small number of large tumors can be successfully treated by transplantation and points to the need to include markers of HCC biologic behavior beyond size and tumor burden to transplant criteria.
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Affiliation(s)
- A Daoud
- Kasr Alainy Faculty of Medicine, Cairo University, Cairo, Egypt; Houston Methodist Hospital, Houston, TX.
| | - L Teeter
- Houston Methodist Hospital, Houston, TX
| | | | | | - S Mogawer
- Kasr Alainy Faculty of Medicine, Cairo University, Cairo, Egypt
| | - A Sholkamy
- Kasr Alainy Faculty of Medicine, Cairo University, Cairo, Egypt
| | - M El-Shazli
- Kasr Alainy Faculty of Medicine, Cairo University, Cairo, Egypt
| | - A O Gaber
- Houston Methodist Hospital, Houston, TX
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Kuang X, Ye J, Xie Z, Bai T, Chen J, Gong W, Qi L, Zhong J, Ma L, Peng N, Xiang B, Wu F, Wu G, Ye H, Wang C, Li L. Adjuvant transarterial chemoembolization to improve the prognosis of hepatocellular carcinoma following curative resection. Oncol Lett 2018; 16:4937-4944. [PMID: 30214612 PMCID: PMC6126172 DOI: 10.3892/ol.2018.9244] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2016] [Accepted: 07/27/2017] [Indexed: 02/06/2023] Open
Abstract
The present study aimed to investigate the prognostic factors for recurrence of hepatocellular carcinoma (HCC) following curative resection, and evaluate the efficacy of postoperative adjuvant transarterial chemoembolization (TACE) in improving prognosis. A total of 166 patients who underwent curative resection followed by adjuvant TACE, and 190 patients who underwent curative resection alone were studied retrospectively. Univariate and multivariate analyses were performed to investigate the risk factors of recurrence. Separated based on risk factors, subgroup studies were conducted and the association between TACE and recurrence rates was examined. Postoperative overall survival rates were determined using the Kaplan-Meier method and differences between the two therapeutic strategies were identified through log-rank analysis. Computerized tomography (CT)/magnetic resonance imaging (MRI) images were used to evaluate the function of postoperative adjuvant TACE for enhancing the efficacy of CT/MRI in detecting recurrence. The results of the univariate and multivariate analyses revealed that tumor capsule invasion, vascular invasion, and multiple nodules were risk factors of early recurrence. For patients with these risk factors, recurrence rates were markedly decreased at 6 and 12 months, but not at 18 and 24 months, if TACE was added to curative resection. The hepatitis B virus (HBV) was a risk factor for late recurrence. Postoperative TACE was not effective in reducing the recurrence rate in patients with HBV. Survival increased following curative resection with TACE compared with curative resection alone. Furthermore, adjuvant TACE enhanced the efficacy of CT/MRI in detecting recurrence. Postoperative adjuvant TACE may improve the prognosis of HCC following curative resection.
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Affiliation(s)
- Xuejun Kuang
- Department of Hepatobiliary Surgery, The Affiliated Hospital of Xiangnan University, Chenzhou, Hunan 423000, P.R. China
| | - Jiazhou Ye
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Zhibo Xie
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Tao Bai
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Jie Chen
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Wenfeng Gong
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Lunan Qi
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Jianhong Zhong
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Liang Ma
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Ningfu Peng
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Bangde Xiang
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Feixiang Wu
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Guobin Wu
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Haihong Ye
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Minzu Hospital of Guangxi Medical University, Nanning, Guangxi 530001, P.R. China
| | - Changmiao Wang
- Department of General Surgery, The First Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
| | - Lunqun Li
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
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Pavel MC, Fuster J. Expansion of the hepatocellular carcinoma Milan criteria in liver transplantation: Future directions. World J Gastroenterol 2018; 24:3626-3636. [PMID: 30166858 PMCID: PMC6113720 DOI: 10.3748/wjg.v24.i32.3626] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2018] [Revised: 06/24/2018] [Accepted: 06/30/2018] [Indexed: 02/06/2023] Open
Abstract
Milan criteria are currently the benchmark related to liver transplantation (LT) for hepatocellular carcinoma. However, several groups have proposed different expanded criteria with acceptable results. In this article, we review the current status of LT beyond the Milan criteria in three different scenarios-expanded criteria with cadaveric LT, downstaging to Milan criteria before LT, and expansion in the context of adult living donor LT. The review focuses on three main questions: what would the impact of the expansion beyond Milan criteria be on the patients on the waiting list; whether the dichotomous criteria (yes/no) currently used are appropriate for LT or continuous survival estimations, such as the one of “Metroticket” and whether it should enter into the clinical practice; and, whether the use of living donor LT in the context of expansion beyond Milan criteria is justified.
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Affiliation(s)
- Mihai-Calin Pavel
- HepatoBilioPancreatic Surgery and Transplant Unit, Department of Surgery, Digestive and Metabolic Diseases Institute, Hospital Clínic, University of Barcelona, Barcelona, Catalonia 08036, Spain
| | - Josep Fuster
- HepatoBilioPancreatic Surgery and Transplant Unit, Department of Surgery, Digestive and Metabolic Diseases Institute, Hospital Clínic, University of Barcelona, Barcelona, Catalonia 08036, Spain
- Barcelona-Clínic Liver Cancer Group (BCLC), Liver Unit, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CIBEREHD, Universitat de Barcelona, Barcelona, Catalonia 08036, Spain
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Kobayashi T, Kawai H, Nakano O, Abe S, Kamimura H, Sakamaki A, Kamimura K, Tsuchiya A, Takamura M, Yamagiwa S, Terai S. Rapidly declining skeletal muscle mass predicts poor prognosis of hepatocellular carcinoma treated with transcatheter intra-arterial therapies. BMC Cancer 2018; 18:756. [PMID: 30041616 PMCID: PMC6056944 DOI: 10.1186/s12885-018-4673-2] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2017] [Accepted: 07/18/2018] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND The impact of sarcopenia on the prognosis of patients with hepatocellular carcinoma (HCC) who receive transcatheter intra-arterial therapies, including transcatheter arterial chemoembolization and transcatheter arterial infusion chemotherapy, remains unclear. We investigated the prognostic value of skeletal muscle loss (SML) stratified by cutoffs for sarcopenia and rate of change in skeletal muscle mass over 6 months. METHODS We retrospectively evaluated 102 patients with HCC treated with transcatheter intra-arterial therapies between 2005 and 2015. Computed tomography images of the third lumbar vertebra (L3) were analyzed to obtain the skeletal muscle area normalized for the height squared, defined as the skeletal muscle index at L3 (L3 SMI), before and 6 months after treatment. Low or high SMI was defined using cutoff values of 42 cm2/m2 in men and 38 cm2/m2 in women. The rate of change in skeletal muscle mass (ΔL3 SMI) over 6 months was calculated. Overall survival (OS) was compared in groups classified by baseline L3 SMI and ΔL3 SMI; prognostic significance was assessed with univariate and multivariate analyses, using Cox proportional hazards models. RESULTS OS did not differ significantly between groups with low (n = 31) and high (n = 71) SMI at baseline (P = 0.172), but OS was significantly poorer in patients with SML (n = 41), defined as ΔL3 SMI < - 4.6% over 6 months than in those without SML (n = 61, P = 0.018). On multivariate analysis, SML (hazard ratio [HR], 1.675; 95% confidence interval [CI], 1.031-2.721; P = 0.037), serum alpha-fetoprotein ≥20 ng/mL (HR, 2.550; 95% CI, 1.440-4.515; P = 0.001), and maximum tumor diameter ≥ 30 mm (HR, 1.925; 95% CI, 1.166-3.179; P = 0.010) were independent predictors of poor OS. Baseline L3 SMI was not significantly associated with OS (HR, 1.405; 95% CI, 0.861-2.293; P = 0.174). CONCLUSIONS ΔL3 SMI was an independent prognostic factor in patients with HCC treated with transcatheter intra-arterial therapies. Further study is required to reveal whether prevention of skeletal muscle depletion might be a new therapeutic strategy to contribute to improved clinical outcomes in patients with HCC.
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Affiliation(s)
- Takamasa Kobayashi
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori Chuo-ku, Niigata, 951-8510 Japan
| | - Hirokazu Kawai
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori Chuo-ku, Niigata, 951-8510 Japan
| | - Oki Nakano
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori Chuo-ku, Niigata, 951-8510 Japan
| | - Satoshi Abe
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori Chuo-ku, Niigata, 951-8510 Japan
| | - Hiroteru Kamimura
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori Chuo-ku, Niigata, 951-8510 Japan
| | - Akira Sakamaki
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori Chuo-ku, Niigata, 951-8510 Japan
| | - Kenya Kamimura
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori Chuo-ku, Niigata, 951-8510 Japan
| | - Atsunori Tsuchiya
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori Chuo-ku, Niigata, 951-8510 Japan
| | - Masaaki Takamura
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori Chuo-ku, Niigata, 951-8510 Japan
| | - Satoshi Yamagiwa
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori Chuo-ku, Niigata, 951-8510 Japan
| | - Shuji Terai
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori Chuo-ku, Niigata, 951-8510 Japan
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Evolutionary Distance Predicts Recurrence After Liver Transplantation in Multifocal Hepatocellular Carcinoma. Transplantation 2018; 102:e424-e430. [PMID: 29994984 PMCID: PMC7598094 DOI: 10.1097/tp.0000000000002356] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
Background Liver transplantation (LTx) is a potentially curative treatment option for hepatocellular carcinoma (HCC) in cirrhosis. However, patients, where HCC is already a systemic disease, LTx may be individually harmful and has a negative impact on donor organ usage. Thus, there is a need for improved selection criteria beyond nodule morphology to select patients with a favorable outcome for LTx in multifocal HCC. Evolutionary distance measured from genome-wide single-nucleotide polymorphism data between tumor nodules and the cirrhotic liver may be a prognostic marker of survival after LTx for multifocal HCC. Methods In a retrospective multicenter study, clinical data and formalin-fixed paraffin-embedded specimens of the liver and 2 tumor nodules were obtained from explants of 30 patients in the discovery and 180 patients in the replication cohort. DNA was extracted from formalin-fixed paraffin-embedded specimens followed by genome wide single-nucleotide polymorphism genotyping. Results Genotype quality criteria allowed for analysis of 8 patients in the discovery and 17 patients in the replication set. DNA concentrations of a total of 25 patients fulfilled the quality criteria and were included in the analysis. Both, in the discovery (P = 0.04) and in the replication data sets (P = 0.01), evolutionary distance was associated with the risk of recurrence of HCC after transplantation (combined P = 0.0002). In a univariate analysis, evolutionary distance (P = 7.4 × 10−6) and microvascular invasion (P = 1.31 × 10−5) were significantly associated with survival in a Cox regression analysis. Conclusions Evolutionary distance allows for the determination of a high-risk group of recurrence if preoperative liver biopsy is considered. The authors of this multicenter retrospective study assess whether the evolutionary distance measured from genome-wide single nucleotide polymorphism (SNP) data between tumor nodules and the cirrhotic liver may be a prognostic marker of survival after liver transplantation for multifocal hepatocellular carcinoma. Supplemental digital content is available in the text.
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Pavel M, Sanchez Cabus S, Crespo G, Ferrer J, Fondevila C, Fuster J, Garcia-Valdecasas J. Role of Adult Living Donor Liver Transplantation in the Treatment of Hepatocellular Carcinoma Within and Beyond Milan Criteria: A Comparative Study. Transplant Proc 2018; 50:1386-1395. [DOI: 10.1016/j.transproceed.2018.02.093] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2018] [Accepted: 02/17/2018] [Indexed: 02/07/2023]
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Liu S, Guo L, Li H, Zhang B, Sun J, Zhou C, Zhou J, Fan J, Ye Q. Postoperative Adjuvant Trans-Arterial Chemoembolization for Patients with Hepatocellular Carcinoma and Portal Vein Tumor Thrombus. Ann Surg Oncol 2018; 25:2098-2104. [DOI: 10.1245/s10434-018-6438-1] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2017] [Indexed: 12/23/2022]
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Lungren MP, Towbin AJ, Roebuck DJ, Monroe EJ, Gill AE, Thakor A, Towbin RB, Cahill AM, Matthew Hawkins C. Role of interventional radiology in managing pediatric liver tumors : Part 1: Endovascular interventions. Pediatr Radiol 2018; 48:555-564. [PMID: 29362840 DOI: 10.1007/s00247-018-4068-1] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2017] [Revised: 12/02/2017] [Accepted: 01/03/2018] [Indexed: 12/14/2022]
Abstract
Primary liver malignancies are rare in children. Hepatoblastoma and hepatocellular carcinoma (HCC) together represent the overwhelming majority of cases. Overall survival of hepatoblastoma approaches 80% with multimodal treatment approaches that include chemotherapy, surgery and transplantation. However, there remains a subset of children with hepatoblastoma in whom resection or transplantation is not possible. The 5-year survival for children diagnosed with HCC is less than 30% and remains a significant therapeutic challenge. The poor outcomes for children with primary liver tumors motivate investigation of new therapeutic alternatives. Interventional oncology offers a broad scope of percutaneous and transcatheter endovascular cancer therapies that might provide clinical benefits. Minimally invasive approaches are distinct from medical, surgical and radiation oncologic treatments, and in adults these approaches have been established as the fourth pillar of cancer care. Transarterial chemoembolization is a minimally invasive locoregional treatment option performed by interventional radiologists with level-I evidence as standard of care in adults with advanced liver malignancy; transarterial chemoembolization in adults has served to prolong disease-free progression, downstage and bridge patients for surgical and transplant interventions, and improve overall survival. However, while several groups have reported that transarterial chemoembolization is feasible in children, the published experience is limited primarily to small retrospective case series. The lack of prospective trial evidence has in part limited the utilization of transarterial chemoembolization in the pediatric patient population. The purpose of this article is to provide an overview of the role of interventional radiology in the diagnosis and endovascular management of hepatic malignancies in children.
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Affiliation(s)
- Matthew P Lungren
- Department of Radiology, Lucile Packard Children's Hospital, Stanford University School of Medicine, 725 Welch Road Room 1862, Stanford, CA, 94305-5913, USA.
| | - Alexander J Towbin
- Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Derek J Roebuck
- Department of Radiology, Great Ormond Street Hospital, London, UK
| | - Eric J Monroe
- Department of Radiology, Division of Interventional Radiology, Seattle Children's Hospital, Seattle, WA, USA
| | - Anne E Gill
- Department of Radiology and Imaging Sciences, Division of Interventional Radiology and Image-guided Medicine, Emory University School of Medicine, Atlanta, GA, USA.,Department of Radiology and Imaging Sciences, Division of Pediatric Radiology, Emory University School of Medicine, Children's Healthcare of Atlanta at Egleston, Atlanta, GA, USA
| | - Avnesh Thakor
- Department of Radiology, Lucile Packard Children's Hospital, Stanford University School of Medicine, 725 Welch Road Room 1862, Stanford, CA, 94305-5913, USA
| | - Richard B Towbin
- Department of Radiology, Phoenix Children's Hospital, Phoenix, AZ, USA
| | - Anne Marie Cahill
- Department of Radiology, Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - C Matthew Hawkins
- Department of Radiology and Imaging Sciences, Division of Interventional Radiology and Image-guided Medicine, Emory University School of Medicine, Atlanta, GA, USA.,Department of Radiology and Imaging Sciences, Division of Pediatric Radiology, Emory University School of Medicine, Children's Healthcare of Atlanta at Egleston, Atlanta, GA, USA
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Llovet JM, Pavel M, Rimola J, Diaz MA, Colmenero J, Saavedra-Perez D, Fondevila C, Ayuso C, Fuster J, Ginès P, Bruix J, Garcia-Valdecasas JC. Pilot study of living donor liver transplantation for patients with hepatocellular carcinoma exceeding Milan Criteria (Barcelona Clinic Liver Cancer extended criteria). Liver Transpl 2018; 24:369-379. [PMID: 29140601 DOI: 10.1002/lt.24977] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2017] [Revised: 10/25/2017] [Accepted: 10/29/2017] [Indexed: 12/15/2022]
Abstract
A subset of patients with hepatocellular carcinoma (HCC) beyond Milan criteria might obtain acceptable survival outcomes after liver transplantation. Living donor liver transplantation (LDLT) has emerged as a feasible alternative to overcome the paucity of donors. In 2001, we started a protocol for LDLT in Child A-B patients with HCC fulfilling a set of criteria-the Barcelona Clinic Liver Cancer (BCLC) expanded criteria-that expanded the conventional indications of transplantation: 1 tumor ≤ 7 cm, 5 tumors ≤ 3 cm, and 3 tumors ≤ 5 cm without macrovascular invasion or downstaging to Milan after locoregional therapies. We present a prospective cohort of 22 patients with BCLC extended indications based on size/number (n = 17) or downstaging (n = 5) treated with LDLT between 2001 and 2014. Characteristics of the patients were as follows: median age, 57 years old; males/female, n = 20/2; Child-Pugh A/B, n = 16/6; and alpha fetoprotein < 100 ng/mL, n = 21. Twelve patients received neoadjuvant locoregional therapies. At the time of transplantation, 12 patients had HCC staging beyond Milan criteria and 10 within. Pathological reports showed that 50% exceeded BCLC expanded criteria. Perioperative mortality was 0%. After a median follow-up of 81 months, the 1-, 3-, 5-, and 10-year survival was 95.5%, 86.4%, 80.2%, and 66.8%, respectively. Overall, 7 patients recurred (range, 9-108 months), and the 5-year and 10-year actuarial recurrence rates were 23.8% and 44.4%, respectively. In conclusion, a proper selection of candidates for extended indications of LDLT for HCC patients provide survival outcomes comparable to those obtained within the Milan criteria, but these results need confirmation. Liver Transplantation 24 369-379 2018 AASLD.
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Affiliation(s)
- Josep M Llovet
- Barcelona Clinic Liver Cancer Group, Liver Unit, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clinic Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Catalonia, Spain.,Mount Sinai Liver Cancer Program, Icahn School of Medicine at Mount Sinai, New York, NY.,Institució Catalana de Recerca i Estudis Avançats, Barcelona, Catalonia, Spain
| | - Mihai Pavel
- Liver Transplant Unit, Barcelona, Catalonia, Spain
| | - Jordi Rimola
- Barcelona Clinic Liver Cancer Group, Liver Unit, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clinic Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Catalonia, Spain
| | - Maria Alba Diaz
- Pathology Department, Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain
| | - Jordi Colmenero
- Liver Transplant Unit, Barcelona, Catalonia, Spain.,Liver Unit, Digestive and Metabolic Diseases Institute, Barcelona, Catalonia, Spain
| | | | | | - Carmen Ayuso
- Barcelona Clinic Liver Cancer Group, Liver Unit, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clinic Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Catalonia, Spain
| | - Josep Fuster
- Barcelona Clinic Liver Cancer Group, Liver Unit, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clinic Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Catalonia, Spain.,Liver Transplant Unit, Barcelona, Catalonia, Spain
| | - Pere Ginès
- Liver Transplant Unit, Barcelona, Catalonia, Spain.,Liver Unit, Digestive and Metabolic Diseases Institute, Barcelona, Catalonia, Spain
| | - Jordi Bruix
- Barcelona Clinic Liver Cancer Group, Liver Unit, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clinic Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Catalonia, Spain.,Liver Unit, Digestive and Metabolic Diseases Institute, Barcelona, Catalonia, Spain
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Zhu R, Weng D, Lu S, Lin D, Wang M, Chen D, Lv J, Li H, Lv F, Xi L, Zhou J, Ma D, Li N. Double-Dose Adenovirus-Mediated Adjuvant Gene Therapy Improves Liver Transplantation Outcomes in Patients with Advanced Hepatocellular Carcinoma. Hum Gene Ther 2018; 29:251-258. [PMID: 29446997 DOI: 10.1089/hum.2017.114] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
Affiliation(s)
- Ruidong Zhu
- 1 Beijing YouAn Hospital affiliated with Capital Medical University , Beijing, P.R. China
| | - Danhui Weng
- 2 Tumor Molecular Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, Hubei, P.R. China
| | - Shichun Lu
- 1 Beijing YouAn Hospital affiliated with Capital Medical University , Beijing, P.R. China
| | - Dongdong Lin
- 1 Beijing YouAn Hospital affiliated with Capital Medical University , Beijing, P.R. China
| | - Menglong Wang
- 1 Beijing YouAn Hospital affiliated with Capital Medical University , Beijing, P.R. China
| | - Dongdong Chen
- 1 Beijing YouAn Hospital affiliated with Capital Medical University , Beijing, P.R. China
| | - Jun Lv
- 1 Beijing YouAn Hospital affiliated with Capital Medical University , Beijing, P.R. China
| | - Hongjun Li
- 1 Beijing YouAn Hospital affiliated with Capital Medical University , Beijing, P.R. China
| | - Fudong Lv
- 1 Beijing YouAn Hospital affiliated with Capital Medical University , Beijing, P.R. China
| | - Ling Xi
- 2 Tumor Molecular Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, Hubei, P.R. China
| | - Jianfeng Zhou
- 2 Tumor Molecular Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, Hubei, P.R. China
| | - Ding Ma
- 2 Tumor Molecular Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, Hubei, P.R. China
| | - Ning Li
- 1 Beijing YouAn Hospital affiliated with Capital Medical University , Beijing, P.R. China
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Li W, Li L, Han J, Wu H. Liver transplantation vs liver resection in patients with HBV-related hepatocellular carcinoma beyond Milan criterion: A meta-analysis. Clin Transplant 2018; 32:e13193. [PMID: 29315813 DOI: 10.1111/ctr.13193] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/27/2017] [Indexed: 02/05/2023]
Abstract
OBJECTIVE The aim of this study was to conduct a meta-analysis of published reports to compare long-term outcomes after liver transplantation (LT) and liver resection (LR), respectively, in patients with HBV-related hepatocellular carcinoma (HCC) beyond the Milan criterion. METHODS A systematic search of the Embase, Medline, PubMed databases, and the Cochrane Library was performed using both medical subject headings (MeSH) and truncated word searches to identify all comparative studies published on this topic. The primary outcomes were postoperative overall survival (OS) and disease-free survival (DFS). We calculated the pooled hazard ratios (HR) with 95% confidence intervals (95% CI) of OS and DFS. RESULTS Pooled analysis of six studies, with a total of 1697 patients with HCC beyond Milan criteria, did not reveal a statistically significant improvement in OS in patients undergoing LT vs LR (LT vs LR, HR: 0.83, 95% CI: 0.68-1.01, P = .06), without significant heterogeneity (χ2 = 8.38, I2 = 40.3%, P = .137). Five studies with a total of 1511 patients were included in pooled analysis of DFS between LT and LR group. In the fixed-effects model, patients in the LT group gained significantly better DFS (LT vs LR, HR: 0.45, 95% CI: 0.37-0.56, P < .001) than patients in the LR group, with no significant heterogeneity (χ2 = 6.80, I2 = 41.6%, P = .144). Four studies provided the data of adjusted HRs (LT vs LR). In the fixed-effects model, patients in the LT group had significantly better OS (HR: 0.58, 95% CI: 0.44-0.77, P < .001, I2 = 0%) and DFS (HR: 0.14, 95% CI: 0.08-0.23, P < .001, I2 = 0%) than those of patients in the LR group. The sensitivity analyses revealed that the results were robust. CONCLUSION Our meta-analysis demonstrated that HBV-related patients with HCC beyond Milan criterion who underwent LT gained better OS and DFS compared with patients who underwent LR after adjusting confounding factors.
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Affiliation(s)
- Wei Li
- Department of Liver Surgery and Liver Transplantation Centre, West China Hospital, Sichuan University, Chengdu, China
| | - Long Li
- Department of General Surgery, Dingxi People's Hospital, Lanzhou University Second Hospital Dingxi Hospital, Dingxi, China
| | - Jun Han
- Department of Critical Care Medicine, Sichuan Provincial Hospital for Women and Children, Chengdu, China
| | - Hong Wu
- Department of Liver Surgery and Liver Transplantation Centre, West China Hospital, Sichuan University, Chengdu, China
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Huang LF, Wan P, Xu DW, Jeong S, Feng MX, Zhang JJ, Xia Q. Nomogram predicting pulmonary metastasis of hepatocellular carcinoma after liver transplantation. Oncotarget 2017; 9:2425-2434. [PMID: 29416782 PMCID: PMC5788650 DOI: 10.18632/oncotarget.23418] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2017] [Accepted: 09/21/2017] [Indexed: 12/12/2022] Open
Abstract
A novel prognostic nomogram predicting post-transplant pulmonary metastasis was established with a primary cohort of 308 HCC patients who received liver transplantation between 2007 and 2011 at Ren Ji Hospital. The C-indexes for predicting pulmonary metastasis was 0.85. The calibration curves fitted well between the predicted and actual outcomes. The decision curve analysis indicated that our nomogram was the optimal decision-making strategy for PM prediction compared to Milan, University of California San Franscisco, and up-to-seven criteria. These results were further validated by data from 103 patients who underwent liver transplantation between 2011 and 2012 at the same institution. In conclusion, our nomogram could be used as an effective tool to predict PM after liver transplantation.
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Affiliation(s)
- Li-Feng Huang
- Department of Hepatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Ping Wan
- Department of Hepatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Dong-Wei Xu
- Department of Hepatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Seogsong Jeong
- Department of Hepatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Ming-Xuan Feng
- Department of Hepatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Jian-Jun Zhang
- Department of Hepatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Qiang Xia
- Department of Hepatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
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Imura S, Teraoku H, Yoshikawa M, Ishikawa D, Yamada S, Saito Y, Iwahashi S, Ikemoto T, Morine Y, Shimada M. Potential predictive factors for microvascular invasion in hepatocellular carcinoma classified within the Milan criteria. Int J Clin Oncol 2017; 23:98-103. [PMID: 28875240 DOI: 10.1007/s10147-017-1189-8] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2017] [Accepted: 08/23/2017] [Indexed: 12/18/2022]
Abstract
BACKGROUND Microvascular invasion (mvi) is an important risk factor for recurrent hepatocellular carcinoma (HCC), even after curative liver resection or orthotopic liver transplantation. However, mvi is difficult to detect preoperatively. The aim of this study was to clarify the risk factors of postoperative recurrence and investigate predictive factors of mvi before hepatectomy for HCC classified within the Milan criteria. METHODS One hundred fifty-nine patients with hepatocellular carcinoma (HCC) classified within the Milan criteria, who underwent hepatectomy, were enrolled in this study. We investigated the risk factors of recurrence. In addition, we divided them into two groups: mvi-negative group and mvi-positive group, based on pathological findings after surgery. We compared the clinicopathological factors between the two groups and determined the risk factors for mvi. RESULTS Overall survival rate at 1, 3, and 5 years were 91.6%, 80.5%, and 74.9%, and the recurrence-free survival rate at 1, 3, and 5-years were 72.3%, 51.6%, and 37.2%. Risk factor analysis for tumor recurrence revealed that total bilirubin, albumin, ICGR15, AFP-L3, tumor number, mvi, and tumor stage had a significant predictive value. Multivariate analysis revealed that tumor number and mvi were significant independent risk factors for tumor recurrence. Predictive analysis for risk factors of mvi revealed that multiple tumors and AFP-L3 > 10% were significant independent risk factors for mvi in HCC classified within the Milan criteria. CONCLUSIONS The mvi was one of the independent risk factors for tumor recurrence in HCC classified within the Milan criteria. Multiple tumors and high AFP-L3 value were independent predictive factors for mvi.
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Affiliation(s)
- Satoru Imura
- Department of Surgery, Tokushima University, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
| | - Hiroki Teraoku
- Department of Surgery, Tokushima University, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Masato Yoshikawa
- Department of Surgery, Tokushima University, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Daichi Ishikawa
- Department of Surgery, Tokushima University, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Shinichiro Yamada
- Department of Surgery, Tokushima University, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Yu Saito
- Department of Surgery, Tokushima University, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Shuichi Iwahashi
- Department of Surgery, Tokushima University, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Tetsuya Ikemoto
- Department of Surgery, Tokushima University, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Yuji Morine
- Department of Surgery, Tokushima University, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Mitsuo Shimada
- Department of Surgery, Tokushima University, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
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Chen DH, Wu QW, Li XD, Wang SJ, Zhang ZM. SYPL1 overexpression predicts poor prognosis of hepatocellular carcinoma and associates with epithelial-mesenchymal transition. Oncol Rep 2017; 38:1533-1542. [DOI: 10.3892/or.2017.5843] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2017] [Accepted: 06/07/2017] [Indexed: 02/07/2023] Open
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Ye JZ, Wang YY, Bai T, Chen J, Xiang BD, Wu FX, Li LQ. Surgical resection for hepatocellular carcinoma with portal vein tumor thrombus in the Asia-Pacific region beyond the Barcelona Clinic Liver Cancer treatment algorithms: a review and update. Oncotarget 2017; 8:93258-93278. [PMID: 29190996 PMCID: PMC5696262 DOI: 10.18632/oncotarget.18735] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2017] [Accepted: 04/25/2017] [Indexed: 01/27/2023] Open
Abstract
Portal vein tumor thrombus (PVTT) usually worsens prognosis of hepatocellular carcinoma (HCC), as characterized by aggressive disease progression, impaired liver function and tolerance to treatment. Conventionally, the European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD) accepted the Barcelona Clinical Liver Cancer (BCLC) treatment algorithms, identifying PVTT as an absolute contra-indication of surgical resection for HCC. HCC-PVTT patients are offered sorafenib as the standard treatment. Evidently, SHARP and Asia-Pacific trials demonstrated that sorafenib only improves overall survival by approximately 3 months in patients with advanced HCC. Besides, BCLC treatment algorithm does not provide different therapeutic recommendations for different degree of PVTT, and only supports single treatment option for each stage of HCC rather than a combination of comprehensive treatments, which limited individual and best care for every HCC-PVTT patients. In the past few years, many surgeons do not restrict surgical resection to HCC with PVTT. There have been new reports demonstrated that surgical treatment is feasible for selected HCC-PVTT patients with resectable tumor and moderate liver function to prolong survival period and elevate life quality as long as PVTT limited to the first-order branch, whereas non-surgical treatments fail to provide comparable therapeutic effects. At present, guidelines on HCC management from mainland China, Japan, and Hong Kong have been updated and a consensus of Asia-Pacific experts has established that portal venous invasion is not an absolute contradiction of surgical resection for HCC. This review summarized the emerging data on surgical resection for HCC-PVTT patients beyond the BCLC treatment algorithms and discussed recent therapeutic conceptualchanges in the Asia-Pacific region.
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Affiliation(s)
- Jia-Zhou Ye
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, PR China
| | - Yan-Yan Wang
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, PR China
| | - Tao Bai
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, PR China
| | - Jie Chen
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, PR China
| | - Bang-De Xiang
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, PR China
| | - Fei-Xiang Wu
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, PR China
| | - Le-Qun Li
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, PR China
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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: 322] [Impact Index Per Article: 40.3] [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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Inappropriate inferences from registry data: Pitfalls of inaccurate data handling? Indian J Gastroenterol 2017; 36:77-80. [PMID: 28357774 DOI: 10.1007/s12664-017-0749-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2017] [Accepted: 03/12/2017] [Indexed: 02/04/2023]
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Bridging locoregional therapy: Longitudinal trends and outcomes in patients with hepatocellular carcinoma. Transplant Rev (Orlando) 2017; 31:136-143. [PMID: 28214240 DOI: 10.1016/j.trre.2017.01.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2016] [Accepted: 01/28/2017] [Indexed: 12/19/2022]
Abstract
The purpose of this article is to analyze longitudinal trends in locoregional therapy (LRT) use and review locoregional therapy's role in the management of hepatocellular carcinoma prior to orthotropic liver transplantation Porrett et al. (2006) . LRT has a role in both bridge to transplantation and downstaging of patients not initially meeting Milan or UCSF Criteria. Due to the lack of randomized controlled trials, no specific bridging LRT modality is recommended over another for treating patients on the waiting list, however each modality has unique and patient-specific advantages. Pre-transplant LRT use in the United States has increased dramatically over the last two decades with more than 50% of the currently listed patients receiving LRT Freeman et al. (2008) . Despite these national trends, significant differences in LRT utilization, referral patterns, recurrence rates and survival have been observed among UNOS regions, socioeconomic levels and races. The use of LRT as a biologic selection tool based on response to treatment has shown promising results in its ability to predict successful post-transplant outcomes.
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Cho Y, Sinn DH, Yu SJ, Gwak GY, Kim JH, Yoo YJ, Jun DW, Kim TY, Lee HY, Cho EJ, Lee JH, Kim YJ, Yoon JH. Survival Analysis of Single Large (>5 cm) Hepatocellular Carcinoma Patients: BCLC A versus B. PLoS One 2016; 11:e0165722. [PMID: 27846227 PMCID: PMC5112776 DOI: 10.1371/journal.pone.0165722] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2016] [Accepted: 10/17/2016] [Indexed: 01/27/2023] Open
Abstract
Background & Aims Single large (>5 cm) hepatocellular carcinoma (HCC) is classified as Barcelona Liver Clinic (BCLC) stage early stage (A). Yet, controversies exist whether single large HCC can be considered as early stage. We have analyzed long-term outcome to see which stage is appropriate for these patients. Methods From 2005 to 2006, 1,546 consecutive patients who were newly diagnosed as HCC (BCLC A or B) at four tertiary hospitals in Korea were analyzed. BCLC A was sub-classified into A1 (single 2–5 cm), A2 (2–3 nodules ≤3 cm), and A3 (single >5 cm). BCLC B1 included patients beyond-Milan criteria, and within up-to-7 criterion. Survival prediction between subgroupings (1: A1 + A2 + A3 vs. B1 and 2: A1 + A2 vs. A3 + B1) was compared based on c-index and Akaike information criterion (AIC). Results The 5-year overall survival (OS) rate was 62.3, 58.6, 36.8, and 42.0% for A1, A2, A3 and B1, respectively. In multivariate Cox-regression analysis, OS was significantly different between A3 + B1 vs. A1 + A2 (hazard ratio [HR] 1.85; P<0.001), but not between A1 + A2 + A3 vs. B1 (HR 1.19; P = 0.258). For A3, surgical resection showed superior OS over transarterial chemoembolization. Survival prediction was superior in subgrouping 2 (AIC 5727.2; c-index 0.652) than subgrouping 1 (AIC 5766.3; c-index 0.619) even after inverse probability weighting. Conclusions This large scale long-term follow-up data shows that single large tumor should be considered as intermediate stage in terms of prognosis. However, in terms of treatment, resection might be the first line treatment option.
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Affiliation(s)
- Yuri Cho
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
- Department of Internal Medicine, CHA Gangnam Medical Center, CHA University, Seoul, Republic of Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Su Jong Yu
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
- * E-mail:
| | - Geum Youn Gwak
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Ji Hoon Kim
- Department of Internal Medicine, Korea University college of Medicine, Guro Hospital, Seoul, Republic of Korea
| | - Yang Jae Yoo
- Department of Internal Medicine, Korea University college of Medicine, Guro Hospital, Seoul, Republic of Korea
| | - Dae Won Jun
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Republic of Korea
| | - Tae Yeob Kim
- Institute of Medical Science, Hanyang University, Seoul, Republic of Korea
| | - Hyo Young Lee
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Republic of Korea
| | - Eun Ju Cho
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jeong-Hoon Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Yoon Jun Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jung-Hwan Yoon
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
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Zhao YN, Zhang YQ, Ye JZ, Liu X, Yang HZ, Cong FY, Xiang BD, Wu FX, Ma L, Li LQ, Ye HH. Hepatic resection versus transarterial chemoembolization for patients with Barcelona Clinic Liver Cancer intermediate stage Child-Pugh A hepatocellular carcinoma. Exp Ther Med 2016; 12:3813-3819. [PMID: 28105115 DOI: 10.3892/etm.2016.3810] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2015] [Accepted: 09/01/2016] [Indexed: 12/13/2022] Open
Abstract
The present study aimed to compare the overall and recurrence-free survival rates following hepatic resection (HR) and transcatheter arterial chemoembolization (TACE) in patients with Barcelona Clinic Liver Cancer (BCLC) classified intermediate-stage Child-Pugh A hepatocellular carcinoma (HCC). A total of 443 patients were examined, among whom 274 underwent HR, whereas 169 received TACE. The overall survival, recurrence-free survival between groups and subgroups, and risk factors with respect to mortality and recurrence, were analyzed. The 1-, 3- and 5-year overall and recurrence-free survival rates were 70, 46 and 37% and 73, 52, and 37%, respectively after HR, compared with 38, 15, and 12% and 44, 25 and 16%, respectively after TACE. Overall and recurrence-free survival rates were significantly increased following HR compared with TACE. Subgroup analysis in the multi-nodule group showed that the 1-, 3- and 5-year overall survival rates were 68, 38 and 30% after HR, compared with 36, 10 and 0% following TACE. In the solitary tumor group, 1-, 3- and 5-year overall survival rates were 71, 50 and 38% after HR, and 41, 22 and 15% after TACE. The overall survival rate after HR was significantly increased compared with that after TACE in the solitary tumor and multi-nodule groups. The risk factors for mortality include solitary tumor diameter >10 cm, multi-nodules, serum albumin level ≥35 g/l, prothrombin time >13 sec, alphafetoprotein levels >400 ng/ml, and patients with hepatitis B virus. Solitary tumor diameter >10 cm, multi-nodules, and hepatitis B virus (P<0.001) were found to be associated with higher recurrence of HCC. Overall and recurrence-free survival rates were improved after HR compared with those after TACE in BCLC stage B, Child-Pugh A, HCC patients.
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Affiliation(s)
- Yin-Nong Zhao
- Department of Hepatobilliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Yong-Quan Zhang
- Department of Hepatobilliary Surgery, The Affiliated Minzu Hospital of Guangxi Medical University, Nanning, Guangxi 530001, P.R. China
| | - Jia-Zhou Ye
- Department of Hepatobilliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Xing Liu
- Department of Hepatobilliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Hong-Zhi Yang
- Department of Hepatobilliary Surgery, The Affiliated Minzu Hospital of Guangxi Medical University, Nanning, Guangxi 530001, P.R. China
| | - Feng-Yun Cong
- Department of Hepatobilliary Surgery, The Affiliated Minzu Hospital of Guangxi Medical University, Nanning, Guangxi 530001, P.R. China
| | - Bang-De Xiang
- Department of Hepatobilliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Fei-Xiang Wu
- Department of Hepatobilliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Liang Ma
- Department of Hepatobilliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Le-Qun Li
- Department of Hepatobilliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Hai-Hong Ye
- Department of Hepatobilliary Surgery, The Affiliated Minzu Hospital of Guangxi Medical University, Nanning, Guangxi 530001, P.R. China
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Hsu HT, Sung MT, Lee CC, Kuo YJ, Chi CW, Lee HC, Hsia CY. Peroxisome Proliferator-Activated Receptor γ Expression Is Inversely Associated with Macroscopic Vascular Invasion in Human Hepatocellular Carcinoma. Int J Mol Sci 2016; 17:1226. [PMID: 27483249 PMCID: PMC5000624 DOI: 10.3390/ijms17081226] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2016] [Revised: 07/18/2016] [Accepted: 07/21/2016] [Indexed: 02/07/2023] Open
Abstract
Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-activated nuclear receptor that regulates cellular lipid and glucose metabolism and also plays an inhibitory role in various cancers. However, the role of PPARγ in hepatocellular carcinoma (HCC) remains controversial. This study aimed to investigate the prognostic value of PPARγ in HCC and its role in inhibiting tumor progression, namely, HCC cell growth, migration, and angiogenesis. Immunohistochemical PPARγ staining was examined in 83 HCC specimens to investigate the clinicopathological correlations between PPARγ expression and various parameters. The functional role of PPARγ was determined via PPARγ overexpression and knockdown in HCC cells. Patients with low HCC tissue PPARγ expression were significantly younger (p = 0.006), and exhibited more tumor numbers (p = 0.038), more macroscopic vascular invasion (MVI) (p = 0.008), and more advanced TNM (size of primary tumor, number of regional lymph nodes, and distant metastasis) stages at diagnosis (p = 0.013) than patients with high HCC tissue PPARγ expression. PPARγ knockdown increased HCC cell growth, migration, and angiogenesis, while PPARγ overexpression reduced HCC cell growth, migration, and angiogenesis. These results suggest that low PPARγ expression is an independent predictor of more MVI in HCC patients. PPARγ contributes to the suppression of HCC cell growth, migration, and angiogenesis. Therefore, PPARγ may be a therapeutic target in HCC patients.
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Affiliation(s)
- Hui-Tzu Hsu
- Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan.
- Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei 112, Taiwan.
| | - Ming-Ta Sung
- Department of Medical Research, Taipei Veterans General Hospital, Taipei 112, Taiwan.
| | - Chih-Chun Lee
- Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan.
- Department of Surgery, Koo Foundation Sun Yat-Sen Cancer Center, Taipei 112, Taiwan.
| | - Yin-Ju Kuo
- Department of Pathology, Taipei Veterans General Hospital, Taipei 112, Taiwan.
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan.
| | - Chin-Wen Chi
- Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan.
- Department of Medical Research, Taipei Veterans General Hospital, Taipei 112, Taiwan.
| | - Hsin-Chen Lee
- Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan.
| | - Cheng-Yuan Hsia
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan.
- Department of Surgery, Taipei Veterans General Hospital, Taipei 112, Taiwan.
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Elshamy M, Aucejo F, Menon KVN, Eghtesad B. Hepatocellular carcinoma beyond Milan criteria: Management and transplant selection criteria. World J Hepatol 2016; 8:874-880. [PMID: 27478537 PMCID: PMC4958697 DOI: 10.4254/wjh.v8.i21.874] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2016] [Revised: 06/17/2016] [Accepted: 07/13/2016] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation (LT) for hepatocellular carcinoma (HCC) has been established as a standard treatment in selected patients for the last two and a half decades. After initially dismal outcomes, the Milan criteria (MC) (single HCC ≤ 5 cm or up to 3 HCCs ≤ 3 cm) have been adopted worldwide to select HCC patients for LT, however cumulative experience has shown that MC can be too strict. This has led to the development of numerous expanded criteria worldwide. Morphometric expansions on MC as well as various criteria which incorporate biomarkers as surrogates of tumor biology have been described. HCC that presents beyond MC initially can be downstaged with locoregional therapy (LRT). Post-LRT monitoring aims to identify candidates with favorable tumor behavior. Similarly, tumor marker levels as response to LRT has been utilized as surrogate of tumor biology. Molecular signatures of HCC have also been correlated to outcomes; these have yet to be incorporated into HCC-LT selection criteria formally. The ongoing discrepancy between organ demand and supply makes patient selection the most challenging element of organ allocation. Further validation of extended HCC-LT criteria models and pre-LT treatment strategies are required.
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Yang P, Zeng ZC, Wang BL, Zhang JY, Fan J, Zhou J, Hu Y. The Degree of Lipiodol Accumulation Can Be an Indicator of Successful Treatment for Unresectable Hepatocellular Carcinoma (HCC) Patients - in the Case of Transcatheter Arterial Chemoembolization (TACE) and External Beam Radiotherapy (EBRT). J Cancer 2016; 7:1413-20. [PMID: 27471557 PMCID: PMC4964125 DOI: 10.7150/jca.15405] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2016] [Accepted: 05/18/2016] [Indexed: 01/26/2023] Open
Abstract
PURPOSE Transcatheter arterial chemoembolization (TACE) in combination with external beam radiotherapy (EBRT) results in improved survival due to better local control in patients with unresectable hepatocellular carcinoma (HCC). The purpose of this study was to investigate lipiodol accumulation, as it reflects tumor burden and is a potential prognostic factor, in HCC patients treated with TACE/EBRT. METHODS AND MATERIALS We retrospectively studied 147 patients with unresectable HCC treated with TACE and EBRT. Clinical features, adverse reactions, and prognostic factors were analyzed. All patients were treated with TACE 1-6 times in combination with EBRT (44-66 Gy) in dose of 2 Gy/fraction given once a day five times a week. Tumor status and laboratory findings were followed. The degree of lipiodol accumulation was assessed by computed tomography before EBRT, and was categorized as either complete/intense or low/moderate. RESULTS The response rate of tumor size after EBRT was 68.2%, median survival was 23.1 months, and overall survival rates were 86.6%, 49.2%, and 28.2% at 1, 2, and 3 years, respectively. Univariate analysis showed that lower hemoglobin levels, higher alkaline phosphatase levels, Child-Pugh B, negative alpha-fetoprotein (AFP) response after EBRT, poor treatment response after EBRT, tumor diameter >10 cm, and poor lipiodol accumulation were unfavorable prognostic factors. On multivariate analysis, higher hemoglobin levels, Child-Pugh A, decreased AFP levels after treatment, Helical Tomotherapy (HT) and intense lipiodol accumulation after TACE were significant favorable predictors. CONCLUSIONS The degree of lipiodol accumulation before EBRT is a prognostic factor in patients with unresectable HCC. Increased AFP levels after EBRT are always associated with poor survival. HT is recommended as a potentially better EBRT modality than three-dimensional conformal radiation therapy (3D-CRT).
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Affiliation(s)
- Ping Yang
- 1. Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Zhao-Chong Zeng
- 1. Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Bin-Liang Wang
- 1. Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Jian-Ying Zhang
- 1. Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Jia Fan
- 2. Department of Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Jian Zhou
- 2. Department of Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Yong Hu
- 1. Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
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Current Treatment Approaches to HCC with a Special Consideration to Transplantation. J Transplant 2016; 2016:7926264. [PMID: 27413539 PMCID: PMC4931061 DOI: 10.1155/2016/7926264] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2016] [Accepted: 05/19/2016] [Indexed: 12/13/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide. The mainstay of treatment of HCC has been both resectional and transplantation surgery. It is well known that, in selected, optimized patients, hepatectomy for HCC may be an option, even in patients with underlying cirrhosis. Resectable patients with early HCC and underlying liver disease are however increasingly being considered for transplantation because of potential for better disease-free survival and resolution of underlying liver disease, although this approach is limited by the availability of donor livers, especially in resectable patients. Outcomes following liver transplantation improved dramatically for patients with HCC following the implementation of the Milan criteria in the late 1990s. Ever since, the rather restrictive nature of the Milan criteria has been challenged with good outcomes. There has also been an increase in the donor pool with marginal donors including organs retrieved following cardiac death being used. Even so, patients still continue to die while waiting for a liver transplant. In order to reduce this attrition, bridging techniques and methods for downstaging disease have evolved. Additionally new techniques for organ preservation have increased the prospect of this potentially curative procedure being available for a greater number of patients.
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Lauerer M, Kaiser K, Nagel E. Organ Transplantation in the Face of Donor Shortage - Ethical Implications with a Focus on Liver Allocation. Visc Med 2016; 32:278-285. [PMID: 27722165 DOI: 10.1159/000446382] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Transplantation medicine is associated with several ethical issues related to the lack of organs. Major questions concern the regulations for giving permission for organ removal, informing the public about organ donation, setting of organ allocation priorities, waiting list access, and strategies to counteract scarcity. METHODS This contribution is based on analyses of legal regulations, guidelines of self-regulatory bodies, administrative data, and literature from medical, normative, and empiric disciplines. It addresses the above-mentioned issues descriptively with a focus on Germany and liver transplantation. RESULTS The basic principle of beneficence justifies a shift from voluntariness towards an obligation to document one's decision regarding organ donation. Organ allocation is obviously tangent to fundamental values and concepts of justice. At that, there is no consistent agreement on whether to prioritize the sickest patient or to maximize the overall health benefit. Restrictions relating to waiting list access are the subject of controversies. The reasons for denial of access are largely related to high demands on the prospect of success. Strategies to counteract organ scarcity partly conflict with the respect for autonomy, non-maleficence, beneficence, or justice. CONCLUSION We propose to focus on recent most promising strategies to counteract scarcity in the short-term: demanding a documented decision on organ donation and an orientation towards the Spanish model of organization. Concepts for waiting list access should constantly be reviewed considering all medical evidence and must not be based on moralism. Moreover, we suggest to consider public preferences for organ allocation and strengthen the confidence in transplantation medicine.
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Affiliation(s)
- Michael Lauerer
- Institut für Medizinmanagement und Gesundheitswissenschaften, Universität Bayreuth, Bayreuth, Germany
| | - Katharina Kaiser
- Institut für Medizinmanagement und Gesundheitswissenschaften, Universität Bayreuth, Bayreuth, Germany
| | - Eckhard Nagel
- Institut für Medizinmanagement und Gesundheitswissenschaften, Universität Bayreuth, Bayreuth, Germany
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