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1
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Reddy SHS, Mehta N, Dodge JL, Hakeem AR, Khorsandi SE, Jassem W, Vilca-Melendez H, Cortes-Cerisuelo M, Srinivasan P, Prachalias A, Heneghan MA, Aluvihare V, Suddle A, Miquel R, Rela M, Heaton ND, Menon KV. Liver transplantation for HCC: validation of prognostic power of the RETREAT score for recurrence in a UK cohort. HPB (Oxford) 2022; 24:596-605. [PMID: 34702624 DOI: 10.1016/j.hpb.2021.09.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Revised: 08/23/2021] [Accepted: 09/08/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND The Risk Estimation of Tumor Recurrence After Transplant (RETREAT) score as a prognostic index for recurrence has been reported previously and has not been validated outside the USA. Our study has validated the score in a single center UK cohort of patients being transplanted for HCC. METHODS LT for HCC between 2008 and 2018 at our center were analyzed. Recurrence-free survival (RFS) was compared by the RETREAT score and validated using Net Reclassification Improvement (NRI) by comparing it to Milan criteria. RESULTS 346 adult HCC patients were transplanted of whom 313 were included. 28 (8.9%) had a recurrence. Summation of largest diameter and total number of viable tumors (HR = 1.19, p < 0.001), micro-/macro-vascular invasion (HR = 3.74, p = 0.002) and AFP>20 ng/ml (HR = 3.03, p = 0.005) were associated with recurrence on multivariate analysis. RFS decreased with increasing RETREAT score (log-rank p = 0.016). RETREAT performed better than Milan with significant NRI at 1- and 2-years post-transplant (0.43 (p = 0.004) and 0.38 (p = 0.03) respectively). CONCLUSION LT outcomes using the revised UK criteria are equivalent to Milan criteria. Further, RETREAT score was validated as a prognostic index for the first time in a UK cohort and may assist risk stratification, selection for adjuvant therapies and guide surveillance.
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Affiliation(s)
- Shruthi H S Reddy
- Liver Transplant Surgery, Institute of Liver Studies, King's College Hospital, London, SE5 9RS, United Kingdom
| | - Neil Mehta
- Hepatology, Department of Medicine, University of California, San Francisco, United States
| | - Jennifer L Dodge
- Biostatistics, Department of Medicine and Preventive Medicine, University of Southern California, Los Angeles, United States
| | - Abdul R Hakeem
- Hepatobiliary and Liver Transplant Surgery, St James's University Hospital, Leeds, LS97TF, United Kingdom
| | - Shirin E Khorsandi
- Liver Transplant Surgery, Institute of Liver Studies, King's College Hospital, London, SE5 9RS, United Kingdom; Institute of Hepatology, Foundation for Liver Research, London, United Kingdom
| | - Wayel Jassem
- Liver Transplant Surgery, Institute of Liver Studies, King's College Hospital, London, SE5 9RS, United Kingdom
| | - Hector Vilca-Melendez
- Liver Transplant Surgery, Institute of Liver Studies, King's College Hospital, London, SE5 9RS, United Kingdom
| | - Miriam Cortes-Cerisuelo
- Liver Transplant Surgery, Institute of Liver Studies, King's College Hospital, London, SE5 9RS, United Kingdom
| | - Parthi Srinivasan
- Liver Transplant Surgery, Institute of Liver Studies, King's College Hospital, London, SE5 9RS, United Kingdom
| | - Andreas Prachalias
- Liver Transplant Surgery, Institute of Liver Studies, King's College Hospital, London, SE5 9RS, United Kingdom
| | - Michael A Heneghan
- Hepatology, Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Varuna Aluvihare
- Hepatology, Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Abid Suddle
- Hepatology, Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Rosa Miquel
- Liver Histopathology, Department of Histopathology, Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Mohamed Rela
- Liver Transplant and HPB Surgery, Dr Rela Institute & Medical Center, Chennai, India
| | - Nigel D Heaton
- Liver Transplant Surgery, Institute of Liver Studies, King's College Hospital, London, SE5 9RS, United Kingdom
| | - Krishna V Menon
- Liver Transplant Surgery, Institute of Liver Studies, King's College Hospital, London, SE5 9RS, United Kingdom.
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Role of Pretransplant Treatments for Patients with Hepatocellular Carcinoma Waiting for Liver Transplantation. Cancers (Basel) 2022; 14:cancers14020396. [PMID: 35053558 PMCID: PMC8773674 DOI: 10.3390/cancers14020396] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 01/09/2022] [Accepted: 01/12/2022] [Indexed: 02/01/2023] Open
Abstract
Simple Summary Hepatocellular carcinoma (HCC) is the fifth most common cancer in men worldwide and the second leading cause of cancer death. Liver transplantation (LT) is one of the treatment options for patients with HCC. Recently, there have been many reports of the usefulness of locoregional therapy, such as transarterial chemoembolization and radiofrequency ablation, for HCC as pretreatment before LT. In Western countries, locoregional therapy is used to bridge until transplantation to prevent drop-outs from the waiting list or for downstaging to treat patients with advanced HCC who initially exceed the criteria for LT. With the progress of locoregional therapy, new reports on the effects of bridging and downstaging locoregional therapy as pretransplant treatment are increasing in number. Abstract Recently, there have been many reports of the usefulness of locoregional therapy such as transarterial chemoembolization and radiofrequency ablation for hepatocellular carcinoma (HCC) as pretreatment before liver transplantation (LT). Locoregional therapy is performed with curative intent in Japan, where living donor LT constitutes the majority of LT due to the critical shortage of deceased donors. However, in Western countries, where deceased donor LT is the main procedure, LT is indicated for early-stage HCC regardless of liver functional reserve, and locoregional therapy is used for bridging until transplantation to prevent drop-outs from the waiting list or for downstaging to treat patients with advanced HCC who initially exceed the criteria for LT. There are many reports of the effect of bridging and downstaging locoregional therapy before LT, and its indications and efficacy are becoming clear. Responses to locoregional therapy, such as changes in tumor markers, the avidity of FDG-PET, etc., are considered useful for successful bridging and downstaging. In this review, the effects of bridging and downstaging locoregional therapy as a pretransplant treatment on the results of transplantation are clarified, focusing on recent reports.
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Benson AB, D'Angelica MI, Abbott DE, Anaya DA, Anders R, Are C, Bachini M, Borad M, Brown D, Burgoyne A, Chahal P, Chang DT, Cloyd J, Covey AM, Glazer ES, Goyal L, Hawkins WG, Iyer R, Jacob R, Kelley RK, Kim R, Levine M, Palta M, Park JO, Raman S, Reddy S, Sahai V, Schefter T, Singh G, Stein S, Vauthey JN, Venook AP, Yopp A, McMillian NR, Hochstetler C, Darlow SD. Hepatobiliary Cancers, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2021; 19:541-565. [PMID: 34030131 DOI: 10.6004/jnccn.2021.0022] [Citation(s) in RCA: 546] [Impact Index Per Article: 136.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
The NCCN Guidelines for Hepatobiliary Cancers focus on the screening, diagnosis, staging, treatment, and management of hepatocellular carcinoma (HCC), gallbladder cancer, and cancer of the bile ducts (intrahepatic and extrahepatic cholangiocarcinoma). Due to the multiple modalities that can be used to treat the disease and the complications that can arise from comorbid liver dysfunction, a multidisciplinary evaluation is essential for determining an optimal treatment strategy. A multidisciplinary team should include hepatologists, diagnostic radiologists, interventional radiologists, surgeons, medical oncologists, and pathologists with hepatobiliary cancer expertise. In addition to surgery, transplant, and intra-arterial therapies, there have been great advances in the systemic treatment of HCC. Until recently, sorafenib was the only systemic therapy option for patients with advanced HCC. In 2020, the combination of atezolizumab and bevacizumab became the first regimen to show superior survival to sorafenib, gaining it FDA approval as a new frontline standard regimen for unresectable or metastatic HCC. This article discusses the NCCN Guidelines recommendations for HCC.
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Affiliation(s)
- Al B Benson
- 1Robert H. Lurie Comprehensive Cancer Center of Northwestern University
| | | | | | | | - Robert Anders
- 5The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
| | | | | | | | | | | | - Prabhleen Chahal
- 11Case Comprehensive Cancer Center, University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute
| | | | - Jordan Cloyd
- 13The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute
| | | | - Evan S Glazer
- 14St. Jude Children's Research HospitalThe University of Tennessee Health Science Center
| | | | - William G Hawkins
- 16Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
| | | | | | - R Kate Kelley
- 19UCSF Helen Diller Family Comprehensive Cancer Center
| | - Robin Kim
- 20Huntsman Cancer Institute at the University of Utah
| | - Matthew Levine
- 21Abramson Cancer Center at the University of Pennsylvania
| | | | - James O Park
- 23Fred Hutchinson Cancer Research CenterSeattle Cancer Care Alliance
| | | | | | | | | | | | | | | | - Alan P Venook
- 19UCSF Helen Diller Family Comprehensive Cancer Center
| | - Adam Yopp
- 31UT Southwestern Simmons Comprehensive Cancer Center; and
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Impact of liver-directed therapy and non-therapy on the waiting time list of patient candidates for liver transplantation: retrospective survival analysis. Clin Exp Hepatol 2021; 6:304-312. [PMID: 33511277 PMCID: PMC7816629 DOI: 10.5114/ceh.2020.102175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Accepted: 07/23/2020] [Indexed: 11/22/2022] Open
Abstract
Aim of the study To determine whether liver-directed therapies (LDT) and no therapy affect waiting list times for liver transplant candidates from a single center. Material and methods This retrospective study included patients > 12 years of age diagnosed with hepatocellular carcinoma between January 2014 and June 2019 and followed until the date of transplant, date of delisting, loss to follow-up, or date of death. Waiting list time and associated factors were analyzed using Kaplan-Meier and Cox proportional-hazards methods. Results A total of 181 patients met the selection criteria. The mean age was 60 years with standard deviation (SD) of 7.8 years. Sixty-six percent underwent transplant, and 64% were classified within the Milan criteria. Men had a lower median waiting list time than women (191 days vs. 236 days, p = 0.0093). The overall median survival time or time to transplant for 50% of the population was 218 days (95% CI: 195-235). Men displayed a 3.1-fold (95% CI: 1.5-6.2) higher probability of transplantation than women (p = 0.002). Patients who received no therapy had a 5-fold higher probability of undergoing transplantation than patients under arterial LDT (HR [95% CI]: 5 [1.2, 20], p = 0.02). Patients under combined LDT displayed a 70% reduced probability of transplantation compared to patients who received arterial LDTs (p = 0.0009). Conclusions LDT was associated with a prolonged stay on the transplant list, likely due to the presence of an aggressive liver tumor. However, LDTs allow the patient to remain active on the liver transplant list, increasing their chances of undergoing transplantation.
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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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Abstract
Despite advancements in early diagnosis and medico-surgical treatment, hepatocellular carcinoma (HCC) is still a major cancer that causes substantial mortality in Asian countries. Liver transplantation (LT) has been accepted worldwide as the most effective treatment modality for patients with HCC; however, with the high incidence of HCC and low organ donation rate, Asia has developed distinctive features of indications and strategies for the application of LT. Unlike Western countries, living donor liver transplantation (LDLT) accounts for most LT cases for HCC in Asian countries, and most major transplantation centers perform LDLT for HCC patients with extended criteria. This article reviewed the current practice and outcome of LDLT for HCC from an Asian perspective and summarized the strategies that the high-volume LT centers in Asia use to obtain satisfactory oncologic results.
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Achieving Complete Remission of Hepatocellular Carcinoma: A Significant Predictor for Recurrence-Free Survival after Liver Transplantation. Can J Gastroenterol Hepatol 2019; 2019:5796074. [PMID: 30729099 PMCID: PMC6341263 DOI: 10.1155/2019/5796074] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2018] [Accepted: 01/01/2019] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Liver transplantation (LT) is a curative treatment for hepatocellular carcinoma (HCC) and the underlying primary liver disease; however, tumor recurrence is still a major issue. Therefore, the aim of this study was to assess predictors and risk factors for HCC recurrence after LT in patients within and outside the Milan criteria with a special focus on the impact of different bridging strategies. METHODS All patients who underwent LT for HCC between 07/2002 and 09/2016 at the University Hospital of Muenster were consecutively included in this retrospective study. Database research was performed and a multivariable regression analysis was conducted to explore potential risk factors for HCC recurrence. RESULTS A total of 82 patients were eligible for the statistical analysis. Independent of bridging strategy, achieving complete remission (CR) was significantly associated with a lower risk for tumor recurrence (p = 0.029; OR = 0.426, 95% CI 0.198-0.918). A maximal diameter of lesion < 3 cm was also associated with lower recurrence rates (p = 0.040; OR = 0.140, 95% CI 0.022-0.914). Vascular invasion proved to be an independent risk factor for HCC recurrence (p = 0.004; OR = 11.357, 95% CI 2.142-60.199). CONCLUSION Achieving CR prior to LT results in a significant risk reduction of HCC recurrence after LT independent of the treatment modalities applied.
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Impact of Pretransplant Bridging Locoregional Therapy for Patients With Hepatocellular Carcinoma Within Milan Criteria Undergoing Liver Transplantation: Analysis of 3601 Patients From the US Multicenter HCC Transplant Consortium. Ann Surg 2017; 266:525-535. [PMID: 28654545 DOI: 10.1097/sla.0000000000002381] [Citation(s) in RCA: 140] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE To evaluate the effect of pretransplant bridging locoregional therapy (LRT) on hepatocellular carcinoma (HCC) recurrence and survival after liver transplantation (LT) in patients meeting Milan criteria (MC). SUMMARY BACKGROUND DATA Pre-LT LRT mitigates tumor progression and waitlist dropout in HCC patients within MC, but data on its impact on post-LT recurrence and survival remain limited. METHODS Recurrence-free survival and post-LT recurrence were compared among 3601 MC patients with and without bridging LRT utilizing competing risk Cox regression in consecutive patients from 20 US centers (2002-2013). RESULTS Compared with 747 LT recipients not receiving LRT, 2854 receiving LRT had similar 1, 3, and 5-year recurrence-free survival (89%, 77%, 68% vs 85%, 75%, 68%; P = 0.490) and 5-year post-LT recurrence (11.2% vs 10.1%; P = 0.474). Increasing LRT number [3 LRTs: hazard ratio (HR) 2.1, P < 0.001; 4+ LRTs: HR 2.5, P < 0.001), and unfavorable waitlist alphafetoprotein trend significantly predicted post-LT recurrence, whereas LRT modality did not. Treated patients achieving complete pathologic response (cPR) had superior 5-year RFS (72%) and lower post-LT recurrence (HR 0.52, P < 0.001) compared with both untreated patients (69%; P = 0.010; HR 1.0) and treated patients not achieving cPR (67%; P = 0.010; HR 1.31, P = 0.039), who demonstrated increased recurrence compared with untreated patients in multivariate analysis controlling for pretransplant and pathologic factors (HR 1.32, P = 0.044). CONCLUSIONS Bridging LRT in HCC patients within MC does not improve post-LT survival or HCC recurrence in the majority of patients who fail to achieve cPR. The need for increasing LRT treatments and lack of alphafetoprotein response to LRT independently predict post-LT recurrence, serving as a surrogate for underlying tumor biology which can be utilized for prioritization of HCC LT candidates.
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Györi GP, Felsenreich DM, Silberhumer GR, Soliman T, Berlakovich GA. Multimodality locoregional treatment strategies for bridging HCC patients before liver transplantation. Eur Surg 2017; 49:236-243. [PMID: 29104589 PMCID: PMC5653748 DOI: 10.1007/s10353-017-0487-8] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2017] [Accepted: 07/24/2017] [Indexed: 12/14/2022]
Abstract
BACKGROUND It is current practice that patients with hepatocellular carcinoma (HCC) listed for liver transplantation should receive locoregional treatment if the suspected waiting time for transplantation is longer than 6 months, even in the absence of prospective randomized data. Aim of this study was the comparison of single versus multimodality locoregional treatment strategies on outcomes after liver transplantation. METHODS This is a retrospective analysis of 150 HCC patients listed for liver transplantation at our center between 2004 and 2011. Outcomes were analyzed according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) in relation to intention-to-treat and overall survival after liver transplantation. RESULTS Overall, 92 patients (63%) were transplanted in this cohort. The intention-to-treat 1‑, 3‑, 5‑year waiting list survival was 80, 59, and 50% respectively. In RFA-(radiofrequency ablative) and TACE-(transarterial chemoembolisation)-based regimens, rates of transplanted patients were comparable (69 vs. 58%, p = ns). No difference was seen in overall survival after liver transplantation when comparing TACE- and RFA-based regimens. Patients receiving multimodality locoregional therapy had lower overall survival after transplantation (p = 0.05). CONCLUSION TACE- and RFA-based regimens showed equal outcomes in terms of transplantation rate, tumor response, and post-transplant survival. Patients in need of more than one treatment modality might identify a cohort with poorer post-transplant survival. POINTS OF NOVELTY Direct comparison of TACE and RFA in a multimodality setting, analysis according to mRECIST.
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Affiliation(s)
- Georg P. Györi
- Department of Surgery, Division of Transplantation, Medical University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, Austria
| | - D. Moritz Felsenreich
- Department of Surgery, Division of Transplantation, Medical University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, Austria
| | - Gerd R. Silberhumer
- Department of Surgery, Division of Transplantation, Medical University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, Austria
| | - Thomas Soliman
- Department of Surgery, Division of Transplantation, Medical University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, Austria
| | - Gabriela A. Berlakovich
- Department of Surgery, Division of Transplantation, Medical University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, Austria
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Sapisochin G, Barry A, Doherty M, Fischer S, Goldaracena N, Rosales R, Russo M, Beecroft R, Ghanekar A, Bhat M, Brierley J, Greig PD, Knox JJ, Dawson LA, Grant DR. Stereotactic body radiotherapy vs. TACE or RFA as a bridge to transplant in patients with hepatocellular carcinoma. An intention-to-treat analysis. J Hepatol 2017; 67:92-99. [PMID: 28257902 DOI: 10.1016/j.jhep.2017.02.022] [Citation(s) in RCA: 216] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2016] [Revised: 01/20/2017] [Accepted: 02/18/2017] [Indexed: 12/04/2022]
Abstract
BACKGROUND & AIMS There is limited information on the use of stereotactic body radiotherapy (SBRT) as a bridge to liver transplantation for hepatocellular carcinoma and no study comparing its efficacy to transarterial chemoembolization (TACE) and radiofrequency ablation (RFA). We aimed to ascertain the safety and efficacy of SBRT on an intention-to-treat basis compared with TACE and RFA as a bridge to liver transplantation in a large cohort of patients with hepatocellular carcinoma. METHODS Outcomes between groups were compared from the time of listing and from the time of transplant. Between July 2004 and December 2014, 379 patients were treated with either SBRT (n=36, SBRT group), TACE (n=99, TACE group) or RFA (n=244, RFA group). RESULTS The drop-out rate was similar between groups (16.7% SBRT group vs. 20.2% TACE group and 16.8% RFA group, p=0.7); 30 patients were transplanted in the SBRT group, 79 in the TACE group and 203 in the RFA group. Postoperative complications were similar between groups. Patients in the RFA group had more tumor necrosis in the explant. The 1-, 3- and 5-year actuarial patient survival from the time of listing was 83%, 61% and 61% in the SBRT group vs. 86%, 61% and 56% in the TACE group, and 86%, 72% and 61% in the RFA group, p=0.4. The 1-, 3- and 5-year survival from the time of transplant was 83%, 75% and 75% in the SBRT group vs. 96%, 75% and 69% in the TACE group, and 95%, 81% and 73% in the RFA group, p=0.7. CONCLUSIONS In conclusion, SBRT can be safely utilized as a bridge to LT in patients with HCC, as an alternative to conventional bridging therapies. LAY SUMMARY Patients with liver cancer included in the waiting list for liver transplantation are at risk of tumor progression and death. Stereotactic body radiotherapy may be a good alternative to conventional therapies to reduce this risk.
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Affiliation(s)
- Gonzalo Sapisochin
- Multi-Organ Transplant, Toronto General Surgery, Canada; Department of General Surgery, University of Toronto, Canada.
| | - Aisling Barry
- Radiation Medicine Program, Princess Margaret Cancer Centre, Department of Radiation Oncology, University of Toronto, Canada
| | - Mark Doherty
- Department of Medical Oncology, University of Toronto, Canada
| | | | - Nicolas Goldaracena
- Multi-Organ Transplant, Toronto General Surgery, Canada; Department of General Surgery, University of Toronto, Canada
| | | | - Moises Russo
- Radiation Medicine Program, Princess Margaret Cancer Centre, Department of Radiation Oncology, University of Toronto, Canada
| | - Rob Beecroft
- Division of Interventional Radiology, University of Toronto, Canada
| | - Anand Ghanekar
- Multi-Organ Transplant, Toronto General Surgery, Canada; Department of General Surgery, University of Toronto, Canada
| | - Mamatha Bhat
- Multi-Organ Transplant, Toronto General Surgery, Canada
| | - James Brierley
- Radiation Medicine Program, Princess Margaret Cancer Centre, Department of Radiation Oncology, University of Toronto, Canada
| | - Paul D Greig
- Multi-Organ Transplant, Toronto General Surgery, Canada; Department of General Surgery, University of Toronto, Canada
| | - Jennifer J Knox
- Department of Medical Oncology, University of Toronto, Canada
| | - Laura A Dawson
- Radiation Medicine Program, Princess Margaret Cancer Centre, Department of Radiation Oncology, University of Toronto, Canada
| | - David R Grant
- Multi-Organ Transplant, Toronto General Surgery, Canada; Department of General Surgery, University of Toronto, Canada
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Al Sebayel MI, Elsiesy H, Al-Hamoudi W, Alabbad S, ElSheikh Y, Elbeshbeshy H, Salih I, Yousif S, Saleh Y, Eldali A, Abaalkhail FA. Effect of Downstaging and Bridging of Hepatocellular Carcinoma on Survival Following Liver Transplant: A Single Center Experience. EXP CLIN TRANSPLANT 2017; 15:7-11. [PMID: 28301992 DOI: 10.6002/ect.tond16.l4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES Hepatocellular carcinoma is among the leading causes of cancer death. The Milan criteria are the first and most widely used criteria for selecting patients with hepatocellular carcinoma for a good transplant outcome. Studies have shown that patients with hepatocellular carcinoma outside the Milan criteria have good outcomes if they are successfully downstaged before transplant. We report our experience with locoregional therapy for hepatocellular carcinoma, either for bridging or for downstaging prior to transplant. MATERIALS AND METHODS We retrospectively reviewed the electronic charts and our institutional database for adult patients diagnosed with hepatocellular carcinoma between 2001 and 2016. We recorded patient demographics, the type of transplant (living donor or deceased donor), radiologic findings, the type of locoregional intervention, and overall survival. RESULTS A total of 642 adult liver transplants were performed during the study period (290 living donor and 352 deceased donor), of which 158 (24.6%) were conducted in patients with hepatocellular carcinoma (104 men and 54 women). Hepatocellular carcinoma was associated with hepatitis C in 80 patients (51%), hepatitis B in 44 (28%), and was cryptogenic in 13 (8%). Patients were grouped based on their radiologic staging (within Milan, within and beyond University of California, San Francisco), and subsequently described by whether they received locoregional therapy. Median survival and mortality were noted. Kaplan-Meier survival curves showed no statistically significant difference for patients within the Milan criteria, with or without locoregional therapy (P = .5). When patients within the Milan criteria were combined with patients within the University of California, San Francisco criteria, those who were downstaged from outside the latter criteria had similar survival. CONCLUSIONS We demonstrate that carefully selected patients beyond the Milan criteria and even beyond the University of California, San Francisco criteria can be bridged and downstaged successfully for liver transplant.
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Affiliation(s)
- Mohammed I Al Sebayel
- Department of Liver & Small Bowel Transplantation and Hepatobiliary-Pancreatic Surgery, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
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12
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Ma KW, Cheung TT. When to consider liver transplantation in hepatocellular carcinoma patients? Hepat Oncol 2017; 4:15-24. [PMID: 30191050 PMCID: PMC6095144 DOI: 10.2217/hep-2016-0010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2016] [Accepted: 04/06/2017] [Indexed: 12/12/2022] Open
Abstract
Orthotopic liver transplantation (LT) has been regarded as the best cure among the three curative treatment modalities. However, when to consider LT in hepatocellular carcinoma (HCC) patients remains a complicated clinical question. In this article, we will look into the recent updates in the context of LT for HCC, including the timing of orthotopic LT (primary or salvage LT), patient selection criteria, newer prognostic markers and scoring systems, down-staging and bridging therapy, salvage LT and treatment option of post-LT HCC recurrence. Evolution of immunosuppressive therapy and future development of the LT for HCC will also be discussed.
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Affiliation(s)
- Ka Wing Ma
- Department of Surgery, Queen Mary Hospital, the University of Hong Kong, Hong Kong
| | - Tan To Cheung
- Department of Surgery, Queen Mary Hospital, the University of Hong Kong, Hong Kong
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Cillo U, Giuliani T, Polacco M, Herrero Manley LM, Crivellari G, Vitale A. Prediction of hepatocellular carcinoma biological behavior in patient selection for liver transplantation. World J Gastroenterol 2016; 22:232-252. [PMID: 26755873 PMCID: PMC4698488 DOI: 10.3748/wjg.v22.i1.232] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2015] [Revised: 08/14/2015] [Accepted: 11/09/2015] [Indexed: 02/06/2023] Open
Abstract
Morphological criteria have always been considered the benchmark for selecting hepatocellular carcinoma (HCC) patients for liver transplantation (LT). These criteria, which are often inappropriate to express the tumor’s biological behavior and aggressiveness, offer only a static view of the disease burden and are frequently unable to correctly stratify the tumor recurrence risk after LT. Alpha-fetoprotein (AFP) and its progression as well as AFP-mRNA, AFP-L3%, des-γ-carboxyprothrombin, inflammatory markers and other serological tests appear to be correlated with post-transplant outcomes. Several other markers for patient selection including functional imaging studies such as 18F-FDG-PET imaging, histological evaluation of tumor grade, tissue-specific biomarkers, and molecular signatures have been outlined in the literature. HCC growth rate and response to pre-transplant therapies can further contribute to the transplant evaluation process of HCC patients. While AFP, its progression, and HCC response to pre-transplant therapy have already been used as a part of an integrated prognostic model for selecting patients, the utility of other markers in the transplant setting is still under investigation. This article intends to review the data in the literature concerning predictors that could be included in an integrated LT selection model and to evaluate the importance of biological aggressiveness in the evaluation process of these patients.
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Waller LP, Deshpande V, Pyrsopoulos N. Hepatocellular carcinoma: A comprehensive review. World J Hepatol 2015; 7:2648-2663. [PMID: 26609342 PMCID: PMC4651909 DOI: 10.4254/wjh.v7.i26.2648] [Citation(s) in RCA: 137] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2015] [Revised: 05/19/2015] [Accepted: 10/14/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is rapidly becoming one of the most prevalent cancers worldwide. With a rising rate, it is a prominent source of mortality. Patients with advanced fibrosis, predominantly cirrhosis and hepatitis B are predisposed to developing HCC. Individuals with chronic hepatitis B and C infections are most commonly afflicted. Different therapeutic options, including liver resection, transplantation, systemic and local therapy, must be tailored to each patient. Liver transplantation offers leading results to achieve a cure. The Milan criteria is acknowledged as the model to classify the individuals that meet requirements to undergo transplantation. Mean survival remains suboptimal because of long waiting times and limited donor organ resources. Recent debates involve expansion of these criteria to create options for patients with HCC to increase overall survival.
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Affiliation(s)
- Lisa P Waller
- Lisa P Waller, Vrushak Deshpande, Nikolaos Pyrsopoulos, Division of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
| | - Vrushak Deshpande
- Lisa P Waller, Vrushak Deshpande, Nikolaos Pyrsopoulos, Division of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
| | - Nikolaos Pyrsopoulos
- Lisa P Waller, Vrushak Deshpande, Nikolaos Pyrsopoulos, Division of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
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15
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Agopian VG, Harlander-Locke M, Zarrinpar A, Kaldas FM, Farmer DG, Yersiz H, Finn RS, Tong M, Hiatt JR, Busuttil RW. A novel prognostic nomogram accurately predicts hepatocellular carcinoma recurrence after liver transplantation: analysis of 865 consecutive liver transplant recipients. J Am Coll Surg 2014; 220:416-27. [PMID: 25690672 DOI: 10.1016/j.jamcollsurg.2014.12.025] [Citation(s) in RCA: 195] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2014] [Accepted: 12/17/2014] [Indexed: 02/06/2023]
Abstract
BACKGROUND Although radiologic size criteria (Milan/University of California, San Francisco [UCSF]) have led to improved outcomes after liver transplantation (LT) for hepatocellular carcinoma (HCC), recurrence remains a significant challenge. We analyzed our 30-year experience with LT for HCC to identify predictors of recurrence. STUDY DESIGN A novel clinicopathologic risk score and prognostic nomogram predicting post-transplant HCC recurrence was developed from a multivariate competing-risk Cox regression analysis of 865 LT recipients with HCC between 1984 and 2013. RESULTS Overall patient and recurrence-free survivals were 83%, 68%, 60% and 79%, 63%, and 56% at 1-, 3-, and 5-years, respectively. Hepatocellular carcinoma recurred in 117 recipients, with a median time to recurrence of 15 months, involving the lungs (59%), abdomen/pelvis (38%), liver (35%), bone (28%), pleura/mediastinum (12%), and brain (5%). Multivariate predictors of recurrence included tumor grade/differentiation (G4/poor diff hazard ratio [HR] 8.86; G2-3/mod-poor diff HR 2.56), macrovascular (HR 7.82) and microvascular (HR 2.42) invasion, nondownstaged tumors outside Milan criteria (HR 3.02), nonincidental tumors with radiographic maximum diameter ≥ 5 cm (HR 2.71) and <5 cm (HR 1.55), and pretransplant neutrophil-to-lymphocyte ratio (HR 1.77 per log unit), maximum alpha fetoprotein (HR 1.21 per log unit), and total cholesterol (HR 1.14 per SD). A pretransplantation model incorporating only known radiographic and laboratory parameters had improved accuracy in predicting HCC recurrence (C statistic 0.79) compared with both Milan (C statistic 0.64) and UCSF (C statistic 0.64) criteria alone. A novel clinicopathologic prognostic nomogram included explant pathology and had an excellent ability to predict post-transplant recurrence (C statistic 0.85). CONCLUSIONS In the largest single-institution experience with LT for HCC, excellent long-term survival was achieved. Incorporation of routine pretransplantation biomarkers to existing radiographic size criteria significantly improves the ability to predict post-transplant recurrence, and should be considered in recipient selection. A novel clinicopathologic prognostic nomogram accurately predicts HCC recurrence after LT and may guide frequency of post-transplantation surveillance and adjuvant therapy.
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Affiliation(s)
- Vatche G Agopian
- Dumont-UCLA Transplant and Liver Cancer Centers, Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles, CA
| | - Michael Harlander-Locke
- Dumont-UCLA Transplant and Liver Cancer Centers, Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles, CA
| | - Ali Zarrinpar
- Dumont-UCLA Transplant and Liver Cancer Centers, Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles, CA
| | - Fady M Kaldas
- Dumont-UCLA Transplant and Liver Cancer Centers, Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles, CA
| | - Douglas G Farmer
- Dumont-UCLA Transplant and Liver Cancer Centers, Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles, CA
| | - Hasan Yersiz
- Dumont-UCLA Transplant and Liver Cancer Centers, Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles, CA
| | - Richard S Finn
- Division of Hematology/Oncology, David Geffen School of Medicine at University of California, Los Angeles, CA
| | - Myron Tong
- Dumont-UCLA Transplant and Liver Cancer Centers, Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles, CA
| | - Jonathan R Hiatt
- Dumont-UCLA Transplant and Liver Cancer Centers, Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles, CA
| | - Ronald W Busuttil
- Dumont-UCLA Transplant and Liver Cancer Centers, Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles, CA.
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16
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Agrawal S, Dhiman RK. Hepatobiliary quiz-12 (2014). J Clin Exp Hepatol 2014; 4:376-9. [PMID: 25755586 PMCID: PMC4298632 DOI: 10.1016/j.jceh.2014.11.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Affiliation(s)
| | - Radha K. Dhiman
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
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17
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Lee SY, Konstantinidis IT, Eaton AA, Gönen M, Kingham TP, D’Angelica MI, Allen PJ, Fong Y, DeMatteo RP, Jarnagin WR. Predicting recurrence patterns after resection of hepatocellular cancer. HPB (Oxford) 2014; 16:943-53. [PMID: 25041404 PMCID: PMC4238862 DOI: 10.1111/hpb.12311] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2014] [Accepted: 06/04/2014] [Indexed: 12/12/2022]
Abstract
BACKGROUND The reliable prediction of hepatocellular carcinoma (HCC) recurrence patterns potentially allows for the prioritization of patients for liver resection (LR) or transplantation. OBJECTIVES The aim of this study was to analyse clinicopathological factors and preoperative Milan criteria (MC) status in predicting patterns of HCC recurrence. METHODS During 1992-2012, 320 patients undergoing LR for HCC were categorized preoperatively as being within or beyond the MC, as were recurrences. RESULTS After a median follow-up of 47 months, 183 patients developed recurrence, giving a 5-year cumulative incidence of recurrence of 62.5%. Patients with preoperative disease within the MC had better survival outcomes than those with preoperative disease beyond the MC (median survival: 102 months versus 45 months; P < 0.001). Overall, 31% of patients had preoperative disease within the MC and 69% had preoperative disease beyond the MC. Estimated rates of recurrence-free survival at 5 years were 61.8% for all patients and 53.8% for patients with initial beyond-MC status. Independent factors for recurrence beyond-MC status included preoperative disease beyond the MC, the presence of microsatellite or multiple tumours and lymphovascular invasion (all: P < 0.001). A clinical risk score was used to predict survival and the likelihood of recurrence beyond the MC; patients with scores of 0, 1, 2 and 3 had 5- year incidence of recurring beyond-MC of 9.0%, 29.5%, 48.8% and 75.4%, respectively (P < 0.0001). CONCLUSIONS Regardless of initial MC status, at 5 years the majority of patients remained disease-free or experienced recurrence within the MC after LR, and thus were potentially eligible for salvage transplantation (ST). Incorporating clinicopathological parameters into the MC allows for better risk stratification, which improves the selection of patients for ST and identifies patients in need of closer surveillance.
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Affiliation(s)
- Ser Yee Lee
- Department of Surgery, Memorial SloanKettering Cancer CenterNew York, NY, USA,Department of Epidemiology and Biostatistics, Memorial SloanKettering Cancer CenterNew York, NY, USA,Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General HospitalSingapore, Singapore,Department of Surgical Oncology, National Cancer CentreSingapore, Singapore
| | | | - Anne A Eaton
- Department of Epidemiology and Biostatistics, Memorial SloanKettering Cancer CenterNew York, NY, USA
| | - Mithat Gönen
- Department of Epidemiology and Biostatistics, Memorial SloanKettering Cancer CenterNew York, NY, USA
| | - T Peter Kingham
- Department of Surgery, Memorial SloanKettering Cancer CenterNew York, NY, USA
| | | | - Peter J Allen
- Department of Surgery, Memorial SloanKettering Cancer CenterNew York, NY, USA
| | - Yuman Fong
- Department of Surgery, Memorial SloanKettering Cancer CenterNew York, NY, USA
| | - Ronald P DeMatteo
- Department of Surgery, Memorial SloanKettering Cancer CenterNew York, NY, USA
| | - William R Jarnagin
- Department of Surgery, Memorial SloanKettering Cancer CenterNew York, NY, USA,Correspondence: William R. Jarnagin, Department of Surgery, Memorial Sloan–Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. Tel: + 1 212 639 3624. Fax: + 1 917 432 2387. E-mail:
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Preresection transarterial chemoembolization for hepatocellular carcinoma: an experience with 23 patients. Indian J Gastroenterol 2014; 33:432-9. [PMID: 25037076 DOI: 10.1007/s12664-014-0490-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2014] [Accepted: 06/30/2014] [Indexed: 02/04/2023]
Abstract
PURPOSE The routine use of transarterial chemoembolization (TACE) prior to resection for hepatocellular carcinoma (HCC) is not recommended, although its use in the transplant setting is gaining popularity. In the absence of other effective neoadjuvant or adjuvant treatment options, TACE may benefit selected patients. The aim was to evaluate the feasibility and outcomes of preoperative TACE for selected patients with HCC. METHODS From November 2010 to October 2012, 23 patients of HCC were selected by a multidisciplinary team to undergo TACE prior to resection. RESULTS TACE was successful in all patients with no intraprocedural complications. TACE reduced the mean maximum tumor diameter from 9.2 to 8.2 cm and increased the mean future liver remnant (FLR) from 37.7 % to 49.1 %. Nineteen resections were completed with negative margins, of which only three patients (15.8 %) had cirrhosis. Two patients (10.5 %) experienced postoperative bile leaks and six patients (31.5 %) developed postoperative liver failure, two (10.5 %) of which succumbed to grade C liver failure. From the date of surgery, the median follow up time was 17.1 months. Four patients (17 %) did not undergo curative resection due to disease progression in three patients and severe TACE toxicity in one patient. None of the resected patients developed disease recurrence and the overall survival was 21 months. CONCLUSION Encouraging outcomes in terms of disease recurrence and overall survival need to be balanced with the risk of surgical drop out and perioperative complications when selecting patients for TACE prior to resection.
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Tabrizian P, Roayaie S, Schwartz ME. Current management of hepatocellular carcinoma. World J Gastroenterol 2014; 20:10223-10237. [PMID: 25132740 PMCID: PMC4130831 DOI: 10.3748/wjg.v20.i30.10223] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2014] [Revised: 05/08/2014] [Accepted: 05/26/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and leading cause of death among patients with cirrhosis. Treatment guidelines are based according to the Barcelona Clinic Liver Cancer staging system. The choice among therapeutic options that include liver resection, liver transplantation, locoregional, and systemic treatments must be individualized for each patient. The aim of this paper is to review the outcomes that can be achieved in the treatment of HCC with the heterogeneous therapeutic options currently available in clinical practice.
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20
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Kumar A, Acharya SK, Singh SP, Saraswat VA, Arora A, Duseja A, Goenka MK, Jain D, Kar P, Kumar M, Kumaran V, Mohandas KM, Panda D, Paul SB, Ramachandran J, Ramesh H, Rao PN, Shah SR, Sharma H, Thandassery RB, (The INASL Task-Force on Hepatocellular Carcinoma). The Indian National Association for Study of the Liver (INASL) Consensus on Prevention, Diagnosis and Management of Hepatocellular Carcinoma in India: The Puri Recommendations. J Clin Exp Hepatol 2014; 4:S3-S26. [PMID: 25755608 PMCID: PMC4284289 DOI: 10.1016/j.jceh.2014.04.003] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2013] [Accepted: 04/08/2014] [Indexed: 02/08/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the major causes of morbidity, mortality and healthcare expenditure in patients with chronic liver disease. There are no consensus guidelines on diagnosis and management of HCC in India. The Indian National Association for Study of the Liver (INASL) set up a Task-Force on HCC in 2011, with a mandate to develop consensus guidelines for diagnosis and management of HCC, relevant to disease patterns and clinical practices in India. The Task-Force first identified various contentious issues on various aspects of HCC and these issues were allotted to individual members of the Task-Force who reviewed them in detail. The Task-Force used the Oxford Center for Evidence Based Medicine-Levels of Evidence of 2009 for developing an evidence-based approach. A 2-day round table discussion was held on 9th and 10th February, 2013 at Puri, Odisha, to discuss, debate, and finalize the consensus statements. The members of the Task-Force reviewed and discussed the existing literature at this meeting and formulated the INASL consensus statements for each of the issues. We present here the INASL consensus guidelines (The Puri Recommendations) on prevention, diagnosis and management of HCC in India.
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Key Words
- AFP, alpha-fetoprotein
- AIIMS, All India Institute of Medical Sciences
- ASMR, age standardized mortality rate
- BCLC, Barcelona-Clinic Liver Cancer
- CEUS, contrast enhanced ultrasound
- CT, computed tomography
- DCP, des-gamma-carboxy prothrombin
- DDLT, deceased donor liver transplantation
- DE, drug eluting
- FNAC, fine needle aspiration cytology
- GPC-3, glypican-3
- GS, glutamine synthase
- Gd-EOB-DTPA, gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid
- HBV, Hepatitis B virus
- HCC, hepatocellular carcinoma
- HCV, Hepatitis C virus
- HSP-70, heat shock protein-70
- HVPG, hepatic venous pressure gradient
- ICG, indocyanine green
- ICMR, Indian Council of Medical Research
- INASL, Indian National Association for Study of the Liver
- LDLT, living donor liver transplantation
- MRI, magnetic resonance imaging
- Mabs, monoclonal antibodies
- NAFLD, non-alcoholic fatty liver disease
- OLT, orthotopic liver transplantation
- PAI, percutaneous acetic acid injection
- PEI, percutaneous ethanol injection
- PET, positron emission tomography
- PVT, portal vein thrombosis
- RECIST, Response Evaluation Criteria in Solid Tumors
- RFA
- RFA, radio frequency ablation
- SVR, sustained viral response
- TACE
- TACE, transarterial chemoembolization
- TART, trans-arterial radioisotope therapy
- UCSF, University of California San Francisco
- liver cancer
- targeted therapy
- transplant
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Affiliation(s)
- Ashish Kumar
- Department of Gastroenterology & Hepatology, Sir Ganga Ram Hospital, New Delhi, India
| | - Subrat K. Acharya
- Department of Gastroenterology, All India Institute of Medical Sciences, Ansari Road, New Delhi 110 029, India
| | - Shivaram P. Singh
- Department of Gastroenterology, SCB Medical College, Cuttack, Odisha, India
| | - Vivek A. Saraswat
- Department of Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Anil Arora
- Department of Gastroenterology & Hepatology, Sir Ganga Ram Hospital, New Delhi, India
| | - Ajay Duseja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Mahesh K. Goenka
- Department of Gastroenterology, Apollo Gleneagles Hospital, 58, Canal Circular Road, Kolkata, West Bengal 700 054, India
| | - Deepali Jain
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Premashish Kar
- Department of Medicine, Maulana Azad Medical College, University of Delhi, New Delhi, India
| | - Manoj Kumar
- Department of Hepatology, Institute of Liver & Biliary Sciences, New Delhi, India
| | - Vinay Kumaran
- Department of Surgical Gastroenterology and Liver Transplantation, Sir Ganga Ram Hospital, New Delhi, India
| | - Kunisshery M. Mohandas
- Department of Digestive Diseases, Tata Medical Center, Kolkata, West Bengal 700156, India
| | - Dipanjan Panda
- Department of Oncology, Institute of Liver & Biliary Sciences, New Delhi, India
| | - Shashi B. Paul
- Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India
| | - Jeyamani Ramachandran
- Department of Hepatology, Christian Medical College, Vellore, Tamil Nadu 632 004, India
| | - Hariharan Ramesh
- Department of Surgical Gastroenterology, Lakeshore Hospital and Research Center, Cochin, Kerala, India
| | - Padaki N. Rao
- Department of Medical Gastroenterology, Asian Institute of Gastroenterology, Somajiguda, Hyderabad, India
| | - Samir R. Shah
- Department of Gastroenterology, Jaslok Hospital and Research Centre, Peddar Road, Mumbai, Maharashtra 400 026, India
| | - Hanish Sharma
- Department of Gastroenterology, All India Institute of Medical Sciences, Ansari Road, New Delhi 110 029, India
| | - Ragesh B. Thandassery
- Department of Gastroenterology, Apollo Gleneagles Hospital, 58, Canal Circular Road, Kolkata, West Bengal 700 054, India
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Pompili M, Francica G, Ponziani FR, Iezzi R, Avolio AW. Bridging and downstaging treatments for hepatocellular carcinoma in patients on the waiting list for liver transplantation. World J Gastroenterol 2013; 19:7515-7530. [PMID: 24282343 PMCID: PMC3837250 DOI: 10.3748/wjg.v19.i43.7515] [Citation(s) in RCA: 86] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2013] [Revised: 09/30/2013] [Accepted: 10/18/2013] [Indexed: 02/06/2023] Open
Abstract
Several therapeutic procedures have been proposed as bridging treatments for patients with hepatocellular carcinoma (HCC) awaiting liver transplantation (LT). The most used treatments include transarterial chemoembolization and radiofrequency ablation. Surgical resection has also been successfully used as a bridging procedure, and LT should be considered a rescue treatment in patients with previous HCC resection who experience tumor recurrence or post-treatment severe decompensation of liver function. The aims of bridging treatments include decreasing the waiting list dropout rate before transplantation, reducing HCC recurrence after transplantation, and improving post-transplant overall survival. To date, no data from prospective randomized studies are available; however, for HCC patients listed for LT within the Milan criteria, prolonging the waiting time over 6-12 mo is a risk factor for tumor spread. Bridging treatments are useful in containing tumor progression and decreasing dropout. Furthermore, the response to pre-LT treatments may represent a surrogate marker of tumor biological aggressiveness and could therefore be evaluated to prioritize HCC candidates for LT. Lastly, although a definitive conclusion can not be reached, the experiences reported to date suggest a positive impact of these treatments on both tumor recurrence and post-transplant patient survival. Advanced HCC may be downstaged to achieve and maintain the current conventional criteria for inclusion in the waiting list for LT. Recent studies have demonstrated that successfully downstaged patients can achieve a 5-year survival rate comparable to that of patients meeting the conventional criteria without requiring downstaging.
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Cescon M, Cucchetti A, Ravaioli M, Pinna AD. Hepatocellular carcinoma locoregional therapies for patients in the waiting list. Impact on transplantability and recurrence rate. J Hepatol 2013; 58:609-18. [PMID: 23041304 DOI: 10.1016/j.jhep.2012.09.021] [Citation(s) in RCA: 111] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2012] [Revised: 09/27/2012] [Accepted: 09/29/2012] [Indexed: 02/07/2023]
Abstract
The practice of treating candidates for liver transplantation (LT) for hepatocellular carcinoma (HCC), with locoregional therapies, is common in most transplant centers. However, for T1 tumors and expected waiting times to LT <6 months, there is no evidence that these treatments are beneficial. For T2 tumors and for longer waiting times, neo-adjuvant treatments are usually performed with transarterial chemoembolization (TACE), ablation techniques and liver resection in selected cases. The treatment choice should be based on the BCLC staging system. At present, there is no evidence of the superiority of ablation/resection vs. TACE, but some studies showed better results of the former in achieving a complete response. The response to neo-adjuvant treatments should be evaluated through mRECIST criteria, but few studies adopted these criteria and properly analyzed factors affecting response. The simultaneous evaluation of the impact of neo-adjuvant therapies on dropout rate, post-LT HCC recurrence and patient survival is rarely reported. Tumor stage and volume, alpha-fetoprotein levels, response to treatments and liver function affect pre-LT outcomes. These same factors, together with vascular invasion and poor tumor differentiation, are major determinants of poor post-LT outcomes. Due to the low number of prospective studies with well-defined entry criteria and the variability of results, the role of downstaging is still to be defined. Novel molecular markers seem promising for the estimation of prognosis and/or response to treatments. With a persistent scarcity of organ donors, neo-adjuvant treatments can help identify patients with different probabilities of cancer progression, and consequently balance the priority of HCC and non-HCC-candidates through revised additional scores for HCC.
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Affiliation(s)
- Matteo Cescon
- General Surgery and Transplant Unit, Department of General Surgery and Organ Transplantation, University of Bologna, Bologna, Italy.
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23
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Lu DS, Siripongsakun S, Kyong Lee J, Wei SH, Cheng PM, Sabounchi S, Lee JS, Raman S, Tong MJ, Busuttil RW, Sayre J. Complete tumor encapsulation on magnetic resonance imaging: a potentially useful imaging biomarker for better survival in solitary large hepatocellular carcinoma. Liver Transpl 2013; 19:283-91. [PMID: 23280814 DOI: 10.1002/lt.23597] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2012] [Accepted: 12/13/2012] [Indexed: 02/07/2023]
Abstract
The aim of this study was to determine the prognostic value of complete tumor encapsulation as visualized on magnetic resonance imaging (MRI) in patients with a solitary large hepatocellular carcinoma (HCC) beyond the Milan criteria for liver transplantation (LT). Between December 2000 and March 2011, 57 patients who had a solitary HCC exceeding 5 cm in diameter at the time of initial MRI before any treatment were identified. MRI images of the patients were independently reviewed by 2 experienced readers for the presence of complete tumoral encapsulation. The medical records of the patients were reviewed for an outcome analysis. Thirty of the 57 patients had completely encapsulated HCC according to MRI. There was excellent interobserver agreement between the 2 readers for the assessment of complete encapsulation (κ=0.86). Overall survival was significantly longer for patients with completely encapsulated HCC versus patients with incompletely or nonencapsulated tumors (P<0.001), and this included a subanalysis of 33 patients who received locoregional treatment (LRT; P=0.04). The presence of complete encapsulation was a strong predictor for survival in these patients according to both univariate [hazard ratio (HR)=0.24, 95% confidence interval (CI)=0.12-0.52, P<0.001] and multivariate analyses (HR=0.25, 95% CI=0.07-0.85, P=0.03). The rates of down-staging (P<0.001) and eventual LT (P=0.02) after LRT were also significantly higher in the patients with completely encapsulated tumors. In conclusion, complete tumor encapsulation on MRI is a potentially useful predictor for favorable biology in patients with a solitary large HCC. This new imaging biomarker may have a role in treatment selection for patients whose tumors exceed the Milan criteria size limits.
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Affiliation(s)
- David S Lu
- Department of Radiology, University of California Los Angeles, Los Angeles, CA 90095, USA.
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Abstract
Hepatocellular carcinoma (HCC) is a highly prevalent and lethal neoplasia, the management of which has significantly improved during the last few years. A better knowledge of the natural history of the tumor and the development of staging systems that stratify patients according to the characteristics of the tumor, the liver disease, and the performance status, such as the BCLC (Barcelona Clinic Liver Cancer) system, have led to a better prediction of prognosis and to a most appropriate treatment approach. Today curative therapies (resection, transplantation, ablation) can improve survival in patients diagnosed at an early HCC stage and offer a potential long-term cure. Patients with intermediate stage HCC benefit from chemoembolization and those diagnosed at advanced stage benefit from sorafenib, a multikinase inhibitor with antiangiogenic and antiproliferative effects. In this article we review the current management in HCC and the new advances in this field.
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Affiliation(s)
- Carlos Rodríguez de Lope
- Barcelona Clinic Liver Cancer Group, Liver Unit, ICMDM, Hospital Clínic, IDIBAPS, University of Barcelona, Spain
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25
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[Multimodality treatment for hepatocellular carcinoma]. Internist (Berl) 2010; 51:1374-81. [PMID: 20938626 DOI: 10.1007/s00108-010-2673-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Hepatocellular carcinoma represents one of the most important tumor entities worldwide. The great majority of these cases in Germany can be attributed to chronic liver disease (alcohol, viral hepatitis among others), which lead to development of liver cirrhosis and ultimately to hepatocellular carcinoma. While our understanding of the pathophysiological principles underlying the origin of hepatocellular carcinoma has increased considerably in recent years, the prognosis of the majority of these patients remains poor. However, a combined interdisciplinary approach involving internists, surgeons, and radiologists can often achieve effective palliative treatment of the disease. This has recently been reinforced by applying systemic therapies which specifically influence the important biological processes of hepatocellular carcinoma. It can be assumed that by adhering to well-defined treatment algorithms and using improved drug therapy the prognosis of patients with this form of cancer will improve in the future.
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Toso C, Mentha G, Kneteman NM, Majno P. The place of downstaging for hepatocellular carcinoma. J Hepatol 2010; 52:930-6. [PMID: 20385428 DOI: 10.1016/j.jhep.2009.12.032] [Citation(s) in RCA: 106] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2009] [Revised: 12/14/2009] [Accepted: 12/14/2009] [Indexed: 02/06/2023]
Abstract
In the treatment of hepatocellular carcinomas, therapies such as trans-arterial chemo-embolisation, trans-arterial radioembolisation, percutaneous ethanol injection and radio-frequency ablation can decrease the size (and overall viability) of the tumours, thus potentially increasing the proportion of patients qualifying for resection and transplantation. While the use of such downstaging therapies is straightforward when resection is the aim, in a similar way to other neo-adjuvant treatments in the surgery of tumours that are too large or awkwardly placed to be primarily resected the issues related to transplantation are more complex. In the context of transplantation the word "downstaging" designates not only a neo-adjuvant treatment, but also a selection strategy to allow patients who are initially outside accepted listing criteria to benefit from transplantation should the neo-adjuvant therapy be successful in reducing tumour burden. The effectiveness of downstaging as a selection strategy, at first questioned because of methodological bias in the studies that described it, has been recently demonstrated by more solid prospective investigations. Several issues however remain open, such as inclusion criteria before the strategy is implemented (size/number, surrogate markers of differentiation/vascular invasion such as alpha-fetoprotein), the choice of which downstaging therapy, the end-points of treatment, and the need and duration of a period of observation proving disease response or stabilisation before the patient can be listed. The present review discusses which treatments and strategies are available for downstaging HCC on the basis of the published literature.
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Affiliation(s)
- Christian Toso
- Transplantation Unit, Department of Surgery, Geneva University Hospitals, Geneva, Switzerland.
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Pleguezuelo M, Marelli L, Misseri M, Germani G, Calvaruso V, Xiruochakis E, Manousou P, Burroughs AK. TACE versus TAE as therapy for hepatocellular carcinoma. Expert Rev Anticancer Ther 2009; 8:1623-41. [PMID: 18925854 DOI: 10.1586/14737140.8.10.1623] [Citation(s) in RCA: 63] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Transarterial chemoembolization (TACE) improves survival in cirrhotic patients with hepatocellular carcinoma (HCC). The optimal schedule, best anticancer agent and best technique are still unclear. TACE may not be better than transarterial embolization (TAE). HCC is very chemoresistant, thus embolization may be more important than chemotherapy. Lipiodol cannot be considered as an embolic agent and there are no data to show that it can release chemotherapeutic agents slowly. It can mask residual vascularity on CT imaging and its use is not recommended. Both TACE and TAE result in hypoxia, which stimulates angiogenesis, promoting tumor growth; thus combination of TACE with antiangiogenic agents may improve current results. To date, there is no evidence that TACE pre-liver transplantation or resection helps to expand current selection criteria for patients with HCC, nor results in less recurrence after surgery. Combination with other techniques, such as radiofrequency ablation and drugs, may enhance the effect of TACE. New trials are being conducted to clarify these issues.
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Affiliation(s)
- Maria Pleguezuelo
- Department of Surgery & Liver Transplantation, The Royal Free Sheila Sherlock Liver Centre, Royal Free Hospital, Hampstead Heath, London, UK.
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