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Wang M, Bonne L, Laenen A, Dekervel J, Monbaliu D, Laleman W, Vandecaveye V, Pirenne J, Verslype C, Maleux G. Long-Term Outcome of Liver Transplantation for Hepatocellular Carcinoma After Bridging or Downstaging with Doxorubicin-Eluting Superabsorbent Polymer Microspheres. Cardiovasc Intervent Radiol 2025; 48:472-484. [PMID: 39961859 DOI: 10.1007/s00270-025-03981-4] [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: 04/18/2024] [Accepted: 01/26/2025] [Indexed: 04/01/2025]
Abstract
PURPOSE To retrospectively evaluate the long-term outcomes of patients treated with liver transplantation after neoadjuvant or induction transarterial chemoembolization using doxorubicin-eluting superabsorbent polymer microspheres and to assess risk factors associated with disease recurrence and death after transplantation. MATERIALS AND METHODS Between January 2006 and April 2021, 286 patients underwent liver transplantation related to cirrhosis and early hepatocellular carcinoma (HCC). Demographic, angiographic imaging, and clinical follow-up data were collected from patients' electronic medical records. Kaplan-Meier method was used to estimate disease-free survival. The prognostic effect of patient and disease characteristics on HCC recurrence was analyzed using logistic regression models. RESULTS Fifty-three out of 286 patients (19%) underwent neoadjuvant or induction chemoembolization with doxorubicin-eluting superabsorbent polymer microspheres as bridging (n = 36) or as downstaging (n = 17) treatment. Time between diagnosis and liver transplantation was 311 days (range:225-440). Post-transplant follow-up revealed HCC recurrence in n = 1 (3%) and n = 4 (23.5%) patients in the bridging and downstaging groups, respectively, and disease-free survival at 5 years of 86% and 65% (p < 0.05) in the bridging and downstaging groups, respectively. Prognostic factors for post-transplant HCC recurrence include number of HCC lesions (p = 0.0088) and total tumor size (p = 0.0188) at diagnosis, as well as number of lesions (p = 0.0181) and largest tumor size (p = 0.0179) at explant analysis. CONCLUSION Neoadjuvant or induction chemoembolization with doxorubicin-eluting superabsorbent polymer microspheres is associated with a low incidence of post-transplant HCC recurrence; number and total size of HCC lesions at diagnosis and at explant analysis are risk factors for post-transplant HCC recurrence.
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Affiliation(s)
- Maud Wang
- Department of Radiology and Department of Imaging and Pathology, University Hospitals KU Leuven, Leuven, Belgium
| | - Lawrence Bonne
- Department of Radiology and Department of Imaging and Pathology, University Hospitals KU Leuven, Leuven, Belgium
| | - Annouschka Laenen
- Department of Biostatistics and Statistical Bioinformatics, University Hospitals KU Leuven, Leuven, Belgium
| | - Jeroen Dekervel
- Department of Gastroenterology and Hepatology, University Hospitals KU Leuven, Leuven, Belgium
| | - Diethard Monbaliu
- Department of Abdominal Transplantation Surgery, University Hospitals KU Leuven, Leuven, Belgium
| | - Wim Laleman
- Department of Gastroenterology and Hepatology, University Hospitals KU Leuven, Leuven, Belgium
| | - Vincent Vandecaveye
- Department of Radiology and Department of Imaging and Pathology, University Hospitals KU Leuven, Leuven, Belgium
| | - Jacques Pirenne
- Department of Abdominal Transplantation Surgery, University Hospitals KU Leuven, Leuven, Belgium
| | - Chris Verslype
- Department of Gastroenterology and Hepatology, University Hospitals KU Leuven, Leuven, Belgium
| | - Geert Maleux
- Department of Radiology and Department of Imaging and Pathology, University Hospitals KU Leuven, Leuven, Belgium.
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Kaslow SR, Torres-Hernandez A, Su F, Liapakis A, Griesemer A, Halazun KJ. Survival benefit of living donor liver transplant for patients with hepatocellular carcinoma. Updates Surg 2024:10.1007/s13304-024-01947-8. [PMID: 39037684 DOI: 10.1007/s13304-024-01947-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Accepted: 07/12/2024] [Indexed: 07/23/2024]
Abstract
With the increasing incidence of hepatocellular carcinoma (HCC) in both the United States and globally, the role of liver transplantation in management continues to be an area of active conversation as it is often considered the gold standard in the treatment of HCC. The use of living donor liver transplantation (LDLT) and the indications in the setting of malignancy, both generally and in HCC specifically, are frequently debated. In terms of both overall survival and recurrence-free survival, LDLT is at least equivalent to DDLT, especially when performed for disease within Milan criteria. Emerging and compelling evidence suggests that LDLT is superior to DDLT in treating HCC as there is a significant decrease in waitlist mortality. As the oncologic indications for liver transplantation continue to expand and the gap between organ demand and organ availability continues to worsen, high volumes centers should consider using LDLT to shrink the ever-expanding waitlist.
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Affiliation(s)
- Sarah R Kaslow
- Department of Surgery, New York University Grossman School of Medicine, New York, NY, USA
| | - Alejandro Torres-Hernandez
- Department of Surgery, New York University Grossman School of Medicine, New York, NY, USA
- New York University Langone Transplant Institute, New York, NY, USA
| | - Feng Su
- New York University Langone Transplant Institute, New York, NY, USA
- Department of Medicine, New York University Grossman School of Medicine, New York, NY, USA
| | - AnnMarie Liapakis
- New York University Langone Transplant Institute, New York, NY, USA
- Department of Medicine, New York University Grossman School of Medicine, New York, NY, USA
| | - Adam Griesemer
- Department of Surgery, New York University Grossman School of Medicine, New York, NY, USA
- New York University Langone Transplant Institute, New York, NY, USA
| | - Karim J Halazun
- Department of Surgery, New York University Grossman School of Medicine, New York, NY, USA.
- New York University Langone Transplant Institute, New York, NY, USA.
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3
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Lee VHF, Vardhanabhuti V, Wong TCL, Lam KO, Choi HCW, Chiu KWH, Ho PPY, Leung DKC, Szeto MHM, Choi KF, Chan SC, Leung TW, Khong PL, Lo CM. Stereotactic Body Radiotherapy and Liver Transplant for Liver Cancer: A Nonrandomized Controlled Trial. JAMA Netw Open 2024; 7:e2415998. [PMID: 38857045 PMCID: PMC11165380 DOI: 10.1001/jamanetworkopen.2024.15998] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2023] [Accepted: 04/09/2024] [Indexed: 06/11/2024] Open
Abstract
Importance Whether stereotactic body radiotherapy (SBRT) as a bridge to liver transplant for hepatocellular carcinoma (HCC) is effective and safe is still unknown. Objective To investigate the feasibility of SBRT before deceased donor liver transplant (DDLT) for previously untreated unresectable HCC. Design, Setting, and Participants In this phase 2 nonrandomized controlled trial conducted between June 1, 2015, and October 18, 2019, 32 eligible patients within UCSF (University of California, San Francisco) criteria underwent dual-tracer (18F-fluorodeoxyglucose and 11C-acetate [ACC]) positron emission tomography with computed tomography (PET-CT) and magnetic resonance imaging (MRI) with gadoxetate followed by SBRT of 35 to 50 Gy in 5 fractions, and the same imaging afterward while awaiting DDLT. Statistical analysis was performed on an intention-to-treat basis between October 1 and 31, 2023. Intervention Patients received SBRT followed by DDLT when matched deceased donor grafts were available. Main Outcomes and Measures Coprimary end points were progression-free survival (PFS) and objective response rates (ORRs) by the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1), modified RECIST (mRECIST), and PET Response Criteria in Solid Tumors (PERCIST). Secondary end points were local control rate, overall survival (OS), and safety. Results A total of 32 patients (median age, 59 years [IQR, 54-63 years]; 22 men [68.8%]) with 56 lesions received SBRT. After a median follow-up of 74.6 months (IQR, 40.1-102.9 months), the median PFS was 17.6 months (95% CI, 6.6-28.6 months), and the median OS was 60.5 months (95% CI, 29.7-91.2 months). The 5-year PFS was 39.9% (95% CI, 19.9%-59.9%), and the 5-year OS was 51.3% (95% CI, 31.7%-70.9%). In terms of number of patients, ORRs were 62.5% ([n = 20] 95% CI, 54.2%-68.7%) by RECIST 1.1, 71.9% ([n = 23] 95% CI, 63.7%-79.0%) by mRECIST, and 78.1% ([n = 25] 95% CI, 73.2%-86.7%) by PERCIST. In terms of number of lesions, ORRs were 75.0% ([n = 42] 95% CI, 61.6%-80.8%) by RECIST 1.1, 83.9% ([n = 47] 95% CI, 74.7%-90.6%) by mRECIST, and 87.5% ([n = 49] 95% CI, 81.3%-98.6%) by PERCIST. Twenty patients with 36 lesions received DDLT, of whom 15 patients (75.0%) with 21 lesions (58.3%) exhibited pathologic complete response. Multivariable analyses revealed that pretreatment metabolic tumor volume (MTV) based on ACC (hazard ratio [HR], 1.06 [95% CI, 1.01-1.10]; P = .01) and complete metabolic response (CMR) by PERCIST (HR, 0.31 [95% CI, 0.10-0.96]; P = .04) were associated with PFS, while pretreatment MTV based on ACC (HR, 1.07 [95% CI, 1.03-1.16]; P = .01), total lesion activity based on ACC (HR, 1.01 [95% CI, 1.00-1.02]; P = .02), and CMR by PERCIST (HR, 0.21 [95% CI, 0.07-0.73]; P = .01) were associated with OS. Toxic effects associated with SBRT were reported for 9 patients (28.1%), with 1 grade 3 event. Conclusions and Relevance This phase 2 nonrandomized controlled trial demonstrated promising survival and safety outcomes of SBRT before DDLT for unresectable HCC. Future randomized clinical trials are warranted.
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Affiliation(s)
- Victor Ho-Fun Lee
- Department of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Department of Clinical Oncology, Queen Mary Hospital, Hong Kong, China
| | - Varut Vardhanabhuti
- Department of Diagnostic Radiology, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Tiffany Cho-Lam Wong
- Department of Surgery, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Department of Surgery, Queen Mary Hospital, Hong Kong, China
| | - Ka-On Lam
- Department of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Department of Clinical Oncology, Queen Mary Hospital, Hong Kong, China
| | - Horace Cheuk-Wai Choi
- Department of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Keith Wan-Hang Chiu
- Department of Diagnostic Radiology, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Patty Pui-Ying Ho
- Department of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Department of Clinical Oncology, Queen Mary Hospital, Hong Kong, China
| | | | - Matthew Ho-Man Szeto
- Department of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Department of Clinical Oncology, Queen Mary Hospital, Hong Kong, China
| | - Kwok-Fung Choi
- Department of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Department of Clinical Oncology, Queen Mary Hospital, Hong Kong, China
| | - See-Ching Chan
- Department of Surgery, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - To-Wai Leung
- Department of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Department of Clinical Oncology, Queen Mary Hospital, Hong Kong, China
| | - Pek-Lan Khong
- Department of Diagnostic Radiology and Clinical Imaging Research Center, National University of Singapore, Singapore
| | - Chung-Mau Lo
- Department of Surgery, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Department of Surgery, Queen Mary Hospital, Hong Kong, China
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4
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Howell TC, Rhodin KE, Shaw B, Bao J, Kanu E, Masoud S, Bartholomew AJ, Gao Q, Anwar IJ, Ladowski JM, Nussbaum DP, Blazer DG, Zani S, Allen PJ, Barbas AS, Lidsky ME. Contemporary trends and outcomes after liver transplantation and resection for intrahepatic cholangiocarcinoma. J Gastrointest Surg 2024; 28:738-745. [PMID: 38704208 DOI: 10.1016/j.gassur.2024.02.029] [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: 06/27/2023] [Revised: 11/10/2023] [Accepted: 02/17/2024] [Indexed: 05/06/2024]
Abstract
BACKGROUND Liver transplantation (LT) has been shown to be superior to resection in highly selected patients with perihilar cholangiocarcinoma (CCA), yet has traditionally been contraindicated for intrahepatic CCA (iCCA). Herein, we aimed to examine contemporary trends and outcomes for surgical resection and LT for iCCA. METHODS The National Cancer Database was queried for patients presenting with stage I-III iCCA between 2010 and 2018 who underwent resection or LT. Overall survival (OS) was compared with Kaplan-Meier and multivariable Cox proportional hazards methods stratified by management. Secondary analysis of patients undergoing transplant for CCA was performed with the United Network for Organ Sharing database. RESULTS Of 2565 patients, 2412 (94.0%) underwent resection and 153 (5.96%) LT of whom 84 (54.9%) received neoadjuvant therapy. Utilization of LT remained between 3.9% and 7.8% annually. Unadjusted 5-year OS was higher for LT than resection (59.8% vs 39.9%, P = .0067), yet adjusted analysis revealed no significant difference in mortality (hazard ratio, 0.91; 95% CI, 0.66-1.27; P = .58). On secondary analysis including 437 patients with all subtypes of CCA, unadjusted 5-year OS was higher for non-CCA indications (79% vs 52%-54%, P < .001). CONCLUSION Utilization of LT for iCCA remains low and many cases are likely incidental. Although partial hepatectomy remains the standard of care for patients with resectable disease, our findings suggest that highly selected patients with unresectable iCCA may achieve favorable outcomes after LT. Granular, prospective data are needed to identify patients most likely to benefit from transplant and allocate scarce liver grafts.
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Affiliation(s)
- Thomas Clark Howell
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Kristen E Rhodin
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Brian Shaw
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Jiayin Bao
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Elishama Kanu
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Sabran Masoud
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Alex J Bartholomew
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Qimeng Gao
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Imran J Anwar
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Joseph M Ladowski
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Daniel P Nussbaum
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Dan G Blazer
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Sabino Zani
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Peter J Allen
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Andrew S Barbas
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Michael E Lidsky
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States.
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5
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Alhasan AS, Daqqaq TS, Alhasan MS, Ghunaim HA, Aboualkheir M. Complication Rates and Risk of Recurrence After Percutaneous Radiofrequency Ablation and Microwave Ablation for the Treatment of Liver Tumors: a Meta-analysis. Acad Radiol 2024; 31:1288-1301. [PMID: 38087720 DOI: 10.1016/j.acra.2023.11.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2023] [Revised: 10/25/2023] [Accepted: 11/01/2023] [Indexed: 04/14/2024]
Abstract
RATIONALE AND OBJECTIVES The rate of complications and risk of local recurrence following percutaneous radiofrequency ablation (RFA) and microwave ablation (MWA) for liver tumors varies significantly between investigations. This meta-analysis aimed to assess complication rates and risk of local recurrence after percutaneous RFA and MWA. MATERIALS AND METHODS PubMed, Medline, Web of Science, the Cochrane Library, Embase, Google Scholar, and CINAHL were systematically searched from database inception until August 2022 to retrieve articles reporting the complication rates and risk of recurrence after percutaneous RFA and MWA for the treatment of liver tumors. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated and displayed by forest plots. To measure heterogeneity, Cochran Q and I2 statistics were also applied. Egger's test and funnel plots were also performed to assess any potential publication bias. Additionally, subgroup analysis was done to investigate the source of heterogeneity. RESULTS 26 studies including 2026 and 1974 patients for RFA and MWA, respectively, were included. The rate of minor complications was significantly higher after MWA compared to RFA, yielding an overall OR of 0.688 (95% CI: 0.549-0.862, P = 0.001). Similarly, the rate of major complications was significantly higher after MWA than RFA (P = 0.012), yielding an overall OR of 0.639 (95% CI: 0.450-0.907). No significant difference was found between RFA and MWA in terms of local recurrence after ablation (P > 0.05). In addition, there was no statistical evidence of publication bias. CONCLUSION When most factors are considered equally, percutaneous RFA and MWA can be considered safe modalities for the treatment of liver tumors, with RFA superior in terms of the incidence of minor and major complications.
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Affiliation(s)
- Ayman S Alhasan
- Department of Radiology and Medical Imaging, College of Medicine, Taibah University, Madinah, Saudi Arabia (A.S.A., T.S.D., M.S.A., H.A.G., M.A.); Department of Radiology, King Faisal Specialist Hospital and Research Centre, Madinah, Saudi Arabia (A.S.A.).
| | - Tareef S Daqqaq
- Department of Radiology and Medical Imaging, College of Medicine, Taibah University, Madinah, Saudi Arabia (A.S.A., T.S.D., M.S.A., H.A.G., M.A.)
| | - Mustafa S Alhasan
- Department of Radiology and Medical Imaging, College of Medicine, Taibah University, Madinah, Saudi Arabia (A.S.A., T.S.D., M.S.A., H.A.G., M.A.)
| | - Hadeel A Ghunaim
- Department of Radiology and Medical Imaging, College of Medicine, Taibah University, Madinah, Saudi Arabia (A.S.A., T.S.D., M.S.A., H.A.G., M.A.)
| | - Mervat Aboualkheir
- Department of Radiology and Medical Imaging, College of Medicine, Taibah University, Madinah, Saudi Arabia (A.S.A., T.S.D., M.S.A., H.A.G., M.A.); Department of Clinical Science /College of Medicine/Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia (M.A.)
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6
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Shurin MR, Kirichenko VA, Shurin GV, Lee D, Crane C, Kirichenko AV. Radiomodulating Properties of Superparamagnetic Iron Oxide Nanoparticle (SPION) Agent Ferumoxytol on Human Monocytes: Implications for MRI-Guided Liver Radiotherapy. Cancers (Basel) 2024; 16:1318. [PMID: 38610996 PMCID: PMC11011128 DOI: 10.3390/cancers16071318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Revised: 03/26/2024] [Accepted: 03/26/2024] [Indexed: 04/14/2024] Open
Abstract
Superparamagnetic iron oxide nanoparticles (SPION) have attracted great attention not only for therapeutic applications but also as an alternative magnetic resonance imaging (MRI) contrast agent that helps visualize liver tumors during MRI-guided stereotactic body radiotherapy (SBRT). SPION can provide functional imaging of liver parenchyma based upon its uptake by the hepatic resident macrophages or Kupffer cells with a relative enhancement of malignant tumors that lack Kupffer cells. However, the radiomodulating properties of SPION on liver macrophages are not known. Utilizing human monocytic THP-1 undifferentiated and differentiated cells, we characterized the effect of ferumoxytol (Feraheme®), a carbohydrate-coated ultrasmall SPION agent at clinically relevant concentration and therapeutically relevant doses of gamma radiation on cultured cells in vitro. We showed that ferumoxytol affected both monocytes and macrophages, increased the resistance of monocytes to radiation-induced cell death and inhibition of cell activity, and supported the anti-inflammatory phenotype of human macrophages under radiation. Its effect on human cells depended on the duration of SPION uptake and was radiation dose-dependent. The results of this pilot study support a strong mechanism-based optimization of SPION-enhanced MRI-guided liver SBRT for primary and metastatic liver tumors, especially in patients with liver cirrhosis awaiting a liver transplant.
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Affiliation(s)
- Michael R. Shurin
- Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA;
| | - Vladimir A. Kirichenko
- Department of Radiation Oncology, Allegheny Health Network Cancer Institute, Pittsburgh, PA 15224, USA; (V.A.K.); (D.L.)
| | - Galina V. Shurin
- Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA;
| | - Danny Lee
- Department of Radiation Oncology, Allegheny Health Network Cancer Institute, Pittsburgh, PA 15224, USA; (V.A.K.); (D.L.)
| | - Christopher Crane
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA;
| | - Alexander V. Kirichenko
- Department of Radiation Oncology, Allegheny Health Network Cancer Institute, Pittsburgh, PA 15224, USA; (V.A.K.); (D.L.)
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7
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Famularo S, Cillo U, Lauterio A, Donadon M, Vitale A, Serenari M, Cipriani F, Fazio F, Giuffrida M, Ardito F, Dominioni T, Garancini M, Lai Q, Nicolini D, Molfino S, Perri P, Pinotti E, Conci S, Ferrari C, Zanello M, Patauner S, Zimmitti G, Germani P, Chiarelli M, Romano M, De Angelis M, La Barba G, Troci A, Ferraro V, Izzo F, Antonucci A, Belli A, Memeo R, Crespi M, Ercolani G, Boccia L, Zanus G, Tarchi P, Hilal MA, Frena A, Jovine E, Griseri G, Ruzzenente A, Zago M, Grazi G, Baiocchi GL, Vivarelli M, Rossi M, Romano F, Maestri M, Giuliante F, Valle RD, Ferrero A, Aldrighetti L, De Carlis L, Cescon M, Torzilli G. Survival benefit of second line therapies for recurrent hepatocellular carcinoma: repeated hepatectomy, thermoablation and second-line transplant referral in a real life national scenario. HPB (Oxford) 2023; 25:1223-1234. [PMID: 37357112 DOI: 10.1016/j.hpb.2023.06.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Revised: 05/05/2023] [Accepted: 06/10/2023] [Indexed: 06/27/2023]
Abstract
BACKGROUND Despite second-line transplant(SLT) for recurrent hepatocellular carcinoma(rHCC) leads to the longest survival after recurrence(SAR), its real applicability has never been reported. The aim was to compare the SAR of SLT versus repeated hepatectomy and thermoablation(CUR group). METHODS Patients were enrolled from the Italian register HE.RC.O.LE.S. between 2008 and 2021. Two groups were created: CUR versus SLT. A propensity score matching (PSM) was run to balance the groups. RESULTS 743 patients were enrolled, CUR = 611 and SLT = 132. Median age at recurrence was 71(IQR 6575) years old and 60(IQR 53-64, p < 0.001) for CUR and SLT respectively. After PSM, median SAR for CUR was 43 months(95%CI = 37 - 93) and not reached for SLT(p < 0.001). SLT patients gained a survival benefit of 9.4 months if compared with CUR. MilanCriteria(MC)-In patients were 82.7% of the CUR group. SLT(HR 0.386, 95%CI = 0.23 - 0.63, p < 0.001) and the MELD score(HR 1.169, 95%CI = 1.07 - 1.27, p < 0.001) were the only predictors of mortality. In case of MC-Out, the only predictor of mortality was the number of nodules at recurrence(HR 1.45, 95%CI= 1.09 - 1.93, p = 0.011). CONCLUSION It emerged an important transplant under referral in favour of repeated hepatectomy or thermoablation. In patients with MC-Out relapse, the benefit of SLT over CUR was not observed.
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Affiliation(s)
- Simone Famularo
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy; Surgical Data Science Team, Research Institute Against Digestive Cancer (IRCAD), Strasbourg, France.
| | - Umberto Cillo
- Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padova, Second General Surgical Unit, Padova Teaching Hospital, Padua, Italy
| | - Andrea Lauterio
- Department of General and Transplant Surgery, Grande Ospedale Metropolitano Niguarda, School of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy
| | - Matteo Donadon
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Alessandro Vitale
- Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padova, Second General Surgical Unit, Padova Teaching Hospital, Padua, Italy
| | - Matteo Serenari
- Hepato-biliary Surgery and Transplant Unit, Policlinico Sant'Orsola IRCCS, Department of Medical and Surgical Sciences, University of Bologna, Italy
| | - Federica Cipriani
- Hepatobiliary Surgery Division, "Vita e Salute" University, Ospedale San Raffaele IRCCS, Milano, Italy
| | - Federico Fazio
- Department of General and Oncological Surgery, Mauriziano Hospital "Umberto I", Turin, Italy
| | - Mario Giuffrida
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Francesco Ardito
- Hepatobiliary Surgery Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Catholic University of the Sacred Heart, Rome, Italy
| | - Tommaso Dominioni
- Unit of General Surgery 1, University of Pavia and Foundation IRCCS Policlinico San Matteo, Pavia, Italy
| | - Mattia Garancini
- School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy
| | - Quirino Lai
- General Surgery and Organ Transplantation Unit, Sapienza University of Rome, Umberto I Polyclinic of Rome, Rome, Italy
| | - Daniele Nicolini
- HPB Surgery and Transplantation Unit, Department of Clinical and Experimental Medicine, Polytechnic University of Marche, Ancona, Italy
| | - Sarah Molfino
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - Pasquale Perri
- Division of Hepatobiliarypancreatic Unit, IRCCS - Regina Elena National Cancer Institute, Rome, Italy
| | - Enrico Pinotti
- Department of Surgery, Ponte San Pietro Hospital, Bergamo, Italy
| | - Simone Conci
- Division of General and Hepatobiliary Surgery, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy
| | | | - Matteo Zanello
- Alma Mater Studiorum, University of Bologna, AOU Sant'Orsola Malpighi, IRCCS at Maggiore Hospital, Bologna, Italy
| | - Stefan Patauner
- Department of General and Pediatric Surgery, Bolzano Central Hospital, Bolzano, Italy
| | - Giuseppe Zimmitti
- Department of General Surgery, Poliambulanza Foundation Hospital, Brescia, Italy
| | - Paola Germani
- Division of General Surgery, Department of Medical and Surgical Sciences, ASUGI, Trieste, Italy
| | - Marco Chiarelli
- Department of Emergency and Robotic Surgery, ASST Lecco, Lecco, Italy
| | - Maurizio Romano
- Department of Surgical, Oncological and Gastroenterological Science (DISCOG), University of Padua, Hepatobiliary and Pancreatic Surgery Unit - Treviso Hospital, Italy
| | | | - Giuliano La Barba
- General and Oncologic Surgery, Morgagni-Pierantoni Hospital, Department of Medical and Surgical Sciences - University of Bologna Forlì, Italy
| | - Albert Troci
- Department of Surgery, L. Sacco Hospital, Milan, Italy
| | - Valentina Ferraro
- Department of Hepato-Pancreatic-Biliary Surgery, Miulli Hospital, Bari, Italy
| | - Francesco Izzo
- Division of Epatobiliary Surgical Oncology, Istituto Nazionale Tumori IRCCS Fondazione Pascale-IRCCS di Napoli, Naples, Italy
| | | | - Andrea Belli
- Division of Epatobiliary Surgical Oncology, Istituto Nazionale Tumori IRCCS Fondazione Pascale-IRCCS di Napoli, Naples, Italy
| | - Riccardo Memeo
- Department of Hepato-Pancreatic-Biliary Surgery, Miulli Hospital, Bari, Italy
| | | | - Giorgio Ercolani
- General and Oncologic Surgery, Morgagni-Pierantoni Hospital, Department of Medical and Surgical Sciences - University of Bologna Forlì, Italy
| | - Luigi Boccia
- Department of General Surgery, Ospedale Carlo Poma, Mantua, Italy
| | - Giacomo Zanus
- Department of Surgical, Oncological and Gastroenterological Science (DISCOG), University of Padua, Hepatobiliary and Pancreatic Surgery Unit - Treviso Hospital, Italy
| | - Paola Tarchi
- Division of General Surgery, Department of Medical and Surgical Sciences, ASUGI, Trieste, Italy
| | - Moh'd Abu Hilal
- Department of General Surgery, Poliambulanza Foundation Hospital, Brescia, Italy
| | - Antonio Frena
- Department of General and Pediatric Surgery, Bolzano Central Hospital, Bolzano, Italy
| | - Elio Jovine
- Alma Mater Studiorum, University of Bologna, AOU Sant'Orsola Malpighi, IRCCS at Maggiore Hospital, Bologna, Italy
| | - Guido Griseri
- HPB Surgical Unit, San Paolo Hospital, Savona, Italy
| | - Andrea Ruzzenente
- Division of General and Hepatobiliary Surgery, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy
| | - Mauro Zago
- Department of Surgery, Ponte San Pietro Hospital, Bergamo, Italy; Department of Emergency and Robotic Surgery, ASST Lecco, Lecco, Italy
| | - Gianluca Grazi
- Division of Hepatobiliarypancreatic Unit, IRCCS - Regina Elena National Cancer Institute, Rome, Italy
| | - Gian L Baiocchi
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - Marco Vivarelli
- HPB Surgery and Transplantation Unit, Department of Clinical and Experimental Medicine, Polytechnic University of Marche, Ancona, Italy
| | - Massimo Rossi
- General Surgery and Organ Transplantation Unit, Sapienza University of Rome, Umberto I Polyclinic of Rome, Rome, Italy
| | - Fabrizio Romano
- School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy
| | - Marcello Maestri
- Unit of General Surgery 1, University of Pavia and Foundation IRCCS Policlinico San Matteo, Pavia, Italy
| | - Felice Giuliante
- Hepatobiliary Surgery Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Catholic University of the Sacred Heart, Rome, Italy
| | - Raffaele D Valle
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Alessandro Ferrero
- Department of General and Oncological Surgery, Mauriziano Hospital "Umberto I", Turin, Italy
| | - Luca Aldrighetti
- Hepatobiliary Surgery Division, "Vita e Salute" University, Ospedale San Raffaele IRCCS, Milano, Italy
| | - Luciano De Carlis
- Department of General and Transplant Surgery, Grande Ospedale Metropolitano Niguarda, School of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy
| | - Matteo Cescon
- Hepato-biliary Surgery and Transplant Unit, Policlinico Sant'Orsola IRCCS, Department of Medical and Surgical Sciences, University of Bologna, Italy
| | - Guido Torzilli
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
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8
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Di Martino M, Ferraro D, Pisaniello D, Arenga G, Falaschi F, Terrone A, Maniscalco M, Galeota Lanza A, Esposito C, Vennarecci G. Bridging therapies for patients with hepatocellular carcinoma awaiting liver transplantation: A systematic review and meta-analysis on intention-to-treat outcomes. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2023; 30:429-438. [PMID: 36207763 DOI: 10.1002/jhbp.1248] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Revised: 08/16/2022] [Accepted: 09/08/2022] [Indexed: 04/28/2023]
Abstract
INTRODUCTION Locoregional therapies are commonly used as bridging strategies to decrease the drop-out of patients with hepatocellular carcinoma (HCC) awaiting liver transplantation (LT). The present paper aims to assess the outcomes of bridging therapies in patients with HCC considered for LT according to an intention-to-treat (ITT) survival analysis. MATERIAL AND METHODS Medline and Web of Science databases were searched for reports published before May 2021. Papers assessing adult patients with HCC considered for LT and reporting ITT survival outcomes were included. Two reviewers independently identified, extracted the data, and evaluated the papers according to Newcastle-Ottawa criteria. Outcomes analyzed were: drop-out rate; time on the waiting list; 1-, 3-, and 5-year survival after LT and based on an ITT analysis. RESULTS The search identified 3106 records; six papers (1043 patients) met the inclusion criteria. Patients with HCC, listed for LT and submitted to bridging therapies presented a longer waiting time before LT (MD 3.77, 95% CI 2.07-5.48) in comparison with the non-interventional group. However, they presented a raised post LT after 1-year (OR 2.00, 95% CI 1.18-3.41), 3-years (OR 1.47, 95% CI 1.01-2.15), and 5-years (OR 1.50, 95% CI 1.06-2.13) survival. CONCLUSION Patients submitted to bridging procedures, despite having a longer interval on the waiting list, presented better post-LT survival outcomes. Bridging therapies for selected patients at low risk of post-procedural complications and long expected intervals on the waiting list should be encouraged. However, further clinical trials should confirm the survival benefit of bridging therapies in patients with HCC listed for LT.
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Affiliation(s)
- Marcello Di Martino
- Division of Hepatobiliary and Liver Transplantation Surgery, Department of Transplantation Surgery, A.O.R.N. Cardarelli, Napoli, Italy
- Division of Haepatology, Department of Transplantation Surgery, A.O.R.N. Cardarelli, Napoli, Italy
| | - Daniele Ferraro
- Division of Hepatobiliary and Liver Transplantation Surgery, Department of Transplantation Surgery, A.O.R.N. Cardarelli, Napoli, Italy
| | - Donatella Pisaniello
- Division of Hepatobiliary and Liver Transplantation Surgery, Department of Transplantation Surgery, A.O.R.N. Cardarelli, Napoli, Italy
| | - Giuseppe Arenga
- Division of Hepatobiliary and Liver Transplantation Surgery, Department of Transplantation Surgery, A.O.R.N. Cardarelli, Napoli, Italy
| | - Federica Falaschi
- Division of Hepatobiliary and Liver Transplantation Surgery, Department of Transplantation Surgery, A.O.R.N. Cardarelli, Napoli, Italy
| | - Alfonso Terrone
- Division of Hepatobiliary and Liver Transplantation Surgery, Department of Transplantation Surgery, A.O.R.N. Cardarelli, Napoli, Italy
| | - Marilisa Maniscalco
- Division of Hepatobiliary and Liver Transplantation Surgery, Department of Transplantation Surgery, A.O.R.N. Cardarelli, Napoli, Italy
| | - Alfonso Galeota Lanza
- Division of Haepatology, Department of Transplantation Surgery, A.O.R.N. Cardarelli, Napoli, Italy
| | - Ciro Esposito
- Liver Intesive Care Unit, Department of Transplantation Surgery, A.O.R.N. Cardarelli, Napoli, Italy
| | - Giovanni Vennarecci
- Division of Hepatobiliary and Liver Transplantation Surgery, Department of Transplantation Surgery, A.O.R.N. Cardarelli, Napoli, Italy
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9
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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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10
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Lima HA, Moazzam Z, Endo Y, Alaimo L, Shaikh C, Munir MM, Resende V, Guglielmi A, Marques HP, Cauchy F, Lam V, Poultsides GA, Popescu I, Alexandrescu S, Martel G, Hugh T, Endo I, Kitago M, Shen F, Pawlik TM. TBS-Based Preoperative Score to Predict Non-transplantable Recurrence and Identify Candidates for Upfront Resection Versus Transplantation for Hepatocellular Carcinoma. Ann Surg Oncol 2023; 30:3363-3373. [PMID: 36820934 DOI: 10.1245/s10434-023-13273-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Accepted: 02/06/2023] [Indexed: 02/24/2023]
Abstract
BACKGROUND Recurrence following liver resection (LR) for hepatocellular carcinoma (HCC) can be as high as 50-70%. While salvage liver transplantation may be feasible, patients may develop a non-transplantable recurrence (NTR) (recurrence beyond Milan criteria). We sought to identify preoperative risk factors to predict NTR after resection. PATIENTS AND METHODS Patients who underwent curative-intent LR for HCC were identified from a multi-institutional database. Preoperative factors associated with NTR were identified and a risk score model (NTR score) was developed and validated. RESULTS Among 1620 patients, 842 (52.0%) developed recurrence; among patients with recurrence, NTR occurred in 341 (40.5%) with a median recurrence-free survival (RFS) of 30 months (24.7-35.3 months). On multivariable analysis, factors associated with NTR included alpha fetoprotein (AFP) > 400 ng/mL [hazard ratio (HR) 1.71, 95% confidence interval (CI) 1.33-2.19], albumin-bilirubin grade (ALBI) (referent low, medium ALBI: HR 1.41, 95% CI 1.10-1.81, high ALBI: HR 2.47, 95% CI 0.91-6.68), and tumor burden score (TBS) (referent low, high TBS: HR 2.55, 95% CI, 1.99-3.28). A simplified TBS-based NTR score was developed using the β-coefficients of each factor (C-index 0.68, 95% CI 0.65-0.71). Higher NTR score was associated with incrementally worse 5-year RFS (low 44.8%, medium 37.5%, high 24.5%) [area under the curve (AUC) 0.59] and increased incidence of NTR (low 13.7%, medium 25.4%, high 38.2%) (AUC 0.65) (both p < 0.001). Moreover, higher NTR score was associated with higher risk of extrahepatic recurrence (low 11.3%, medium 28.8%, high 37.5%) (p < 0.001). CONCLUSION NTR following curative-intent resection of HCC occurred in one in five patients. A simple TBS-based NTR score accurately predicted the risk of NTR and may help identify candidates for upfront resection versus transplantation.
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Affiliation(s)
- Henrique A Lima
- Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, Health Services Management and Policy, Wexner Medical Center and James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.,Federal University of Minas Gerais School of Medicine, Belo Horizonte, Brazil
| | - Zorays Moazzam
- Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, Health Services Management and Policy, Wexner Medical Center and James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
| | - Yutaka Endo
- Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, Health Services Management and Policy, Wexner Medical Center and James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
| | - Laura Alaimo
- Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, Health Services Management and Policy, Wexner Medical Center and James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
| | - Chanza Shaikh
- Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, Health Services Management and Policy, Wexner Medical Center and James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
| | - Muhammad Musaab Munir
- Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, Health Services Management and Policy, Wexner Medical Center and James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
| | - Vivian Resende
- Federal University of Minas Gerais School of Medicine, Belo Horizonte, Brazil
| | | | - Hugo P Marques
- Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal
| | - François Cauchy
- Department of Hepatibiliopancreatic Surgery, APHP, Beaujon Hospital, Clichy, France
| | - Vincent Lam
- Department of Surgery, Westmead Hospital, Sydney, NSW, Australia
| | | | - Irinel Popescu
- Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania
| | | | | | - Tom Hugh
- Department of Surgery, School of Medicine, The University of Sydney, Sydney, NSW, Australia
| | - Itaru Endo
- Yokohama City University School of Medicine, Yokohama, Japan
| | - Minoru Kitago
- Department of Surgery, Keio University, Tokyo, Japan
| | - Feng Shen
- Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | - Timothy M Pawlik
- Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, Health Services Management and Policy, Wexner Medical Center and James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
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11
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Tampaki M, Papatheodoridis GV, Cholongitas E. Management of Hepatocellular Carcinoma in Decompensated Cirrhotic Patients: A Comprehensive Overview. Cancers (Basel) 2023; 15:1310. [PMID: 36831651 PMCID: PMC9954723 DOI: 10.3390/cancers15041310] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Revised: 02/14/2023] [Accepted: 02/16/2023] [Indexed: 02/22/2023] Open
Abstract
Primary liver cancer is the sixth most common cancer and the fourth leading cause of cancer-related death. Hepatocellular carcinoma (HCC) accounts for 75% of primary liver cancer cases, mostly on the basis of cirrhosis. However, the data and therapeutic options for the treatment of HCC in patients with decompensated cirrhosis are rather limited. This patient category is often considered to be in a terminal stage without the possibility of a specific treatment except liver transplantation, which is restricted by several criteria and liver donor shortages. Systemic treatments may provide a solution for patients with Child Pugh class B or C since they are less invasive. Although most of the existing trials have excluded patients with decompensated cirrhosis, there are increasing data from real-life settings that show acceptable tolerability and satisfying efficacy in terms of response. The data on the administration of locoregional treatments in such patients are also limited, but the overall survival seems to be potentially prolonged when patients are carefully selected, and close adverse event monitoring is applied. The aim of this review is to analyze the existing data regarding the administration of treatments in decompensated patients with HCC, evaluate the effect of therapy on overall survival and highlight the potential risks in terms of tolerability.
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Affiliation(s)
- Maria Tampaki
- Academic Department of Gastroenterology, General Hospital of Athens “Laiko”, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - George V. Papatheodoridis
- Academic Department of Gastroenterology, General Hospital of Athens “Laiko”, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Evangelos Cholongitas
- First Department of Internal Medicine, General Hospital of Athens “Laiko”, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
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12
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de Freitas ACT, Espinoza FDS, Mattar CA, Coelho JCU. INDICATION FOR LIVER TRANSPLANTATION DUE TO HEPATOCELLULAR CARCINOMA: ANALYSIS OF 1,706 PROCEDURES OVER THE PAST DECADE IN THE STATE OF PARANÁ. ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA : ABCD = BRAZILIAN ARCHIVES OF DIGESTIVE SURGERY 2022; 35:e1701. [PMID: 36542003 PMCID: PMC9767419 DOI: 10.1590/0102-672020220002e1701] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Accepted: 08/30/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND Patients listed for liver transplantation and hepatocellular carcinoma are considered priority on the waiting list, and this could overly favor them. AIM This study aimed to evaluate the impact of this prioritization. METHODS We analyzed the liver transplants performed in adults from 2011 to 2020 and divided into three groups: adjusted Model of End-Stage Liver Disease (MELD) score for hepatocellular carcinoma, other adjusted Model of End-Stage Liver Disease situations, and no adjusted Model of End-Stage Liver Disease. RESULTS A total of 1,706 patients were included in the study, of which 70.2% were male. Alcoholism was the main etiology of cirrhosis (29.6%). Of the total, 305 patients were with hepatocellular carcinoma, 86 with other adjusted Model of End-Stage Liver Disease situations, and 1,315 with no adjusted Model of End-Stage Liver Disease. Patients with hepatocellular carcinoma were older (58.9 vs. 53.5 years). The predominant etiology of cirrhosis was viral hepatitis (60%). The findings showed that group with adjusted Model of End-Stage Liver Disease had lower physiological Model of End-Stage Liver Disease (10.9), higher adjusted Model of End-Stage Liver Disease (22.6), and longer waiting list time (131 vs. 110 days), as compared to the group with no adjusted Model of End-Stage Liver Disease. The total number of transplants and the proportion of patients transplanted for hepatocellular carcinoma increased from 2011 to 2020. There was a reduction in the proportion of patients with hepatocellular carcinoma and adjusted Model of End-Stage Liver Disease of 20 and there was an increase on waiting list time in this group. There was an increase in the proportion of those with adjusted Model of End-Stage Liver Disease of 24 and 29, but the waiting list time remained stable. CONCLUSION Over the past decade, prioritization of hepatocellular carcinoma resulted in an increased proportion of transplanted patients in relation to those with no priority. It also increased waiting list time, requiring higher adjusted Model of End-Stage Liver Disease to transplant an organ.
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Affiliation(s)
| | | | - Cristina Alvarez Mattar
- Universidade Federal do Paraná, Department of Surgery and Liver Transplant Unit – Curitiba (PR), Brazil
| | - Júlio Cezar Uili Coelho
- Universidade Federal do Paraná, Department of Surgery and Liver Transplant Unit – Curitiba (PR), Brazil
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13
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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: 80] [Impact Index Per Article: 26.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 10/28/2022] [Indexed: 11/18/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
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14
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Minoux K, Lassailly G, Ningarhari M, Lubret H, El Amrani M, Canva V, Truant S, Mathurin P, Louvet A, Lebuffe G, Goria O, Nguyen-Khac E, Boleslawski E, Dharancy S. Neo-Adjuvant Use of Sorafenib for Hepatocellular Carcinoma Awaiting Liver Transplantation. Transpl Int 2022; 35:10569. [PMID: 36438781 PMCID: PMC9681796 DOI: 10.3389/ti.2022.10569] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Accepted: 10/21/2022] [Indexed: 12/01/2023]
Abstract
Data on efficacy and safety of sorafenib in a neoadjuvant setting for HCC awaiting liver transplantation (LT) are heterogeneous and scarce. We aimed to investigate the trajectory of patients treated with sorafenib while awaiting LT. All patients listed for HCC and treated with sorafenib were included in a monocentric observational study. A clinical and biological evaluation was performed every month. Radiological tumor response evaluation was realized every 3 months on the waiting list and every 6 months after LT. Among 327 patients listed for HCC, 62 (19%) were treated with Sorafenib. Sorafenib was initiated for HCC progression after loco-regional therapy (LRT) in 50% of cases and for impossibility of LRT in 50% of cases. The mean duration of treatment was 6 months. Thirty six patients (58%) dropped-out for tumor progression and 26 (42%) patients were transplanted. The 5-year overall and recurrent-free survival after LT was 77% and 48% respectively. Patients treated for impossibility of LRT had acceptable 5-year intention-to-treat overall and post-LT survivals. Conversely, patients treated for HCC progression presented high dropout rate and low intention-to-treat survival. Our results suggest that it is very questionable in terms of utility that patients treated for HCC progression should even be kept listed once the tumor progression has been observed.
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Affiliation(s)
- Kate Minoux
- CHU Lille, Department of Hepatogastroenterology, Lille, France
- INSERM U995, University of Lille, Lille, France
| | - Guillaume Lassailly
- CHU Lille, Department of Hepatogastroenterology, Lille, France
- INSERM U995, University of Lille, Lille, France
| | - Massih Ningarhari
- CHU Lille, Department of Hepatogastroenterology, Lille, France
- INSERM U995, University of Lille, Lille, France
| | - Henri Lubret
- CHU Lille, Department of Hepatogastroenterology, Lille, France
- INSERM U995, University of Lille, Lille, France
| | - Medhi El Amrani
- CHU Lille, Department of Digestive Surgery and Transplantation, University of Lille, Lille, France
| | - Valérie Canva
- CHU Lille, Department of Hepatogastroenterology, Lille, France
- INSERM U995, University of Lille, Lille, France
| | - Stéphanie Truant
- CHU Lille, Department of Digestive Surgery and Transplantation, University of Lille, Lille, France
| | - Philippe Mathurin
- CHU Lille, Department of Hepatogastroenterology, Lille, France
- INSERM U995, University of Lille, Lille, France
| | - Alexandre Louvet
- CHU Lille, Department of Hepatogastroenterology, Lille, France
- INSERM U995, University of Lille, Lille, France
| | - Gilles Lebuffe
- CHU Lille, Department of Anesthesiology, Resuscitation, and Critical Care Anesthesiology, University of Lille, Lille, France
| | - Odile Goria
- CHU Rouen, Department of Hepatogastroenterology, Hôpital Charles Nicolle, Rouen, France
| | - Eric Nguyen-Khac
- CHU Amiens-Picardie, Hôpital Sud, Department of Hepatogastroenterology, Amiens, France
- CHU Amiens, Centre Universitaire de Recherche en Santé (CURS), Université de Picardie-Jules-Verne (UPJV), Groupe de Recherche sur l’alcool et les Pharmacodépendances (GRAP), Inserm U1247, Amiens, France
| | - Emmanuel Boleslawski
- CHU Lille, Department of Digestive Surgery and Transplantation, University of Lille, Lille, France
| | - Sebastien Dharancy
- CHU Lille, Department of Hepatogastroenterology, Lille, France
- INSERM U995, University of Lille, Lille, France
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15
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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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16
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Lin X, Xiao M, Gu YJ, Zhu HK, Li MX, Zhuang L, Zheng SS, Li QY. The "No-touch" technique improves the survival of patients with advanced hepatocellular carcinomas treated by liver transplantation: A single-center prospective randomized controlled trial. Hepatobiliary Pancreat Dis Int 2022; 22:253-262. [PMID: 35568681 DOI: 10.1016/j.hbpd.2022.05.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Accepted: 04/07/2022] [Indexed: 02/05/2023]
Abstract
BACKGROUND Liver transplantation (LT) is the best treatment for patients with hepatocellular carcinoma (HCC). However, the surgical technique needs to be improved. The present study aimed to evaluate the "no-touch" technique in LT. METHODS From January 2018 to December 2019, we performed a prospective randomized controlled trial on HCC patients who underwent LT. The patients were randomized into two groups: a no-touch technique LT group (NT group, n = 38) and a conventional LT technique group (CT group, n = 46). Operative outcomes and survival in the two groups were analyzed. RESULTS The perioperative parameters were comparable between the two groups (P > 0.05). There was no significant difference between the two groups in disease-free survival (DFS) (P = 0.732) or overall survival (OS) (P = 0.891). Of 36 patients who were beyond the Hangzhou criteria for LT, the DFS of the patients in the NT group was significantly longer than that in the CT group (median 402 vs. 126 days, P = 0.025). In 31 patients who had portal vein tumor thrombosis (PVTT), DFS and OS in the NT group were significantly better than those in the CT group (median DFS 420 vs. 167 days, P = 0.022; 2-year OS rate 93.8% vs. 66.7%, P = 0.043). In 14 patients who had diffuse-type HCCs, DFS and OS were significantly better in the NT group than in the CT group (median DFS 141 vs. 56 days, P = 0.008; 2-year OS rate 75.0% vs. 33.3%, P = 0.034). Multivariate analysis showed that for patients with PVTT and diffuse-type HCCs, the no-touch technique was an independent favorable factor for OS (PVTT: HR = 0.018, 95% CI: 0.001-0.408, P = 0.012; diffuse-type HCCs: HR = 0.034, 95% CI: 0.002-0.634, P = 0.024). CONCLUSIONS The no-touch technique improved the survival of patients with advanced HCC compared with the conventional technique. The no-touch technique may provide a new and effective LT technique for advanced HCCs.
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Affiliation(s)
- Xin Lin
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, #848 Dongxin Road, Hangzhou 310000, China; Zhejiang University School of Medicine, Hangzhou 310000, China; Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250117, China
| | - Min Xiao
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, #848 Dongxin Road, Hangzhou 310000, China; Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250117, China
| | - Yang-Jun Gu
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, #848 Dongxin Road, Hangzhou 310000, China; Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250117, China
| | - Heng-Kai Zhu
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, #848 Dongxin Road, Hangzhou 310000, China; Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250117, China
| | - Meng-Xia Li
- Zhejiang University School of Medicine, Hangzhou 310000, China
| | - Li Zhuang
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, #848 Dongxin Road, Hangzhou 310000, China
| | - Shu-Sen Zheng
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, #848 Dongxin Road, Hangzhou 310000, China; Zhejiang University School of Medicine, Hangzhou 310000, China; Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250117, China
| | - Qi-Yong Li
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, #848 Dongxin Road, Hangzhou 310000, China; Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250117, China.
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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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Gao Q, Anwar IJ, Abraham N, Barbas AS. Liver Transplantation for Hepatocellular Carcinoma after Downstaging or Bridging Therapy with Immune Checkpoint Inhibitors. Cancers (Basel) 2021; 13:6307. [PMID: 34944927 PMCID: PMC8699137 DOI: 10.3390/cancers13246307] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2021] [Revised: 12/13/2021] [Accepted: 12/14/2021] [Indexed: 12/12/2022] Open
Abstract
Liver transplantation offers excellent outcomes for patients with HCC. For those who initially present within the Milan criteria, bridging therapy is essential to control disease while awaiting liver transplant. For those who present beyond the Milan criteria, a liver transplant may still be considered following successful downstaging. Since the introduction of atezolizumab as part of the first-line treatment for HCC in 2020, there has been increasing interest in the use of ICIs as bridging or downstaging therapies prior to liver transplant. A total of six case reports/series have been published on this topic, with mixed outcomes. Overall, liver transplantation can be performed safely following prolonged ICI use, though ICIs may increase the risk of fulminant acute rejection early in the post-operative period. A minimal washout period between the last dose of ICI and liver transplantation has been identified as an important factor predicting transplant outcomes; however, further research is needed.
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Affiliation(s)
| | | | | | - Andrew S. Barbas
- Department of Surgery, Duke University Medical Center, Durham, NC 27705, USA; (Q.G.); (I.J.A.); (N.A.)
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Yamamoto M, Kobayashi T, Honmyo N, Oshita A, Abe T, Kohashi T, Onoe T, Fukuda S, Omori I, Imaoka Y, Ohdan H. Liver resection is associated with good outcomes for hepatocellular carcinoma patients beyond the Barcelona Clinic Liver Cancer criteria: A multicenter study with the Hiroshima Surgical study group of Clinical Oncology. Surgery 2021; 171:1303-1310. [PMID: 34756748 DOI: 10.1016/j.surg.2021.09.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 09/09/2021] [Accepted: 09/11/2021] [Indexed: 01/27/2023]
Abstract
BACKGROUND Liver resection for hepatocellular carcinoma beyond the Barcelona Clinic Liver Cancer criteria remains controversial. Strict candidate selection is crucial to achieve optimal results in this population. This study explored postoperative outcomes and developed a preoperative predictive formula to identify patients most likely to benefit from liver resection. METHODS In total, 382 patients who underwent liver resection for hepatocellular carcinoma beyond the Barcelona Clinic Liver Cancer resection criteria between 2000 and 2017 were identified from a multicenter database with the Hiroshima Surgical study group of Clinical Oncology. An overall survival prediction model was developed, and patients were classified by risk status. RESULTS The 5-year overall survival after curative resection was 50.0%. Overall survival multivariate analysis identified that a high a-fetoprotein level, macrovascular invasion, and high total tumor burden were independent prognostic risk factors; these factors were used to formulate risk scores. Patients were divided into low-, moderate-, and high-risk groups; the 5-year overall survival was 65.7%, 49.5%, and 17.0% (P < .001), and the 5-year recurrence-free survival was 31.3%, 26.2%, and 0%, respectively (P < .001). The model performance was good (C-index, 0.76). Both the early and extrahepatic recurrence increased with higher risk score. CONCLUSION The prognosis of patients with hepatocellular carcinoma beyond the Barcelona Clinic Liver Cancer resection criteria depended on a high a-fetoprotein level, macrovascular invasion, and high total tumor burden, and risk scores based on these factors stratified the prognoses. Liver resection should be considered in patients with hepatocellular carcinoma beyond the Barcelona Clinic Liver Cancer criteria with a low or moderate-risk score.
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Affiliation(s)
- Masateru Yamamoto
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Tsuyoshi Kobayashi
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.
| | - Naruhiko Honmyo
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Akihiko Oshita
- Department of Gastroenterological Surgery, Hiroshima Prefectural Hospital, Hiroshima, Japan
| | - Tomoyuki Abe
- Department of Surgery, Onomichi General Hospital, Onomichi, Japan
| | - Toshihiko Kohashi
- Department of Surgery, Hiroshima City Asa Citizens Hospital, Hiroshima, Japan
| | - Takashi Onoe
- National Hospital Organization, Kure Medical Center/Chugoku Cancer Center, Institute for Clinical Research, Hiroshima, Japan
| | - Saburo Fukuda
- Department of Surgery, Chugoku Rosai Hospital, Kure, Japan
| | - Ichiro Omori
- Department of Surgery, National Hospital Organization Higashihiroshima Medical Center, Hiroshima, Japan
| | - Yasuhiro Imaoka
- Department of Surgery, National Hospital Organization Hiroshima-Nishi Medical Center, Hiroshima, Japan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
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Muhammad H, Tehreem A, Ting PS, Gurakar M, Li SY, Simsek C, Alqahtani SA, Kim AK, Kohli R, Gurakar A. Hepatocellular Carcinoma and the Role of Liver Transplantation: A Review. J Clin Transl Hepatol 2021; 9:738-748. [PMID: 34722189 PMCID: PMC8516838 DOI: 10.14218/jcth.2021.00125] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 05/01/2021] [Accepted: 05/18/2021] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer deaths worldwide and liver transplantation (LT) is the only potentially curative treatment. Over the years, Milan criteria has been used for patient selection. There is ongoing research in this field with introduction of new biomarkers for HCC that can help guide future treatment. Furthermore, newer therapies for downstaging of the tumor are being implemented to prevent dropout from the transplant list. In addition, combination therapies for better outcome are under investigation. Interestingly, the concept of living-donor LT and possible use of hepatitis C virus-positive donors has been implemented as an attempt to expand the organ pool. However, there is a conflict of opinion between different centers regarding its efficacy and data is scarce. The aim of this review article is to outline the various selection criteria for LT, discuss the outcomes of LT in HCC patients, and explore future directions of LT for HCC. Therefore, a comprehensive PubMed/MEDLINE review was conducted. To expand our search, references of the retrieved articles were also screened for additional data. After selecting the studies, the authors independently reviewed them to identify the relevant studies. After careful evaluation 120 studies relevant to out topic are cited in the manuscript. Three tables and two figures are also included. In conclusion LT for HCC has evolved over the years. With the introduction of several expanded criteria beyond Milan, the introduction of bridging therapies, such as transcatheter arterial chemoembolization and radiofrequency ablation, and the approval of newer systemic therapies, it is evident that there will be more LT recipients in the future. It is promising to see ongoing trials and the continuous evolution of protocols. Prospective studies are needed to guide the development of a pre-LT criteria that can ensure low HCC recurrence risk and is not overly stringent, clarify the role of LDLT, and determine the optimal bridging therapies to LT.
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Affiliation(s)
- Haris Muhammad
- Department of Internal Medicine, Greater Baltimore Medical Center, MD, USA
| | - Aniqa Tehreem
- Department of Internal Medicine, Sinai Hospital, Baltimore, MD, USA
| | - Peng-Sheng Ting
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Merve Gurakar
- Department of Medicine, Osler Residency Program, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | | | - Cem Simsek
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Saleh A. Alqahtani
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Amy K. Kim
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Ruhail Kohli
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Ahmet Gurakar
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- Correspondence to: Ahmet Gurakar, Section of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross Research Building, Suite 918 Baltimore, MD 21205, USA. ORCID: https://orcid.org/0000-0002-2221-9148. Tel: +1-410-614-3369, Fax: +1-443-683-8349, E-mail:
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21
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Rim CH. Differences in radiotherapy application according to regional disease characteristics of hepatocellular carcinoma. JOURNAL OF LIVER CANCER 2021; 21:113-123. [PMID: 37383087 PMCID: PMC10035685 DOI: 10.17998/jlc.2021.05.26] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Revised: 05/25/2021] [Accepted: 06/01/2021] [Indexed: 06/30/2023]
Abstract
There are differences in opinion regarding the application of external beam radiotherapy in the treatment of hepatocellular carcinoma. Some major guidelines state that external beam radiotherapy is yet to attain a sufficient level of evidence. However, caution should be exercised when attempting to understand the clinical need for external beam radiotherapy solely based on the level of evidence. Previously, external beam radiotherapy had low applicability in the treatment of hepatocellular carcinoma before computed tomography-based planning was popularized. Modern external beam radiotherapy can selectively target tumor cells while sparing normal liver tissues. Recent technologies such as stereotactic body radiotherapy have enabled more precise treatment. The characteristics of hepatocellular carcinoma differ significantly according to the regional etiology. The main cause of hepatocellular carcinoma is the hepatitis B virus. It is commonly diagnosed as a locally advanced tumor but with relatively preserved hepatic function. The majority of these hepatocellular carcinoma cases are found in the East Asian population. Hepatocellular carcinoma caused by hepatitis C virus or other benign hepatitis tends to be diagnosed as a less locally aggressive tumor but with deteriorated liver function. The western world and Japan tend to have patients with such causes. External beam radiotherapy has been more commonly performed for the former, although the use of external beam radiotherapy in the latter might have more concerns with regard to hepatic toxicity. This review discusses the above subjects along with perspectives regarding external beam radiotherapy in recent guidelines.
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Affiliation(s)
- Chai Hong Rim
- Department of Radiation Oncology, Korea University Ansan Hospital, Ansan, Korea
- Korea University Medical College, Seoul, Korea
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22
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Long-term outcomes of deceased donor liver transplantation in hepatocellular carcinoma patients with portal vein tumor thrombus: A multicenter study. Eur J Surg Oncol 2021; 48:121-132. [PMID: 34456082 DOI: 10.1016/j.ejso.2021.08.014] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 07/25/2021] [Accepted: 08/09/2021] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND The incidence of portal vein tumor thrombus (PVTT) has been reported to be as high as approximately 10%-40% in patients with hepatocellular carcinoma (HCC). The long-term prognosis of deceased donor liver transplantation (DDLT) in HCC patients with PVTT remains unknown. METHODS Data of 961 HCC patients who underwent DDLT between 2015 and 2018 in six centers were analyzed. Based on the Milan criteria (MC) and Cheng's classification of PVTT, the patients were divided into 4 groups: within MC, beyond MC without PVTT, type 1 PVTT, and type 2 PVTT groups. RESULTS 489 (50.9%) were within the MC, 296 (30.8%) beyond the MC but without PVTT, 83 (8.6%) type 1 PVTT, and 93 (9.7%) type 2 PVTT. Kaplan-Meier analysis showed that type 1 or 2 PVTT patients with alpha-fetoprotein (AFP) ≤ 100 ng/mL had overall survival (OS) similar to that of patients within the MC (P = 0.957), and superior OS (P = 0.003 and 0.009) and recurrence-free survival (RFS) (P = 0.038 and <0.001) than those of patients beyond the MC and PVTT patients with AFP > 100 ng/mL. Multivariable Cox-regression analysis identified type 1 and 2 PVTT to be independent risk factor for RFS [hazard ratio (HR) 1.523 95% confidence interval (CI) 1.162-1.997, P = 0.002], but not for OS (HR 1.283, 95%CI 0.922-1.786, P = 0.139). CONCLUSION HCC patients with type 1 or 2 PVTT may be acceptable candidates for DDLT. To achieve better outcomes, preoperative AFP levels should be seriously considered when selecting patients with PVTT for DDLT.
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Glantzounis GK, Karampa A, Peristeri DV, Pappas-Gogos G, Tepelenis K, Tzimas P, Cyrochristos DJ. Recent advances in the surgical management of hepatocellular carcinoma. Ann Gastroenterol 2021; 34:453-465. [PMID: 34276183 PMCID: PMC8276352 DOI: 10.20524/aog.2021.0632] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Accepted: 02/19/2021] [Indexed: 02/07/2023] Open
Abstract
The incidence of hepatocellular carcinoma (HCC) is increasing, despite effective antiviral treatment for hepatitis B (HBV) and C virus infection and the application of preventive measures such as vaccination at birth against HBV infection. This is mainly due to the increase in metabolic syndrome and its hepatic components, nonalcoholic fatty liver disease and steatohepatitis. Liver resection and transplantation are the main treatment options, offering long-term survival and potential cure. In this review, the recent advances in the surgical management of HCC are presented. More specifically, the role of liver resection in the intermediate and advanced stages, according to the Barcelona Clinic Liver Cancer classification, is analyzed. In addition, the roles of minimally invasive surgery and of living-related liver transplantation in the management of patients with HCC are discussed. Finally, recent data on the role of molecular markers in the early diagnosis and recurrence of HCC are presented. The management of HCC is complex, as there are several options for each stage of the disease. In order for, each patient to get the maximum benefit, an individualized approach is suggested, in specialized liver units, where cases are discussed in multidisciplinary tumor boards.
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Affiliation(s)
- Georgios K. Glantzounis
- HPB Unit, Department of Surgery (Georgios K. Glantzounis, Anastasia Karampa, Dimitra V. Peristeri, George Pappas-Gogos, Kostas Tepelenis, Dimitrios J. Cyrochristos)
| | - Anastasia Karampa
- HPB Unit, Department of Surgery (Georgios K. Glantzounis, Anastasia Karampa, Dimitra V. Peristeri, George Pappas-Gogos, Kostas Tepelenis, Dimitrios J. Cyrochristos)
| | - Dimitra V. Peristeri
- HPB Unit, Department of Surgery (Georgios K. Glantzounis, Anastasia Karampa, Dimitra V. Peristeri, George Pappas-Gogos, Kostas Tepelenis, Dimitrios J. Cyrochristos)
| | - George Pappas-Gogos
- HPB Unit, Department of Surgery (Georgios K. Glantzounis, Anastasia Karampa, Dimitra V. Peristeri, George Pappas-Gogos, Kostas Tepelenis, Dimitrios J. Cyrochristos)
| | - Kostas Tepelenis
- HPB Unit, Department of Surgery (Georgios K. Glantzounis, Anastasia Karampa, Dimitra V. Peristeri, George Pappas-Gogos, Kostas Tepelenis, Dimitrios J. Cyrochristos)
| | - Petros Tzimas
- Department of Anesthesiology (Petros Tzimas), University Hospital of Ioannina and School of Medicine, University of Ioannina, Ioannina, Greece
| | - Dimitrios J. Cyrochristos
- HPB Unit, Department of Surgery (Georgios K. Glantzounis, Anastasia Karampa, Dimitra V. Peristeri, George Pappas-Gogos, Kostas Tepelenis, Dimitrios J. Cyrochristos)
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24
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Goldberg D, Mantero A, Newcomb C, Delgado C, Forde KA, Kaplan DE, John B, Nuchovich N, Dominguez B, Emanuel E, Reese PP. Predicting survival after liver transplantation in patients with hepatocellular carcinoma using the LiTES-HCC score. J Hepatol 2021; 74:1398-1406. [PMID: 33453328 PMCID: PMC8137533 DOI: 10.1016/j.jhep.2020.12.021] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Revised: 11/24/2020] [Accepted: 12/18/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Liver transplant priority in the US and Europe follows the 'sickest-first' principle. However, for patients with hepatocellular carcinoma (HCC), priority is based on binary tumor criteria to expedite transplant for patients with 'acceptable' post-transplant outcomes. Newer risk scores developed to overcome limitations of these binary criteria are insufficient to be used for waitlist priority as they focus solely on HCC-related pre-transplant variables. We sought to develop a risk score to predict post-transplant survival for patients using HCC- and non-HCC-related variables. METHODS We performed a retrospective cohort study using national registry data on adult deceased-donor liver transplant (DDLT) recipients with HCC from 2/27/02-12/31/18. We fit Cox regression models focused on 5- and 10-year survival to estimate beta coefficients for a risk score using manual variable selection. We then calculated absolute predicted survival time and compared it to available risk scores. RESULTS Among 6,502 adult DDLT recipients with HCC, 11 variables were selected in the final model. The AUCs at 5- and 10-years were: 0.62, 95% CI 0.57-0.67 and 0.65, 95% CI 0.58-0.72, which was not statistically significantly different to the Metroticket and HALT-HCC scores. The LiTES-HCC score was able to discriminate patients based on post-transplant survival among those meeting Milan and UCSF criteria. CONCLUSION We developed and validated a risk score to predict post-transplant survival for patients with HCC. By including HCC- and non-HCC-related variables (e.g., age, chronic kidney disease), this score could allow transplant professionals to prioritize patients with HCC in terms of predicted survival. In the future, this score could be integrated into survival benefit-based models to lead to meaningful improvements in life-years at the population level. LAY SUMMARY We created a risk score to predict how long patients with liver cancer will live if they get a liver transplant. In the future, this could be used to decide which waitlisted patients should get the next transplant.
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Affiliation(s)
- David Goldberg
- Division of Digestive Health and Liver Diseases, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA.
| | - Alejandro Mantero
- Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL
| | - Craig Newcomb
- Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Cindy Delgado
- Division of Digestive Health and Liver Diseases, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL
| | - Kimberly A. Forde
- Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA,Division of Gastroenterology and Hepatology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - David E. Kaplan
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA,Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA
| | - Binu John
- Bruce Carter VA Medica Center, Miami, FL
| | - Nadine Nuchovich
- Division of Digestive Health and Liver Diseases, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL
| | - Barbara Dominguez
- Division of Digestive Health and Liver Diseases, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL
| | - Ezekiel Emanuel
- Department of Medical Ethics and Health Policy, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Peter P. Reese
- Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA,Renal-Electrolye and Hypertension Division, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
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Doğan SM, Kutlutürk K. Living Donor Versus Deceased Donor Liver Transplantation for HCC. J Gastrointest Cancer 2021; 51:1104-1106. [PMID: 32833221 DOI: 10.1007/s12029-020-00481-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
INTRODUCTION Liver transplantation is the definitive treatment modality of the patients having an end-stage liver disease with hepatocellular carcinoma. DISCUSSION The number of living donor liver transplantations has been increased because of the deceased donor organ shortage, especially in Asian countries. CONCLUSION Reports of different clinics about the postoperative course and tumor recurrence rates comparing living donor versus deceased donor liver transplantations, besides patient selection criteria, are reviewed along with our clinic's experiences.
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Affiliation(s)
- Sait Murat Doğan
- Department of Surgery and Liver Transplantation Institute, İnönü University Faculty of Medicine, Elazığ yolu 10.km, 44280, Malatya, Turkey.
| | - Koray Kutlutürk
- Department of Surgery and Liver Transplantation Institute, İnönü University Faculty of Medicine, Elazığ yolu 10.km, 44280, Malatya, Turkey
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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: 545] [Impact Index Per Article: 136.3] [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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Minici R, Ammendola M, Manti F, Siciliano MA, Giglio E, Minici M, Melina M, Currò G, Laganà D. Safety and Efficacy of Degradable Starch Microspheres Transcatheter Arterial Chemoembolization as a Bridging Therapy in Patients with Early Stage Hepatocellular Carcinoma and Child-Pugh Stage B Eligible for Liver Transplant. Front Pharmacol 2021; 12:634084. [PMID: 33897421 PMCID: PMC8062923 DOI: 10.3389/fphar.2021.634084] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Accepted: 02/19/2021] [Indexed: 12/12/2022] Open
Abstract
In patients with early-stage hepatocellular carcinoma, awaiting liver transplantation, current guidelines by AASLD and ESMO recommend a bridging therapy with a loco-regional treatment to prevent progression outside transplantation criteria. The standard of care in delaying disease progression has been recognized to be the transarterial chemoembolization. Permanent occlusion of tumor feeding vessels has effects on tumour stromal microenvironment by inducing intra- and intercellular signaling processes counteracting hypoxia, such as the release of vascular endothelial growth factor, a promoter of neoangiogenesis, tumour proliferation and metastatic growth. Among chemoembolization interventions, TACE with degradable starch microspheres represents an alternative to conventional cTACE and DEB-TACE and it minimizes detrimental effects on tumour stromal microenvironment, guaranteeing a transient occlusion of tumour feeding arteries and avoiding VEGF overexpression.Between January 2015 and September 2020, 54 consecutive patients with early-stage hepatocellular carcinoma and Child-Pugh stage B, who had undergone DSM-TACE as a bridging therapy while awaiting liver transplantation, were eligible for the study. A total of 154 DSM-TACE was performed, with a mean number of 2.85 procedures per patient. 18 patients (33.3%) succeeded in achieving liver transplantation, with a mean waiting time-to-transplantation of 11.7 months. The cumulative rates of patients still active on the WL at 6 months were about 91 and 93% when considering overall drop-out and tumour-specific drop-out respectively. Overall survival was about 96% at 6 months and 92% at 12 months. 17 patients experienced adverse events after the chemoembolizations. For patients with HCC in the transplant waiting list and within the Child-Pugh B stage, life expectancy may be dominated by the liver dysfunction, rather than by the tumour progression itself. In this population subset, the choice of LRT is critical because LRT itself could become a dangerous tool that is likely to precipitate liver dysfunction to an extent that survival is shortened rather than prolonged. Hence, the current study demonstrates that DSM-TACE is not far from being an ideal LRT, because it has an excellent safety profile, maintaining an efficacy that guarantees a clear advantage on the dropout rate with respect to the non-operative strategy, thus justifying its use.
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Affiliation(s)
- Roberto Minici
- Radiology Unit, Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy
| | - Michele Ammendola
- Digestive Surgery Unit, Science of Health Department, Magna Graecia University, Catanzaro, Italy
| | - Francesco Manti
- Radiology Unit, Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy
| | - Maria Anna Siciliano
- Medical Oncology Unit, Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy
| | - Enrica Giglio
- Medical Oncology Unit, University Hospital-Marche Polytechnic University, Ancona, Italy
| | - Marco Minici
- National Research Council (Cnr), Institute for High Performance Computing and Networking (ICAR), Rende, Italy
| | - Marica Melina
- Department of Medical and Surgical Sciences, Sant’Orsola Malpighi Hospital, Alma Mater Studiorum University of Bologna, Bologna, Italy
| | - Giuseppe Currò
- General Surgery Unit, Science of Health Department, Magna Graecia University, Catanzaro, Italy
| | - Domenico Laganà
- Radiology Unit, Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy
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Mehta N, Dodge JL, Roberts JP, Yao FY. A novel waitlist dropout score for hepatocellular carcinoma - identifying a threshold that predicts worse post-transplant survival. J Hepatol 2021; 74:829-837. [PMID: 33188904 PMCID: PMC7979440 DOI: 10.1016/j.jhep.2020.10.033] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 10/08/2020] [Accepted: 10/29/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS It has been suggested that patients with hepatocellular carcinoma (HCC) at high risk of wait-list dropout would have done poorly after liver transplantation (LT) because of tumour aggressiveness. To test this hypothesis, we analysed risk of wait-list dropout among patients with HCC in long-wait regions (LWRs) to create a dropout risk score, and applied this score in short (SWRs) and mid-wait regions (MWRs) to evaluate post-LT outcomes. We sought to identify a threshold in dropout risk that predicts worse post-LT outcome. METHODS Using the United Network for Organ Sharing database, including all patients with T2 HCC receiving priority listing from 2010 to 2014, a dropout risk score was created from a developmental cohort of 2,092 patients in LWRs, and tested in a validation cohort of 1,735 patients in SWRs and 2,894 patients in MWRs. RESULTS On multivariable analysis, 1 tumour (3.1-5 cm) or 2-3 tumours, alpha-fetoprotein (AFP) >20 ng/ml, and increasing Child-Pugh and model for end-stage liver disease-sodium scores significantly predicted wait-list dropout. A dropout risk score using these 4 variables (C-statistic 0.74) was able to stratify 1-year cumulative incidence of dropout from 7.1% with a score ≤7 to 39.5% with a score >23. Patients with a dropout risk score >30 had 5-year post-LT survival of 60.1% vs. 71.8% for those with a score ≤30 (p = 0.004). There were no significant differences in post-LT survival below this threshold. CONCLUSIONS This study provided evidence that patients with HCC with the highest dropout risk have aggressive tumour biology that would also result in poor post-LT outcomes when transplanted quickly. Below this threshold risk score of ≤30, priority status for organ allocation could be stratified based on the predicted risks of wait-list dropout without significant differences in post-LT survival. LAY SUMMARY Prioritising patients with hepatocellular carcinoma for liver transplant based on risk of wait-list dropout has been considered but may lead to inferior post-transplant survival. In this study of nearly 7,000 patients, we created a threshold dropout risk score based on tumour and liver-related factors beyond which patients with hepatocellular carcinoma will likely have poor post-liver transplant outcomes (60% at 5 years). For patients below this risk score threshold, priority status could be stratified based on the predicted risk of wait-list dropout without compromising post-transplant survival.
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Affiliation(s)
- Neil Mehta
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
| | - Jennifer L Dodge
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, USA
| | - John P Roberts
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, USA
| | - Francis Y Yao
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA; Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, USA
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Cheung TT, Ma KW, She WH. A review on radiofrequency, microwave and high-intensity focused ultrasound ablations for hepatocellular carcinoma with cirrhosis. Hepatobiliary Surg Nutr 2021; 10:193-209. [PMID: 33898560 DOI: 10.21037/hbsn.2020.03.11] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Importance Hepatocellular carcinoma (HCC) is usually accompanied by liver cirrhosis, which makes treatment of this disease challenging. Liver transplantation theoretically provides an ultimate solution to the disease, but the maximal surgical stress and the scarcity of liver graft make this treatment option impossible for some patients. In an ideal situation, a treatment that is safe and effective should provide a better outcome for patients with the dilemma. Objective This article aims to give a comprehensive review of various types of loco-ablative treatment for HCC. Evidence Review Loco-ablative treatment bridges the gap between surgical resection and transarterial chemotherapy. Various types of ablative therapy have their unique ability, and evidence-based outcome analysis is the most important key to assisting clinicians to choose the most suitable treatment modality for their patients. Findings Radiofrequency ablation (RFA) has a relatively longer history and more evidence to support its effectiveness. Microwave ablation (MWA) is gaining momentum because of its shorter ablation time and consistent ablation zone. High-intensity focused ultrasound (HIFU) ablation is a relatively new technology that provides non-invasive treatment for patients with HCC. It has been carried out at centers of excellence and it is a safe and effective treatment option for selected patients with HCC and liver cirrhosis. Conclusion and Relevance Selective use of different loco-ablative therapies will enhance clinicians' treatment options for treatment of HCC.
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Affiliation(s)
- Tan To Cheung
- Department of Surgery, The University of Hong Kong, 102 Pok Fu Lam Road, Hong Kong, China
| | - Ka Wing Ma
- Department of Surgery, The University of Hong Kong, 102 Pok Fu Lam Road, Hong Kong, China
| | - Wong Hoi She
- Department of Surgery, The University of Hong Kong, 102 Pok Fu Lam Road, Hong Kong, China
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Shehta A, Farouk A, Fouad A, Aboelenin A, Elghawalby AN, Said R, Elshobary M, El Nakeeb A. Post-hepatectomy liver failure after hepatic resection for hepatocellular carcinoma: a single center experience. Langenbecks Arch Surg 2021; 406:87-98. [PMID: 32778915 DOI: 10.1007/s00423-020-01956-2] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Accepted: 08/03/2020] [Indexed: 12/24/2022]
Abstract
PURPOSE Post-hepatectomy liver failure (PHLF) is one of the most feared morbidities after liver resection (LR) for hepatocellular carcinoma (HCC). We aimed to investigate the incidence and predictors of PHLF after LR for HCC and its impact on survival outcomes. METHODS We reviewed the patients who underwent LR for HCC during the period between January 2010 and 2019. RESULTS Two hundred sixty-eight patients were included. Patients were divided into two groups according to the occurrence of PHLF, defined according to ISGLS. The non-PHLF group included 138 patients (51.5%), while the PHLF group included 130 patients (48.5%). Two hundred forty-six patients (91.8%) had hepatitis C virus. Major liver resections were more performed in the PHLF group (40 patients (30.8%) vs. 18 patients (13%), p = 0.001). Longer operation time (3 vs. 2.5 h, p = 0.001), more blood loss (1000 vs. 500 cc, p = 0.001), and transfusions (81 patients (62.3%) vs. 52 patients (37.7%), p = 0.001) occurred in PHLF group. The 1-, 3-, and 5-year Kaplan-Meier overall survival rates for the non-PHLF group were 93.9%, 79.5%, and 53.9% and 73.2%, 58.7%, and 52.4% for the PHLF group, respectively (log rank, p = 0.003). The 1-, 3-, and 5-year Kaplan-Meier disease-free survival rates for the non-PHLF group were 77.7%, 42.5%, and 29.4%, and 73.3%, 42.9%, and 25.3% for the PHLF group, respectively (log rank, p = 0.925). Preoperative albumin, bilirubin, INR, and liver cirrhosis were significant predictors of PHLF in the logistic regression analysis. CONCLUSION Egyptian patients with HCC experienced higher PHLF incidence after LR for HCC. PHLF significantly affected the long-term survival of those patients.
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Affiliation(s)
- Ahmed Shehta
- Gastrointestinal Surgery Center, College of Medicine, Mansoura University, Gehan Street, Mansoura, 35516, Egypt.
| | - Ahmed Farouk
- Gastrointestinal Surgery Center, College of Medicine, Mansoura University, Gehan Street, Mansoura, 35516, Egypt
| | - Amgad Fouad
- Gastrointestinal Surgery Center, College of Medicine, Mansoura University, Gehan Street, Mansoura, 35516, Egypt
| | - Ahmed Aboelenin
- Gastrointestinal Surgery Center, College of Medicine, Mansoura University, Gehan Street, Mansoura, 35516, Egypt
| | - Ahmed Nabieh Elghawalby
- Gastrointestinal Surgery Center, College of Medicine, Mansoura University, Gehan Street, Mansoura, 35516, Egypt
| | - Rami Said
- Gastrointestinal Surgery Center, College of Medicine, Mansoura University, Gehan Street, Mansoura, 35516, Egypt
| | - Mohamed Elshobary
- Gastrointestinal Surgery Center, College of Medicine, Mansoura University, Gehan Street, Mansoura, 35516, Egypt
| | - Ayman El Nakeeb
- Gastrointestinal Surgery Center, College of Medicine, Mansoura University, Gehan Street, Mansoura, 35516, Egypt
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Novelli PM, Orons PD. The role of interventional radiology in the pre-liver transplant patient. Abdom Radiol (NY) 2021; 46:124-133. [PMID: 32840652 DOI: 10.1007/s00261-020-02704-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2019] [Revised: 01/11/2020] [Accepted: 08/08/2020] [Indexed: 11/25/2022]
Abstract
Each year approximately 8500 patients undergo liver transplantation in the USA for acute and chronic liver failure. Over the years, the success of liver transplantation has led to more clinical indications for liver transplantation. These expanded indications, without a proportionate increase in donors, result in increased competition for the limited pool of transplantable whole or partial grafts. The likelihood of receiving a deceased donor graft depends on many clinical variables, including the acute and chronic fitness of the candidate aligning with the timing of donor organ availability. Several types of patients are candidates for transplant: patients with acute fulminant hepatic failure who will die without a transplant, patients with decompensated cirrhosis, and patients with HCC and compensated cirrhosis. Interventional radiology can preserve equity between these subgroups and reduce patient dropout by increasing the physiologic and anatomic fitness of the candidate before and after formal listing. The primary determinants of candidacy fitness and dropout are the severity of clinical symptoms related to portal hypertension and the presence of hepatocellular cancer. There is a subgroup of patients whose disease severity is not accurately reflected by the Model for End-stage Liver Disease (MELD), such as patients with chronic cholestasis that also may benefit from IR management.
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Affiliation(s)
- Paula M Novelli
- Department of Radiology, UPMC, 200 Lothrop St, Pittsburgh, PA, 15213, USA.
| | - Philip D Orons
- Department of Radiology, UPMC, 200 Lothrop St, Pittsburgh, PA, 15213, USA
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Gelli M, Sebagh M, Porcher R, Romanelli E, Vibert E, Sa Cunha A, Castaing D, Rosmorduc O, Samuel D, Adam R, Cherqui D. Liver Resection for Early Hepatocellular Carcinoma: Preoperative Predictors of Non Transplantable Recurrence and Implications for Treatment Allocation. Ann Surg 2020; 272:820-826. [PMID: 32833755 DOI: 10.1097/sla.0000000000004259] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND AND AIMS LR and LT are the standard curative options for early HCC. LT provides best long-term survival but is limited by organ shortage. LR, readily available, is hampered by high recurrence rates. Salvage liver transplantation is an efficient treatment of recurrences within criteria. The aim of the study was to identify preoperative predictors of non transplantable recurrence (NTR) to improve patient selection for upfront LR or LT at initial diagnosis. STUDY DESIGN Consecutive LR for transplantable HCC between 2000 and 2015 were studied. A prediction model for NTR based on preoperative variables was developed using sub-distribution hazard ratio after multiple imputation and internal validation by bootstrapping. Model performance was evaluated by the concordance index after correction for optimism. RESULTS A total of 148 patients were included. Five-year overall survival and recurrence free survival were 73.6% and 29.3%, respectively (median follow-up 45.8 months). Recurrence rate was 54.8%. NTR rate was 38.2%. Preoperative model for NTR identified >1 nodule [sub-distribution hazard ratio 2.35 95% confidence interval (CI) 1.35-4.09], AFP >100 ng/mL (2.14 95% CI 1.17-3.93), and F4 fibrosis (1.93 95% CI 1.03-3.62). The apparent concordance index of the model was 0.664 after correction for optimism. In the presence of 0, 1, and ≥2 factors, NTR rates were 2.6%, 22.7%, and 40.9%, respectively. The number of prognostic factors was significantly associated with the pattern of recurrence (P = 0.001) and 5-year recurrence free survival (P < 0.001). CONCLUSIONS Cirrhosis, >1 nodule, and AFP >100 ng/mL were identified as preoperative predictors of NTR. In the presence of 2 factors or more upfront transplantation should be probably preferred to resection in regard of organ availability. Other patients are good candidates for LR and salvage liver transplantation should be encouraged in eligible patients with recurrence.
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Affiliation(s)
- Maximiliano Gelli
- Hepatobiliary Center Paul Brousse Hospital, APHP-Université Paris Saclay, Villejuif, France
| | - Mylène Sebagh
- Department of Pathology, APHP - Université Paris Saclay, Hôpital Paul Brousse, Villejuif, France
| | - Raphaël Porcher
- Centre de Recherche Épidémiologie et Statistique (CRESS-UMR1153) Université Paris Descartes-Hôpital Hôtel-Dieu, Paris, France
| | - Elena Romanelli
- Hepatobiliary Center Paul Brousse Hospital, APHP-Université Paris Saclay, Villejuif, France
| | - Eric Vibert
- Hepatobiliary Center Paul Brousse Hospital, APHP-Université Paris Saclay, Villejuif, France
| | - Antonio Sa Cunha
- Hepatobiliary Center Paul Brousse Hospital, APHP-Université Paris Saclay, Villejuif, France
| | - Denis Castaing
- Hepatobiliary Center Paul Brousse Hospital, APHP-Université Paris Saclay, Villejuif, France
| | - Olivier Rosmorduc
- Hepatobiliary Center Paul Brousse Hospital, APHP-Université Paris Saclay, Villejuif, France
| | - Didier Samuel
- Hepatobiliary Center Paul Brousse Hospital, APHP-Université Paris Saclay, Villejuif, France
| | - René Adam
- Hepatobiliary Center Paul Brousse Hospital, APHP-Université Paris Saclay, Villejuif, France
| | - Daniel Cherqui
- Hepatobiliary Center Paul Brousse Hospital, APHP-Université Paris Saclay, Villejuif, France
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Piñero F, Tanno M, Aballay Soteras G, Tisi Baña M, Dirchwolf M, Fassio E, Ruf A, Mengarelli S, Borzi S, Fernández N, Ridruejo E, Descalzi V, Anders M, Mazzolini G, Reggiardo V, Marciano S, Perazzo F, Spina JC, McCormack L, Maraschio M, Lagues C, Gadano A, Villamil F, Silva M, Cairo F, Ameigeiras B. Argentinian clinical practice guideline for surveillance, diagnosis, staging and treatment of hepatocellular carcinoma. Ann Hepatol 2020; 19:546-569. [PMID: 32593747 DOI: 10.1016/j.aohep.2020.06.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2020] [Revised: 06/05/2020] [Accepted: 06/10/2020] [Indexed: 02/08/2023]
Abstract
The A.A.E.E.H has developed this guideline for the best care of patients with hepatocellular carcinoma (HCC) from Argentina. It was done from May 2018 to March 2020. Specific clinical research questions were systematically searched. The quality of evidence and level of recommendations were organized according to GRADE. HCC surveillance is strongly recommended with abdominal ultrasound (US) every six months in the population at risk for HCC (cirrhosis, hepatitis B or hepatitis C); it is suggested to add alpha-feto protein (AFP) levels in case of inexeperienced sonographers. Imaging diagnosis in patients at risk for HCC has high specificity and tumor biopsy is not mandatory. The Barcelona Clinic Liver Cancer algorithm is strongly recommended for HCC staging and treatment-decision processes. Liver resection is strongly recommended for patients without portal hypertension and preserved liver function. Composite models are suggested for liver transplant selection criteria. Therapies for HCC with robust clinical evidence include transarterial chemoembolization (TACE) and first to second line systemic treatment options (sorafenib, lenvatinib, regorafenib, cabozantinib and ramucirumab). Immunotherapy with nivolumab and pembrolizumab has failed to show statistical benefit but the novel combination of atezolizumab plus bevacizumab has recently shown survival benefit over sorafenib in frontline.
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Affiliation(s)
- Federico Piñero
- Hepatology and Liver Unit, Hospital Universitario Austral, School of Medicine, Austral University, B1629HJ Buenos Aires, Argentina.
| | - Mario Tanno
- Hospital Centenario de Rosario, Santa Fe, Argentina
| | | | - Matías Tisi Baña
- Internal Medicine and Epidemiology Department, Hospital Universitario Austral, School of Medicine, Austral University, B1629HJ Buenos Aires, Argentina
| | | | | | - Andrés Ruf
- Hospital Privado de Rosario, Santa Fe, Argentina
| | | | - Silvia Borzi
- Instituto Rossi, La Plata, Buenos Aires, Argentina
| | | | - Ezequiel Ridruejo
- Hepatology and Liver Unit, Hospital Universitario Austral, School of Medicine, Austral University, B1629HJ Buenos Aires, Argentina; Centro de Educación Médica e Investigaciones Clínicas (CEMIC), Ciudad de Buenos Aires, Argentina
| | | | | | - Guillermo Mazzolini
- Hepatology and Liver Unit, Hospital Universitario Austral, School of Medicine, Austral University, B1629HJ Buenos Aires, Argentina
| | | | | | | | | | | | | | - Cecilia Lagues
- Hepatology and Liver Unit, Hospital Universitario Austral, School of Medicine, Austral University, B1629HJ Buenos Aires, Argentina
| | | | | | - Marcelo Silva
- Hepatology and Liver Unit, Hospital Universitario Austral, School of Medicine, Austral University, B1629HJ Buenos Aires, Argentina
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Ouyang G, Pan G, Xu H, Wu Y, Liu Z, Lu W, Yi B, Chen X. Sorafenib Plus Hepatic Arterial Infusion Chemotherapy in Advanced Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis. J Clin Gastroenterol 2020; 54:675-681. [PMID: 32569032 DOI: 10.1097/mcg.0000000000001384] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
BACKGROUND AND AIM The clinical utility of sorafenib plus hepatic arterial infusion chemotherapy (SoraHAIC) in advanced hepatocellular carcinoma (HCC) patients remains unclear. We, therefore, conducted the current meta-analysis to systematically evaluate the efficacy and safety of SoraHAIC therapy on major outcomes with advanced HCC patients. METHODS A systematic search of The Cochrane Library, PubMed, and Embase databases was performed. The major outcomes in patients with advanced HCC were divided into SoraHAIC group and sorafenib group, which included overall response rate, overall survival, progressive disease, and adverse events. RESULTS Involving a total of 726 patients from 5 included studies, our meta-analysis demonstrated that SoraHAIC showed significantly more improvement than sorafenib alone in overall response rate [risk ratio=3.08; 95% confidence interval (CI), 1.38-6.89; P=0.006] and complete response (risk ratio=5.84; 95% CI, 1.85-18.45; P=0.003). With regard to survival outcome, the combination therapy also significantly prolongs the median overall survival than sorafenib monotherapy (hazard ratio=0.59; 95% CI, 0.35-1.00; P=0.05). In addition, the risk of adverse events such as anemia, neutropenia, and thrombocytopenia was significantly greater in the combination group than in the sorafenib group (P<0.05 for all). CONCLUSIONS This meta-analysis indicated that SoraHAIC seems to be efficient and safe for advanced HCC patients. However, additional large-scale randomized controlled trials are needed to further investigate the clinical benefit.
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Affiliation(s)
- Guoqing Ouyang
- Department of Hepatobiliary Surgery, Liuzhou People's Hospital, Liuzhou, Guangxi
| | - Guangdong Pan
- Department of Hepatobiliary Surgery, Liuzhou People's Hospital, Liuzhou, Guangxi
| | - Honglai Xu
- Department of Hepatobiliary Surgery, Liuzhou People's Hospital, Liuzhou, Guangxi
| | - Yongrong Wu
- Department of Hepatobiliary Surgery, Liuzhou People's Hospital, Liuzhou, Guangxi
| | - Zhen Liu
- Department of Hepatobiliary Surgery, Liuzhou People's Hospital, Liuzhou, Guangxi
| | - Wuhang Lu
- Department of Hepatobiliary Surgery, Liuzhou People's Hospital, Liuzhou, Guangxi
| | - Bin Yi
- Department of Cardiothoracic Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong
| | - Xiang Chen
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
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35
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Chisthi MM. Commentary on 'The efficacy of microwave ablation versus liver resection in the treatment of hepatocellular carcinoma and liver metastases: A systematic review and meta-analysis'. Int J Surg 2020; 78:19-20. [PMID: 32304890 DOI: 10.1016/j.ijsu.2020.04.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2020] [Accepted: 04/01/2020] [Indexed: 11/26/2022]
Affiliation(s)
- Meer M Chisthi
- Department of General Surgery, Government Medical College, Trivandrum, Kerala, 695011, India.
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Yamamoto M, Kobayashi T, Oshita A, Abe T, Kohashi T, Onoe T, Fukuda S, Omori I, Imaoka Y, Honmyo N, Ohdan H. Laparoscopic versus open limited liver resection for hepatocellular carcinoma with liver cirrhosis: a propensity score matching study with the Hiroshima Surgical study group of Clinical Oncology (HiSCO). Surg Endosc 2019; 34:5055-5061. [PMID: 31828498 DOI: 10.1007/s00464-019-07302-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2019] [Accepted: 11/28/2019] [Indexed: 12/16/2022]
Abstract
BACKGROUND Laparoscopic liver resection (LLR) has evolved as a safe and effective alternative to conventional open liver resection (OLR) for malignant lesions. However, LLR in cirrhotic patients remains challenging. This study analyzed the perioperative and oncological outcomes of LLR for hepatocellular carcinoma (HCC) with cirrhosis compared with OLR using propensity score matching. METHODS A multicenter retrospective analysis of records of patients who underwent limited liver resection for HCC and were histologically diagnosed with liver cirrhosis between January 2009 and December 2017 in the eight institutions belonging to the Hiroshima Surgical study group of Clinical Oncology was performed. The patients were divided into two groups: the LLR and OLR groups. After propensity score matching, we compared clinicopathological features and outcomes. RESULTS In total 256 patients with histological liver cirrhosis who underwent limited liver resection for HCC were included in this study; 58 patients had undergone LLR, and the remaining 198 patients OLR. The number of tumors was higher, tumor size was larger, and difficulty score was significantly higher in the OLR group before propensity matching. After the matching, the data of the well-matched 58 patients in each group were evaluated; the intraoperative blood loss was lower in the LLR group (p = 0.004), and incidence of the postoperative complications was significantly higher in the OLR group (p = 0.019). The duration of the postoperative hospital stay was significantly shorter in the LLR group (p < 0.001). There were no differences between two groups in overall survival and recurrent-free survival. CONCLUSIONS LLR decreased the incidences of postoperative complications, shortened the duration of postoperative hospital stay. Thus, LLR is a safe and feasible procedure even in patients with cirrhosis.
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Affiliation(s)
- Masateru Yamamoto
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Science, Hiroshima University Hospital, 1-2-3 Kasumi, Minami Ward, Hiroshima, 734-8551, Japan
| | - Tsuyoshi Kobayashi
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Science, Hiroshima University Hospital, 1-2-3 Kasumi, Minami Ward, Hiroshima, 734-8551, Japan.
| | - Akihiko Oshita
- Department of Gastroenterological Surgery, Hiroshima Prefectural Hospital, 1-5-54 Ujinakanda, Minami Ward, Hiroshima, 734-8530, Japan
| | - Tomoyuki Abe
- Department of Surgery, Onomichi General Hospital, 1-10-23 Hirahara, Onomichi, 722-8508, Japan
| | - Toshihiko Kohashi
- Department of Surgery, Hiroshima City Asa Citizens Hospital, 2-1-1 Kabeminami, Asakita Ward, Hiroshima, 731-0293, Japan
| | - Takashi Onoe
- National Hospital Organization, Kure Medical Center/Chugoku Cancer Center, Institute for Clinical Research, 3-1, Aoyamacho, Kure, Hiroshima, 737-0023, Japan
| | - Saburo Fukuda
- Department of Surgery, Chugoku Rosai Hospital, 1-5-1 Hirotagaya, Kure, 737-0193, Japan
| | - Ichiro Omori
- Department of Surgery, National Hospital Organization Higashihiroshima Medical Center, 513, Jike, Saijyo-cho, Higashihiroshima, Hiroshima, 739-0041, Japan
| | - Yasuhiro Imaoka
- Department of Surgery, National Hospital Organization Hiroshima-Nishi Medical Center, 4-1-1 Kuba, Otake, Hiroshima, 739-0696, Japan
| | - Naruhiko Honmyo
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Science, Hiroshima University Hospital, 1-2-3 Kasumi, Minami Ward, Hiroshima, 734-8551, Japan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Science, Hiroshima University Hospital, 1-2-3 Kasumi, Minami Ward, Hiroshima, 734-8551, Japan
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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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Sandow T, Pavlus J, Field D, Lacayo E, Cohen E, Lynskey G, Caridi T, Buckley D, Cardella J, Kallakury B, Spies J, Kim AY. Bridging Hepatocellular Carcinoma to Transplant: Transarterial Chemoembolization Response, Tumor Biology, and Recurrence after Transplantation in a 12-Year Transplant Cohort. J Vasc Interv Radiol 2019; 30:995-1003. [PMID: 31109853 DOI: 10.1016/j.jvir.2018.12.736] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2018] [Revised: 12/09/2018] [Accepted: 12/18/2018] [Indexed: 02/08/2023] Open
Abstract
PURPOSE To evaluate tumor response to transarterial chemoembolization as well as biologic characteristics of the tumor as predictors of recurrence after transplantation in patients with hepatocellular carcinoma (HCC) who were bridged or down-staged to liver transplantation. MATERIALS AND METHODS An institutional review board-approved, Health Insurance Portability and Accountability Act-compliant, single-institution retrospective analysis was performed on all patients with HCC who were treated with the use of conventional transarterial chemoembolization or transarterial chemoembolization with drug-eluting embolics (DEE) over a 12-year period and who subsequently underwent liver transplantation (n = 142). Treatment response was based on modified Response Evaluation Criteria in Solid Tumors (mRECIST) imaging criteria and then correlated with tumor characteristics and recurrence. Of the 142 patients followed after transplantation, 127 had imaging after transarterial chemoembolization but before transplantation. Imaging response and post-transplantation recurrence were correlated with patient demographics, liver function, and tumor morphology. HCC recurred in 9 patients (mean time from transplantation, 526 days). Recurrence was analyzed with the use of univariate and multivariate statistics. Kaplan-Meier recurrence-free survival curves were calculated based on immediate imaging response before transplantation with the use of the log-rank test. RESULTS Before transplantation, 57% of patients (72/127) demonstrated complete response (CR) and 24% (31/127) showed partial response (PR). Complete pathologic necrosis occurred in 54% (39/72) of CR patients and 20% (6/31) of PR patients. Poor treatment response, defined as stable disease (SD) or progressive disease (PD), occurred in 18% of patients (24/127) before transplantation and was present in 67% of cases of recurrence (6/9; P < .001). Post-transplantation recurrence was present in 1.4% of patients (1/71) with CR and in 6.5% of patients (2/31) with PR. In patients with SD after transarterial chemoembolization, HCC recurred in 18.8% of transplant patients (3/16) and in 43% of patients (3/7) with PD. Larger pretreatment tumor size (P = .05), higher Child-Pugh score (P = .002), higher tumor grade at explantation (P = .04), and lymphovascular invasion at explantation (P = .008) also were associated with increased incidence of post-transplantation recurrence. CONCLUSIONS Poor tumor response to transarterial chemoembolization before transplantation identifies patients at increased risk for post-transplantation recurrence.
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Affiliation(s)
- Tyler Sandow
- Department of Radiology, Ochsner Health System, New Orleans, Louisiana
| | - John Pavlus
- Department of Radiology, Medstar Georgetown University Hospital, 3800 Reservoir Rd, Washington, DC 20007
| | - David Field
- Department of Radiology, Medstar Georgetown University Hospital, 3800 Reservoir Rd, Washington, DC 20007
| | - Eduardo Lacayo
- Department of Radiology, Medstar Georgetown University Hospital, 3800 Reservoir Rd, Washington, DC 20007
| | - Emil Cohen
- Department of Radiology, Medstar Georgetown University Hospital, 3800 Reservoir Rd, Washington, DC 20007
| | - George Lynskey
- Department of Radiology, Medstar Georgetown University Hospital, 3800 Reservoir Rd, Washington, DC 20007
| | - Theresa Caridi
- Department of Radiology, Medstar Georgetown University Hospital, 3800 Reservoir Rd, Washington, DC 20007
| | - Donna Buckley
- Department of Radiology, Medstar Georgetown University Hospital, 3800 Reservoir Rd, Washington, DC 20007
| | - John Cardella
- Department of Radiology, Medstar Georgetown University Hospital, 3800 Reservoir Rd, Washington, DC 20007
| | - Bhaskar Kallakury
- Department of Pathology, Medstar Georgetown University Hospital, 3800 Reservoir Rd, Washington, DC 20007
| | - James Spies
- Department of Radiology, Medstar Georgetown University Hospital, 3800 Reservoir Rd, Washington, DC 20007
| | - Alexander Y Kim
- Department of Radiology, Medstar Georgetown University Hospital, 3800 Reservoir Rd, Washington, DC 20007.
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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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Abstract
Liver transplantation is the definitive treatment for patients with end-stage liver disease. Liver transplantation is also the optimal treatment for patients with hepatocellular carcinoma (HCC), especially in the setting of chronic liver disease. Unfortunately, due to the worldwide shortage of organs, this treatment is not available for all patients with HCC. Strict selection criteria have been developed in order to obtain optimal results. A surgical perspective of the preoperative selection, perioperative management, and postoperative care of patients is reviewed in depth and provides an overview for obtaining optimal long-term results from liver transplantation for HCC. With rigorous selection and patient management, excellent long-term outcomes can be obtained with liver transplantation for patients with HCC.
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Abstract
Identifying the optimal allocation policy with regard to hepatocellular carcinoma has been a persistent and evolving challenge. The current criteria for LT for HCC endorsed by the United Network of Organ Sharing (UNOS) are based on the Milan Criteria: a solitary tumor < 5 cm, or maximum of three tumors ≤ 3 cm each, without vascular invasion or evidence of extrahepatic spread. Contraindications to HCC exception points include: stage 1 HCC, ruptured HCC, extrahepatic HCC, and main portal or hepatic vein HCC invasion. Based upon projected waitlist dropout rates due to tumor growth, patients with HCC are assigned MELD standardized exception points. In addition to tumor size and number, AFP levels are an important predictor of recurrence of HCC following liver transplantation. Standardized exception points for HCC patients are not awarded to patients with AFP levels > 1000 ng/mL that do not decrease to < 500 ng/mL with treatment. Appeals for MELD exception points for patients with HCC vary widely between UNOS regions, with success of nonstandardized exception point appeals varying from 3.1 to 21% between regions. In an effort to make prioritization for HCC more consistent, a national liver review board (NLRB)is being convened that will focus on developing a national guidance for assessing common requests and addressing exception points, including for HCC.
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Han B, Li C, Meng H, Gomes Romeiro F, Mancuso A, Zhou Z, Levi Sandri GB, Xu Y, Han T, Han L, Shao L, Qi X. Efficacy and safety of external-beam radiation therapy for hepatocellular carcinoma: An overview of current evidence according to the different target population. Biosci Trends 2019; 13:10-22. [PMID: 30799321 DOI: 10.5582/bst.2018.01261] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. During the recent years, external-beam radiation therapy (EBRT) has been safely and effectively employed for the management of HCC. We overviewed the current evidence regarding the efficacy and safety of EBRT for HCC according to the different target population. PubMed database was searched for identifying English-language full-text articles regarding EBRT for the treatment of HCC. Search items were "hepatocellular carcinoma AND radiation therapy". Until now, preliminary evidence has suggested the following role of EBRT for HCC. 1) EBRT, especially stereotactic body radiation therapy, is an emerging choice of therapy for small HCC. 2) EBRT combined with non-surgical treatment can achieve an excellent intrahepatic tumor control and a potential survival benefit for huge HCC. 3)Adjunctive EBRT may improve the efficacy of transarterial chemoembolization for HCC with portal vein tumor thrombosis. 4) EBRT can relieve the pain and improve the quality of life for patients with extrahepatic metastases. 5) EBRT may be a bridge to liver transplantation by minimizing the tumor progression. 6) Adjunctive EBRT may reduce the tumor recurrence and improve the survival after resection. In summary, EBRT is a promising choice of treatment of HCC. However, more high-quality evidence is needed to further establish the status of EBRT for the management of HCC.
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Affiliation(s)
- Bing Han
- Department of Gastroenterology, General Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area)
- Postgraduate College, Jinzhou Medical University
- Department of Gastroenterology, No. 463 Hospital of Chinese PLA
| | - Chuan Li
- Section of Medical Service, General Hospital of Norther Northern Command (formerly General Hospital of Shenyang Military Area)
| | - Hao Meng
- Department of Thoracic Surgery, General Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area)
| | - Fernando Gomes Romeiro
- Department of Internal Medicine, Botucatu Medical School, Universidade Estadual Paulista (UNESP)
| | - Andrea Mancuso
- Epatologiae Gastroenterologia, Ospedale Niguarda Ca' Granda
- Medicina Internal, Azienda di Rilievo Nazionale ad Alta Specializzazione Civico - Di Cristina - Benfratelli
| | - Zhirui Zhou
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center
| | | | - Ying Xu
- Department of Radiotherapy, General Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area)
| | - Tao Han
- Department of Oncology, Cancer Center, General Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area)
| | - Lei Han
- Department of Hepatobiliary Surgery, General Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area)
| | - Lichun Shao
- Department of Gastroenterology, No. 463 Hospital of Chinese PLA
| | - Xingshun Qi
- Department of Gastroenterology, General Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area)
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Martinez-Insfran LA, Ramirez P, Cascales P, Alconchel F, Ferreras D, Febrero B, Martinez M, González MR, Sanchez-Bueno F, Robles R, Parrilla P. Early Outcomes of Liver Transplantation Using Donors After Circulatory Death in Patients With Hepatocellular Carcinoma: A Comparative Study. Transplant Proc 2019; 51:359-364. [PMID: 30879541 DOI: 10.1016/j.transproceed.2018.10.021] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2018] [Accepted: 10/23/2018] [Indexed: 12/17/2022]
Abstract
INTRODUCTION Donation after circulatory death (DCD) has increased in the last decade, although a slight increase in surgical complications has been reported in liver transplantation (LT). Therefore, DCD is not overall recommended because it entails an added risk. However, DCD in selected patients shows acceptable results. OBJECTIVE The objective was to analyze the characteristics, early outcomes, and survival at 1 year post-LT from a single institute (January 2015 to May 2017). MATERIALS AND METHODS We included 18 DCD-LTs and compared them with a control group of 18 donation after brain death (DBD) LTs. We analyzed pre- and posttransplant variables related to donors, recipients, and intraoperative early outcomes within patients transplanted due to hepatocellular carcinoma (HCC). A descriptive analysis, Mann-Whitney U test, χ2, or Fisher test was performed when appropriate, as well as multivariate analysis in case of statistical significance. A variable is considered as statistically significant when it reaches a value of P < .05. RESULTS In DBD, we found a lower length of stay in the intensive care unit before retrieval and a higher rate of alcoholism and diabetes mellitus, Model for End-Stage Liver Disease score, and Child B and C score (P < .05). Most of the DCD were originally from the same LT recipient center, and a higher donor mean post-LT alanine aminotransferase level was found (P < .05). Survival for the DBD group was 88% and 75% in the DCD group at 1 year post-LT, being not significant (NS). CONCLUSION HCC recipients who are transplanted with good quality DCD livers do no worse than those transplanted with livers from DBD donors, although a good selection of them is crucial.
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Affiliation(s)
- L A Martinez-Insfran
- General and Digestive Surgery Department, University Hospital Virgen de la Arrixaca, El Palmar, Murcia, Spain.
| | - P Ramirez
- General and Digestive Surgery Department, University Hospital Virgen de la Arrixaca, El Palmar, Murcia, Spain
| | - P Cascales
- General and Digestive Surgery Department, University Hospital Virgen de la Arrixaca, El Palmar, Murcia, Spain
| | - F Alconchel
- General and Digestive Surgery Department, University Hospital Virgen de la Arrixaca, El Palmar, Murcia, Spain
| | - D Ferreras
- General and Digestive Surgery Department, University Hospital Virgen de la Arrixaca, El Palmar, Murcia, Spain
| | - B Febrero
- General and Digestive Surgery Department, University Hospital Virgen de la Arrixaca, El Palmar, Murcia, Spain
| | - M Martinez
- Intensive Care Unit, University Hospital Virgen de la Arrixaca, El Palmar, Murcia, Spain
| | - M R González
- Hepatology Unit, University Hospital Virgen de la Arrixaca, El Palmar, Murcia, Spain
| | - F Sanchez-Bueno
- General and Digestive Surgery Department, University Hospital Virgen de la Arrixaca, El Palmar, Murcia, Spain
| | - R Robles
- General and Digestive Surgery Department, University Hospital Virgen de la Arrixaca, El Palmar, Murcia, Spain
| | - P Parrilla
- General and Digestive Surgery Department, University Hospital Virgen de la Arrixaca, El Palmar, Murcia, Spain
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Hodgson A, Almansouri Z, Adeyi O, Fischer SE. Gross and microscopic changes of liver neoplasms and background hepatic structures following neoadjuvant therapy. J Clin Pathol 2019; 72:112-119. [PMID: 30670563 DOI: 10.1136/jclinpath-2018-205596] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2018] [Accepted: 11/26/2018] [Indexed: 01/03/2023]
Abstract
Liver transplantation is a surgical option with curative intent used in the management of some cases of hepatocellular carcinoma and cholangiocarcinoma (hilar, rarely intrahepatic). A number of different therapeutic modalities including ablative techniques, arterially directed therapies, radiation and chemotherapy are used in the neoadjuvant setting prior to liver transplantation with the goals of preventing tumour progression, decreasing post-transplant recurrence and possibly downstaging patients with tumour burden beyond what is acceptable by current transplant criteria. Pathologists evaluating hepatic explants must be aware of these neoadjuvant therapies and the alterations induced by them in both tumourous and non-tumourous tissue. In this review, we discuss common neoadjuvant therapies used in in this setting, as well as the gross and microscopic changes induced by these presurgical treatments within hepatic neoplasms as well as the background hepatic parenchyma and nearby structures. Select secondary tumours involving the liver which are pretreated will also be discussed. Finally, proper reporting of these changes will be mentioned.
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Affiliation(s)
- Anjelica Hodgson
- Department of Pathobiology and Laboratory Medicine, The University of Toronto, Toronto, Ontario, Canada.,Department of Pathology, University Health Network, Toronto, Ontario, Canada
| | - Zuhoor Almansouri
- Department of Pathobiology and Laboratory Medicine, The University of Toronto, Toronto, Ontario, Canada.,Department of Pathology, University Health Network, Toronto, Ontario, Canada
| | - Oyedele Adeyi
- Department of Pathobiology and Laboratory Medicine, The University of Toronto, Toronto, Ontario, Canada.,Department of Pathology, University Health Network, Toronto, Ontario, Canada
| | - Sandra E Fischer
- Department of Pathobiology and Laboratory Medicine, The University of Toronto, Toronto, Ontario, Canada .,Department of Pathology, University Health Network, Toronto, Ontario, Canada
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Abstract
Hepatocellular carcinoma (HCC) in proximity to major hepatic vasculature poses a risk for invasion, which would contraindicate liver transplantation, yet, is difficult to treat with thermal ablation. This study was undertaken to evaluate the feasibility of irreversible electroporation (IRE) as a bridge to transplantation for high-risk tumors. All patients with HCC in proximity to major hepatic vasculature treated with laparoscopic IRE as bridge to transplantation were studied. Patient and tumor characteristics, length of stay, and treatment-related complications were recorded. Tumor response was assessed with CT and explant pathology. Five patients with a median Model for End Stage Liver Disease (MELD) of 13 (7–21) underwent IRE. The median tumor size was 2.7 cm (1.5–3.7 cm). Adjacent structures included the right portal vein, hepatic veins/inferior vena cava (IVC) and left portal vein. Length of stay was one day for all patients. One patient suffered portal vein thrombosis. The transplant occurred at a median of 142 days (47–264) after IRE. Pathologic necrosis ranged from 30 to 100 per cent, without any vascular invasion. Four patients remain alive with no evidence of disease with median follow-up of 403 (227–623) days. The remaining patients died because of transplant-related complications onpost IRE day 297. IRE shows promise as a bridge to liver transplant for high risk HCC in a preliminary series, justifying further prospective evaluation.
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Affiliation(s)
- Robert M. Cannon
- Hiram C. Polk Jr., M.D. Department of Surgery, University of Louisville, Louisville, Kentucky; Departments of
| | | | - Jared A. White
- Surgery, University of Alabama at Birmingham, Birmingham, Alabama
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Zhang ZF, Luo YJ, Lu Q, Dai SX, Sha WH. Conversion therapy and suitable timing for subsequent salvage surgery for initially unresectable hepatocellular carcinoma: What is new? World J Clin Cases 2018; 6:259-273. [PMID: 30211206 PMCID: PMC6134280 DOI: 10.12998/wjcc.v6.i9.259] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2018] [Revised: 07/18/2018] [Accepted: 08/07/2018] [Indexed: 02/05/2023] Open
Abstract
AIM To review the conversion therapy for initially unresectable hepatocellular carcinoma (HCC) patients and the suitable timing for subsequent salvage surgery.
METHODS A PubMed search was undertaken from 1987 to 2017 to identify articles using the keywords including “unresectable” “hepatocellular carcinoma”, ”hepatectomy”, ”conversion therapy”, “resection”, “salvage surgery” and “downstaging”. Additional studies were investigated through a manual search of the references from the articles. The exclusion criteria were duplicates, case reports, case series, videos, contents unrelated to the topic, comments, and editorial essays. The main and widely used conversion therapies and the suitable timing for subsequent salvage surgery were discussed in detail. Two members of our group independently performed the literature search and data extraction.
RESULTS Liver volume measurements [future liver remnant (FLR)/total liver volume or residual liver volume/bodyweight ratio] and function tests (scoring systems and liver stiffness) were often performed in order to justify whether patients were suitable candidates for surgery. Successful conversion therapy was usually defined as downstaging the tumor, increasing FLR and providing subsequent salvage surgery, without increasing complications, morbidity or mortality. The requirements for performing salvage surgery after transcatheter arterial chemoembolization were the achievement of a partial remission in radiology, the disappearance of the portal vein thrombosis, and the lack of extrahepatic metastasis. Patients with a standardized FLR (sFLR) > 20% were good candidates for surgery after portal vein embolization, while other predictive parameters like growth rate, kinetic growth rate were treated as an effective supplementary. There was probably not enough evidence to provide a standard operation time after associating liver partition and portal vein ligation for staged hepatectomy or yttrium-90 microsphere radioembolization. The indications of any combinations of conversion therapies and the subsequent salvage surgery time still need to be carefully and comprehensively evaluated.
CONCLUSION Conversion therapy is recommended for the treatment of initially unresectable HCC, and the suitable subsequent salvage surgery time should be reappraised and is closely related to its previous therapeutic effect.
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Affiliation(s)
- Ze-Feng Zhang
- Department of Gastroenterology and Hepatology, Guangdong Geriatrics Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
| | - Yu-Jun Luo
- Department of Gastroenterology and Hepatology, Guangdong Geriatrics Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
| | - Quan Lu
- Department of Gastroenterology and Hepatology, Guangdong Geriatrics Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
| | - Shi-Xue Dai
- Department of Gastroenterology and Hepatology, Guangdong Geriatrics Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
| | - Wei-Hong Sha
- Department of Gastroenterology and Hepatology, Guangdong Geriatrics Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
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Cho CW, Choi GS, Kim JM, Kwon CHD, Kim DJ, Joh JW. Clinical usefulness of transarterial chemoembolization response prior to liver transplantation as predictor of optimal timing for living donor liver transplantation. Ann Surg Treat Res 2018; 95:111-120. [PMID: 30079328 PMCID: PMC6073044 DOI: 10.4174/astr.2018.95.2.111] [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: 08/18/2017] [Revised: 11/22/2017] [Accepted: 12/05/2017] [Indexed: 12/13/2022] Open
Abstract
Purpose Response to preoperative transarterial chemoembolization (TACE) has been recommended as a biological selection criterion for liver transplantation (LT). The aim of our study was to identify optimal timing of living donor liver transplantation (LDLT) after TACE based on the TACE response. Methods We performed a retrospective study to assess recurrence in 128 hepatocellular carcinoma (HCC) patients who underwent LDLT following sequential TACE from January 2002 to March 2015 at a single institute. Cox proportional hazard models and Kaplan-Meier analysis were utilized to estimate HCC recurrence and find optimal timing for LDLT. Results Seventy-three and 61 patients were divided as the responder and nonresponder, respectively. Multivariate analysis showed independent pre-liver transplantation (pre-LT) predictors of recurrence were larger sized tumor (>3 cm, P = 0.024), nonresponse to TACE (P = 0.031), vascular invasion (P = 0.002), and extrahepatic nodal involvement (P = 0.001). In the 3-month time difference between last pre-LT TACE and LDLT subgroup, TACE responders showed significantly higher adjusted hazard ratio (aHR) of recurrence free survival (aHR, 6.284; P = 0.007), cancer specific survival (aHR, 7.033; P = 0.016), and overall survival (aHR, 7.055; P = 0.005). Moreover, for overall patients and responder groups, the significant time difference between last pre-LT TACE and LDLT was 2 months in the minimum P-value approach. Conclusion In selected patients who showed good response to pre-LT TACE, a shorter time interval between TACE and LDLT may be associated with higher recurrence free survival, cancer specific survival, and overall survival.
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Affiliation(s)
- Chan Woo Cho
- Department of Surgery, Yeungnam University College of Medicine, Daegu, Korea
| | - Gyu-Seong Choi
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jong Man Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Choon Hyuck David Kwon
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Doo Jin Kim
- Department of Surgery, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, Korea
| | - Jae-Won Joh
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Jia C, Li H, Wen N, Chen J, Wei Y, Li B. Laparoscopic liver resection: a review of current indications and surgical techniques. Hepatobiliary Surg Nutr 2018; 7:277-288. [PMID: 30221155 DOI: 10.21037/hbsn.2018.03.01] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Laparoscopic liver resection (LLR) has been the most impressive development in the field of liver surgery in recent two decades. Technical innovations and experience accumulation have made LLR a safe and effective procedure with faster postoperative recovery. Despite the fast spreading of the procedure, details regarding the indications, oncological outcomes and technical essentials were still disputable. To address these issues, two international consensus conferences were hold to update the knowledge in this field. The statements of the both conferences were not conclusive and more high-quality researches are required. In this article, we reviewed the development and the current state of LLR. Indications, outcomes, surgical techniques and devices used in LLR were also discussed.
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Affiliation(s)
- Chenyang Jia
- Department of Liver Surgery, Center of Liver Transplantation, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Hongyu Li
- Department of Pancreatic Surgery, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Ningyuan Wen
- College of Clinical Medicine, Sichuan University, Chengdu 610065, China
| | - Junhua Chen
- Department of General surgery, Chengdu First People's Hospital, Chengdu 610200, China
| | - Yonggang Wei
- Department of Liver Surgery, Center of Liver Transplantation, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Bo Li
- Department of Liver Surgery, Center of Liver Transplantation, West China Hospital of Sichuan University, Chengdu 610041, China
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Young S, Taylor AJ, Sanghvi T. Post Locoregional Therapy Treatment Imaging in Hepatocellular Carcinoma Patients: A Literature-based Review. J Clin Transl Hepatol 2018; 6:189-197. [PMID: 29951364 PMCID: PMC6018307 DOI: 10.14218/jcth.2017.00059] [Citation(s) in RCA: 18] [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: 08/30/2017] [Revised: 12/14/2017] [Accepted: 12/22/2017] [Indexed: 12/19/2022] Open
Abstract
Imaging plays a crucial role in the diagnosis of hepatocellular carcinoma (HCC) as well as in determining treatment efficacy, or complications, following therapy. Unlike other cancers, HCC is most commonly treated by locoregional therapies (LRTs) such as thermal ablation, transarterial chemoembolization, and transarterial radioembolization. These treatments can lead to changes on imaging that make determination of residual/recurrent disease difficult. This literature-based review discusses the expected postimaging findings following LRT.
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Affiliation(s)
- Shamar Young
- Department of Radiology, University of Minnesota, Minneapolis, MN, USA
| | - Andrew J. Taylor
- Department of Radiology, University of Minnesota, Minneapolis, MN, USA
- *Correspondence to: Andrew J. Taylor, Department of Radiology, University of Minnesota, 420 Delaware Street SE, MMC 292, Minneapolis, MN 55455, USA. Tel: +1-612-626-6638, Fax: +1-612-626-5505, E-mail:
| | - Tina Sanghvi
- Department of Radiology, University of Minnesota, Minneapolis, MN, USA
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50
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Burt AD, Alves V, Bedossa P, Clouston A, Guido M, Hübscher S, Kakar S, Ng I, Park YN, Reeves H, Wyatt J, Yeh MM, Ellis DW. Data set for the reporting of intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma and hepatocellular carcinoma: recommendations from the International Collaboration on Cancer Reporting (ICCR). Histopathology 2018; 73:369-385. [DOI: 10.1111/his.13520] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Alastair D Burt
- Faculty of Health and Medical Sciences; University of Adelaide; Adelaide Australia
| | - Venâncio Alves
- Department of Pathology; University of São Paulo School of Medicine; São Paulo Brazil
| | - Pierre Bedossa
- Pathology Department; AP-HP; Beaujon Hospital; Clichy France
- Centre de Recherche Bichat-Beaujon; University Paris-Diderot; Paris France
| | - Andrew Clouston
- Envoi Specialist Pathologists; Brisbane Queensland Australia
| | - Maria Guido
- Surgical Pathology and Cytopathology Unit; Department of Medicine-DIMED; University of Padova; Padova Italy
| | - Stefan Hübscher
- Department of Cellular Pathology; Institute of Immunology and Immunotherapy; University of Birmingham; Queen Elizabeth Hospital; Birmingham UK
| | | | - Irene Ng
- Department of Pathology; State Key Laboratory for Liver Research; The University of Hong Kong; Hong Kong Hong Kong
| | - Young N Park
- Department of Pathology Yonsei; Univesity College of Medicine Seodaemun-gu; Seoul Korea
| | - Helen Reeves
- Northern Institute for Cancer Research, Newcastle University; Newcastle upon Tyne UK
| | - Judith Wyatt
- Department of Histopathology; St James University Hospital; Leeds UK
| | - Matthew M Yeh
- Department of Pathology; University of Washington School of Medicine; Seattle WA USA
| | - David W Ellis
- Clinpath Laboratories; Kent Town South Australia Australia
- ICCR Steering Group Representative; Adelaide Australia
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