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Yang L, Huang Y, Deng D, Liu J, Xu L, Yi P. Efficacy and prognostic impact of preoperative risk factors for salvage liver transplantation and repeat hepatectomy in patients with early-stage recurrent hepatocellular carcinoma: a propensity score-matched analysis. Front Oncol 2025; 15:1547054. [PMID: 40066093 PMCID: PMC11891041 DOI: 10.3389/fonc.2025.1547054] [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: 12/17/2024] [Accepted: 02/10/2025] [Indexed: 03/17/2025] Open
Abstract
BACKGROUND The optimal treatment strategy for recurrent hepatocellular carcinoma (rHCC) remains unclear. This study is based on cases of rHCC after liver resection, aiming to evaluate the influence of preoperative risk factors on the long-term prognosis of patients with rHCC by comparing patients who underwent salvage liver transplantation (SLT) with those who underwent repeat hepatectomy (RH). METHODS We retrospectively analyzed 401 consecutive patients with rHCC who underwent SLT or RH between March 2015 and December 2022. Next, we performed propensity score matching, subgroup analyses, and both univariate and multivariate analyses. In addition, Kaplan-Meier analysis was used to estimate the overall survival (OS) and recurrence-free survival (RFS) after recurrence. RESULTS The 1-, 3-, and 5-year OS and RFS rates in the SLT group were significantly higher than those in the RH group (p=0.0131 and p=0.0010, respectively), and similar results were observed after propensity score matching. In the presence of zero or one risk factors, the OS and RFS in the SLT group were significantly better than those in the RH group (p=0.0386 and p=0.0117, respectively). However, in the presence of two to four risk factors, no significant differences in OS or RFS were detected between the two groups (p=0.1119 and p=0.1035, respectively). CONCLUSION Our analysis identified a number of risk factors that were strongly correlated with a long term prognosis for patients with rHCC who underwent SLT and RH: multiple tumors, a maximum tumor diameter ≥5 cm, microvascular invasion, and a recurrence time ≤2 years. Our findings provide important reference guidelines for organ allocation and clinical decision-making.
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Affiliation(s)
- Linfeng Yang
- Department of Hepato-Biliary-Pancrease II, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Yang Huang
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, China
| | - Dawei Deng
- Department of Hepato-Biliary-Pancrease II, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Junning Liu
- Department of Cardiovascular Surgery, Beijing Anzhen Nanchong Hospital of Capital Medical University & Nanchong Central Hospital, The Second Clinical Medical College of North Sichuan Medical College, Nanchong, China
| | - Liangliang Xu
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, China
| | - Pengsheng Yi
- Department of Hepato-Biliary-Pancrease II, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
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Liu J, Zhang G, Yang L, Yan D, Yu J, Wei S, Li J, Yi P. Salvage liver transplantation versus curative treatment for patients with recurrent hepatocellular carcinoma: A systematic review and meta-analysis. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2024; 50:108427. [PMID: 38796968 DOI: 10.1016/j.ejso.2024.108427] [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: 12/19/2023] [Revised: 02/06/2024] [Accepted: 05/18/2024] [Indexed: 05/29/2024]
Abstract
BACKGROUND Salvage liver transplantation (SLT) is an effective treatment option for recurrent hepatocellular carcinoma (rHCC) following primary curative treatment (CUR). However, its efficacy remains controversial compared to that of CURs, including repeat liver resection (RLR) and local ablation. This meta-analysis compared the efficacy and safety of these procedures. METHODS A systematic literature search of the PubMed, Embase, Web of Science, and Cochrane Library databases for studies investigating SLT and CUR was performed. Outcome data, including overall and disease-free survival, tumor response, and operative and postoperative outcomes, were independently extracted and analyzed by two authors using a standardized protocol. RESULTS Fifteen cohort studies comprising 508 and 2050 patients with rHCC, who underwent SLT or CUR, respectively, were included. SLT achieved significantly longer overall survival than both CUR (hazard ratio [HR]: 0.56, 95 % confidence interval [CI]: 0.45-0.68; I2 = 34.6 %, p = 0.105) and RLR (HR: 0.64, 95 % CI: 0.49-0.84; I2 = 0.0 %, p = 0.639). Similar significantly better survival benefits were observed compared with CUR (HR: 0.30, 95 % CI: 0.20-0.45; I2 = 51.1 %, p = 0.038) or RLR (HR: 0.31, 95 % CI: 0.18-0.56; I2 = 65.7 %, p = 0.005) regarding disease-free survival. However, SLT resulted in a longer operative duration and hospital stay, larger amount of blood loss, higher rate of transfusion and postoperative morbidity, and slightly higher postoperative mortality than CUR. CONCLUSION SLT was associated with better long-term survival than CUR or RLR in patients with rHCC after primary curative treatment.
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Affiliation(s)
- Junning Liu
- Department of Hepato-Biliary-Pancreases II, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, China
| | - Guangnian Zhang
- Department of Hepato-Biliary-Pancreases II, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, China
| | - Linfeng Yang
- Department of Hepato-Biliary-Pancreases II, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, China
| | - Duan Yan
- Department of Hepato-Biliary-Pancreases II, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, China
| | - Jiahui Yu
- Department of Hepato-Biliary-Pancreases II, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, China
| | - Song Wei
- Department of Hepato-Biliary-Pancreases II, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, China
| | - Jijiang Li
- Department of Hepato-Biliary-Pancreases II, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, China
| | - Pengsheng Yi
- Department of Hepato-Biliary-Pancreases II, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, China.
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Di Sandro S, Centonze L, Catellani B, Odorizzi R, Caracciolo D, Guidetti C, Magistri P, Esposito G, Guerrini GP, Di Benedetto F. Current role and perspectives of living donor liver transplantation for hepatocellular carcinoma: systematic review of the past 20 years. Updates Surg 2024:10.1007/s13304-024-01862-y. [PMID: 38704462 DOI: 10.1007/s13304-024-01862-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Accepted: 04/19/2024] [Indexed: 05/06/2024]
Abstract
Hepatocellular carcinoma (HCC) poses a significant global health challenge, and liver transplantation (LT) remains the best curative option. Living donor liver transplantation (LDLT) emerged as a potential solution to organ scarcity, reducing waitlist times. This comprehensive review explores LDLT practices, focusing on patient selection criteria and oncologic outcomes. A systematic review following PRISMA guidelines included 50 studies (2004-2023) with 8062 patients. Data encompassed baseline characteristics, HCC features, and oncologic outcomes. Further analysis categorized results by geography and publication year. Heterogeneity in patient demographics, tumor burden, and transplant characteristics was observed. Recent LDLT series demonstrated a shift towards refined selection criteria, increased neoadjuvant treatment, and improved oncologic outcomes. Geographic disparities revealed unique challenges in Eastern and Western practices. LDLT proves effective for HCC, addressing donor shortages. Evolving practices highlight the importance of refining inclusion criteria and optimizing tumor management. While geographic differences exist, LDLT, when judiciously applied, offers promising outcomes.
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Affiliation(s)
- Stefano Di Sandro
- Hepatopancreatobiliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124, Modena, Italy.
| | - Leonardo Centonze
- Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Modena, Italy
| | - Barbara Catellani
- Hepatopancreatobiliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124, Modena, Italy
- Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Modena, Italy
| | - Roberta Odorizzi
- Hepatopancreatobiliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124, Modena, Italy
| | - Daniela Caracciolo
- Hepatopancreatobiliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124, Modena, Italy
| | - Cristiano Guidetti
- Hepatopancreatobiliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124, Modena, Italy
| | - Paolo Magistri
- Hepatopancreatobiliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124, Modena, Italy
| | - Giuseppe Esposito
- Hepatopancreatobiliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124, Modena, Italy
- Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Modena, Italy
| | - Gian Piero Guerrini
- Hepatopancreatobiliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124, Modena, Italy
| | - Fabrizio Di Benedetto
- Hepatopancreatobiliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124, Modena, Italy
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Hou C, Xiong B, Zhou L, Fei Y, Shi C, Zhu X, Xie T, Wu Y. Transarterial chemoembolization with molecular targeted therapies plus camrelizumab for recurrent hepatocellular carcinoma. BMC Cancer 2024; 24:387. [PMID: 38539150 PMCID: PMC10967172 DOI: 10.1186/s12885-024-12144-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Accepted: 03/19/2024] [Indexed: 11/11/2024] Open
Abstract
BACKGROUND The safety and efficacy of transarterial chemoembolization plus molecular targeted therapy (MTT) combined with immune checkpoint inhibitors (ICIs) in primary liver cancer have been demonstrated. However, the evidence for TACE plus MTT combined with ICIs in the treatment of recurrent hepatocellular carcinoma (RHCC) is limited. Given the excellent performance of this combination regimen in primary liver cancer, it is necessary to evaluate the efficacy of TACE plus MTT combined with ICIs in RHCC. METHODS A total of 88 patients with RHCC treated with TACE plus MTT combined with camrelizumab (TACE-TC group, n = 46) or TACE plus MTT (TACE-T group, n = 42) were retrospectively collected and analyzed. In this study, we evaluated the effectiveness and safety of combination therapy for patients with RHCC by analyzing tumor response, progression-free survival (PFS), overall survival (OS), laboratory biochemical indices, and adverse events (AEs). RESULTS TACE-TC was superior to TACE-T in PFS (14.0 vs. 8.9 months, p = 0.034) and OS (31.1 vs. 20.2 months, p = 0.009). Moreover, TACE-TC achieved more preferable benefits with respect to disease control rate (89.1% vs. 71.4%, p = 0.036) and objective response rate (47.8% vs. 26.2%, p = 0.036) compared with TACE-T in patients with RHCC. Compared with the TACE-T group, the AFP level in the TACE-TC group decreased more significantly after 3 months of treatment. Multivariate analysis showed that treatment option was a significant predictor of OS and PFS, while the portal vein tumor thrombus and interval of recurrence from initial treatment were another prognostic factor of PFS. There was no significant difference between the TACE-TC and TACE-T groups for Grade 3-4 adverse events. CONCLUSIONS A combination therapy of TACE, MTT, and camrelizumab significantly improved tumor response and prolonged survival duration, showing a better survival prognosis for RHCC patients.
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Affiliation(s)
- Changlong Hou
- Department of Intervention, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, 107# Huanhu East Road, Shushan District, 230031, Hefei, Anhui, People's Republic of China.
- Graduate School of Bengbu Medical College, Bengbu, Anhui, China.
| | - Baizhu Xiong
- Department of Intervention, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, 107# Huanhu East Road, Shushan District, 230031, Hefei, Anhui, People's Republic of China
- Graduate School of Bengbu Medical College, Bengbu, Anhui, China
| | - Lei Zhou
- Department of Intervention, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, 107# Huanhu East Road, Shushan District, 230031, Hefei, Anhui, People's Republic of China
| | - Yipeng Fei
- Department of Intervention, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, 107# Huanhu East Road, Shushan District, 230031, Hefei, Anhui, People's Republic of China
| | - Changgao Shi
- Department of Intervention, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, 107# Huanhu East Road, Shushan District, 230031, Hefei, Anhui, People's Republic of China
| | - Xianhai Zhu
- Department of Intervention, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, 107# Huanhu East Road, Shushan District, 230031, Hefei, Anhui, People's Republic of China
| | - Tao Xie
- Department of Intervention, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, 107# Huanhu East Road, Shushan District, 230031, Hefei, Anhui, People's Republic of China
| | - Yulin Wu
- Department of Intervention, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, 107# Huanhu East Road, Shushan District, 230031, Hefei, Anhui, People's Republic of China
- Graduate School of Bengbu Medical College, Bengbu, Anhui, China
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Martinino A, Bucaro A, Cardella F, Wazir I, Frongillo F, Ardito F, Giovinazzo F. Liver transplantation vs liver resection in HCC: promoting extensive collaborative research through a survival meta-analysis of meta-analyses. Front Oncol 2024; 14:1366607. [PMID: 38567152 PMCID: PMC10986178 DOI: 10.3389/fonc.2024.1366607] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2024] [Accepted: 02/13/2024] [Indexed: 04/04/2024] Open
Abstract
Background HCC is a major global health concern, necessitating effective treatment strategies. This study conducts a meta-analysis of meta-analyses comparing liver resection (LR) and liver transplantation (LT) for HCC. Methods The systematic review included meta-analyses comparing liver resection vs. liver transplantation in HCC, following PRISMA guidelines. Primary outcomes included 5-year overall survival (OS) and disease-free survival (DFS). AMSTAR-2 assessed study quality. Citation matrix and hierarchical clustering validated the consistency of the included studies. Results A search identified 10 meta-analyses for inclusion. The median Pearson correlation coefficient for citations was 0.59 (IQR 0.41-0.65). LT showed better 5-year survival and disease-free survival in all HCC (OR): 0.79; 95% CI: 0.67-0.93, I^2:57% and OR: 0.44; 95% CI: 0.25-0.75, I^2:96%). Five-year survival in early HCC and ITT was 0.63 (95% CI: 0.50-0.78, I^2:0%) and 0.60 (95% CI: 0.39-0.92, I^2:0%). Salvage LT vs. Primary LT did not differ between 5-year survival and disease-free survival (OR: 0.62; 95% CI: 0.33-1.15, I^2:0% and 0.93; 95% CI: 0.82-1.04, I^2:0%). Conclusion Overall, the study underscores the superior survival outcomes associated with LT over LR in HCC treatment, supported by comprehensive meta-analysis and clustering analysis. There was no difference in survival or recurrence rate between salvage LT and primary LT. Therefore, considering the organ shortage, HCC can be resected and transplanted in case of recurrence.
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Affiliation(s)
| | - Angela Bucaro
- General Surgery and Liver Transplant Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Francesca Cardella
- Surgical Oncology of Gastrointestinal Tract Unit, Vanvitelli University, Naples, Italy
| | - Ishaan Wazir
- Vardhaman Mahavir Medical College & Safdarjung Hospital, New Delhi, India
| | - Francesco Frongillo
- General Surgery and Liver Transplant Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Francesco Ardito
- Hepatobilairy and General Surgery Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Francesco Giovinazzo
- General Surgery and Liver Transplant Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
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Yoshiya S, Harada N, Toshima T, Toshida K, Kosai Y, Tomino T, Nagao Y, Kayashima H, Itoh S, Yoshizumi T. Treatment strategy for hepatocellular carcinoma recurrence in the transplant era: Focusing on the Japan criteria. Surg Today 2024; 54:64-72. [PMID: 37289265 DOI: 10.1007/s00595-023-02710-z] [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: 02/24/2023] [Accepted: 04/17/2023] [Indexed: 06/09/2023]
Abstract
PURPOSE To clarify the Japan criteria (JC), as proposed in 2019, in order to identify the most appropriate treatment methods for hepatocellular carcinoma (HCC) recurrence and assess the feasibility of pre-living donor liver transplantation (LDLT) downstaging within these criteria. METHODS The subjects of this study were 169 LDLT patients with HCC recurrence. We performed univariate and multivariate analyses of the factors contributing to HCC recurrence after LDLT and clarified the post-transplant outcomes of pre-LDLT downstaging. RESULTS Univariate and multivariate analysis identified beyond the JC (p = 0.0018) and a neutrophil-to-lymphocyte ratio > 2.01 (p = 0.029) as independent risk factors. Patients who met the JC had significantly higher recurrence-free and overall survival rates after LDLT (p < 0.0001) than those who did not (p = 0.0002). The post-transplant outcomes of patients within the JC after downstaging were significantly better than those of patients beyond the JC (p = 0.034) and equivalent to those within the JC without downstaging. CONCLUSION Even for HCC recurrence, the JC could play an important role in deciding on the best treatment strategy, and downstaging within the JC had good post-transplant outcomes.
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Affiliation(s)
- Shohei Yoshiya
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.
| | - Noboru Harada
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Takeo Toshima
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Katsuya Toshida
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Yukiko Kosai
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Takahiro Tomino
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Yoshihiro Nagao
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Hiroto Kayashima
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Shinji Itoh
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Tomoharu Yoshizumi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
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Ohira M, Kobayashi T, Hamaoka M, Abe T, Onoe T, Inoue M, Honmyo N, Oishi K, Ohdan H. Prognosis of repeat hepatectomy for liver transplantable hepatocellular carcinoma recurrence after hepatectomy: a Retrospective Cohort Study with the Hiroshima Surgical Study Group of Clinical Oncology (HiSCO). Langenbecks Arch Surg 2023; 408:314. [PMID: 37584772 DOI: 10.1007/s00423-023-03057-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Accepted: 08/09/2023] [Indexed: 08/17/2023]
Abstract
PURPOSE Factors affecting the prognosis of repeat hepatectomy for transplantable hepatocellular carcinoma (HCC) recurrence after hepatectomy remain unclear. We aimed to clarify the prognostic factors for transplantable hepatocellular carcinoma recurrence after hepatectomy. METHODS We included 1758 primary and 486 repeat hepatectomies out of 2244 for HCC performed between 2006 and 2017 using the Hiroshima Study Group for Clinical Oncology and Surgery database. We first compared survival rates of primary and repeat hepatectomy patients. Subsequently, prognostic factors were analyzed in patients who underwent a repeat hepatectomy for transplantable hepatocellular carcinoma recurrence after hepatectomy (defined as age < 70 years at the time of recurrence and recurrent tumor morphology that meets the Milan criteria). RESULTS The 5-year overall survival rate (OS) after repeat hepatectomy was 63.2%, while the 5-year recurrence-free survival rate (RFS) was 23.7%. RFS demonstrated significant inferiority in the repeat hepatectomy group than in the primary hepatectomy group; however, OS did not present a notable difference between the two cohorts. In the transplantable recurrence group, mALBI grade 2b, max tumor size > 20 mm, and multiple tumors were independent prognostic risk factors for overall survival. Patients with two or more risk factors had a significantly lower survival rate (only 30.6% at 5 years) compared to those with one or fewer risk factors (81.8% at 5 years). CONCLUSIONS We identified the risk factors involved in post-hepatectomy survival for patients with transplantable recurrence after hepatectomy. The results are a potential indicator of whether salvage liver transplantation should be considered during repeat hepatectomy.
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Affiliation(s)
- Masahiro Ohira
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, Japan.
- Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan.
| | - Tsuyoshi Kobayashi
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, Japan
| | - Michinori Hamaoka
- Department of Surgery, Hiroshima Prefectural Hospital, Hiroshima, Japan
| | - Tomoyuki Abe
- Department of Surgery, JA Onomichi General Hospital, Onomichi City, Japan
| | - Takashi Onoe
- Department of Surgery, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Kure City, Japan
| | - Masashi Inoue
- Department of Surgery, Higashihiroshima Medical Center, Higashihiroshima City, Japan
| | - Naruhiko Honmyo
- Department of Surgery, Hiroshima City Asa Citizens Hospital, Hiroshima, Japan
| | - Koichi Oishi
- Department of Surgery, Chugoku Rosai Hospital, Kure City, Japan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, Japan
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8
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Hirata Y, Kotera Y, Kato T, Ariizumi S, Kogiso T, Tokushige K, Honda G, Egawa H. The Outcome of Salvage Liver Transplantation and Liver Resection for Recurrent Hepatocellular Carcinoma Using the 5-5-500 Rule, Japanese Extended Liver Transplantation Criteria for Hepatocellular Carcinoma. Transplant Proc 2023:S0041-1345(23)00309-3. [PMID: 37244836 DOI: 10.1016/j.transproceed.2023.04.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Revised: 04/13/2023] [Accepted: 04/19/2023] [Indexed: 05/29/2023]
Abstract
BACKGROUND Liver transplantation (LT) for hepatocellular carcinoma (HCC) is limited to Child-Pugh class C patients according to the Japanese HCC treatment algorithm. However, extended criteria of LT for HCC, known as the 5-5-500 rule, were published in 2019. Hepatocellular carcinoma reportedly has a high recurrence rate after primary treatment. We hypothesized that the outcome of recurrent HCC would be improved if the 5-5-500 rule were adopted for patients with recurrent HCC. We, therefore, analyzed the outcomes of surgical treatment (liver resection [LR] and LT) for recurrent HCC using the 5-5-500 rule in our institute. METHODS Fifty-two patients younger than 70 years of age received surgical treatment for recurrent HCC using our institute's 5-5-500 rule from 2010 to 2019. We divided these patients into the LR and LT groups in the first study. The 10-year overall survival and re-recurrence-free survival were analyzed. The second study analyzed the risk factors of re-recurrence after surgical treatment for recurrent HCC. RESULTS In the first study, the background characteristics of the 2 groups (LR and LT) showed no significant difference, except for age and Child-Pugh classification. There was no significant difference in the overall survival between groups (P = .35), but the re-recurrence-free survival in the LR group was significantly shorter than that in the LT group (P < .01). In the second study, the male sex and LR were risk factors of re-recurrence after surgical treatment for recurrent HCC. Child-Pugh's class did not contribute to re-recurrence. CONCLUSIONS To improve the outcomes of recurrent HCC, LT is the better choice, regardless of the Child-Pugh class.
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Affiliation(s)
- Yoshihiro Hirata
- Department of Hepatobiliary-pancreatic Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan.
| | - Yoshihito Kotera
- Department of Hepatobiliary-pancreatic Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan
| | - Takaaki Kato
- Department of Hepatobiliary-pancreatic Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan
| | - Syunichi Ariizumi
- Department of Hepatobiliary-pancreatic Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan
| | - Tomomi Kogiso
- Institute of Gastroenterology, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan
| | - Katsutoshi Tokushige
- Institute of Gastroenterology, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan
| | - Goro Honda
- Department of Hepatobiliary-pancreatic Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan
| | - Hiroto Egawa
- Department of Hepatobiliary-pancreatic Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan
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9
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Wang L, Liu BX, Long HY. Ablative strategies for recurrent hepatocellular carcinoma. World J Hepatol 2023; 15:515-524. [PMID: 37206650 PMCID: PMC10190693 DOI: 10.4254/wjh.v15.i4.515] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Revised: 02/14/2023] [Accepted: 03/29/2023] [Indexed: 04/20/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is the fifth leading cause of cancer death worldwide and the third leading cause of all diseases worldwide. Liver transplantation, surgical resection and ablation are the three main curative treatments for HCC. Liver transplantation is the optimal treatment option for HCC, but its usage is limited by the shortage of liver sources. Surgical resection is considered the first choice for early-stage HCC, but it does not apply to patients with poor liver function. Therefore, more and more doctors choose ablation for HCC. However, intrahepatic recurrence occurs in up to 70% patients within 5 years after initial treatment. For patients with oligo recurrence after primary treatment, repeated resection and local ablation are both alternative. Only 20% patients with recurrent HCC (rHCC) indicate repeated surgical resection because of limitations in liver function, tumor location and intraperitoneal adhesions. Local ablation has become an option for the waiting period when liver transplantation is unavailable. For patients with intrahepatic recurrence after liver transplantation, local ablation can reduce the tumor burden and prepare them for liver transplantation. This review systematically describes the various ablation treatments for rHCC, including radiofrequency ablation, microwave ablation, laser ablation, high-intensity focused ultrasound ablation, cryablation, irreversible electroporation, percutaneous ethanol injection, and the combination of ablation and other treatment modalities.
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Affiliation(s)
- Lin Wang
- Department of Medical Ultrasound, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
| | - Bao-Xian Liu
- Department of Medical Ultrasound, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
| | - Hai-Yi Long
- Department of Medical Ultrasound, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China.
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10
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Wang D, Xiao M, Wan ZM, Lin X, Li QY, Zheng SS. Surgical treatment for recurrent hepatocellular carcinoma: Current status and challenges. World J Gastrointest Surg 2023; 15:544-552. [PMID: 37206072 PMCID: PMC10190723 DOI: 10.4240/wjgs.v15.i4.544] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 01/05/2023] [Accepted: 03/21/2023] [Indexed: 04/22/2023] Open
Abstract
Primary liver cancer is the sixth most commonly diagnosed cancer and was the third leading cause of cancer deaths worldwide in 2020. It includes hepatocellular carcinoma (HCC) (representing 75%-85% of cases), intrahepatic cholangiocarcinoma (representing 10%-15% of cases), and other rare types. The survival rate of patients with HCC has risen with improved surgical technology and perioperative management in recent years; however, high tumor recurrence rates continue to limit long-term survival, even after radical surgical resection (exceeding 50% recurrence). For resectable recurrent liver cancer, surgical removal [either salvage liver transplantation (SLT) or repeat hepatic resection] remains the most effective therapy that is potentially curative for recurrent HCC. Thus, here, we introduce surgical treatment for recurrent HCC. Areas Covered: A literature search was performed for recurrent HCC using Medline and PubMed up to August 2022. Expert commentary: In general, long-term survival after the re-resection of recurrent liver cancer is usually beneficial. SLT has equivalent outcomes to primary liver transplantation for unresectable recurrent illness in a selected group of patients; however, SLT is constrained by the supply of liver grafts. SLT seems to be inferior to repeat liver resection when considering operative and postoperative results but has the major advantage of disease-free survival. When considering the similar overall survival rate and the current situation of donor shortages, repeat liver resection remains an important option for recurrent HCC.
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Affiliation(s)
- Di Wang
- Division of Hepatobiliary and Pancreatic Surgery, Zhejiang Chinese Medical University, Hangzhou 310000, Zhejiang Province, China
- Division of Hepatobiliary and Pancreatic Surgery, Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250000, Shandong Province, China
| | - Min Xiao
- Division of Hepatobiliary and Pancreatic Surgery, Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250000, Shandong Province, China
- Division of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou 310000, Zhejiang Province, China
| | - Zhen-Miao Wan
- Division of Hepatobiliary and Pancreatic Surgery, Zhejiang Chinese Medical University, Hangzhou 310000, Zhejiang Province, China
- Division of Hepatobiliary and Pancreatic Surgery, Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250000, Shandong Province, China
| | - Xin Lin
- Division of Hepatobiliary and Pancreatic Surgery, Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250000, Shandong Province, China
- Division of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou 310000, Zhejiang Province, China
| | - Qi-Yong Li
- Division of Hepatobiliary and Pancreatic Surgery, Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250000, Shandong Province, China
- Division of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou 310000, Zhejiang Province, China
| | - Shu-Sen Zheng
- Division of Hepatobiliary and Pancreatic Surgery, Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250000, Shandong Province, China
- Division of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou 310000, Zhejiang Province, China
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11
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Chen JL, Chen YS, Ker CG. Network meta-analysis of the prognosis of curative treatment strategies for recurrent hepatocellular carcinoma after hepatectomy. World J Gastrointest Surg 2023; 15:258-272. [PMID: 36896302 PMCID: PMC9988642 DOI: 10.4240/wjgs.v15.i2.258] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 11/28/2022] [Accepted: 01/16/2023] [Indexed: 02/27/2023] Open
Abstract
BACKGROUND Recurrent hepatocellular carcinoma (rHCC) is a common outcome after curative treatment. Retreatment for rHCC is recommended, but no guidelines exist.
AIM To compare curative treatments such as repeated hepatectomy (RH), radiofrequency ablation (RFA), transarterial chemoembolization (TACE) and liver transplantation (LT) for patients with rHCC after primary hepatectomy by conducting a network meta-analysis (NMA).
METHODS From 2011 to 2021, 30 articles involving patients with rHCC after primary liver resection were retrieved for this NMA. The Q test was used to assess heterogeneity among studies, and Egger’s test was used to assess publication bias. The efficacy of rHCC treatment was assessed using disease-free survival (DFS) and overall survival (OS).
RESULTS From 30 articles, a total of 17, 11, 8, and 12 arms of RH, RFA, TACE, and LT subgroups were collected for analysis. Forest plot analysis revealed that the LT subgroup had a better cumulative DFS and 1-year OS than the RH subgroup, with an odds ratio (OR) of 0.96 (95%CI: 0.31-2.96). However, the RH subgroup had a better 3-year and 5-year OS compared to the LT, RFA, and TACE subgroups. Hierarchic step diagram of different subgroups measured by the Wald test yielded the same results as the forest plot analysis. LT had a better 1-year OS (OR: 1.04, 95%CI: 0.34-03.20), and LT was inferior to RH in 3-year OS (OR: 10.61, 95%CI: 0.21-1.73) and 5-year OS (OR: 0.95, 95%CI: 0.39-2.34). According to the predictive P score evaluation, the LT subgroup had a better DFS, and RH had the best OS. However, meta-regression analysis revealed that LT had a better DFS (P < 0.001) as well as 3-year OS (P = 0.881) and 5-year OS (P = 0.188). The differences in superiority between DFS and OS were due to the different testing methods used.
CONCLUSION According to this NMA, RH and LT had better DFS and OS for rHCC than RFA and TACE. However, treatment strategies should be determined by the recurrent tumor characteristics, the patient’s general health status, and the care program at each institution.
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Affiliation(s)
- Jen-Lung Chen
- Department of General Surgery, E-Da Hospital, I-Shou University, Kaohsiung 824, Taiwan
| | - Yaw-Sen Chen
- Department of Surgery, School of Medicine, I-Shou University, Kaohsiung 824, Taiwan
| | - Chen-Guo Ker
- Department of General Surgery, E-Da Hospital, I-Shou University, Kaohsiung 824, Taiwan
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12
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Liang J, Bai Y, Ha FS, Luo Y, Deng HT, Gao YT. Combining local regional therapy and systemic therapy: Expected changes in the treatment landscape of recurrent hepatocellular carcinoma. World J Gastrointest Oncol 2023; 15:1-18. [PMID: 36684055 PMCID: PMC9850755 DOI: 10.4251/wjgo.v15.i1.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2022] [Revised: 12/06/2022] [Accepted: 12/27/2022] [Indexed: 01/10/2023] Open
Abstract
Improvements in early screening, new diagnostic techniques, and surgical treatment have led to continuous downward trends in hepatocellular carcinoma (HCC) morbidity and mortality rates. However, high recurrence and refractory cancer after hepatectomy remain important factors affecting the long-term prognosis of HCC. The clinical characteristics and prognosis of recurrent HCC are heterogeneous, and guidelines on treatment strategies for recurrent HCC are lacking. Therapies such as surgical resection, radiofrequency ablation, and transhepatic arterial chemoembolization are effective for tumors confined to the liver, and targeted therapy is a very important treatment for unresectable recurrent HCC with systemic metastasis. With the deepening of the understanding of the immune microenvironment of HCC, blocking immune checkpoints to enhance the antitumor immune response has become a new direction for the treatment of HCC. In addition, improvements in the tumor immune microenvironment caused by local treatment may provide an opportunity to improve the therapeutic effect of HCC treatment. Ongoing and future clinical trial data of combined therapy may develop the new treatment scheme for recurrent HCC. This paper reviews the pattern of recurrent HCC and the characteristics of the immune microenvironment, demonstrates the basis for combining local treatment and systemic treatment, and reports current evidence to better understand current progress and future approaches in the treatment of recurrent HCC.
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Affiliation(s)
- Jing Liang
- Department of Hepatology, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Nankai University Affiliated Third Center Hospital, Tianjin 300170, China
| | - Yi Bai
- Department of Hepatobiliary Surgery, Tianjin First Central Hospital, Tianjin 300192, China
| | - Fu-Shuang Ha
- Department of Hepatology, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Nankai University Affiliated Third Center Hospital, Tianjin 300170, China
| | - Ying Luo
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Nankai University Affiliated Third Center Hospital, Tianjin 300170, China
| | - Hui-Ting Deng
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Nankai University Affiliated Third Center Hospital, Tianjin 300170, China
| | - Ying-Tang Gao
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Nankai University Affiliated Third Center Hospital, Tianjin 300170, China
- Tianjin Institute of Hepatobiliary Disease, The Third Central Clinical College of Tianjin Medical University, Tianjin 300170, China
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13
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Milana F, Polidoro MA, Famularo S, Lleo A, Boldorini R, Donadon M, Torzilli G. Surgical Strategies for Recurrent Hepatocellular Carcinoma after Resection: A Review of Current Evidence. Cancers (Basel) 2023; 15:508. [PMID: 36672457 PMCID: PMC9856445 DOI: 10.3390/cancers15020508] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Revised: 01/07/2023] [Accepted: 01/10/2023] [Indexed: 01/17/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer, and both liver resection and liver transplantation are considered potentially curative options. However, high recurrence rates affect the prognosis depending both on the primary HCC pathology characteristics or on the type and time of the relapse. While great attention has been usually posted on treatment algorithms for the first HCC, treatment algorithms for recurrent HCC (rHCC) are lacking. In these cases, surgery still represents a curative option with both redo hepatectomy and/or salvage liver transplantation, which are considered valid treatments in selected patients. In the current era of personalised medicine with promises of new systemic-targeted immuno-chemotherapies, we wished to perform a narrative review of the literature on the role of surgical strategies for rHCC.
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Affiliation(s)
- Flavio Milana
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, MI, Italy
- Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, 20089 Rozzano, MI, Italy
| | - Michela Anna Polidoro
- Hepatobiliary Immunopathology Laboratory, IRCCS Humanitas Research Hospital, 20089 Rozzano, MI, Italy
| | - Simone Famularo
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, MI, Italy
- Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, 20089 Rozzano, MI, Italy
| | - Ana Lleo
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, MI, Italy
- Department of Internal Medicine, IRCCS Humanitas Research Hospital, 20089 Rozzano, MI, Italy
| | - Renzo Boldorini
- Department of Health Sciences, Università del Piemonte Orientale, 28100 Novara, NO, Italy
- Department of Pathology, University Maggiore Hospital, 28100 Novara, NO, Italy
| | - Matteo Donadon
- Hepatobiliary Immunopathology Laboratory, IRCCS Humanitas Research Hospital, 20089 Rozzano, MI, Italy
- Department of Health Sciences, Università del Piemonte Orientale, 28100 Novara, NO, Italy
- Department of General Surgery, University Maggiore Hospital, 28100 Novara, NO, Italy
| | - Guido Torzilli
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, MI, Italy
- Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, 20089 Rozzano, MI, Italy
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14
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Iaria M, Bianchi G, Fazio F, Ardito F, Perri P, Pontarolo N, Conci S, Donadon M, Zanello M, Lai Q, Famularo S, Molfino S, Sciannamea I, Fumagalli L, Germani P, Floridi A, Ferrari C, Zimmitti G, Troci A, Zago M, Ferraro V, Cipriani F, Patauner S, La Barba G, Romano M, Zanus G, Ercolani G, Frena A, Aldrighetti L, Memeo R, Pinotti E, Crespi M, Hilal MA, Griseri G, Tarchi P, Chiarelli M, Antonucci A, Baiocchi GL, Romano F, Rossi M, Jovine E, Torzilli G, Ruzzenente A, Maestri M, Grazi GL, Giuliante F, Ferrero A, Dalla Valle R. The largest western experience on salvage hepatectomy for recurrent hepatocellular carcinoma: propensity score-matched analysis on behalf of He.RC.O.Le.Study Group. HPB (Oxford) 2022; 24:1291-1304. [PMID: 35125292 DOI: 10.1016/j.hpb.2022.01.001] [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: 07/05/2021] [Revised: 12/28/2021] [Accepted: 01/03/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND We aimed to evaluate, in a large Western cohort, perioperative and long-term oncological outcomes of salvage hepatectomy (SH) for recurrent hepatocellular carcinoma (rHCC) after primary hepatectomy (PH) or locoregional treatments. METHODS Data were collected from the Hepatocarcinoma Recurrence on the Liver Study Group (He.RC.O.Le.S.) Italian Registry. After 1:1 propensity score-matched analysis (PSM), two groups were compared: the PH group (patients submitted to resection for a first HCC) and the SH group (patients resected for intrahepatic rHCC after previous HCC-related treatments). RESULTS 2689 patients were enrolled. PH included 2339 patients, SH 350. After PSM, 263 patients were selected in each group with major resected nodule median size, intraoperative blood loss and minimally invasive approach significantly lower in the SH group. Long-term outcomes were compared, with no difference in OS and DFS. Univariate and multivariate analyses revealed only microvascular invasion as an independent prognostic factor for OS. CONCLUSION SH proved to be equivalent to PH in terms of safety, feasibility and long-term outcomes, consistent with data gathered from East Asia. In the awaiting of reliable treatment-allocating algorithms for rHCC, SH appears to be a suitable alternative in patients fit for surgery, regardless of the previous therapeutic modality implemented.
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Affiliation(s)
- Maurizio Iaria
- Department of General and Specialized Surgery, Division of General Surgery, Parma University Hospital, Parma, Italy.
| | - Giorgio Bianchi
- Department of General and Specialized Surgery, Division of General Surgery, Parma University Hospital, Parma, Italy
| | - Federico Fazio
- Department of HPB and Digestive Surgery, Ospedale Mauriziano Umberto I, Turin, Italy
| | - Francesco Ardito
- Hepatobiliary Surgery Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Catholic University of the Sacred Heart, Rome, Italy
| | - Pasquale Perri
- Division of Hepatobiliarypancreatic Surgery, IRCCS - Regina Elena National Cancer Institute, Rome, Italy
| | - Nicholas Pontarolo
- Unit of General Surgery 1, University of Pavia and Foundation IRCCS Policlinico San Matteo, Pavia, Italy
| | - Simone Conci
- Division of General and Hepatobiliary Surgery, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy
| | - Matteo Donadon
- Department of Biomedical Science, Humanitas University, Pieve Emanuele, Milan, Italy; Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Matteo Zanello
- Department of Surgery, AOU Sant'Orsola Malpighi, IRCCS, Bologna, Italy
| | - Quirino Lai
- General Surgery and Organ Transplantation Unit, Sapienza University of Rome, Umberto I Polyclinic of Rome, Rome, Italy
| | - Simone Famularo
- Department of Biomedical Science, Humanitas University, Pieve Emanuele, Milan, Italy; Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy; School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
| | - Sarah Molfino
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | | | - Luca Fumagalli
- Department of Emergency and Robotic Surgery, ASST Lecco, Lecco, Italy
| | - Paola Germani
- Department of General Surgery, ASUGI, University Hospital of Trieste, Trieste, Italy
| | | | | | - Giuseppe Zimmitti
- Department of Surgery, Fondazione Poliambulanza - Istituto Ospedaliero, Brescia, Italy
| | - Albert Troci
- Department of Surgery, L. Sacco Hospital, Milan, Italy
| | - Mauro Zago
- Department of Emergency and Robotic Surgery, ASST Lecco, Lecco, Italy; Department of Surgery, Ponte San Pietro Hospital, Bergamo, Italy
| | - Valentina Ferraro
- Department of Hepato-Pancreatic-Biliary Surgery, Miulli Hospital, Bari, Italy
| | - Federica Cipriani
- Hepatobiliary Surgery Division, Ospedale San Raffaele, Milano, Italy
| | - Stefan Patauner
- Department of Surgery, Bolzano Central Hospital, Bolzano, Italy
| | - Giuliano La Barba
- General and Oncologic Surgery, Morgagni-Pierantoni Hospital, Forlì, Italy
| | - Maurizio Romano
- Department of Surgical, Oncological and Gastroenterological Science (DISCOG), University of Padua, Hepatobiliary and Pancreatic Surgery Unit - Treviso Hospital, Treviso, Italy
| | - Giacomo Zanus
- Department of Surgical, Oncological and Gastroenterological Science (DISCOG), University of Padua, Hepatobiliary and Pancreatic Surgery Unit - Treviso Hospital, Treviso, Italy
| | - Giorgio Ercolani
- General and Oncologic Surgery, Morgagni-Pierantoni Hospital, Forlì, Italy; Department of Medical and Surgical Sciences, University of Bologna, Italy
| | - Antonio Frena
- Department of Surgery, Bolzano Central Hospital, Bolzano, Italy
| | - Luca Aldrighetti
- Hepatobiliary Surgery Division, Ospedale San Raffaele, Milano, Italy
| | - Riccardo Memeo
- Department of Hepato-Pancreatic-Biliary Surgery, Miulli Hospital, Bari, Italy
| | - Enrico Pinotti
- Department of Surgery, Ponte San Pietro Hospital, Bergamo, Italy
| | | | - Moh'd Abu Hilal
- Department of Surgery, Fondazione Poliambulanza - Istituto Ospedaliero, Brescia, Italy
| | - Guido Griseri
- HPB Surgical Unit, San Paolo Hospital, Savona, Italy
| | - Paola Tarchi
- Department of General Surgery, ASUGI, University Hospital of Trieste, Trieste, Italy
| | - Marco Chiarelli
- Department of Emergency and Robotic Surgery, ASST Lecco, Lecco, Italy
| | | | - Gian L Baiocchi
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - Fabrizio Romano
- School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; Department of Surgery, San Gerardo Hospital, Monza, Italy
| | - Massimo Rossi
- General Surgery and Organ Transplantation Unit, Sapienza University of Rome, Umberto I Polyclinic of Rome, Rome, Italy
| | - Elio Jovine
- Department of Surgery, AOU Sant'Orsola Malpighi, IRCCS, Bologna, Italy
| | - Guido Torzilli
- Department of Biomedical Science, Humanitas University, Pieve Emanuele, Milan, Italy; Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Andrea Ruzzenente
- Division of General and Hepatobiliary Surgery, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy
| | - Marcello Maestri
- Unit of General Surgery 1, University of Pavia and Foundation IRCCS Policlinico San Matteo, Pavia, Italy
| | - Gian L Grazi
- Division of Hepatobiliarypancreatic Surgery, IRCCS - Regina Elena National Cancer Institute, Rome, Italy
| | - Felice Giuliante
- Hepatobiliary Surgery Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Catholic University of the Sacred Heart, Rome, Italy
| | - Alessandro Ferrero
- Department of HPB and Digestive Surgery, Ospedale Mauriziano Umberto I, Turin, Italy
| | - Raffaele Dalla Valle
- Department of General and Specialized Surgery, Division of General Surgery, Parma University Hospital, Parma, Italy
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15
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Yoon YI, Song GW, Lee S, Moon D, Hwang S, Kang WH, Cho HD, Ha SM, Kim MJ, Kim SH, Na BG, Yang G, Min Kim S, Hyun Shim J, Park JI. Salvage living donor liver transplantation versus repeat liver resection for patients with recurrent hepatocellular carcinoma and Child-Pugh class A liver cirrhosis: A propensity score-matched comparison. Am J Transplant 2022; 22:165-176. [PMID: 34383368 DOI: 10.1111/ajt.16790] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 07/29/2021] [Accepted: 07/31/2021] [Indexed: 01/27/2023]
Abstract
Following curative liver resection (LR), resectable tumor recurrence in patients with preserved liver function leads to deciding between a repeat LR and a salvage liver transplantation (LT), if a donor's liver is available. This retrospective study compared survival outcomes and recurrence pattern following salvage living donor LT (LDLT) and repeat LR in patients with recurrent hepatocellular carcinoma (HCC). We reviewed the medical records of patients who underwent repeat LR (n = 163) or LDLT (n = 84) for recurrent HCC following curative resections, between January 2005 and December 2017 at a single institution. A 1:1 propensity score matching led to 42 patients per group. Disease-specific and recurrence-free survival were significantly better in the salvage LDLT group than in the repeat LR group (p = .042; HR = 2.40; 95% CI, 0.69-6.00 and p < .001; HR = 4.23; 95% CI, 2.05-8.71, respectively). Despite significant differences in recurrence patterns between the two groups (p = .019), the patient death rates, after recurrence, were similar for both groups (p = .760). This study indicates that salvage LDLT is superior to repeat LR for treating patients with transplantable, intrahepatic HCC recurrence, even in patients with Child-Pugh class A liver cirrhosis.
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Affiliation(s)
- Young-In Yoon
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gi-Won Song
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - SungGyu Lee
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - DeokBog Moon
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Shin Hwang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Woo-Hyoung Kang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hwui-Dong Cho
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Su-Min Ha
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Min-Jae Kim
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sang-Hoon Kim
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Byeong-Gon Na
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Geunhyeok Yang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung Min Kim
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ju Hyun Shim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jeong-Ik Park
- Department of Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
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16
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Zheng J, Cai J, Tao L, Kirih MA, Shen Z, Xu J, Liang X. Comparison on the efficacy and prognosis of different strategies for intrahepatic recurrent hepatocellular carcinoma: A systematic review and Bayesian network meta-analysis. Int J Surg 2020; 83:196-204. [PMID: 32980518 DOI: 10.1016/j.ijsu.2020.09.031] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 08/18/2020] [Accepted: 09/17/2020] [Indexed: 02/06/2023]
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Aierken Y, Kong LX, Li B, Liu XJ, Lu S, Yang JY. Liver fibrosis is a major risk factor for liver regeneration: A comparison between healthy and fibrotic liver. Medicine (Baltimore) 2020; 99:e20003. [PMID: 32481371 DOI: 10.1097/md.0000000000020003] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Blood flow factors, such as congestion or ischemia after hepatectomy, have a significant impact on liver regeneration, but with the popularization of precise hepatectomy technology, segmental hepatectomy without congestion or ischemia has become the preferred treatment. Our aim is to investigate the factors affecting liver regeneration after hepatectomy without blood flow changes, and to provide clinical evidence for surgeons on the timing of second hepatectomy for cirrhosis patients with hepatocellular carcinoma (HCC). METHODS This study retrospectively analyzed data from patients who underwent right hepatectomy without middle hepatic vein (MHV) in West China Hospital between January 2016 and January 2018. Eighteen living-donors without MHV as normal group and 45 HCC patients, further classified into 3 subgroups based on the severity of fibrosis using the Scheure system. Demographic data, pre- and postoperative liver function indexes, and remnant liver volume (RLV) were retrospectively compared. We also analyzed the remnant liver regeneration rate (RLRR) post-operatively in each group. The significant indexes in univariate analysis were further analyzed using both receiver operating characteristic (ROC) analysis and multivariate regression analysis. RESULTS Liver regeneration occurred in both living-donor and HCC groups after hepatectomy; the RLRRs at 1 month were 59.46 ± 10.39% and 57.27 ± 4.77% (P = .509), respectively. Regeneration in the cirrhosis group occurred more slowly and less completely compared with that in other groups. The regeneration rate in the first 6 months showed rapid increase and the RLRR reached above 70% in cirrhosis group. Multivariate and ROC analyses revealed that Alb and the hepatic fibrosis grade in the early postoperative period were significant predictors of remnant liver regeneration. CONCLUSION The liver regenerated in all HCC patients; however, regeneration was significantly slower and less complete compared with the normal liver, especially in the patients with cirrhosis. Therefore, it can be concluded that the degree of liver fibrosis is a major predictor of liver regeneration. Furthermore, the optimal time for second resection in recurrent HCC patients with cirrhosis was 6 months after the first operation.
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Affiliation(s)
| | - Ling-Xiang Kong
- Department of Liver Surgery and Liver Transplantation Center
| | - Bo Li
- Department of Liver Surgery and Liver Transplantation Center
| | - Xi-Jiao Liu
- Department of Radiology, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Su Lu
- Department of Radiology, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Jia-Yin Yang
- Department of Liver Surgery and Liver Transplantation Center
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Fang JZ, Xiang L, Hu YK, Yang Y, Zhu HD, Lu CD. Options for the treatment of intrahepatic recurrent hepatocellular carcinoma: Salvage liver transplantation or rehepatectomy? Clin Transplant 2020; 34:e13831. [PMID: 32068916 DOI: 10.1111/ctr.13831] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2019] [Revised: 02/07/2020] [Accepted: 02/16/2020] [Indexed: 01/27/2023]
Abstract
OBJECTIVE To explore prognostic factors by comparing the efficacy of salvage liver transplantation (sLT) and rehepatectomy (RH) for the treatment of recurrent hepatocellular carcinoma after hepatectomy. METHODS Clinical data were collected for 124 patients treated at our center from January 2012 to August 2018. The median follow-up time for the patients was 39 months. By analyzing the clinical data between the sLT group (46 cases) and RH group (78 cases), the factors affecting the prognosis of patients were compared. RESULTS The proportion of alpha-fetoprotein (AFP) ≥ 100 µg/L in the recurrence group was significantly higher than that in the recurrence-free group (70.0% vs 22.2%, P = .014). The postoperative overall survival (OS) and recurrence-free survival (RFS) were better in the sLT group than in the RH group (81.2% vs 36.9%, P < .01; 77.1% vs 55.6%, P = .019). In the sLT group, the OS and RFS in the AFP < 100 µg/L group were superior to those in the AFP ≥ 100 µg/L group (P = .046 and P = .002). CONCLUSION The sLT group had achieved better efficacy than RH group, but when AFP ≥ 100 µg/L, sLT did not achieve better efficacy than RH.
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Affiliation(s)
- Jiong-Ze Fang
- Department of Hepatopancreatobiliary Surgery, Ningbo Medical Centre Lihuili Hospital, Medical School of Ningbo University, Zhejiang, China
| | - Li Xiang
- Department of Hepatopancreatobiliary Surgery, Ningbo Medical Centre Lihuili Hospital, Medical School of Ningbo University, Zhejiang, China
| | - Yang-Ke Hu
- Department of Hepatopancreatobiliary Surgery, Ningbo Medical Centre Lihuili Hospital, Medical School of Ningbo University, Zhejiang, China
| | - Yong Yang
- Department of Hepatopancreatobiliary Surgery, Ningbo Medical Centre Lihuili Hospital, Medical School of Ningbo University, Zhejiang, China
| | - Hong-Da Zhu
- Department of Hepatopancreatobiliary Surgery, Ningbo Medical Centre Lihuili Hospital, Medical School of Ningbo University, Zhejiang, China
| | - Cai-De Lu
- Department of Hepatopancreatobiliary Surgery, Ningbo Medical Centre Lihuili Hospital, Medical School of Ningbo University, Zhejiang, China
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Ahn KS, Kang KJ. Appropriate treatment modality for solitary small hepatocellular carcinoma: Radiofrequency ablation vs. resection vs. transplantation? Clin Mol Hepatol 2019; 25:354-359. [PMID: 31006225 PMCID: PMC6933127 DOI: 10.3350/cmh.2018.0096] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2018] [Accepted: 02/10/2019] [Indexed: 12/12/2022] Open
Abstract
There has been controversy regarding the first-line treatment modality for the patients who have small solitary hepatocellular carcinoma (HCC); radiofrequency ablation (RFA) or percutaneous ethanol injection (PEI), surgical hepatic resection (HR) and liver transplantation (LT). For selection of treatment modality of HCC, it should be considered of hepatic reservoir function as well as the tumor stage. If the liver function is good enough, HR may be the first choice regardless of the tumor size. However, recent studies comparing RFA with resection showed comparable outcome and similar survival rates. RFA, HR and LT provide good outcome for patients who have small HCCs. RFA would be desired in patients who have below 3.0 cm in size and low alpha-fetoprotein (<200 ng/mL). However, in small HCC with high tumor marker, HR should be considered. Better patient selection for the 'resection first' approach and early detection of recurrence can achieve better outcomes of the salvage LT strategy. Another benefit of resection first strategy is that it make possible to do enlist of LT for patients before recurrence at high risk of HCC recurrence after resection on the basis of pathologic aggressiveness, microvascular invasion and/or satellites nodule. They should be applied appropriately according to the tumor size, location, tumor markers and underlying liver parenchymal disease.
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Affiliation(s)
- Keun Soo Ahn
- Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Keimyung University Dongsan Medical Center, Daegu, Korea
| | - Koo Jeong Kang
- Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Keimyung University Dongsan Medical Center, Daegu, Korea
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Wang H, Wu MC, Cong WM. Microvascular invasion predicts a poor prognosis of solitary hepatocellular carcinoma up to 2 cm based on propensity score matching analysis. Hepatol Res 2019; 49:344-354. [PMID: 30117236 DOI: 10.1111/hepr.13241] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2018] [Revised: 08/07/2018] [Accepted: 08/09/2018] [Indexed: 12/11/2022]
Abstract
AIM Microvascular invasion (MVI) is not discussed for solitary hepatocellular carcinoma (HCC) up to 2 cm in the 8th Edition of the American Joint Committee on Cancer Staging Manual. The present study aimed to reappraise the influence of MVI on solitary HCC up to 2 cm in diameter. METHODS Between January 2010 and December 2012, a retrospective cohort of 496 HCC patients from the Eastern Hepatobiliary Surgery Hospital was analyzed. Propensity score matching was carried out to balance the baseline characteristics. Survival analysis was carried out using the Kaplan-Meier method. Risk factors were evaluated using the Cox proportional hazards model. Multivariate logistic regression was used to identify the risk factors associated with MVI. RESULTS All patients were classified into either an MVI-negative group (n = 332) or an MVI-positive group (n = 164). The MVI-positive group had poorer recurrence-free survival and overall survival before and after propensity score matching. The multivariate analysis showed that MVI; being male; increased total bilirubin levels, alanine transaminase levels and γ-glutamyl transpeptidase levels; decreased albumin levels; and HBV DNA load >103 IU/mL were risk factors for recurrence-free survival. MVI, older age, lower albumin levels, and cirrhosis were risk factors for overall survival. Age <50 years, alpha-fetoprotein >20 ng/mL, and lack of or an incomplete capsule were significantly independent predictors for MVI. CONCLUSIONS MVI had a negative impact on the prognosis of solitary HCC up to 2 cm after curative hepatectomy. The 8th edition of the American Joint Committee on Cancer staging system could be improved by subdividing solitary HCC up to 2 cm according to MVI.
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Affiliation(s)
- Han Wang
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.,Key Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer (Second Military Medical University) Ministry of Education, Shanghai, China.,Shanghai Key Laboratory of Hepatobiliary Tumor Biology (Eastern Hepatobiliary Surgery Hospital), Shanghai, China
| | - Meng-Chao Wu
- Department of Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Wen-Ming Cong
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.,Key Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer (Second Military Medical University) Ministry of Education, Shanghai, China.,Shanghai Key Laboratory of Hepatobiliary Tumor Biology (Eastern Hepatobiliary Surgery Hospital), Shanghai, China
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Kostakis I, Machairas N, Prodromidou A, Stamopoulos P, Garoufalia Z, Fouzas I, Sotiropoulos G. Comparison Between Salvage Liver Transplantation and Repeat Liver Resection for Recurrent Hepatocellular Carcinoma: A Systematic Review and Meta-analysis. Transplant Proc 2019; 51:433-436. [DOI: 10.1016/j.transproceed.2019.01.072] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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Wang HL, Mo DC, Zhong JH, Ma L, Wu FX, Xiang BD, Li LQ. Systematic review of treatment strategy for recurrent hepatocellular carcinoma: Salvage liver transplantation or curative locoregional therapy. Medicine (Baltimore) 2019; 98:e14498. [PMID: 30813151 PMCID: PMC6408068 DOI: 10.1097/md.0000000000014498] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2018] [Revised: 12/29/2018] [Accepted: 01/18/2019] [Indexed: 02/07/2023] Open
Abstract
AIMS The aim of our systematic review was to compare the efficacy of salvage liver transplantation (SLT) versus curative locoregional therapy (CLRT) for patients with recurrent hepatocellular carcinoma (HCC). METHODS Studies comparing the SLT with CLRT for patients with recurrent HCC were selected from database of PubMed, EMBASE, and Cochrane library. The outcomes including overall survival, disease-free survival, and complications were abstracted. Individual and pooled odds ratio (OR) with 95% confidence interval of each outcome was analyzed. RESULTS Seven retrospective studies involving 840 patients were included. There is no difference between SLT and CLRT group regarding the1- and 3-year overall survival rates. However, the 5-year overall survival and 1-, 3-, 5-year disease-free survival were significantly higher after SLT than after CLRT (OR = 1.62, 95% CI 1.09-2.39, P = .02; OR = 4.08, 95% CI 1.95-8.54, P = .0002; OR = 3.63, 95% CI 2.21-5.95, P <.00001; OR = 5.71, 95% CI 2.63-12.42, P <.0001, respectively). But CLRT was associated with fewer complications and shorter hospital-stay compared with SLT. For SLT compared with repeat hepatectomy (RH), the subgroup analysis indicated that SLT group had a significantly higher 3- and 5-years disease-free survival than the RH group (OR = 3.23, 95% CI 1.45-7.20, P = .004; OR = 4.79, 95% CI 1.88-12.25, P = .001, respectively). CONCLUSION The efficacy of SLT may be superior to that of CLRT in the treatment of recurrent HCC. However, considering the similar overall survival rate and current situation of donor shortage, RH is still an important option for recurrence HCC.
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Affiliation(s)
- Hong-Liang Wang
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University
| | - Dun-Chang Mo
- Department of Radiotherapy, The Third Affiliated Hospital of Guangxi Medical University
| | - Jian-Hong Zhong
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University
- Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, China
| | - Liang Ma
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University
- Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, China
| | - Fei-Xiang Wu
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University
- Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, China
| | - Bang-De Xiang
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University
- Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, China
| | - Le-Qun Li
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University
- Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, China
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Yamashita YI, Imai K, Kaida T, Yamao T, Tsukamoto M, Nakagawa S, Okabe H, Chikamoto A, Ishiko T, Yoshizumi T, Ikeda T, Maehara Y, Baba H. Multimodal radiofrequency ablation versus laparoscopic hepatic resection for the treatment of primary hepatocellular carcinoma within Milan criteria in severely cirrhotic patients: long-term favorable outcomes over 10 years. Surg Endosc 2019; 33:46-51. [PMID: 29872945 DOI: 10.1007/s00464-018-6264-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2018] [Accepted: 05/31/2018] [Indexed: 01/21/2023]
Abstract
BACKGROUND Less invasiveness is an important consideration for the treatment of hepatocellular carcinoma (HCC) especially in patients with severe cirrhosis. METHODS Between April 2000 and September 2016, 100 patients with liver damage B underwent multimodal radiofrequency ablation (RFA; n = 62) or laparoscopic hepatic resection (Lap-HR; n = 38) for primary HCC as defined by the Milan criteria. We compared the operative outcomes and patients' survival between the two groups. RESULTS The RFA group showed worse liver functions as indicated by indocyanine green retention rate (32.9 vs. 22.4%; p < 0.0001) and serum albumin value (3.3 vs. 3.6 g/dl; p = 0.0029). As expected, RFA was less invasive, as indicated by the differences in operation time (166 vs. 288 min.; p < 0.0001) and blood loss (8 vs. 377 g; p < 0.0001). There was no significant difference in the morbidity rate between the two groups; however, the duration of hospital stay of the RFA group was significantly shorter (7 vs. 11 days; p = 0.0002). There were no significant between-group differences regarding overall or disease-free survival. CONCLUSION Multimodal RFA for HCC in patients with severe cirrhosis is associated with less invasiveness and shorter hospital stays, with no compromise in the patients' survival. In patients with severe cirrhosis, it may be time to consider changing the standard treatment for primary HCC within the Milan criteria to multimodal RFA.
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Affiliation(s)
- Yo-Ichi Yamashita
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjyo, Chuo-ku, Kumamoto, 860-8556, Japan.
| | - Katsunori Imai
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjyo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Takayoshi Kaida
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjyo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Takanobu Yamao
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjyo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Masayo Tsukamoto
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjyo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Shigeki Nakagawa
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjyo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Hirohisa Okabe
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjyo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Akira Chikamoto
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjyo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Takatoshi Ishiko
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjyo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Tomoharu Yoshizumi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Tetsuo Ikeda
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Yoshihiko Maehara
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjyo, Chuo-ku, Kumamoto, 860-8556, Japan
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Wen T, Jin C, Facciorusso A, Donadon M, Han HS, Mao Y, Dai C, Cheng S, Zhang B, Peng B, Du S, Jia C, Xu F, Shi J, Sun J, Zhu P, Nara S, Millis JM. Multidisciplinary management of recurrent and metastatic hepatocellular carcinoma after resection: an international expert consensus. Hepatobiliary Surg Nutr 2018; 7:353-371. [PMID: 30498711 DOI: 10.21037/hbsn.2018.08.01] [Citation(s) in RCA: 80] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Hepatocellular carcinoma (HCC) is the sixth-most common cancer and the third leading cause of cancer-related death in the world. However, 40-70% patients eventually suffer from postoperative recurrence within 5 years. HCC recurrence after surgery severely affects prognosis of the patients. Nevertheless, there is an opportunity to improve patients' prognosis if doctors and researchers can recognize the importance of a standardized perioperative management and study it in clinical and pre-clinical settings. Hence, based on our own experience and published studies from other researchers, we develop this consensus regarding multidisciplinary management of locally recurrent and metastatic hepatocellular carcinoma after resection. This consensus consists of the entire course of recurrent hepatocellular carcinoma (RHCC) management, including prediction of recurrence, prevention, diagnosis, treatment and surveillance of RHCC. Consensus recommendations are presented with grades of evidences (Ia, Ib, IIa, IIb, III and IV), and strength of recommendations (A, B, C, D and E). We also develop a decision-making path for RHCC treatment, which can intuitively demonstrate the management for RHCC. It is hoped that we may make some effort to standardize the management of RHCC and ultimately understand how to improve outcomes.
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Affiliation(s)
- Tianfu Wen
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Chen Jin
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Antonio Facciorusso
- Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Matteo Donadon
- Department of Hepatobiliary & General Surgery, Humanitas University, Humanitas Clinical and Research Center, Milan, Italy
| | - Ho-Seong Han
- Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Yilei Mao
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
| | - Chaoliu Dai
- Department of Hepatobiliary and Splenic Surgery, Shengjing Hospital, China Medical University, Shenyang 110000, China
| | - Shuqun Cheng
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai 200433, China
| | - Bixiang Zhang
- Hepatic Surgery Center, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Baogang Peng
- Department of Liver Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China
| | - Shunda Du
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
| | - Changjun Jia
- Department of Hepatobiliary and Splenic Surgery, Shengjing Hospital, China Medical University, Shenyang 110000, China
| | - Feng Xu
- Department of Hepatobiliary and Splenic Surgery, Shengjing Hospital, China Medical University, Shenyang 110000, China
| | - Jie Shi
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai 200433, China
| | - Juxian Sun
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai 200433, China
| | - Peng Zhu
- Hepatic Surgery Center, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Satoshi Nara
- Hepatobiliary and Pancreatic Surgery Division, National Cancer Center Hospital, Tokyo, Japan
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Rhu J, Kim JM, Choi GS, Kwon CHD, Joh JW. Continuing five or more locoregional therapies before living donor salvage liver transplantation for hepatocellular carcinoma is related to poor recurrence-free survival. Ann Surg Treat Res 2018; 95:152-160. [PMID: 30182022 PMCID: PMC6121165 DOI: 10.4174/astr.2018.95.3.152] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2017] [Revised: 02/03/2018] [Accepted: 02/13/2018] [Indexed: 01/26/2023] Open
Abstract
Purpose This study was designed to analyze factors related to the success of salvage liver transplantation (SLT) in hepatocellular carcinoma (HCC). While liver resection (LR) is considered the best locoregional therapy in HCC, there is a high recurrence rate. SLT may be the best treatment option when feasible. Methods Patients who underwent living donor SLT for recurrent HCC after LR from November 1996 to May 2017 were included. Patient demographic data, clinical and pathologic characteristics, operative data, hospital course, and follow-up data regarding initial LR, locoregional therapy after recurrence and SLT were reviewed. Prognostic factors for recurrence were analyzed using Cox proportional hazard ratio. Results Eighty-five of 123 SLT patients were included. Patients who had five or more locoregional therapies prior to SLT (hazard ratio [HR], 3.74; 95% confidence interval [CI], 1.45-9.64, P = 0.006), hepatitis B (HR, 9.20; 95% CI, 1.13-74.89; P = 0.04), outside Milan criteria at the time of SLT (HR, 2.66, 95% CI, 1.26-5.63; P = 0.011) and an alpha-fetoprotein level above 1,000 ng/mL at the time of recurrence after initial LR (HR, 6.48; 95% CI, 1.83-22.92; P = 0.004) and at the time of transplantation (HR, 3.43; 95% CI, 1.26-5.63; P = 0.011) were related to significant risk of recurrence. Conclusion Continuing five or more locoregional therapies for recurrent HCC after LR is related to poor recurrence-free survival after SLT.
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Affiliation(s)
- Jinsoo Rhu
- 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
| | - Gyu Seong Choi
- 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
| | - Jae-Won Joh
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Matsushima H, Takami Y, Ryu T, Yoshitomi M, Tateishi M, Wada Y, Saitsu H. Prognosis of Hepatocellular Carcinoma Patients Who Achieved Long-Term Recurrence-Free Survival After Curative Therapy: Impact of the ALBI Grade. J Gastrointest Surg 2018; 22:1230-1238. [PMID: 29736665 DOI: 10.1007/s11605-018-3745-6] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2018] [Accepted: 03/12/2018] [Indexed: 01/31/2023]
Abstract
BACKGROUND/AIMS Some patients experience very late recurrence of HCC more than 5 years after initial therapy. We aimed to clarify the predictive factors for very late recurrence of HCC in such cases. METHODS Among 807 HCC patients undergoing surgical resection or ablative therapy with curative intent, the patients who survived for 5 years without any recurrence were reviewed. The prognosis and possible predictive factors for late recurrence were analyzed retrospectively. RESULTS A total of 184 patients survived for more than 5 years without recurrence. Among them, 61 patients experienced recurrence, at a median of 6 years after initial therapy. In univariate analysis, the pre-treatment aspartate aminotransferase, alanine aminotransferase, Child-Pugh class, and ALBI grade were not related to recurrence, but those at 5 years after treatment were significantly related to recurrence. By multivariate analysis, an ALBI grade of 2-3 at 5 years was an independent risk factor for recurrence (P < 0.0001). Moreover, variation of the ALBI grade over the 5 years after the initial treatment was significantly related to recurrence-free survival. CONCLUSIONS The ALBI grade is an effective index of the variation in liver function after curative therapy and may be a useful prognostic factor for the long-term recurrence-free survival of HCC patients.
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Affiliation(s)
- Hajime Matsushima
- Department of Hepato-Biliary-Pancreatic Surgery, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, 1-8-1, Jigyohama, Chuoku, Fukuoka City, 810-8563, Japan. .,Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki City, 852-8501, Japan.
| | - Yuko Takami
- Department of Hepato-Biliary-Pancreatic Surgery, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, 1-8-1, Jigyohama, Chuoku, Fukuoka City, 810-8563, Japan
| | - Tomoki Ryu
- Department of Hepato-Biliary-Pancreatic Surgery, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, 1-8-1, Jigyohama, Chuoku, Fukuoka City, 810-8563, Japan
| | - Munehiro Yoshitomi
- Department of Hepato-Biliary-Pancreatic Surgery, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, 1-8-1, Jigyohama, Chuoku, Fukuoka City, 810-8563, Japan
| | - Masaki Tateishi
- Department of Hepato-Biliary-Pancreatic Surgery, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, 1-8-1, Jigyohama, Chuoku, Fukuoka City, 810-8563, Japan
| | - Yoshiyuki Wada
- Department of Hepato-Biliary-Pancreatic Surgery, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, 1-8-1, Jigyohama, Chuoku, Fukuoka City, 810-8563, Japan
| | - Hideki Saitsu
- Department of Hepato-Biliary-Pancreatic Surgery, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, 1-8-1, Jigyohama, Chuoku, Fukuoka City, 810-8563, Japan
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Yamao T, Imai K, Yamashita YI, Kaida T, Nakagawa S, Mima K, Hashimoto D, Chikamoto A, Ishiko T, Baba H. Surgical treatment strategy for hepatocellular carcinoma in patients with impaired liver function: hepatic resection or radiofrequency ablation? HPB (Oxford) 2018; 20:244-250. [PMID: 28988913 DOI: 10.1016/j.hpb.2017.08.031] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2017] [Revised: 08/05/2017] [Accepted: 08/30/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND To compare the survival impacts of radiofrequency ablation (RFA) as an initial treatment for hepatocellular carcinoma (HCC) in patients with impaired liver functional reserve compared to those of hepatic resection (HR). METHODS In total, 104 patients with liver damage B as defined by the Liver Cancer Study Group of Japan underwent RFA (n = 33) or HR (n = 71) as an initial treatment for hepatocellular carcinoma. The overall survival (OS) and disease-free survival (DFS) rates were compared, and independent prognostic factors were identified. RESULTS The OS tended to be better in the RFA group than in the HR group. There was no significant difference in the DFS rate between the two groups. Independent poor prognostic factors for OS were tumor size >3 cm and red blood cell transfusion, and those for DFS were aspartate aminotransferase level >35 IU/L and multiple tumors. Subgroup analyses revealed that the OS with RFA was significantly better in patients with aspartate aminotransferase >35 IU/L, serum albumin <3.5 g/dL, and 99mTc-galactosyl human serum albumin <0.85. CONCLUSIONS RFA offers comparable results with HR and may be preferable for HCC in the particular setting of liver damage B, especially in those with poorer liver functional reserve.
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Affiliation(s)
- Takanobu Yamao
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, 1-1-1 Honjo, Kumamoto 860-8556, Japan
| | - Katsunori Imai
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
| | - Yo-Ichi Yamashita
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, 1-1-1 Honjo, Kumamoto 860-8556, Japan
| | - Takayoshi Kaida
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, 1-1-1 Honjo, Kumamoto 860-8556, Japan
| | - Shigeki Nakagawa
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, 1-1-1 Honjo, Kumamoto 860-8556, Japan
| | - Kosuke Mima
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, 1-1-1 Honjo, Kumamoto 860-8556, Japan
| | - Daisuke Hashimoto
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, 1-1-1 Honjo, Kumamoto 860-8556, Japan
| | - Akira Chikamoto
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, 1-1-1 Honjo, Kumamoto 860-8556, Japan
| | - Takatoshi Ishiko
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, 1-1-1 Honjo, Kumamoto 860-8556, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, 1-1-1 Honjo, Kumamoto 860-8556, Japan
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Zhang X, Li C, Wen T, Peng W, Yan L, Yang J. Outcomes of Salvage Liver Transplantation and Re-resection/Radiofrequency Ablation for Intrahepatic Recurrent Hepatocellular Carcinoma: A New Surgical Strategy Based on Recurrence Pattern. Dig Dis Sci 2018; 63:502-514. [PMID: 29238896 DOI: 10.1007/s10620-017-4861-y] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2017] [Accepted: 11/19/2017] [Indexed: 02/05/2023]
Abstract
BACKGROUND The treatment of intrahepatic recurrent hepatocellular carcinoma (HCC) has been poorly investigated, and the optimal treatment strategy remains unclear. AIMS The aim of this study was to compare outcomes between salvage liver transplantation (SLT) and re-resection (RR)/radiofrequency ablation (RFA) for intrahepatic recurrent HCC according to recurrence pattern. METHODS Based on postoperative histopathological examination, 122 patients with intrahepatic recurrent HCC were divided into an intrahepatic metastasis (IM, n = 75) group and a multicentric occurrence (MO, n = 47) group. The demographic, clinical, and primary and recurrent tumor characteristics of the IM group and the MO group were collected and compared. Overall survival (OS) and disease-free survival (DFS) were analyzed, and subgroup analysis according to retreatment type (SLT vs. RR/RFA) was conducted. Twenty-nine clinicopathological variables potentially related to prognostic factors affecting survival were analyzed using a Cox proportional hazard model. RESULTS The patients that received SLT treatment exhibited favorable DFS compared to patients that received RR/RFA (P = 0.002). OS (P < 0.001) and DFS (P = 0.008) rates were significantly increased in the MO group compared with in the IM group. Subgroup analysis revealed that DFS was significantly improved for patients in the MO group treated with SLT compared to patients treated with RR/RFA (P = 0.017). Recurrence pattern was an independent prognostic factor for both OS [hazard ratio (HR) = 0.093, 95% confidence interval (CI): 0.026-0.337, P < 0.001] and DFS (HR = 0.318, 95% CI: 0.125-0.810, P = 0.016; HR = 3.334, 95% CI: 1.546-7.18, P = 0.002). CONCLUSIONS For patients with intrahepatic recurrent HCC, an MO recurrence pattern is associated with better long-term outcomes than the IM pattern. SLT is the preferred option for intrahepatic recurrent HCC, especially for MO cases.
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Affiliation(s)
- Xiaoyun Zhang
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Guoxuexiang 37, Chengdu, 610041, Sichuan Province, China
| | - Chuan Li
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Guoxuexiang 37, Chengdu, 610041, Sichuan Province, China
| | - Tianfu Wen
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Guoxuexiang 37, Chengdu, 610041, Sichuan Province, China.
| | - Wei Peng
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Guoxuexiang 37, Chengdu, 610041, Sichuan Province, China
| | - Lunan Yan
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Guoxuexiang 37, Chengdu, 610041, Sichuan Province, China
| | - Jiayin Yang
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Guoxuexiang 37, Chengdu, 610041, Sichuan Province, China
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Itoh S, Yoshizumi T, Tomino T, Nagatsu A, Motomura T, Harada N, Harimoto N, Ikegami T, Soejima Y, Maehara Y. Associations between antibody to hepatitis B core antigen positivity and outcomes in hepatocellular carcinoma patients undergoing hepatic resection. Hepatol Res 2018; 48:E155-E161. [PMID: 28710825 DOI: 10.1111/hepr.12939] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2017] [Revised: 07/11/2017] [Accepted: 07/12/2017] [Indexed: 02/08/2023]
Abstract
AIM We aimed to evaluate the effect of antibody to hepatitis B core antigen (HBcAb) positivity on clinical outcomes after hepatic resection in hepatocellular carcinoma (HCC) patients with negative hepatitis B surface antigen (HBsAg) and hepatitis C virus antibody (HCVAb), termed non-B, non-C HCC (NBNC-HCC), or with HCV-related HCC. METHODS Two hundred and sixty-three patients who underwent hepatic resection for HCC and measurements of HBsAg, HCVAb, and HBcAb were enrolled in this study. RESULTS The percentages of HBcAb positivity were 52.3% (n = 57) and 56.9% (n = 66) in patients with NBNC- and HCV-related HCC, respectively. The proportion of multiple NBNC-HCCs was significantly greater in patients with HBcAb positivity compared to HBcAb negativity (P = 0.028). There were no significant differences in the recurrence-free and overall survival rates between NBNC-HCC patients with HBcAb positivity versus negativity (P = 0.461 and P = 0.190, respectively). Furthermore, for HCV-related HCC patients, there were no significant differences in the baseline factors between patients with positive versus negative HBcAb. The proportion of patients with HBcAb-positive HCV-related HCC who underwent anatomical resection of the liver was significantly greater than that of HBcAb-negative patients, whereas the recurrence-free and overall survival rates were not significantly different (P = 0.158 and P = 0.191, respectively). CONCLUSION In our study, the presence of HBcAb had no impact on surgical outcomes after hepatic resection in patients with NBNB- and HCV-related HCC. Occult HBV infection might be associated with hepatocarcinogenesis in patients with NBNC-related HCC.
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Affiliation(s)
- Shinji Itoh
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Tomoharu Yoshizumi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takahiro Tomino
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Akihisa Nagatsu
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takashi Motomura
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Noboru Harada
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Norifumi Harimoto
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Toru Ikegami
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yuji Soejima
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yoshihiko Maehara
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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Surgery for Hepatocellular Carcinoma in Patients with Child–Pugh B Cirrhosis: Hepatic Resection Versus Living Donor Liver Transplantation. World J Surg 2018; 42:2606-2616. [DOI: 10.1007/s00268-018-4493-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Lim C, Shinkawa H, Hasegawa K, Bhangui P, Salloum C, Gomez Gavara C, Lahat E, Omichi K, Arita J, Sakamoto Y, Compagnon P, Feray C, Kokudo N, Azoulay D. Salvage liver transplantation or repeat hepatectomy for recurrent hepatocellular carcinoma: An intent-to-treat analysis. Liver Transpl 2017; 23:1553-1563. [PMID: 28945955 DOI: 10.1002/lt.24952] [Citation(s) in RCA: 53] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2017] [Revised: 08/09/2017] [Accepted: 09/17/2017] [Indexed: 02/07/2023]
Abstract
The salvage liver transplantation (LT) strategy was conceived for initially resectable and transplantable hepatocellular carcinoma (HCC) to obviate upfront transplantation, with salvage LT in the case of recurrence. The longterm outcomes of a second resection for recurrent HCC have improved. The aim of this study was to perform an intention-to-treat analysis of overall survival (OS) comparing these 2 strategies for initially resectable and transplantable recurrent HCC. From 1994 to 2011, 391 patients with HCC who underwent salvage LT (n = 77) or a second resection (n = 314) were analyzed. Of 77 patients in the salvage LT group, 21 presented with resectable and transplantable recurrent HCC and 18 underwent transplantation. Of 314 patients in the second resection group, 81 presented with resectable and transplantable recurrent HCC and 81 underwent a second resection. The 5-year intention-to-treat OS rates, calculated from the time of primary hepatectomy, were comparable between the 2 strategies (72% for salvage transplantation versus 77% for second resection; P = 0.57). In patients who completed the salvage LT or second resection procedure, the 5-year OS rates, calculated from the time of the second surgery, were comparable between the 2 strategies (71% versus 71%; P = 0.99). The 5-year disease-free survival (DFS) rates were 72% following transplantation and 18% following the second resection (P < 0.001). Similar results were observed after propensity score matching. In conclusion, although the 5-year OS rates were similar in the salvage LT and second resection groups, the salvage LT strategy still achieves better DFS. Second resection for recurrent HCC might be considered to be the best alternative option to LT in the current organ shortage. Liver Transplantation 23 1553-1563 2017 AASLD.
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Affiliation(s)
- Chetana Lim
- Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation and, Henri Mondor Hospital, AP-HP, Paris-Est University, Créteil, France
| | - Hiroji Shinkawa
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Kiyoshi Hasegawa
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Prashant Bhangui
- Medanta Institute of Liver Transplantation and Regenerative Medicine, New Delhi, India
| | - Chady Salloum
- Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation and, Henri Mondor Hospital, AP-HP, Paris-Est University, Créteil, France
| | - Concepcion Gomez Gavara
- Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation and, Henri Mondor Hospital, AP-HP, Paris-Est University, Créteil, France
| | - Eylon Lahat
- Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation and, Henri Mondor Hospital, AP-HP, Paris-Est University, Créteil, France
| | - Kiyohiko Omichi
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Junichi Arita
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Yoshihiro Sakamoto
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Philippe Compagnon
- Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation and, Henri Mondor Hospital, AP-HP, Paris-Est University, Créteil, France
| | - Cyrille Feray
- Department of Hepatology, Henri Mondor Hospital, AP-HP, Paris-Est University, Créteil, France
| | - Norihiro Kokudo
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Daniel Azoulay
- Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation and, Henri Mondor Hospital, AP-HP, Paris-Est University, Créteil, France
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Kornberg A, Schernhammer M, Friess H. 18F-FDG-PET for Assessing Biological Viability and Prognosis in Liver Transplant Patients with Hepatocellular Carcinoma. J Clin Transl Hepatol 2017; 5:224-234. [PMID: 28936404 PMCID: PMC5606969 DOI: 10.14218/jcth.2017.00014] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2017] [Revised: 05/18/2017] [Accepted: 06/05/2017] [Indexed: 12/12/2022] Open
Abstract
Liver transplantation (LT) has become standard of care in patients with non-resectable early stage hepatocellular carcinoma (HCC) in liver cirrhosis. Currently, patient selection for LT is strictly based on tumor size and number, provided by the Milan criteria. This may, however, exclude patients with advanced tumor load but favourable biology from a possibly curative treatment option. It became clear in recent years that biological tumor viability rather than tumor macromorphology determines posttransplant outcome. In particular, microvascular invasion and poor grading reflect tumor aggressiveness and promote the risk of tumor relapse. Pretransplant biopsy is not applicable due to tumor heterogeneity and risk of tumor cell seeding. 18F-fludeoxyglucose (18F-FDG) positron emission tomography (PET), an established nuclear imaging device in oncology, was demonstrated to non-invasively correlate with unfavorable histopathologic features. Currently, there is an increasing amount of evidence that 18F-FDG-PET is very useful for identifying eligible liver transplant patients with HCC beyond standard criteria but less aggressive tumor properties. In order to safely expand the HCC selection criteria and the pool of eligible liver recipients, tumor evaluation with 18F-FDG-PET should be implemented in pretransplant decision process.
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Affiliation(s)
- Arno Kornberg
- *Correspondence to: Arno Kornberg, Department of Surgery, Klinikum rechts der Isar, Technical University Munich, Ismaningerstr. 22, D-81675 Munich, Germany. Tel: +89-41405087, Fax: +89-41404884, E-mail:
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Zhang X, Li C, Wen T, Peng W, Yan L, Yang J. Treatment for intrahepatic recurrence after curative resection of hepatocellular carcinoma: Salvage liver transplantation or re-resection/radiofrequency ablation? A Retrospective Cohort Study. Int J Surg 2017; 46:178-185. [PMID: 28890407 DOI: 10.1016/j.ijsu.2017.09.001] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2017] [Revised: 08/25/2017] [Accepted: 09/03/2017] [Indexed: 02/05/2023]
Abstract
OBJECTIVE The optimal treatment strategy for patients with recurrent hepatocellular carcinoma (HCC) remains unclear. This study was designed to investigate the outcomes of salvage liver transplantation (SLT) and re-resection (RR)/radiofrequency ablation (RFA) with respect to the time to recurrence after initial curative resection. METHODS Between 2007 and 2016, 756 patients underwent curative hepatectomy for HCC in accordance with the Milan criteria. Among them, 152 experienced an intrahepatic recurrence and underwent SLT (n = 36) and RR/RFA (n = 116). Clinical data, overall survival (OS), and disease-free survival (DFS) (including subgroup analyses) according to the time to recurrence were statistically compared between the 2 groups, and prognostic factors were identified. RESULTS The DFS of the patients who underwent SLT was much better than that of the patients who underwent RR/RFA (P = 0.002), particularly those with late recurrence (more than 12 months, P = 0.004). The time to recurrence from initial hepatectomy was found to be an independent predictor of OS and DFS. CONCLUSIONS SLT, rather than re-resection or RFA, should be the preferred treatment option for patients with late recurrence.
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Affiliation(s)
- Xiaoyun Zhang
- Department of Liver Surgery and Liver Transplantation Centre, West China Hospital of Sichuan University, Guoxuexiang 37, Chengdu 610041, Sichuan Province, China
| | - Chuan Li
- Department of Liver Surgery and Liver Transplantation Centre, West China Hospital of Sichuan University, Guoxuexiang 37, Chengdu 610041, Sichuan Province, China
| | - Tianfu Wen
- Department of Liver Surgery and Liver Transplantation Centre, West China Hospital of Sichuan University, Guoxuexiang 37, Chengdu 610041, Sichuan Province, China.
| | - Wei Peng
- Department of Liver Surgery and Liver Transplantation Centre, West China Hospital of Sichuan University, Guoxuexiang 37, Chengdu 610041, Sichuan Province, China
| | - Lunan Yan
- Department of Liver Surgery and Liver Transplantation Centre, West China Hospital of Sichuan University, Guoxuexiang 37, Chengdu 610041, Sichuan Province, China
| | - Jiayin Yang
- Department of Liver Surgery and Liver Transplantation Centre, West China Hospital of Sichuan University, Guoxuexiang 37, Chengdu 610041, Sichuan Province, China
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Changes of alpha-fetoprotein levels could predict recurrent hepatocellular carcinoma survival after trans-arterial chemoembolization. Oncotarget 2017; 8:85599-85611. [PMID: 29156744 PMCID: PMC5689634 DOI: 10.18632/oncotarget.20343] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2017] [Accepted: 07/18/2017] [Indexed: 02/05/2023] Open
Abstract
Background There is paucity of information concerning whether AFP change is a predictor of prognosis for recurrent hepatocellular carcinoma (RHCC) patients after trans-arterial chemoembolization (TACE). Methods A total of 177 RHCC patients who received TACE as first-line therapy were retrospectively analyzed. The patients were classified into three groups according to their pre-TACE and post-TACE AFP levels (group A: AFP decreased, group B: AFP consistent normal, and group C: AFP increased). The recurrence to death survival (RTDS) and overall survival (OS) were estimated by the Kaplan-Meier method, and compared by the log-rank test. Multivariate analyses were performed to identify prognostic factors for OS and RTDS. Results There was no significant difference among the three groups concerning the baseline characteristics. The median overall survival (OS) was 74.5 months in group A (95% confidence interval (CI): 63.5, 85.6), 64.0 months in group B (95% CI: 52.3, 75.7) and 29.0 months in group C (95% CI: 24.1, 33.9; P<0.001). The median recurrence to death survival (RTDS) was 66.5 months (95% CI: 53.4, 79.6) in group A, 50.4 months (95% CI: 39.5, 61.4) in group B and 17.7 months (95% CI: 13.4, 22.1; P<0.001) in group C. Multivariate analysis revealed that tumor size at resection stage, tumor number at recurrent stage, cycles of TACE, mRECIST response and AFP change after TACE were significant independent risk factors for RTDS and OS. Conclusions AFP change could predict the prognoses of patients with RHCC who received trans-arterial chemoembolization, which may help clinicians make subsequent treatment decision.
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Joliat GR, Allemann P, Labgaa I, Demartines N, Halkic N. Treatment and outcomes of recurrent hepatocellular carcinomas. Langenbecks Arch Surg 2017; 402:737-744. [PMID: 28497194 DOI: 10.1007/s00423-017-1582-9] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2016] [Accepted: 04/24/2017] [Indexed: 12/15/2022]
Abstract
PURPOSE Surgery is one of the best options for curative treatment of hepatocellular carcinomas (HCC). Recurrences are nevertheless common (45-75%). This study aimed to compare overall survival (OS) of patients with recurrent HCC after primary resection to OS of patients without recurrence. METHODS A retrospective review of all HCC patients operated between 1993 and 2015 was performed. Median and 5-year OS were calculated. RESULTS This study included 147 HCC patients. Sixty-seven patients presented a recurrence (46%). Patients with recurrence had a worse prognosis than those without recurrence (median OS 63 vs. 82 months, 5-year OS 47 vs. 54%, p = 0.036). First-line performed treatments were radiofrequency ablation (18, RFA), chemo-embolization (16, TACE), repeat hepatectomy (10), systemic chemotherapy (4), radio-embolization (1), and alcoholization (1). Palliative care was performed in 17 patients. Median OS of patients treated by RFA, TACE, or repeat hepatectomy were similar (77, 71, and 84 months, p = 0.735). Patients treated with chemotherapy/palliative care had lower median OS compared to interventional treatments (20 vs. 77 months, p < 0.0001). CONCLUSIONS Recurrence after surgical HCC resection is frequent and negatively impacts OS. Interventional treatments of recurrences offered improved outcomes compared to medical care. In selected patients, RFA, TACE, and repeat hepatectomy allowed similar OS as non-recurrent cases.
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Affiliation(s)
- Gaëtan-Romain Joliat
- Department of Visceral Surgery, University Hospital CHUV, Rue du Bugnon 46, 1011, Lausanne, Switzerland
| | - Pierre Allemann
- Department of Visceral Surgery, University Hospital CHUV, Rue du Bugnon 46, 1011, Lausanne, Switzerland
| | - Ismail Labgaa
- Department of Visceral Surgery, University Hospital CHUV, Rue du Bugnon 46, 1011, Lausanne, Switzerland
| | - Nicolas Demartines
- Department of Visceral Surgery, University Hospital CHUV, Rue du Bugnon 46, 1011, Lausanne, Switzerland.
| | - Nermin Halkic
- Department of Visceral Surgery, University Hospital CHUV, Rue du Bugnon 46, 1011, Lausanne, Switzerland
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Ali MA, Lacin S, Abdel-Wahab R, Uemura M, Hassan M, Rashid A, Duda DG, Kaseb AO. Nonalcoholic steatohepatitis-related hepatocellular carcinoma: is there a role for the androgen receptor pathway? Onco Targets Ther 2017; 10:1403-1412. [PMID: 28424556 PMCID: PMC5344425 DOI: 10.2147/ott.s111681] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
The epidemic of insulin resistance, obesity, and metabolic syndrome has led to the emergence of nonalcoholic steatohepatitis (NASH) as the most common cause of liver disease in the US. Patients with NASH are at an increased risk for hepatic disease-related morbidity and death, and chronic inflammation in NASH patients can lead to hepatocellular carcinoma (HCC). The prevalence of HCC is higher in males than in females, and genetic studies have identified androgen and androgen receptors (ARs) as partially responsible for the gender disparity in the development of liver disease and HCC. Although many factors are known to play important roles in the progression of inflammation in NASH patients, the role of androgen and AR in the progression of NASH to HCC has been understudied. This review summarizes the evidence for a potential role of androgen and the AR pathway in the development of NASH-related HCC and in the treatment of HCC. It has been proposed that AR plays a role in the progression of HCC: inhibitory roles in early stages of hepatocarcinogenesis and tumor-promoting roles in advanced stages. AR can be activated by several pathways, even in the absence of androgen. While AR has been explored as a potential therapeutic target in HCC, several clinical trials have failed to demonstrate a clinical benefit of antiandrogen drugs in HCC. This review discusses the potential reason for these observations and discuss the potential future trials design in this important setting.
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Affiliation(s)
- Mahmoud A Ali
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Sahin Lacin
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Reham Abdel-Wahab
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.,Department of Clinical Oncology, Assiut University, Assiut, Egypt
| | - Mark Uemura
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Manal Hassan
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Asif Rashid
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Dan G Duda
- Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Ahmed O Kaseb
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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Doussot A, Lim C, Lahat E, Salloum C, Osseis M, Gavara CG, Levesque E, Feray C, Compagnon P, Azoulay D. Complications after Hepatectomy for Hepatocellular Carcinoma Independently Shorten Survival: A Western, Single-Center Audit. Ann Surg Oncol 2017; 24:1569-1578. [DOI: 10.1245/s10434-016-5746-6] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2016] [Indexed: 12/13/2022]
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Kanda T, Yokosuka O. The androgen receptor as an emerging target in hepatocellular carcinoma. J Hepatocell Carcinoma 2015; 2:91-9. [PMID: 27508198 PMCID: PMC4918288 DOI: 10.2147/jhc.s48956] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the male-dominant liver diseases with poor prognosis, although treatments for HCC have been progressing in the past decades. Androgen receptor (AR) is a member of the nuclear receptor superfamily. Previous studies reported that AR was expressed in human HCC and non-HCC tissues. AR is activated both ligand-dependently and ligand-independently. The latter is associated with a mitogen-activated protein kinase–, v-akt murine thymoma viral oncogene homolog 1–, or signal-transducer and activator of transcription–signaling pathway, which has been implicated in the development of HCC. It has been reported that more than 200 RNA expression levels are altered by androgen treatment. In the liver, androgen-responsive genes are cytochrome P450s, transforming growth factor β, vascular endothelial growth factor, and glucose-regulated protein 78 kDa, which are also associated with human hepatocarcinogenesis. Recent studies also revealed that AR plays a role in cell migration and metastasis. It is possible that cross-talk among AR-signaling, endoplasmic reticulum stress, and innate immune response is important for human hepatocarcinogenesis and HCC development. This review shows that AR could play a potential role in human HCC and represent one of the important target molecules for the treatment of HCC.
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Affiliation(s)
- Tatsuo Kanda
- Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan
| | - Osamu Yokosuka
- Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan
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