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Xuan W, Zhang X, Fang Y, Zhang Y, Xiang Z, Yu Y, Wu Q, Zhang X. Efficacy and safety of neoadjuvant therapy for hepatocellular carcinoma with portal vein thrombosis: A meta‑analysis. Oncol Lett 2025; 29:122. [PMID: 39807096 PMCID: PMC11726279 DOI: 10.3892/ol.2025.14868] [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: 09/14/2024] [Accepted: 12/05/2024] [Indexed: 01/16/2025] Open
Abstract
Hepatocellular carcinoma (HCC) with coexisting portal vein tumor thrombus (PVTT) is associated with poor patient outcomes. The efficacy and safety of neoadjuvant therapy in patients with HCC with PVTT remain a subject of debate. In the present study, a comprehensive search of electronic databases, including PubMed, Web of Science, Embase and the Cochrane Library, was conducted to identify studies evaluating the outcomes of neoadjuvant therapy in patients with HCC and PVTT. The primary outcomes assessed were overall survival (OS) and relapse-free survival (RFS), with complication rates as a secondary outcome. A total of six studies comprising 750 patients were included in the present meta-analysis. The neoadjuvant therapy group exhibited significantly superior OS [hazard ratio (HR), 0.39; P<0.001] and RFS (HR, 0.31; P<0.001) compared with the primary hepatectomy control group. Compared with the control group, neoadjuvant radiotherapy improved OS (HR, 0.34; P<0.001) and RFS (HR, 0.24; P=0.004). While the neoadjuvant intervention subgroup exhibited an improved OS compared with controls (HR, 0.37; P=0.001), no significant difference in RFS was observed (HR, 0.11; P=0.095). Geographical analysis revealed that the Chinese subgroup demonstrated a significantly improved OS and RFS (HR, 0.41 for both; P<0.001), compared with the control group. However, the Japanese and Korean subgroups showed no improvement in OS (HR, 0.25; P=0.057) compared with the control group, and the results did not reach statistical significance. There were no significant differences between the groups in terms of blood transfusion, blood loss, operation time, bile leakage, ascites, peritoneal infection, postoperative bleeding, complications or mortality (all P>0.05). Overall, neoadjuvant therapy significantly improved survival outcomes in patients with HCC and PVTT without increasing complication rates, supporting its efficacy and manageable safety profile.
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Affiliation(s)
- Wangyi Xuan
- Department of Gastroenterology, Ningbo Zhenhai Hospital of Traditional Chinese Medicine, Ningbo, Zhejiang 315299, P.R. China
| | - Xiaoming Zhang
- The First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China
| | - Yingying Fang
- The First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China
| | - Yueming Zhang
- Intensive Care Unit, Hospital of Zhejiang People's Armed Police, Hangzhou, Zhejiang 310051, P.R. China
| | - Zhiyi Xiang
- The First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China
| | - Yifei Yu
- School of Stomatology, Zhejiang University of Chinese Medicine, Hangzhou, Zhejiang 310053, P.R. China
| | - Qingping Wu
- The First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China
| | - Xingfen Zhang
- Department of Liver Disease, Ningbo No. 2 Hospital, Ningbo, Zhejiang 315010, P.R. China
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Pandrowala S, Patkar S, Goel M, Mirza D, Mathur SK. Surgical resection for large hepatocellular carcinoma and those beyond BCLC: systematic review with proposed management algorithm. Langenbecks Arch Surg 2023; 408:144. [PMID: 37041364 DOI: 10.1007/s00423-023-02881-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Accepted: 04/02/2023] [Indexed: 04/13/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) accounts for the sixth most common cancer and ranks third in mortality worldwide with inhomogeneity in terms of resection for advanced-stage disease. METHODS A systematic review of published literature using the PubMed, Medline, and Google Scholar databases from 1995 to 2020 was conducted to identify studies that reported outcomes of resection for solitary HCC > 10 cm, BCLC B/C, and multinodular HCC. Our aim was to assess overall survival for resection, identify poor prognostic factors, and to compare it to trans-arterial chemotherapy (TACE) where data was available. RESULTS Eighty-nine articles were included after a complete database search in the systematic review as per our predefined criteria. Analysis revealed a 5-year overall survival of 33.5% for resection of HCC > 10 cm, 41.7% for BCLC B, 23.3% for BCLC C, and 36.6% for multinodular HCC. Peri-operative mortality ranged from 0 to 6.9%. Studies comparing resection versus TACE for BCLC B/C had a survival of 40% versus 17%, respectively. CONCLUSION Our systematic review justifies hepatic resection wherever feasible for hepatocellular carcinomas > 10 cm, BCLC B, BCLC C, and multinodular tumors. In addition, we identified and proposed an algorithm with five poor prognostic criteria in this group of patients who may benefit from adjuvant TACE.
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Affiliation(s)
- Saneya Pandrowala
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, India
| | - Shraddha Patkar
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, India
| | - Mahesh Goel
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, India.
| | - Darius Mirza
- Hepato-Pancreato-Biliary and Transplant Surgery, University Hospital Birmingham and Birmingham Children's Hospital, Birmingham, UK
| | - S K Mathur
- Zen Digestive Disease Center, Zen Hospital, Mumbai, India
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Khan AR, Wei X, Xu X. Portal Vein Tumor Thrombosis and Hepatocellular Carcinoma - The Changing Tides. J Hepatocell Carcinoma 2021; 8:1089-1115. [PMID: 34522691 PMCID: PMC8434852 DOI: 10.2147/jhc.s318070] [Citation(s) in RCA: 66] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Accepted: 08/13/2021] [Indexed: 12/12/2022] Open
Abstract
Portal vein involvement is considered one of the most fearful complications of hepatocellular carcinoma (HCC). Portal vein tumor thrombosis (PVTT) is associated with aggressive tumor biology (high grade), high tumor burden (number and size of lesions), high levels of serum markers (AFP), poor liver function (deranged LFT), and poor performance status of patients. The Barcelona Clinic Liver Cancer staging system places HCC patients with PVTT in advanced stage (BCLC Stage-C). This group contains a fairly heterogeneous patient population, previously considered candidates for palliative systemic therapy with sorafenib. However, this provided modest overall survival (OS) benefit. The results of a recent Phase III (IMbrave150) trial favor the combination of atezolizumab and bevacizumab over sorafenib as a standard of care in advanced unresectable HCC. While only lenvatinib proved to be non-inferior against sorafenib in a phase III (REFLECT trial), regorafenib (RESORCE trial), ramucirumab (REACH-2), and cabozantinib (CELESTIAL) have been approved second-line therapy in phase III clinical trials. Recently, the data on the prospect of other modalities in the management of HCC with PVTT is mounting with favorable results. Targeting multiple pathways in the HCC cascade using a combination of drugs and other modalities such as RT, TACE, TARE, and HAIC appear effective for systemic and loco-regional control. The quest for the ideal combination therapy and the sequence set is still widely unanswered and prospective trials are lacking. With the armament of available therapeutic options and the advances and refinements in the delivery system, down-staging patients to make them eligible for curative resection has been reported. In a rapidly evolving treatment landscape, performing surgery when appropriate, in the form of LR and even LT to achieve cure does not seem farfetched. Likewise, adjuvant therapy and prompt management of the recurrences holds the key to prolong OS and DFS. This review discusses the management options of HCC patients with PVTT.
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Affiliation(s)
- Abdul Rehman Khan
- Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, People's Republic of China.,Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People's Republic of China.,NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, People's Republic of China
| | - Xuyong Wei
- Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, People's Republic of China.,NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, People's Republic of China.,Institute of Organ Transplantation, Zhejiang University, Hangzhou, 310003, People's Republic of China
| | - Xiao Xu
- Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, People's Republic of China.,Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People's Republic of China.,NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, People's Republic of China.,Institute of Organ Transplantation, Zhejiang University, Hangzhou, 310003, People's Republic of China
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Shehta A, Farouk A, Elghawalby AN, Elshobary M, Aboelenin A, Fouad A, Ali MA. Outcomes of Hepatic Resection for Hepatocellular Carcinoma Associated with Portal Vein Invasion. J Surg Res 2021; 266:269-283. [PMID: 34038849 DOI: 10.1016/j.jss.2021.04.011] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Revised: 04/02/2021] [Accepted: 04/10/2021] [Indexed: 01/27/2023]
Abstract
BACKGROUND To evaluate our experience of liver resection for hepatocellular carcinoma (HCC) patients associated with macroscopic portal vein invasion (PVI). METHODS Consecutive HCC patients who underwent liver resection for HCC between November 2009 & June 2019 were included. To overcome selection bias between patients with and without macroscopic PVI, we performed 1:1 match using propensity score matching (PSM). RESULTS Macroscopic PVI was detected in 37 patients (12.8%). We divided our patients into two groups according to the presence of macroscopic PVI. After PSM, 36 patients of PVI group were matched with 36 patients from Non-PVI group. After PSM, both groups were well balanced regarding tumor site, number, liver resection extent and type. Longer operation time and more blood loss were noted in PVI group. Higher incidence of post-operative morbidities occurred in PVI group especially, post-hepatectomy liver dysfunction. The 1-, 2-, and 3-y overall survival rates for Non-PVI group were 85.3%, 64.6%, and 64.6% & 69.8%, 42%, and 0% for PVI group, respectively (P = 0.009). There were no significant differences regarding the recurrence rate, site, and its management. The 1-, 2-, and 3-y disease-free survival (DFS) rates for Non-PVI group were 81.7%, 72.3%, and 21.7% & 67.7%, 42.3%, and 0% for PVI group, respectively (P = 0.172). CONCLUSION Surgical management of advanced HCCs with macroscopic PVI is feasible, and associated with comparable DFS but poorer overall survival, compared to patients without PVI.
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Affiliation(s)
- Ahmed Shehta
- Gastrointestinal Surgery Center, Department of Surgery, College of Medicine, Mansoura University, Mansoura, Egypt.
| | - Ahmed Farouk
- Gastrointestinal Surgery Center, Department of Surgery, College of Medicine, Mansoura University, Mansoura, Egypt
| | - Ahmed Nabieh Elghawalby
- Gastrointestinal Surgery Center, Department of Surgery, College of Medicine, Mansoura University, Mansoura, Egypt
| | - Mohamed Elshobary
- Gastrointestinal Surgery Center, Department of Surgery, College of Medicine, Mansoura University, Mansoura, Egypt
| | - Ahmed Aboelenin
- Gastrointestinal Surgery Center, Department of Surgery, College of Medicine, Mansoura University, Mansoura, Egypt
| | - Amgad Fouad
- Gastrointestinal Surgery Center, Department of Surgery, College of Medicine, Mansoura University, Mansoura, Egypt
| | - Mahmoud Abdelwahab Ali
- Gastrointestinal Surgery Center, Department of Surgery, College of Medicine, Mansoura University, Mansoura, Egypt
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Cortese S, Morales J, Martín L, Kayser S, Colón A, Ramón E, Tellado JM. Resección hepática con trombectomía en el tratamiento del carcinoma hepatocelular con invasión vascular macroscópica. Cir Esp 2020; 98:9-17. [DOI: 10.1016/j.ciresp.2019.06.013] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2018] [Revised: 05/19/2019] [Accepted: 06/27/2019] [Indexed: 01/27/2023]
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Zhang ZY, Dong KS, Zhang EL, Zhang LW, Chen XP, Dong HH. Resection might be a meaningful choice for hepatocellular carcinoma with portal vein thrombosis: A systematic review and meta-analysis. Medicine (Baltimore) 2019; 98:e18362. [PMID: 31852141 PMCID: PMC6922393 DOI: 10.1097/md.0000000000018362] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND According to the Barcelona Clinic Liver Cancer (BCLC) staging system, the presence of portal vein tumor thrombosis (PVTT) is considered to indicate an advanced stage of hepatocellular carcinoma (HCC) with nearly no cure. Hepatic resection and transarterial chemoembolization (TACE) have recently been recommended for treatment of HCC with PVTT. METHODS We conducted a systematic review to compare the overall survival between patients with HCC and PVTT undergoing hepatectomy, TACE or conservative treatment including sorafenib chemotherapy. The PubMed, Web of Science, and Cochrane Library databases were searched. All relevant studies were considered. Hazard ratios with 95% confidence intervals were calculated for comparison of the cumulative overall survival. Ten retrospective studies met the inclusion criteria and were included in the review. RESULTS Overall survival was not higher in the hepatectomy group than TACE group. But survival rate was higher in hepatectomy group than conservative group. The subgroup analysis demonstrated that hepatectomy was superior in patients without PVTT in the main trunk than in patients with main portal vein invasion. In patients without main PVTT, hepatectomy has showed more benefit than TACE. However, there has been no significant difference between the hepatectomy and TACE groups among patients with main PVTT. CONCLUSION For patients with resectable HCC and PVTT, hepatectomy might be more effective in patients without PVTT in the main trunk than TACE or conservative treatment.
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Gon H, Kido M, Tanaka M, Kinoshita H, Komatsu S, Tsugawa D, Awazu M, Toyama H, Matsumoto I, Itoh T, Fukumoto T. Growth velocity of the portal vein tumor thrombus accelerated by its progression, alpha-fetoprotein level, and liver fibrosis stage in patients with hepatocellular carcinoma. Surgery 2018; 164:1014-1022. [DOI: 10.1016/j.surg.2018.06.025] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2018] [Revised: 06/01/2018] [Accepted: 06/12/2018] [Indexed: 12/11/2022]
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Yang B, Li CL, Guo WH, Qin TQ, Jiao H, Fei ZJ, Zhou X, Duan LJ, Liao ZY. Intra-arterial ethanol embolization augments response to TACE for treatment of HCC with portal venous tumor thrombus. BMC Cancer 2018; 18:101. [PMID: 29378532 PMCID: PMC5789611 DOI: 10.1186/s12885-018-3989-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2017] [Accepted: 01/15/2018] [Indexed: 02/07/2023] Open
Abstract
Background The prognosis of hepatocellular carcinoma with portal vein tumor thrombus remains extremely poor. This pilot study aimed to evaluate the technical feasibility, effectiveness and safety of transcatheter chemoembolization for tumors in the liver parenchyma plus intra-arterial ethanol embolization for portal vein tumor thrombus. Methods A pilot study was carried out on 31 patients in the treatment group (transcatheter chemoembolization plus intra-arterial ethanol embolization) and 57 patients in the control group (transcatheter chemoembolization alone). Enhanced computed tomography/magnetic resonance images were repeated 4 weeks after the procedure to assess the response. Overall survival and complications were assessed until the patient died or was lost to follow-up. Results Median survival was 10.5 months in the treatment group (2.4 ± 1.7 courses) and 3.9 months in the control group (1.9 ± 1 courses) (P = 0.001). Patients in the treatment group had better overall survival (at 3, 6 and 12 months, respectively), compared to patients in the control group (90.3% vs. 59.6%, 64.5% vs. 29.8%, and 41.9% vs. 10.6%; p = 0.001). Furthermore, the rate of portal vein tumor thrombus regression was higher in the treatment group (93.1%) than in the control group (32.1%) (P < 0.001). Conclusions Based on the results of this study, transcatheter chemoembolization combined with intra-arterial ethanol embolization may be more effective than transcatheter chemoembolization alone for treating hepatocellular carcinoma with portal vein tumor thrombus. Intra-arterial ethanol embolization for treating portal vein tumor thrombus is safe, feasible and prolongs overall survival.
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Affiliation(s)
- Biao Yang
- Department of Abdominal Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Guoxue Lane No. 37, Chengdu, Sichuan Province, 610041, People's Republic of China
| | - Chun-Lin Li
- Department of Abdominal Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Guoxue Lane No. 37, Chengdu, Sichuan Province, 610041, People's Republic of China
| | - Wen-Hao Guo
- Department of Abdominal Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Guoxue Lane No. 37, Chengdu, Sichuan Province, 610041, People's Republic of China
| | - Tian-Qiang Qin
- Chinese Evidence-Based Medicine Centre, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China
| | - He Jiao
- Department of Radiology, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China
| | - Ze-Jun Fei
- Department of Radiology, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China
| | - Xuan Zhou
- Department of Radiology, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China
| | - Lin-Jia Duan
- Department of Radiology, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China
| | - Zheng-Yin Liao
- Department of Abdominal Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Guoxue Lane No. 37, Chengdu, Sichuan Province, 610041, People's Republic of China.
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9
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Zhang YF, Le Y, Wei W, Zou RH, Wang JH, OuYang HY, Xiao CZ, Zhong XP, Shi M, Guo RP. Optimal surgical strategy for hepatocellular carcinoma with portal vein tumor thrombus: a propensity score analysis. Oncotarget 2018; 7:38845-38856. [PMID: 27072577 PMCID: PMC5122434 DOI: 10.18632/oncotarget.8642] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2015] [Accepted: 03/29/2016] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVES The optimal surgical resection method for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) that maximizes both safety and long-term outcome has not yet been determined. The aim of this study was to compare the clinical outcomes following peeling off versus en bloc resection for PVTT. METHODS From 2005 to 2012, 252 patients with HCC and type I/II PVTT who underwent hepatic resection were divided into two groups according to whether they received en bloc resection (n = 113) or peeling off resection (n = 139). The clinical outcomes were compared before and after propensity score matching. RESULTS The propensity model matched 113 patients with en bloc resection for further analyses. After matching, overall survival (OS) and disease-free survival (DFS) rates were significantly increased in the en bloc group compared with the peeling off group (p = 0.011 and p = 0.015). A multivariate analysis indicated that en bloc resection independently improved both OS and DFS (HR = 1.471, 95% CI: 1.071-2.018, p = 0.017 and HR = 1.415, 95% CI: 1.068-1.874, P=0.016). The adverse events were not significantly different between the two groups. However, the peeling off group showed a significantly increased recurrence rate of vascular invasion compared with the en bloc group (23.9% vs. 9.7%, p = 0.005). Similar results were also demonstrated prior to the matched analysis. CONCLUSIONS An en bloc resection is safe and confers a survival advantage compared with a peeling off resection in HCC patients with PVTT; thus, en bloc resection should be recommended as a standard treatment for these patients when possible.
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Affiliation(s)
- Yong-Fa Zhang
- Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer Center, Guangzhou, P.R. China.,State Key Laboratory of Oncology in South China, Guangzhou, P.R. China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, P.R. China
| | - Yong Le
- Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer Center, Guangzhou, P.R. China.,State Key Laboratory of Oncology in South China, Guangzhou, P.R. China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, P.R. China
| | - Wei Wei
- Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer Center, Guangzhou, P.R. China.,State Key Laboratory of Oncology in South China, Guangzhou, P.R. China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, P.R. China
| | - Ru-Hai Zou
- Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer Center, Guangzhou, P.R. China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, P.R. China.,Department of Ultrasonography of Sun Yat-sen University Cancer Center, Guangzhou, P.R. China
| | - Jia-Hong Wang
- Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer Center, Guangzhou, P.R. China.,State Key Laboratory of Oncology in South China, Guangzhou, P.R. China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, P.R. China
| | - Han-Yue OuYang
- Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer Center, Guangzhou, P.R. China.,State Key Laboratory of Oncology in South China, Guangzhou, P.R. China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, P.R. China
| | - Cheng-Zuo Xiao
- Department of General surgery, Shenzhen Shajing Affiliated Hospital of Guangzhou Medical University, Shenzhen, P.R. China
| | - Xiao-Ping Zhong
- Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer Center, Guangzhou, P.R. China.,State Key Laboratory of Oncology in South China, Guangzhou, P.R. China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, P.R. China
| | - Ming Shi
- Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer Center, Guangzhou, P.R. China.,State Key Laboratory of Oncology in South China, Guangzhou, P.R. China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, P.R. China
| | - Rong-Ping Guo
- Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer Center, Guangzhou, P.R. China.,State Key Laboratory of Oncology in South China, Guangzhou, P.R. China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, P.R. China
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10
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Glantzounis GK, Paliouras A, Stylianidi MC, Milionis H, Tzimas P, Roukos D, Pentheroudakis G, Felekouras E. The role of liver resection in the management of intermediate and advanced stage hepatocellular carcinoma. A systematic review. Eur J Surg Oncol 2017; 44:195-208. [PMID: 29258719 DOI: 10.1016/j.ejso.2017.11.022] [Citation(s) in RCA: 61] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2017] [Revised: 11/15/2017] [Accepted: 11/23/2017] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND The ideal management for patients with intermediate and advanced stage hepatocellular carcinoma (HCC) is controversial. The main purpose of this systematic review is to examine the role of liver resection in patients with intermediate stage HCC (multinodular HCCs) and in advanced stage HCC [mainly patients with portal vein tumor thrombosis (PVTT)]. METHODS A systematic search of the literature was performed in Pud Med and the Cochrane Library from 01.01.2000 to 30.06.2016. RESULTS Twenty-three articles with 2412 patients with multinodular HCCs were selected. Also, 29 studies with 3659 patients with HCCs with macrovascular invasion were selected. In patients with multinodular HCCs the median post-operative morbidity was 25% and the 90-day mortality was 2.7%. The median survival was 37 months and the 5-year survival 35%. The 5-year survival was much better for patients with a number of HCCs ≤3 vs. HCCs >3 (49% vs. 23%). In patients with macrovascular invasion, who underwent hepatic resection, the median post-operative morbidity was 33% and the in-hospital mortality 2.7%. The median survival was 15 months. The 3 and 5year survival was 33% and 20% respectively. Moreover a significant difference in survival was noted according to PVTT stage: 5- year survival for distal PVTT, PVTT of the main intrahepatic PV branch and PVTT extending to the main PV was 45%, 19% and 14.5% respectively. CONCLUSIONS Liver resection in patients with multinodular HCCs and HCCs with PVTT offers satisfactory long-term survival and should be considered in selected patients.
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Affiliation(s)
- G K Glantzounis
- Department of Surgery, University Hospital of Ioannina and School of Medicine, University of Ioannina, 45 500, Ioannina, Greece.
| | - A Paliouras
- Department of Surgery, University Hospital of Ioannina and School of Medicine, University of Ioannina, 45 500, Ioannina, Greece
| | - M-C Stylianidi
- Department of Surgery, University Hospital of Ioannina and School of Medicine, University of Ioannina, 45 500, Ioannina, Greece
| | - H Milionis
- Department of Internal Medicine, University Hospital of Ioannina and School of Medicine, University of Ioannina, Ioannina, Greece
| | - P Tzimas
- Department of Anesthesia and Postoperative Intensive Care, University Hospital of Ioannina and School of Medicine, University of Ioannina, Ioannina, Greece
| | - D Roukos
- Department of Surgery, University Hospital of Ioannina and School of Medicine, University of Ioannina, 45 500, Ioannina, Greece
| | - G Pentheroudakis
- Department of Medical Oncology, University Hospital of Ioannina and School of Medicine, University of Ioannina, Ioannina, Greece
| | - E Felekouras
- 1st Department of Surgery, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece
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11
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Li-Shuai Q, Yu-Yan C, Hai-Feng Z, Jin-Xia L, Cui-Hua L. Pre-S deletions of hepatitis B virus predict recurrence of hepatocellular carcinoma after curative resection. Medicine (Baltimore) 2017; 96:e8311. [PMID: 29069001 PMCID: PMC5671834 DOI: 10.1097/md.0000000000008311] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
The relationship between hepatitis B virus (HBV) and the prognosis of hepatocellular carcinoma (HCC) after surgery remains uncertain. A retrospective cohort study was performed to evaluate the impact of pre-S deletions, T1762/A1764, and A1896 mutations on prognosis of HCC after curative resection. A total of 113 patients with positive serum HBV DNA (>200 IU/mL) who had underwent curative resection of pathologically proven HCC were recruited to determine the risk factors affecting the prognosis.The median follow-up time was 36.5 months and recurrence was detected in 67 patients (59.3%). The cumulative recurrence rates and overall survival rates at 1-, 3-, and 5-year after curative resection were 18.0%, 49.7%, 70.3%, and 93.7%, 61.0%, 42.5%, respectively. Patients with pre-S deletions showed significantly higher recurrence rates compared with those with wild type infection (HR: 1.822, P = .018), but not related with a significantly poor survival (HR: 1.388, P = .235). Subgroup analysis indicated that the patients with type III deletion had significant higher tumor recurrence rates than other deletion types (HR: 2.211, 95% confidence intervals [CI]: 1.008-4.846, P = .048). Multivariate analysis revealed that pre-S deletion, tumor size >3 cm in diameter, and the presence of microvascular invasion were independent risk factors for tumor recurrence. HBV pre-S deletions were found to be clustered primarily in the 5' end of pre-S2 region and were more often found between amino acids 120 and 142 of the pre-S2 domain. The domains most frequently potentially involved were the transactivator domain in pre-S2 and polymerized human serum albumin binding site.Our cohort showed that pre-S deletions at the time of resection could predict tumor recurrence in HCC patients after curative resection.
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Affiliation(s)
| | | | - Zhang Hai-Feng
- Department of Infectious Disease, Affiliated Hospital of Nantong University, Jiangsu, China
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12
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Sakamoto K, Nagano H. Surgical treatment for advanced hepatocellular carcinoma with portal vein tumor thrombus. Hepatol Res 2017; 47:957-962. [PMID: 28618075 DOI: 10.1111/hepr.12923] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2017] [Revised: 05/29/2017] [Accepted: 06/13/2017] [Indexed: 12/13/2022]
Abstract
The Barcelona Clinic Liver Cancer staging system recommends a tyrosine kinase inhibitor (sorafenib) as standard therapy in advanced hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT). Sorafenib has been shown to prolong median overall survival (OS) by approximately 3 months in advanced HCC patients with PVTT (8.1 vs. 4.9 months). However, its clinical effectiveness is still controversial and standard treatment with sorafenib is not established in Japan. Surgical resection is considered a potentially curative treatment and provides an acceptable outcome for carefully selected patients. The surgical mortality rate in patients with PVTT who receive surgical resection ranges from 0% to 10%. The median survival time and 1-year OS rate in HCC patients with PVTT who undergo surgical resection have been found to range from 8 to 22 months and 21.7% to 69.6%, respectively. But improvement in therapeutic outcome is difficult with surgical treatment alone. Combination treatment in conjunction with such methods as transarterial chemoembolization, hepatic artery infusion chemotherapy, and radiotherapy has been found to improve the prognosis (median survival time, 11.5-37 months; 1-year OS rate, 46.8-100%). Yet, many problems remain, such as surgical indications and surgical techniques. After resolving these points, a multidisciplinary strategy based on surgical treatment should be established for advanced HCC with PVTT.
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Affiliation(s)
- Kazuhiko Sakamoto
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
| | - Hiroaki Nagano
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
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13
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Ye JZ, Wang YY, Bai T, Chen J, Xiang BD, Wu FX, Li LQ. Surgical resection for hepatocellular carcinoma with portal vein tumor thrombus in the Asia-Pacific region beyond the Barcelona Clinic Liver Cancer treatment algorithms: a review and update. Oncotarget 2017; 8:93258-93278. [PMID: 29190996 PMCID: PMC5696262 DOI: 10.18632/oncotarget.18735] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2017] [Accepted: 04/25/2017] [Indexed: 01/27/2023] Open
Abstract
Portal vein tumor thrombus (PVTT) usually worsens prognosis of hepatocellular carcinoma (HCC), as characterized by aggressive disease progression, impaired liver function and tolerance to treatment. Conventionally, the European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD) accepted the Barcelona Clinical Liver Cancer (BCLC) treatment algorithms, identifying PVTT as an absolute contra-indication of surgical resection for HCC. HCC-PVTT patients are offered sorafenib as the standard treatment. Evidently, SHARP and Asia-Pacific trials demonstrated that sorafenib only improves overall survival by approximately 3 months in patients with advanced HCC. Besides, BCLC treatment algorithm does not provide different therapeutic recommendations for different degree of PVTT, and only supports single treatment option for each stage of HCC rather than a combination of comprehensive treatments, which limited individual and best care for every HCC-PVTT patients. In the past few years, many surgeons do not restrict surgical resection to HCC with PVTT. There have been new reports demonstrated that surgical treatment is feasible for selected HCC-PVTT patients with resectable tumor and moderate liver function to prolong survival period and elevate life quality as long as PVTT limited to the first-order branch, whereas non-surgical treatments fail to provide comparable therapeutic effects. At present, guidelines on HCC management from mainland China, Japan, and Hong Kong have been updated and a consensus of Asia-Pacific experts has established that portal venous invasion is not an absolute contradiction of surgical resection for HCC. This review summarized the emerging data on surgical resection for HCC-PVTT patients beyond the BCLC treatment algorithms and discussed recent therapeutic conceptualchanges in the Asia-Pacific region.
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Affiliation(s)
- Jia-Zhou Ye
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, PR China
| | - Yan-Yan Wang
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, PR China
| | - Tao Bai
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, PR China
| | - Jie Chen
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, PR China
| | - Bang-De Xiang
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, PR China
| | - Fei-Xiang Wu
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, PR China
| | - Le-Qun Li
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, PR China
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14
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Fukumoto T, Kido M, Takebe A, Tanaka M, Kinoshita H, Kuramitsu K, Komatsu S, Tsugawa D, Goto T, Asari S, Toyama H, Ajiki T, Ku Y. New macroscopic classification and back-flow thrombectomy for advanced hepatocellular carcinoma with portal vein tumor thrombus invading the contralateral second portal branch. Surg Today 2017; 47:1094-1103. [PMID: 28324163 DOI: 10.1007/s00595-017-1507-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2016] [Accepted: 01/10/2017] [Indexed: 12/13/2022]
Abstract
PURPOSE Patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) invading the portal trunk (Vp4) are poor surgical candidates because of the technical difficulties involved. To overcome the limitations, we developed a technique of back-flow thrombectomy (BFT) based on the inherent portal hemodynamics and the macroscopic form of PVTT. METHODS Forty-six patients with multiple HCC and Vp4 PVTT underwent hepatectomy with tumor thrombectomy. We used the BFT to treat 24 patients, 18 of whom had PVTT in the contralateral second portal branch. The form of PVTT was classified macroscopically into the floating and expansive types. RESULTS The rate of complete removal by BFT of PVTT in the contralateral second portal branch was 89%. The patency rates at the thrombectomy site in all 46 patients and in the 24 BFT patients, 3 months after hepatectomy were 93 and 90%, respectively. The median OS of all 46 patients was 15 months, with 1- and 3-year OS rates of 58.5 and 17.1%, respectively. The median OS of the 24 patients treated with BFT vs. the 22 not treated with BFT was 14 and 15 months, respectively. CONCLUSIONS BFT can expand the therapeutic time window for patients with HCC and deep-seated PVTT and may improve their survival.
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Affiliation(s)
- Takumi Fukumoto
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
| | - Masahiro Kido
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Atsushi Takebe
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Motofumi Tanaka
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Hisoka Kinoshita
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Kaori Kuramitsu
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Shohei Komatsu
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Daisuke Tsugawa
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Tadahiro Goto
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Sadaki Asari
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Hirochika Toyama
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Tetsuo Ajiki
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Yonson Ku
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
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15
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Ma KW, Cheung TT. Surgical resection of localized hepatocellular carcinoma: patient selection and special consideration. J Hepatocell Carcinoma 2016; 4:1-9. [PMID: 28097107 PMCID: PMC5207474 DOI: 10.2147/jhc.s96085] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Localized hepatocellular carcinoma (HCC) refers to a solitary or few tumors located within either the left or right hemiliver without evidence of bilobar or extrahepatic spread. This term encompasses a heterogeneous morphology with no regard to stage of prognosis of the disease. Surgical resection remains the mainstay of curative treatment for the localized HCC. Various biochemical and radiological tests constitute an indispensible part of preoperative assessment. Emergence of laparoscopic hepatectomy has brought liver resection into a new era. Improved understanding of the pathophysiology of HCC allows more aggressive surgical resection without compromising outcomes. New insights into the management of special situations, such as ruptured HCC, pyogenic transformation of HCC, and HCC with portal vein tumor thrombus, rekindle the hopes of curative resection in these terminal events. Amalgamating salvage liver transplantation into the surgical management of resectable HCC has revolutionized the treatment paradigm of this deadly disease.
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Affiliation(s)
- Ka Wing Ma
- Department of Surgery, Queen Mary Hospital, The University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Tan To Cheung
- Department of Surgery, Queen Mary Hospital, The University of Hong Kong, Pok Fu Lam, Hong Kong
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16
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Yang B, You X, Yuan ML, Qin TQ, Duan LJ, He J, Fei ZJ, Zhou X, Zan RY, Liao ZY. Transarterial Ethanol Ablation Combined with Transarterial Chemoembolization for Hepatocellular Carcinoma with Portal Vein Tumor Thrombus. HEPATITIS MONTHLY 2016; 16:e37584. [PMID: 27799963 PMCID: PMC5075224 DOI: 10.5812/hepatmon.37584] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/04/2016] [Revised: 05/23/2016] [Accepted: 06/19/2016] [Indexed: 02/05/2023]
Abstract
BACKGROUND The prognosis for hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is extremely poor. OBJECTIVES This study aimed to evaluate the safety and effectiveness of transarterial ethanol ablation (TEA) for the treatment of HCC with PVTT. METHODS Patients were treated with TEA for PVTT under cone-beam computed tomography and traditional transarterial chemoembolization (TACE) with epirubicin for intrahepatic lesions. RESULTS Seventeen men were successfully treated with TACE plus TEA. The mean overall survival was 18.3 ± 9.0 months (95% CI: 13.7 - 3.0 months). The quality of life (QoL) score increased from 56.9 ± 15.7 before the procedure to 88.5 ± 11.7 at 4 weeks after the procedure. Lipiodol accumulation grades of 3, 2, 1, and 0 were obtained in 3 (17.6%), 8 (47.1%), 6 (35.3%), and 0 (0%) patients, respectively. CONCLUSIONS TEA is a safe and effective method for treating patients with PVTT, offering advantages for QoL, response rate after TEA, and OS.
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Affiliation(s)
- Biao Yang
- Department of Abdominal Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
| | - Xin You
- Department of Abdominal Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
| | - Min lan Yuan
- Psychiatry Centre, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
| | - Tian Qiang Qin
- Chinese Evidence-Based Medicine Centre, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
| | - Lin Jia Duan
- Department of Radiology, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
| | - Jiao He
- Department of Radiology, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
| | - Ze Jun Fei
- Department of Radiology, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
| | - Xuan Zhou
- Department of Radiology, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
| | - Rui Yu Zan
- Department of Abdominal Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
| | - Zheng Yin Liao
- Department of Abdominal Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
- Corresponding Author: Zheng Yin Liao, Department of Abdominal Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China. Tel: +86-13981717611, E-mail:
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Arai K, Fukumoto T, Tanaka M, Kuramitsu K, Kido M, Kinoshita H, Matsumoto T, Toyama H, Asari S, Goto T, Ajiki T, Ku Y. Pathological complete response after percutaneous isolated hepatic perfusion in hepatocellular carcinoma with portal vein tumor thrombosis: a case report. Surg Case Rep 2016; 2:50. [PMID: 27230652 PMCID: PMC4881067 DOI: 10.1186/s40792-016-0178-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2016] [Accepted: 05/21/2016] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Although the effectiveness of perioperative adjuvant therapy in the treatment of hepatocellular carcinoma (HCC) has been investigated, the efficacy of preoperative therapy is unclear. Herein, we report a case of pathological complete response after percutaneous isolated hepatic perfusion (PIHP) for HCC involving portal vein tumor thrombosis (PVTT). CASE PRESENTATION A 77-year-old woman was referred to our institute with a liver mass detected on a routine health screening. Computed tomography revealed a 28 × 25 mm HCC in the left lobe of the liver and a tumor thrombus in the left and right portal branches (T4N0M0, stage IVA). The patient received a single dose of preoperative PIHP with doxorubicin plus mitomycin C, without severe toxicity. After the chemotherapy, she underwent extended left hepatic lobectomy and thrombectomy of the PVTT. No cancer cells were detected during histopathological analysis, indicating pathological complete response. She remained relapse-free 12 months after the surgery. CONCLUSIONS We experienced a case of pathological complete response after preoperative PIHP with doxorubicin plus mitomycin C for HCC involving PVTT.
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Affiliation(s)
- Keisuke Arai
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Graduate School of Medicine,, Kobe University, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan.
| | - Takumi Fukumoto
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Graduate School of Medicine,, Kobe University, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
| | - Motofumi Tanaka
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Graduate School of Medicine,, Kobe University, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
| | - Kaori Kuramitsu
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Graduate School of Medicine,, Kobe University, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
| | - Masahiro Kido
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Graduate School of Medicine,, Kobe University, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
| | - Hisoka Kinoshita
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Graduate School of Medicine,, Kobe University, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
| | - Taku Matsumoto
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Graduate School of Medicine,, Kobe University, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
| | - Hirochika Toyama
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Graduate School of Medicine,, Kobe University, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
| | - Sadaki Asari
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Graduate School of Medicine,, Kobe University, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
| | - Tadahiro Goto
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Graduate School of Medicine,, Kobe University, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
| | - Tetsuo Ajiki
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Graduate School of Medicine,, Kobe University, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
| | - Yonson Ku
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Graduate School of Medicine,, Kobe University, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
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18
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Wei XB, Xu J, Li N, Yu Y, Shi J, Guo WX, Cheng HY, Wu MC, Lau WY, Cheng SQ. The role of three-dimensional imaging in optimizing diagnosis, classification and surgical treatment of hepatocellular carcinoma with portal vein tumor thrombus. HPB (Oxford) 2016; 18:287-95. [PMID: 27017169 PMCID: PMC4814596 DOI: 10.1016/j.hpb.2015.10.007] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2015] [Accepted: 10/12/2015] [Indexed: 12/12/2022]
Abstract
BACKGROUND Accurate assessment of characteristics of tumor and portal vein tumor thrombus is crucial in the management of hepatocellular carcinoma. AIMS Comparison of the three-dimensional imaging with multiple-slice computed tomography in the diagnosis and treatment of hepatocellular carcinoma with portal vein tumor thrombus. METHOD Patients eligible for surgical resection were divided into the three-dimensional imaging group or the multiple-slice computed tomography group according to the type of preoperative assessment. The clinical data were collected and compared. RESULTS 74 patients were enrolled into this study. The weighted κ values for comparison between the thrombus type based on preoperative evaluation and intraoperative findings were 0.87 for the three-dimensional reconstruction group (n = 31) and 0.78 for the control group (n = 43). Three-dimensional reconstruction was significantly associated with a higher rate of en-bloc resection of tumor and thrombus (P = 0.025). Using three-dimensional reconstruction, significant correlation existed between the predicted and actual volumes of the resected specimens (r = 0.82, P < 0.01), as well as the predicted and actual resection margins (r = 0.97, P < 0.01). Preoperative three-dimensional reconstruction significantly decreased tumor recurrence and tumor-related death, with hazard ratios of 0.49 (95% confidential interval, 0.27-0.90) and 0.41 (95% confidential interval, 0.21-0.78), respectively. CONCLUSION For hepatocellular carcinoma with portal vein tumor thrombus, three-dimensional imaging was efficient in facilitating surgical treatment and benefiting postoperative survivals.
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Affiliation(s)
- Xu-Biao Wei
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Jie Xu
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Nan Li
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Ying Yu
- Department of Radiology, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Jie Shi
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Wei-Xing Guo
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Hong-Yan Cheng
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Meng-Chao Wu
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Wan-Yee Lau
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China,Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China
| | - Shu-Qun Cheng
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China,Correspondence Shu Qun Cheng, Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 168 Changhai Road, Yangpu District, Shanghai, 200433, China. Tel: +86 2113901746139. Fax: +86 2181875251.
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Ye LY, Chen W, Bai XL, Xu XY, Zhang Q, Xia XF, Sun X, Li GG, Hu QD, Fu QH, Liang TB. Hypoxia-Induced Epithelial-to-Mesenchymal Transition in Hepatocellular Carcinoma Induces an Immunosuppressive Tumor Microenvironment to Promote Metastasis. Cancer Res 2016; 76:818-30. [PMID: 26837767 DOI: 10.1158/0008-5472.can-15-0977] [Citation(s) in RCA: 215] [Impact Index Per Article: 23.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2015] [Accepted: 10/20/2015] [Indexed: 12/31/2022]
Abstract
Portal vein tumor thrombosis (PVTT) is a significant risk factor for metastasis in hepatocellular carcinoma (HCC) patients and is therefore associated with poor prognosis. The presence of PVTT frequently accompanies substantial hypoxia within the tumor microenvironment, which is suggested to accelerate tumor metastasis, but it is unclear how this occurs. Recent evidence has shown that the hypoxia-inducible factor HIF-1α induces epithelial-to-mesenchymal transition (EMT) in tumor cells to facilitate metastasis. In this study, we investigated whether hypoxia-induced EMT in cancer cells also affects immune cells in the tumor microenvironment to promote immunosuppression. We found that hypoxia-induced EMT increased the expression of the CCL20 cytokine in hepatoma cells. Furthermore, coculture of monocyte-derived macrophages with hypoxic hepatoma cells revealed that the expression of indoleamine 2, 3-dioxygenase (IDO) was induced in monocyte-derived macrophages in a CCL20-dependent manner. In turn, these IDO-expressing monocyte-derived macrophages suppressed T-cell proliferation and promoted the expansion of immunosuppressive regulatory T cells. Moreover, high CCL20 expression in HCC specimens was associated with PVTT and poor patient survival. Collectively, our findings suggest that the HIF-1α/CCL20/IDO axis in hepatocellular carcinoma is important for accelerating tumor metastasis through both the induction of EMT and the establishment of an immunosuppressive tumor microenvironment, warranting further investigation into the therapeutic effects of blocking specific nodes of this signaling network.
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Affiliation(s)
- Long-Yun Ye
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, P.R. China. Key Laboratory of Cancer Prevention and Intervention, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, P.R. China
| | - Wei Chen
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, P.R. China
| | - Xue-Li Bai
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, P.R. China. Key Laboratory of Cancer Prevention and Intervention, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, P.R. China
| | - Xing-Yuan Xu
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, P.R. China. Key Laboratory of Cancer Prevention and Intervention, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, P.R. China
| | - Qi Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, P.R. China. Key Laboratory of Cancer Prevention and Intervention, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, P.R. China
| | - Xue-Feng Xia
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, P.R. China
| | - Xu Sun
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, P.R. China
| | - Guo-Gang Li
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, P.R. China
| | - Qi-Da Hu
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, P.R. China
| | - Qi-Han Fu
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, P.R. China
| | - Ting-Bo Liang
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, P.R. China. Key Laboratory of Cancer Prevention and Intervention, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, P.R. China Collaborative Innovation Center for Cancer Medicine, Zhejiang University, Hangzhou, P.R. China.
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Shaohua L, Qiaoxuan W, Peng S, Qing L, Zhongyuan Y, Ming S, Wei W, Rongping G. Surgical Strategy for Hepatocellular Carcinoma Patients with Portal/Hepatic Vein Tumor Thrombosis. PLoS One 2015; 10:e0130021. [PMID: 26076461 PMCID: PMC4468137 DOI: 10.1371/journal.pone.0130021] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2014] [Accepted: 05/16/2015] [Indexed: 02/06/2023] Open
Abstract
Background Portal/hepatic vein tumor thrombosis (PVTT/HVTT) in hepatocellular carcinoma (HCC) is a sign of advanced stage disease and is associated with poor prognosis. This study investigated the surgical outcomes of patients with HCC and PVTT/HVTT to determine the most appropriate surgical treatment strategy for these patients. Materials and Methods The study population included 77 HCC patients from January 2004 to June 2009 who underwent hepatectomy in our department and were diagnosed with PVTT/HVTT based on pathological examination. The patients were divided into two groups: in group 1, PVTT/HVTT was located in the hepatic resection area and removed with the tumor en bloc (38 cases); in group 2, PVTT/HVTT was beyond the resection line and removed by suction or thrombectomy (39 cases). Concerning the factor of surgical margins, the patients were further divided into four subgroups: group 1A: patients in group 1 with surgical margins ≤1 cm (28 cases); group 1B: patients in group 1 with surgical margins >1 cm (9 cases); group 2A: patients in group 2 with surgical margins ≤1 cm (28 cases); and group 2B: patients in group 2 with surgical margins >1 cm (9 cases). Results Most of the characteristics of groups 1 and 2 were similar. Patients in group 2 had significantly higher median blood loss (p=0.002) and higher blood transfusion rate (p=0.002) during the operation, which were not considered prognostic factors (p=0.323 and 0.571, respectively). The median overall survival (OS) duration in group 1 was significantly longer than that in group 2 (14.3 vs. 10.4 months, p=0.047). The median OS durations in groups 1A, 1B, 2A, and 2B were 14.3, 42.7, 7.5, and 18.0 months, respectively, which were significantly different(p=0.018). Conclusions When PVTT/HVTT is located in the hepatic resection area and removed with the tumor en bloc, the median OS duration is longer. Based on this finding, widening the surgical margins when technically possible may increase OS.
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Affiliation(s)
- Li Shaohua
- Department of Hepatobiliary Surgery, Cancer Center of Sun Yat-Sen University, Guangzhou, China
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center of Sun Yat-Sen University, Guangzhou, China
| | - Wang Qiaoxuan
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center of Sun Yat-Sen University, Guangzhou, China
- Department of Radiation Oncology, Cancer Center of Sun Yat-Sen University, Guangzhou, China
| | - Sun Peng
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center of Sun Yat-Sen University, Guangzhou, China
- Department of Anesthesia, Cancer Center of Sun Yat-Sen University, Guangzhou, China
| | - Li Qing
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center of Sun Yat-Sen University, Guangzhou, China
- Department of Ultrasound, Cancer Center of Sun Yat-Sen University, Guangzhou, China
| | - Yang Zhongyuan
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center of Sun Yat-Sen University, Guangzhou, China
- Department of Head and Neck Surgery, Cancer Center of Sun Yat-Sen University, Guangzhou, China
| | - Shi Ming
- Department of Hepatobiliary Surgery, Cancer Center of Sun Yat-Sen University, Guangzhou, China
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center of Sun Yat-Sen University, Guangzhou, China
| | - Wei Wei
- Department of Hepatobiliary Surgery, Cancer Center of Sun Yat-Sen University, Guangzhou, China
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center of Sun Yat-Sen University, Guangzhou, China
- * E-mail: (WW); (GR)
| | - Guo Rongping
- Department of Hepatobiliary Surgery, Cancer Center of Sun Yat-Sen University, Guangzhou, China
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center of Sun Yat-Sen University, Guangzhou, China
- * E-mail: (WW); (GR)
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21
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Pesi B, Ferrero A, Grazi GL, Cescon M, Russolillo N, Leo F, Boni L, Pinna AD, Capussotti L, Batignani G. Liver resection with thrombectomy as a treatment of hepatocellular carcinoma with major vascular invasion: results from a retrospective multicentric study. Am J Surg 2015; 210:35-44. [PMID: 25935229 DOI: 10.1016/j.amjsurg.2014.09.041] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2014] [Revised: 09/09/2014] [Accepted: 09/15/2014] [Indexed: 12/13/2022]
Abstract
BACKGROUND The role of liver resection (LR) of hepatocellular carcinoma with macroscopic vascular thrombosis (MVT) remains controversial. The aim of this study is to evaluate whether the presence of MVT should still be considered a contraindication for LR. METHODS Retrospective study was carried out on 62 patients who underwent LR and thrombectomy for hepatocellular carcinoma complicated by MVT. Of the 62 patients, 15 (36.5%) had tumor thrombus (TT) in the peripheral portal vein (Vp1), 5 (12.2%) in second branch (Vp2), and 21 (51.3%) in the first branch/portal vein trunk (Vp3), while on the hepatic/cava vein side, 8 (12.9%) had TT in the main trunk of the hepatic veins (Vv2) and 3 (4.8%) had TT reaching the vena cava/right atrium (Vv3). RESULTS Perioperative major morbidity was 14.5%, while in-hospital mortality was 4.8%. Overall, 1, 3, and 5-year survival rates were 53.3%, 30.1%, and 20%, and disease-free survival rates were 31.7%, 20.8%, and 15.6%, respectively. There were no differences in survival about the MVT localized in Vp1, Vp2, or Vp3 (P = .77), while we found a statistical trend between patients with Vv2 and Vv3 (P = .06). CONCLUSION Surgical resection seems to be justified in these patients, and the presence of MVT should no longer be considered an absolute contraindication for LR.
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Affiliation(s)
- Benedetta Pesi
- Gastrointestinal Surgery Unit, Department of Surgery and Translational Medicine, Careggi University Hospital, Largo Brambilla 3, Florence 50134, Italy
| | - Alessandro Ferrero
- Department of HPB and Digestive Surgery, Mauriziano Umberto I Hospital, Turin, Italy
| | - Gianluca L Grazi
- Liver Surgery and Transplantation Unit, Department of Emergency, Surgery and Transplants, S. Orsola-Malpighi University Hospital, Bologna, Italy
| | - Matteo Cescon
- Liver Surgery and Transplantation Unit, Department of Emergency, Surgery and Transplants, S. Orsola-Malpighi University Hospital, Bologna, Italy
| | - Nadia Russolillo
- Department of HPB and Digestive Surgery, Mauriziano Umberto I Hospital, Turin, Italy
| | - Francesca Leo
- Gastrointestinal Surgery Unit, Department of Surgery and Translational Medicine, Careggi University Hospital, Largo Brambilla 3, Florence 50134, Italy
| | - Luca Boni
- Department of Oncology/Core Research Laboratory, Careggi University Hospital, Florence, Italy
| | - Antonio D Pinna
- Liver Surgery and Transplantation Unit, Department of Emergency, Surgery and Transplants, S. Orsola-Malpighi University Hospital, Bologna, Italy
| | - Lorenzo Capussotti
- Department of HPB and Digestive Surgery, Mauriziano Umberto I Hospital, Turin, Italy
| | - Giacomo Batignani
- Gastrointestinal Surgery Unit, Department of Surgery and Translational Medicine, Careggi University Hospital, Largo Brambilla 3, Florence 50134, Italy.
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Yamamoto Y, Ikoma H, Morimura R, Shoda K, Konishi H, Murayama Y, Komatsu S, Shiozaki A, Kuriu Y, Kubota T, Nakanishi M, Ichikawa D, Fujiwara H, Okamoto K, Sakakura C, Ochiai T, Otsuji E. Post-hepatectomy survival in advanced hepatocellular carcinoma with portal vein tumor thrombosis. World J Gastroenterol 2015; 21:246-253. [PMID: 25574098 PMCID: PMC4284342 DOI: 10.3748/wjg.v21.i1.246] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2014] [Revised: 06/07/2014] [Accepted: 07/11/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To analyze hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) using the tumor-node-metastasis (TNM) staging system.
METHODS: We retrospectively analyzed 372 patients with HCC who underwent hepatectomy between 1980 and 2009. We studied the outcomes of HCC patients with PVTT to evaluate the American Joint Committee on Cancer TNM staging system (7th edition) for stratifying and predicting the prognosis of a large cohort of HCC patients after hepatectomy in a single-center. Portal vein invasion (vp) 1 was defined as an invasion or tumor thrombus distal to the second branch of the portal vein, vp2 as an invasion or tumor thrombus in the second branch of the portal vein, vp3 as an invasion or tumor thrombus in the first branch of the portal vein, and vp4 as an invasion or tumor thrombus in the portal trunk or extending to a branch on the contralateral side.
RESULTS: The cumulative 5-year overall survival (5yrOS) and 5-year disease-free survival (5yrDFS) rates of the 372 patients were 58.3% and 31.3%, respectively. The 5yrDFS and 5yrOS of vp3-4 patients (n = 10) were 20.0%, and 30.0%, respectively, which was comparable with the corresponding survival rates of vp1-2 patients (P = 0.466 and 0.586, respectively). In the subgroup analysis of patients with macroscopic PVTT (vp2-4), the OS of the patients who underwent preoperative transarterial chemoembolization was comparable to that of patients who did not (P = 0.747). There was a significant difference in the DFS between patients with stage I HCC and those with stage II HCC (5yrDFS 39.2% vs 23.1%, P < 0.001); however, the DFS for stage II was similar to that for stage III (5yrDFS 23.1% vs 13.8%, P = 0.330). In the subgroup analysis of stage II-III HCC (n = 148), only alpha-fetoprotein (AFP) > 100 mg/dL was independently associated with DFS.
CONCLUSION: Hepatectomy for vp3-4 HCC results in a survival rate similar to hepatectomy for vp1-2. AFP stratified the stage II-III HCC patients according to prognosis.
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Zhong JH, Rodríguez AC, Ke Y, Wang YY, Wang L, Li LQ. Hepatic resection as a safe and effective treatment for hepatocellular carcinoma involving a single large tumor, multiple tumors, or macrovascular invasion. Medicine (Baltimore) 2015; 94:e396. [PMID: 25621684 PMCID: PMC4602643 DOI: 10.1097/md.0000000000000396] [Citation(s) in RCA: 102] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2014] [Revised: 11/25/2014] [Accepted: 11/26/2014] [Indexed: 01/27/2023] Open
Abstract
This systematic review examined whether the available evidence justifies using hepatic resection (HR) during later stages of hepatocellular carcinoma (HCC), which contravenes treatment guidelines but is current practice at many medical centers.Official guidelines and retrospective studies recommend different roles for HR for patients with large/multinodular HCC or with HCC involving macrovascular invasion (MVI).Several databases were systematically searched for studies examining the safety and efficacy of HR for treating HCC involving a single large tumor (>5 cm) or multiple tumors, or for treating HCC involving MVI.We identified 50 studies involving 14, 808 patients that investigated the use of HR to treat large/multinodular HCC, and 24 studies with 4389 patients that investigated HR to treat HCC with MVI. Median in-hospital mortality for patients with either type of HCC was significantly lower in Asian studies (2.7%) than in non-Asian studies (7.3%, P < 0.001). Median overall survival (OS) was significantly higher for all Asian patients with large/multinodular HCC than for all non-Asian patients at both 1 year (81% vs 65%, P < 0.001) and 5 years (42% vs 32%, P < 0.001). Similar results were obtained for median disease-free survival at 1 year (61% vs 50%, P < 0.001) and 5 years (26% vs 24%, P < 0.001). However, median OS was similar for Asian and non-Asian patients with HCC involving MVI at 1 year (50% vs 52%, P = 0.45) and 5 years (18% vs 14%, P = 0.94). There was an upward trend in 5-year OS in patients with either type of HCC.HR is reasonably safe and effective at treating large/multinodular HCC and HCC with MVI. The available evidence argues for expanding the indications for HR in official treatment guidelines.
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Affiliation(s)
- Jian-Hong Zhong
- From the Department of Hepatobiliary Surgery (J-HZ, ACR, Y-YW, L-QL), Affiliated Tumor Hospital of Guangxi Medical University, Nanning; Department of Research (ACR), Creaducate Enterprises Ltd, Kowloon, Hong Kong; and Department of Hepatobiliary Surgery (YK, LW), The Second Affiliated Hospital of Kunming Medical University, Kunming, PR China
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Morise Z, Kawabe N, Tomishige H, Nagata H, Kawase J, Arakawa S, Yoshida R, Isetani M. Recent advances in the surgical treatment of hepatocellular carcinoma. World J Gastroenterol 2014; 20:14381-14392. [PMID: 25339825 PMCID: PMC4202367 DOI: 10.3748/wjg.v20.i39.14381] [Citation(s) in RCA: 71] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2014] [Revised: 05/25/2014] [Accepted: 07/16/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. The treatment of HCC is complex and complicated by the severity of associated chronic liver disease, the stage of HCC, and the clinical condition of the patient. Liver resection (LR) is one of the most efficient treatments for patients with HCC, with an expected 5-year survival of 38%-61% depending on the stage of the disease. Improved liver function assessment, increased understanding of segmental liver anatomy from advanced imaging studies, and surgical technical progress are important factors that have led to reduced mortality in patients with HCC. The indication for LR may be expanded due to emerging evidences from laparoscopic hepatectomies and combined treatments with newly developed chemotherapies. Liver transplantation (LT) is considered as an ideal treatment for removal of existing tumors and the injured/preneoplastic underlying liver tissue with impaired liver function and the risk of multicentric carcinogenesis that results from chronically injured liver. However, LT is restricted to patients with minimal risk of tumor recurrence under immunosuppression. The expansion of criteria for LT in HCC patients is still under trial and discussion. Limited availability of grafts, as well as the risk and the cost of transplantation have led to considerable interest in expansion of the donor pool, living donor-related transplantation, and combined treatment involving LR and LT. This highlight presents evidence concerning recent studies evaluating LR and LT in HCC patients. In addition, alternative therapies for the treatment of early stage tumors and the management of patients on transplant waiting lists are discussed.
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Chok KSH, Cheung TT, Chan SC, Poon RTP, Fan ST, Lo CM. Surgical outcomes in hepatocellular carcinoma patients with portal vein tumor thrombosis. World J Surg 2014; 38:490-6. [PMID: 24132826 DOI: 10.1007/s00268-013-2290-4] [Citation(s) in RCA: 76] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Different approaches to surgical treatment of portal vein tumor thrombosis (PVTT) have been advocated. This study investigated the outcomes of different surgical approaches in hepatocellular carcinoma (HCC) patients with PVTT. METHODS We reviewed prospectively collected data for all patients who underwent hepatectomy for HCC at our hospital between December 1989 and December 2010. Patients were excluded from analysis if they had extrahepatic disease, PVTT reaching the level of the superior mesenteric vein, or hepatectomy with a positive resection margin. The remaining patients were divided into three groups for comparison: group 1, with ipsilateral PVTT resected in a hepatectomy; group 2, with PVTT extending to or beyond the portal vein bifurcation, treated by en bloc resection followed by portal vein reconstruction; group 3, with PVTT extending to or beyond the portal vein bifurcation, treated by thrombectomy. RESULTS A total of 88 patients, with a median age of 54 years, were included in the analysis. Group 2 patients were younger, with a median age of 43.5 years versus 57 in group 1 and 49 in group 3 (p = 0.017). Group 1 patients had higher preoperative serum alpha-fetoprotein levels, with a median of 8,493 ng/mL versus 63.25 in group 2 and 355 in group 3 (p = 0.004), and shorter operation time, with a median of 467.5 min versus 663.5 in group 2 and 753 in group 3 (p = 0.018). No patient had thrombus in the main portal vein. Two (2.8 %) hospital deaths occurred in group 1 and one (10 %) in group 2, but none in group 3 (p = 0.440). The rates of complication in groups 1, 2, and 3 were 31.9, 50.0, and 71.4 %, respectively (p = 0.079). The median overall survival durations were 10.91, 9.4, and 8.58 months, respectively (p = 0.962), and the median disease-free survival durations were 4.21, 3.78, and 1.51 months, respectively (p = 0.363). The groups also had similar patterns of disease recurrence (intrahepatic: 33.8 vs. 28.6 vs. 40.0 %; extrahepatic: 16.9 vs. 14.3 vs. 0 %; both: 28.2 vs. 42.9 vs. 40.0 %; no recurrence: 21.1 vs. 14.3 vs. 20.0 %; p = 0.836). CONCLUSIONS The three approaches have similar outcomes in terms of survival, complication, and recurrence. Effective adjuvant treatments need to be developed to counteract the high incidence of recurrence.
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Affiliation(s)
- Kenneth S H Chok
- Department of Surgery, The University of Hong Kong, 102 Pok Fu Lam Road, Hong Kong, China,
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Xu B, Cai Z, Zeng Y, Chen L, Du X, Huang A, Liu X, Liu J. α-Methylacyl-CoA racemase (AMACR) serves as a prognostic biomarker for the early recurrence/metastasis of HCC. J Clin Pathol 2014; 67:974-9. [PMID: 25092674 PMCID: PMC4215266 DOI: 10.1136/jclinpath-2014-202378] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
AIMS Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, and it is still lacking effective prognostic biomarkers so far. Previous results of the iTRAQ-based quantitative proteomics study (iTRAQ-2DLC-MS/MS) have shown that α-methylacyl-CoA racemase (AMACR) might be a promising prognostic biomarker for the early recurrence/metastasis of hepatocellular carcinoma (HCC). Here a large-scale cohort clinical study was performed to evaluate its prognostic potential. METHODS HCC samples from patients (n=158) were used for the construction of tissue microarray. The expression level of AMACR was determined by immunohistochemical staining. A large-scale cohort clinical study between the expression of AMACR and some major clinical parameter has been performed to assess the prognostic potential of AMACR for the early recurrence/metastasis of HCC. RESULTS Some important clinical parameters such as α-fetoprotein, tumour numbers, dissemination to regional lymph nodes, tumour capsule and portal vein tumour thrombosis are significantly associated with the low expression of AMACR. The expression of AMACR was an independent factor for the survival of patients with HCC. The median survival time was 17 months in the low-expression group compared with 45 months in the high-expression group. CONCLUSIONS This study reveals that the AMACR might be a potential prognostic marker for predicting early recurrence/metastasis of HCC after hepatectomy.
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Affiliation(s)
- Bo Xu
- Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People's Republic of China The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, People's Republic of China The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, People's Republic of China
| | - Zhixiong Cai
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, People's Republic of China The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, People's Republic of China
| | - Yongyi Zeng
- Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People's Republic of China The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, People's Republic of China The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, People's Republic of China
| | - Lihong Chen
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, People's Republic of China The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, People's Republic of China Department of Pathology, School of Basic Medical Science, Fujian Medical University, Fuzhou, People's Republic of China
| | - Xiaobo Du
- Department of Urology, The First People's Hospital of Yueyang, Yueyang, People's Republic of China
| | - Aimin Huang
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, People's Republic of China The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, People's Republic of China Department of Pathology, School of Basic Medical Science, Fujian Medical University, Fuzhou, People's Republic of China
| | - Xiaolong Liu
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, People's Republic of China The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, People's Republic of China
| | - Jingfeng Liu
- Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People's Republic of China The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, People's Republic of China The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, People's Republic of China
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Qu LS, Liu JX, Kuai XL, Xu ZF, Jin F, Zhou GX. Significance of viral status on recurrence of hepatitis B-related hepatocellular carcinoma after curative therapy: A meta-analysis. Hepatol Res 2014; 44:750-60. [PMID: 23710537 DOI: 10.1111/hepr.12172] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2013] [Revised: 05/05/2013] [Accepted: 05/21/2013] [Indexed: 12/14/2022]
Abstract
AIM The impact of viral status on recurrence of hepatitis B-related hepatocellular carcinoma (HCC) after curative therapy remains controversial. This meta-analysis aimed to determine whether the presence of viral load, genotype, specific mutation and antiviral therapy influenced HCC recurrence after curative therapy. METHODS We performed a meta-analysis including 20 studies to assess the effect of viral status and antiviral therapy with nucleoside analog on recurrence of HCC after curative therapy. The pooled odds ratios (OR) were calculated using a random or fixed effects model. PUBMED, MEDLINE, EMBASE and the Cochrane Database were searched for articles published from 1990 to December 2012. RESULTS Our results showed that the presence of high viral load significantly increased overall HCC recurrence risk after curative therapy. Pooled data from four studies on the recurrence rate among patients with genotype C infection compared with genotype B showed an increased risk of recurrence. Basal core promoter (BCP) mutation was associated with a significant risk in the recurrence of HCC. The pooled estimate of treatment effect was significantly in favor of a preventive effectiveness of antiviral therapy. CONCLUSION The present study suggested that HCC patients with high viral load, genotype C and BCP mutation had a significantly higher risk of recurrence. Antiviral therapy has potential beneficial effects after the curative treatment of HCC in terms of tumor recurrence.
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Affiliation(s)
- Li-Shuai Qu
- Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong
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Morise Z, Kawabe N, Tomishige H, Nagata H, Kawase J, Arakawa S, Yoshida R, Isetani M. Recent advances in liver resection for hepatocellular carcinoma. Front Surg 2014; 1:21. [PMID: 25593945 PMCID: PMC4286985 DOI: 10.3389/fsurg.2014.00021] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2014] [Accepted: 06/03/2014] [Indexed: 12/11/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. The association of HCC with chronic liver disease (CLD) is well known and making treatment complex and challenging. The treatment of HCC must take into consideration, the severity of CLD, the stage of HCC, and the clinical condition of the patient. Liver resection (LR) is one of the most efficient treatments for patients with HCC. Better liver function assessment, increased understanding of segmental liver anatomy using more accurate imaging studies, and surgical technical progress are the important factors that have led to reduced mortality, with an expected 5 year survival of 38–61% depending on the stage of the disease. However, the procedure is applicable to <30% of all HCC patients, and 80% of the patients after LR recurred within 5 years. There are recent advances and prospects in LR for HCC in several aspects. Three-dimensional computed tomography imaging assisted preoperative surgical planning facilitates unconventional types of LR. Emerging evidences of laparoscopic hepatectomy and prospects for the use of newly developing chemotherapies as a combined therapy may lead to expanding indication of LR. LR and liver transplantation could be associated rather than considered separately with the current concepts of “bridging LR” and “salvage transplantation.”
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Affiliation(s)
- Zenichi Morise
- Department of Surgery, Banbuntane Houtokukai Hospital, Fujita Health University School of Medicine , Nagoya , Japan
| | - Norihiko Kawabe
- Department of Surgery, Banbuntane Houtokukai Hospital, Fujita Health University School of Medicine , Nagoya , Japan
| | - Hirokazu Tomishige
- Department of Surgery, Banbuntane Houtokukai Hospital, Fujita Health University School of Medicine , Nagoya , Japan
| | - Hidetoshi Nagata
- Department of Surgery, Banbuntane Houtokukai Hospital, Fujita Health University School of Medicine , Nagoya , Japan
| | - Jin Kawase
- Department of Surgery, Banbuntane Houtokukai Hospital, Fujita Health University School of Medicine , Nagoya , Japan
| | - Satoshi Arakawa
- Department of Surgery, Banbuntane Houtokukai Hospital, Fujita Health University School of Medicine , Nagoya , Japan
| | - Rie Yoshida
- Department of Surgery, Banbuntane Houtokukai Hospital, Fujita Health University School of Medicine , Nagoya , Japan
| | - Masashi Isetani
- Department of Surgery, Banbuntane Houtokukai Hospital, Fujita Health University School of Medicine , Nagoya , Japan
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Pesi B, Moraldi L, Zambonin D, Giudici F, Cavalli T, Addasi R, Leo F, Scaringi S, Batignani G. Vascular Invasion, Satellite Nodules and Absence of Tumor Capsule Strongly Correlate with Disease-Free Survival and Long-Term Outcome in Patients Resected for Hepatocellular Carcinoma. ACTA ACUST UNITED AC 2014. [DOI: 10.4236/jct.2014.514134] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Peng B, Guo C, Guan H, Liu S, Sun MZ. Annexin A5 as a potential marker in tumors. Clin Chim Acta 2013; 427:42-8. [PMID: 24121031 DOI: 10.1016/j.cca.2013.09.048] [Citation(s) in RCA: 74] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2013] [Revised: 09/20/2013] [Accepted: 09/28/2013] [Indexed: 10/26/2022]
Abstract
Annexin A5 (Anxa5) promotes pancreatic adenocarcinoma, sarcoma, tumorigenesis and progression of breast cancer and prostate cancer stem cells. It is involved with metastasis, invasion and development of squamous cell carcinoma, and facilitates nodal progression of bladder cancer and angiogenesis and progression of glioma. Anxa5 de-regulation is associated with drug resistance in nasopharyngeal carcinoma and gastric cancer. Although Anxa5 protein up-regulation promotes cervical cancer progression, it is markedly suppressed in cervical carcinoma cells. Anxa5 is negatively correlated with thyroid cancer malignancy. In this review, we explore the mechanisms of Anxa5 action in tumors. Anxa5 could be a predictive biomarker for tumor development, metastasis and invasion, and be of diagnostic, prognostic and therapeutic significance in cancer.
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Affiliation(s)
- Boya Peng
- Department of Biotechnology, Dalian Medical University, Dalian 116044, China
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Roayaie S, Jibara G, Taouli B, Schwartz M. Resection of hepatocellular carcinoma with macroscopic vascular invasion. Ann Surg Oncol 2013; 20:3754-60. [PMID: 23884750 DOI: 10.1245/s10434-013-3074-7] [Citation(s) in RCA: 69] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2013] [Indexed: 12/13/2022]
Abstract
BACKGROUND Survival for Child's A patients with hepatocellular cancer (HCC) and macroscopic vascular invasion (MVI) has been reported as approximately 8.1 months with sorafenib. The role of surgery for these patients remains controversial. METHODS The records of all patients undergoing resection of HCC at a single center were reviewed. Only patients with pathologically proven MVI were included. Inclusion criteria for resection required Child's A liver disease, no clinical portal hypertension (after 2002), and no extrahepatic disease. The superior mesenteric vein and portal vein branch to the remaining lobe had to be patent. RESULTS We identified 165 patients with MVI treated with hepatic resection between June 1992 and March 2010. Median follow-up was 11.9 months with 127 deaths, including 12 (7.3%) perioperative mortalities. Median and 5-year survivals were 13.1 months and 14%. Multivariate analysis found α-fetoprotein (AFP) >30 ng/ml (hazard ratio 2.07), tumor size >7 cm (hazard ratio 1.59), and extent of vascular invasion (hazard ratio 1.74) to be independently associated with survival. Those with invasion of hepatic veins or vena cava had a median survival of only 4.7 months. CONCLUSIONS The results for resection of HCC with MVI remain somewhat disappointing but are better than what is reported with medical therapy in similar patients. Tumor size, AFP, and extent of vascular invasion can help select those that will benefit most from hepatic resection. Resection of patients with hepatic vein or vena cava involvement may not be justified, given such poor results.
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Affiliation(s)
- Sasan Roayaie
- Mount Sinai Liver Cancer Program, Mount Sinai Medical Center, New York, NY, USA,
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Qu LS, Zhu J, Chen H, Jin F, Ni RZ, Lu CH. Effects of hepatitis B e-antigen on recurrence of hepatitis B-related hepatocellular carcinoma after curative resection: A meta-analysis. Hepatol Res 2013; 43:347-54. [PMID: 22900967 DOI: 10.1111/j.1872-034x.2012.01079.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
AIM The impact of hepatitis B e-antigen (HBeAg) on recurrence of hepatocellular carcinoma (HCC) after curative resection remains controversial. This meta-analysis aimed to determine whether the presence of HBeAg influenced the recurrence of HCC after curative resection. METHODS We performed a meta-analysis including six studies (a total of 865 patients) to assess the effect of HBeAg on recurrence of HCC after curative resection. The pooled odds ratios (OR) were calculated using a random or fixed effects model. PUBMED, MEDLINE, EMBASE and the Cochrane Database were searched for articles published from 1990 to March 2012. Sensitivity analysis and publication bias estimate were also performed to evaluate the potential risk bias in the overall results of pooled analysis. RESULTS Our results showed that the presence of HBeAg significantly increased the overall HCC recurrence risk after curative resection (OR = 1.63, 95% confidence interval (CI) = 1.11-2.40; P = 0.01). Pooled data from three studies on the risk of early recurrence among HBeAg positive patients compared with HBeAg negative patients showed an increased risk of early recurrence (OR = 1.50, 95% CI = 1.02-2.19; P = 0.04). However, there was no significant difference in late HCC recurrence between HBeAg positive and negative patients (OR = 1.17, 95% CI = 0.62-2.19; P = 0.62). CONCLUSION The present study suggested that HBeAg positive patients had a significantly higher risk of early recurrence after curative resection of HCC.
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Affiliation(s)
- Li-Shuai Qu
- Department of Gastroenterology, Affiliated Hospital of Nantong University, Jiangsu Department of Gastroenterology, Shanghai Xuhui Central Hospital, Shanghai, China
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NAGANO HIROAKI, KOBAYASHI SHOGO, MARUBASHI SHIGERU, WADA HIROSHI, EGUCHI HIDETOSHI, TANEMURA MASAHIRO, TOMIMARU YOSHITO, UMESHITA KOJI, DOKI YUICHIRO, MORI MASAKI. Combined IFN-α and 5-FU treatment as a postoperative adjuvant following surgery for hepatocellular carcinoma with portal venous tumor thrombus. Exp Ther Med 2013; 5:3-10. [PMID: 23251233 PMCID: PMC3524132 DOI: 10.3892/etm.2012.736] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2011] [Accepted: 11/30/2011] [Indexed: 12/13/2022] Open
Abstract
The efficacy of combination therapy with subcutaneous interferon (IFN)-α and intra-arterial 5-fluorouracil (5-FU) as a postoperative adjuvant for resectable advanced hepatocellular carcinoma (HCC) invading the major branches of the portal vein (PVTT) was examined. The prognosis of HCC with PVTT (Vp3 or 4) is extremely poor. Recently, we reported the possibility of combination therapy with IFN-α and intra-arterial 5-FU for intractable HCC with PVTT as a postoperative adjuvant and this is the second report. Patients with HCC with PVTT were included (n=50). Thirty consecutive patients with HCC and PVTT were treated with 3 cycles of a combination therapy consisting of arterial 5-FU infusion (300 mg/mm(3)/day, 5 days/week, for the initial 2 weeks) and IFN subcutaneous injection (5 MIU, 3 times/week, 4 weeks) as a postoperative adjuvant following hepatic resection; another 20 patients receiving no IFN/5-FU chemotherapy acted as controls. Results for the IFN/5-FU adjuvant treatment group were as follows: disease-free survival (n=9, 15-109 months), survival with recurrence (n=6, 30-92 months), cancer death (n=9, 14-60 months), death from other causes but no recurrence (n=5, 13-87 months) and death from other causes with recurrence (n=1, 22 months). The 1-year survival rate was 100% in patients treated with IFN/5-FU, and 30% in those without IFN/5-FU as historical controls (n=20). There was a significant difference in disease-free and overall survival rates between the two groups (P<0.0001). In conclusion, IFN/5-FU combination therapy may be a very promising postoperative adjuvant treatment for HCC with PVTT.
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Affiliation(s)
| | | | | | | | | | | | | | - KOJI UMESHITA
- Health Science, Graduate School of Medicine, Osaka University, Osaka,
Japan
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Hepatic resection can provide long-term survival of patients with non-early-stage hepatocellular carcinoma: extending the indication for resection? Surgery 2012; 152:809-20. [PMID: 22766361 DOI: 10.1016/j.surg.2012.03.024] [Citation(s) in RCA: 84] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2011] [Accepted: 03/22/2012] [Indexed: 02/06/2023]
Abstract
BACKGROUND Indications for resection of non-early-stage hepatocellular carcinoma (HCC) remain controversial. This study aimed to identify factors that affect outcome of patients with Barcelona Clinical Liver Cancer Classification (BCLC) stage B or stage C HCC after hepatic resection. METHODS From 1991 to 2006, 478 patients with HCC (BCLC stage B, n = 318 and BCLC stage C, n = 160) who underwent resection were enrolled. Factors in terms of overall survival and recurrence were analyzed. RESULTS After a median follow-up of 29.5 months, 304 patients had died. The cumulative overall survival rate at 5 years was 46.5% in BCLC stage B patients and 29.1% in stage C patients (P < .001). Multivariate analysis disclosed that serum albumin levels ≤4 g/dL, indocyanine green retention rate at 15 minutes >10%, serum creatinine >1.2 mg/dL, multinodularity, Edmondson stage III or IV in tumor cell differentiation, and the presence of macroscopic vascular invasion were independent risk factors of poor overall survival. There were 331 patients with tumor recurrence after resection. Recurrence rate was less in BCLC stage B than that in BCLC stage C (P = .001). Multivariate analysis showed that serum albumin level ≤4 g/dL, multinodularity, cut margin ≤1 cm, and Edmondson stage III or IV were associated with the recurrence of HCC. CONCLUSION Hepatic resection can provide long-term survival benefit in selected BCLC stage B or C patients with compensated liver function, especially in those presenting with a single neoplasm without vascular invasion.
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Peng ZW, Guo RP, Zhang YJ, Lin XJ, Chen MS, Lau WY. Hepatic resection versus transcatheter arterial chemoembolization for the treatment of hepatocellular carcinoma with portal vein tumor thrombus. Cancer 2012; 118:4725-36. [PMID: 22359112 DOI: 10.1002/cncr.26561] [Citation(s) in RCA: 125] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2011] [Revised: 07/11/2011] [Accepted: 08/12/2011] [Indexed: 02/06/2023]
Abstract
BACKGROUND The long-term survival outcomes of hepatic resection (HR) compared with transcatheter arterial chemoembolization (TACE) for resectable hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) are unclear. MATERIALS AND METHODS Between December 2002 and December 2007, 201 consecutive patients diagnosed with resectable HCC with PVTT received HR as an initial treatment in our center. These patients were compared with 402 case-matched controls selected from a pool of 1798 patients (with a 1:2 ratio) who received TACE as an initial treatment during the study period. PVTT was classified to 4 types: PVTT involving the segmental branches of the portal vein or above (type I), PVTT extending to involve the right/left portal vein (type II), the main portal vein (type III), or the superior mesenteric vein (type IV). RESULTS The 1-, 3-, and 5-year overall survivals for the HR and TACE groups were 42.0%, 14.1%, and 11.1% and 37.8%, 7.3%, and 0.5%, respectively (P < .001). On subgroup analyses, the overall survivals for the HR group were better than the TACE group for type I PVTT, type II PVTT, single tumor, and tumor size >5 cm (P < .001, P = .002, P < .001, P < .001, respectively), but not for type III PVTT, type IV PVTT, multiple tumors, and tumor size <5 cm (P = .541, P = .371, P = .264, P = .338, P = .125, respectively). Multivariate analysis showed the type of PVTT and initial treatment allocation were significant prognostic factors for overall survival. CONCLUSIONS Compared with TACE, HR provided survival benefits for patients with resectable HCC with PVTT, especially for those with a type I PVTT or a type II PVTT.
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Affiliation(s)
- Zhen-Wei Peng
- Department of Hepatobiliary Surgery, Cancer Centre of Sun Yat-Sen University, Guangzhou, People's Republic of China
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Chen JS, Wang Q, Chen XL, Huang XH, Liang LJ, Lei J, Huang JQ, Li DM, Cheng ZX. Clinicopathologic characteristics and surgical outcomes of hepatocellular carcinoma with portal vein tumor thrombosis. J Surg Res 2011; 175:243-50. [PMID: 21601221 DOI: 10.1016/j.jss.2011.03.072] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2010] [Revised: 02/20/2011] [Accepted: 03/28/2011] [Indexed: 12/23/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) has a high predilection for portal vein invasion. Furthermore, the treatment of HCC with portal vein tumor thrombosis (PVTT) is controversial. The objective of this study was to investigate clinicopathologic characteristics and surgical outcomes of HCC patients with PVTT. METHODS The clinicopathologic data and surgical outcomes of 88 patients HCC with PVTT and 211 patients without PVTT who underwent surgery were retrospectively reviewed. The risk factors and the prognosis of HCC patients with PVTT were determined. RESULTS Cirrhosis, serum alkaline phosphatase (ALP) > 100 IU/L, tumor size > 8 cm, incomplete tumor capsule, and adjacent organ invasion were risk factors for PVTT in HCC on multivariate analysis. Furthermore, HCC patients with PVTT received more major hepatectomies, had more intraoperative blood loss and greater blood transfusion requirements, and higher incidence of postoperative mortality compared with HCC patients without PVTT. The median overall survival of HCC patients with PVTT after surgery was 9 mo, with the 1-, 2-, and 3-y overall survival rates of 31.1%, 18.3%, and 15.2 %, respectively. AFP level, adjacent organ invasion, and PVTT location predicted overall survival of HCC patients with PVTT. CONCLUSIONS High serum ALP level, cirrhosis, large tumor, incomplete tumor capsule and adjacent organ invasion are predictors of PVTT in HCC. Surgery is a valid therapy for selected HCC patients with PVTT.
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Affiliation(s)
- Jing-Song Chen
- Department of General Surgery, the First Affiliated Hospital of Guangzhou Medical College, Guangzhou, China
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Zhou YM, Li B, Xu DH, Yang JM. Safety and efficacy of partial hepatectomy for huge (≥10 cm) hepatocellular carcinoma: a systematic review. Med Sci Monit 2011; 17:RA76-83. [PMID: 21358616 PMCID: PMC3524737 DOI: 10.12659/msm.881443] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2010] [Accepted: 09/23/2010] [Indexed: 02/06/2023] Open
Abstract
Huge (≥10 cm) hepatocellular carcinoma (HCC) is not uncommon at clinical presentation, and the surgical outcomes of such tumors are poor. This systematic review aimed to assess the safety and efficacy of partial hepatectomy for huge HCC. We performed a search on Medline and PubMed databases for all relevant studies published prior to December 2009. After exclusions, 21 studies remained for appraisal and data extraction. All studies were classified as level-4 evidence. The median overall perioperative morbidity and mortality rates were 29.2% (range: 13.6-72%) and 3.5% (range: 0-18.2%), respectively. The overall median survival since the partial hepatectomy was 20.7 months (range: 10.1-32 months), with median 1-, 3- and 5-year survival of 60.7% (range: 41-72.2%), 34% (range: 0-60.3%) and 28.6% (range: 0-54%), respectively. The median disease-free survival since the partial hepatectomy was 11.3 months (range: 5.5-32 months), with median 1-, 3- and 5-year disease-free survival rates of 48.7% (range: 32-65.4%), 27.5% (range: 14.1-49%) and 20.7% (range: 9.5-43%), respectively. Partial hepatectomy can be performed safely and is associated with long-term survival in a subset of patients with huge HCC, but the evidence of benefit is currently weak.
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Affiliation(s)
- Yan-Ming Zhou
- Department of Hepato-Biliary-Pancreato-Vascular Surgery, 1 affiliated Hospital of Xiamen University, Xiamen, China
- Department of Special Treatment and Liver transplantation, Eastern Hepatobiliary Surgery Hospital, 2 Military Medical University, Shanghai, China
| | - Bin Li
- Department of Hepato-Biliary-Pancreato-Vascular Surgery, 1 affiliated Hospital of Xiamen University, Xiamen, China
| | - Dong-Hui Xu
- Department of Hepato-Biliary-Pancreato-Vascular Surgery, 1 affiliated Hospital of Xiamen University, Xiamen, China
| | - Jia-Mei Yang
- Department of Special Treatment and Liver transplantation, Eastern Hepatobiliary Surgery Hospital, 2 Military Medical University, Shanghai, China
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Qu LS, Jin F, Huang XW, Shen XZ. Interferon-α therapy after curative resection prevents early recurrence and improves survival in patients with hepatitis B virus-related hepatocellular carcinoma. J Surg Oncol 2010; 102:796-801. [PMID: 20886584 DOI: 10.1002/jso.21741] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Qu LS, Jin F, Huang XW, Shen XZ. High hepatitis B viral load predicts recurrence of small hepatocellular carcinoma after curative resection. J Gastrointest Surg 2010; 14:1111-20. [PMID: 20422305 DOI: 10.1007/s11605-010-1211-1] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2010] [Accepted: 04/13/2010] [Indexed: 01/31/2023]
Abstract
A retrospective cohort study was conducted to identify risk factors for recurrence of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative resection. A total of 317 patients who had received curative resection of pathologically proven small HCC (< or = 3 cm in diameter) were analyzed to ascertain the factors affecting recurrence. The median follow-up period was 33.7 months. Cumulative recurrence rates at 1, 3, and 5 years after resection were 23.5%, 49.5%, and 65.5%, respectively. Male sex, alpha-fetoprotein (AFP) > or = 400 ng/mL, HBV DNA level > or = 4 log(10) copies/mL, prolonged prothrombin time, tumor size > or = 2 cm, microvascular invasion, absence of capsular formation, moderate/poor tumor differentiation, and absence of postoperative interferon-alpha (IFN-alpha) treatment were associated with increased cumulative risk of HCC recurrence. By multivariate analysis, HBV DNA level > or = 4 log(10) copies/mL (P < 0.001, hazard ratio (HR) 2.110), AFP > or = 400 ng/mL (P = 0.011, HR 1.574), microvascular invasion (P < 0.001, HR 1.767), and postoperative IFN-alpha treatment (P = 0.022, HR 0.562) remained to be independently associated with HCC recurrence. Those contributing to late recurrence (>2 years) were older age and HBV DNA level > or = 4 log(10) copies/mL. Patients with persistent HBV DNA level > or = 4 log(10) copies/mL at resection and follow-up had the highest recurrence risk (P < 0.001, HR 4.129). HBV DNA level > or = 4 log(10) copies/mL at the time of resection was the most important risk factor for recurrence. Postoperative IFN-alpha treatment significantly decreased the recurrence risk after resection.
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Affiliation(s)
- Li-Shuai Qu
- Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, 180# Fenglin Road, Shanghai 200032, China
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Treatment outcome of hepatocellular carcinoma patients with high-risk vascular invasion: a retrospective analysis. ASIAN BIOMED 2010. [DOI: 10.2478/abm-2010-0062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Abstract
Background: Invasion of major hepatic vessels in hepatocellular carcinoma (HCC) generally prohibits the surgical treatment. Objective: Analyze outcomes of non-surgical approaches in this group of HCC. Methods: Retrospective review of medical records of 648 HCC admitted to King Chulalongkorn Memorial Hospital between January 2003 and December 2005 was carried out to select only patients who had unresectable HCC with vascular invasion and hepatic functions-Child-Pugh class-A. Vascular invasion was defined as involvement of portal vein, inferior vena cava (IVC), or their branches identified by imaging techniques. Non-surgical treatments were either transarterial chemoembolization (TACE) or systemic chemotherapy (SCT) in addition to general supportive care. Treatment outcomes of the patients were analyzed. Results: Out of 71 unresectable HCC patients enrolled, 57patients were treated with TACE, while 14 received SCT. In the TACE group, 39 (68%), 7 (12%) and 11 (19%) patients had portal vein, IVC, and both vessels invasion, respectively. In the SCT group; 11 (78%), 1 (7%) and 2 (14%) had invasion of portal vein, IVC, and both vessels, respectively. Median overall survival in both groups was 158 days. Univariate analysis demonstrated that AFP level <1000 ng/mL, tumor size <10 cm, and SCT treatment significantly influenced survival. Additional multivariate analysis confirmed that diameters of tumor, and SCT were independent prognostic factors for good survival. A survival analysis showed longer survival in the SCT group than that of TACE (210 vs. 149 days, p=0.03) group. Conclusion: Survival of HCC patients with major vessels invasion was better when treated with SCT compared to TACE. Future prospective study in larger populations to test the hypothesis is warranted.
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An aggressive approach leads to improved survival in hepatocellular carcinoma patients with portal vein tumor thrombus. J Cancer Res Clin Oncol 2010; 137:139-49. [PMID: 20340033 PMCID: PMC3015200 DOI: 10.1007/s00432-010-0868-x] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2010] [Accepted: 03/09/2010] [Indexed: 02/06/2023]
Abstract
PURPOSE Many physicians express a relatively nihilistic approach to the treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). Consensus among surgeons regarding the indications for an aggressive approach has not been reached. Current study was aimed to determine whether an aggressive approach, with an extended resection with thrombectomy and adjuvant therapy, would lead to an improved survival for HCC patients with PVTT. METHODS A retrospective review of 116 HCC patients with PVTT admitted from 1996 to 2006 was conducted. Patients were divided into 2 time-period (TP) cohorts, of them, 51 cases in the first 5 years (TP1) and 65 in the last 5 years (TP2). RESULTS Surgical operations were performed on 68 patients. Twenty-one surgical resections were performed in TP1 and forty-seven in TP2. The extent of liver resections, as well as the frequency of thrombectomy, was greater in TP2 (P = 0.039). During both time-periods, an aggressive therapy was associated with improved survival (P < 0.02 TP1, P < 0.001 TP2). Overall survival of all patients in TP2 was significantly greater than in TP1 (P < 0.001), with a median survival of 15 months in TP2, whereas in TP1, the survival was only 9 months. The median 1-, 3-year survivals in TP2 (54 and 34%, respectively) were also greater than that in TP1 (31 and 7%, respectively). A multiple logistic regression analysis revealed that radical resection and adjuvant therapy were the independent predictors of overall survival. CONCLUSIONS An aggressive approach, combining extended liver resection with thrombectomy and adjuvant therapy, leads to an improved survival in the HCC patients with PVTT.
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Tanaka S, Mogushi K, Yasen M, Noguchi N, Kudo A, Nakamura N, Ito K, Miki Y, Inazawa J, Tanaka H, Arii S. Gene-expression phenotypes for vascular invasiveness of hepatocellular carcinomas. Surgery 2010; 147:405-14. [PMID: 19945130 DOI: 10.1016/j.surg.2009.09.037] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2008] [Accepted: 09/29/2009] [Indexed: 01/16/2023]
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Shi J, Lai ECH, Li N, Guo WX, Xue J, Lau WY, Wu MC, Cheng SQ. Surgical treatment of hepatocellular carcinoma with portal vein tumor thrombus. Ann Surg Oncol 2010; 17:2073-80. [PMID: 20131013 DOI: 10.1245/s10434-010-0940-4] [Citation(s) in RCA: 216] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2009] [Indexed: 02/06/2023]
Abstract
BACKGROUND The role of liver resection in patients with hepatocellular carcinoma (HCC) accompanying with portal vein tumor thrombus (PVTT) remains controversial. This article aimed to evaluate the significance of different location and extent of PVTT on surgical outcomes after liver resection for HCC. MATERIALS AND METHODS A retrospective study was carried out on patients who underwent partial hepatectomy with or without portal thrombectomy for HCC with PVTT in a single tertiary center from January 2001 to December 2003. According to the extent, PVTT was divided into 4 types (I-segmental/sectoral branches of portal vein, II-left and/or right portal vein, III-main portal vein trunk, and IV-superior mesenteric vein). RESULTS A total of 406 patients with HCC and PVTT who underwent partial hepatectomy were studied. The complication rate and hospital mortality rate were 32.8 and 0.2%, respectively. After a median follow-up of 6.4 months, 128 patients (31.5%) died. The 1- and 3-year overall survival rates were 34.4 and 13.0%, respectively. The 1- and 3-year disease-free survival rates were 13.3 and 4.7%, respectively. Patients with PVTT located in the segmental, sectoral, or right and/or left portal veins (types I and II) showed significantly better survival than those with PVTT extended to the main trunk of the portal vein or the superior mesenteric vein (types III and IV). CONCLUSIONS Liver resection is justified in selected patients with PVTT located in the segmental or sectoral branches of the portal vein. However, surgical resection for PVTT involving the portal bifurcation or the main trunk is still controversial.
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Affiliation(s)
- Jie Shi
- Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
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Iguchi T, Aishima S, Sanefuji K, Fujita N, Sugimachi K, Gion T, Taketomi A, Shirabe K, Maehara Y, Tsuneyoshi M. Both fibrous capsule formation and extracapsular penetration are powerful predictors of poor survival in human hepatocellular carcinoma: a histological assessment of 365 patients in Japan. Ann Surg Oncol 2009; 16:2539-46. [PMID: 19533247 DOI: 10.1245/s10434-009-0453-1] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2008] [Revised: 01/13/2009] [Accepted: 01/13/2009] [Indexed: 12/26/2022]
Abstract
BACKGROUND A new definition of infiltration to the capsule (fc-inf) has been proposed as a novel marker for predicting the prognosis of 88 patients with hepatocellular carcinoma (HCC). The current aim was to present evidence to develop the fibrous capsule and fc-inf, from the Japanese histological findings for HCC, and to validate their biological significances and predictive power of survival in a large series. METHODS A total of 365 HCCs were divided into HCCs without the fibrous capsule (NC type; n = 135) and HCCs with the fibrous capsule (FC type; n = 230). Then, FC type was subclassified into two types: extracapsular infiltrating (EC) type (n = 125), in which cancer cells penetrated outside the fibrous capsule, and intracapsular (IC) type (n = 105), in which the infiltrating cancer cells stayed inside the fibrous capsule. RESULTS The proportion of less histological differentiation and portal venous invasion was higher in FC type than in NC type. The fibrous capsule came to be observed according to the increase of tumor size (P < 0.0001). FC type had significantly poorer outcome for overall survival than NC type (P = 0.0022). EC type showed more intrahepatic metastasis than IC type. The macroscopic subclassifications were significantly affected the presence of fc-inf. EC type had significantly poorer outcome for disease-free survival than IC type (P = 0.0132) and was an independent prognostic factor for disease-free survival (P = 0.0482). CONCLUSIONS Fc-inf defined as extracapsular penetration was verified to be a novel marker for predicting prognosis, and presence of fc-inf might be predicted by tumor gross features.
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Affiliation(s)
- Tomohiro Iguchi
- Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
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Zhong C, Guo RP, Li JQ, Shi M, Wei W, Chen MS, Zhang YQ. A randomized controlled trial of hepatectomy with adjuvant transcatheter arterial chemoembolization versus hepatectomy alone for Stage III A hepatocellular carcinoma. J Cancer Res Clin Oncol 2009; 135:1437-45. [PMID: 19408012 DOI: 10.1007/s00432-009-0588-2] [Citation(s) in RCA: 92] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2008] [Accepted: 04/08/2009] [Indexed: 12/15/2022]
Abstract
PURPOSE Hepatectomy is considered as the potentially curative treatment for hepatocellular carcinoma (HCC) and used in some selected Stage IIIA HCC, which include multiple tumors more than 5 cm or tumor involving a major branch of the portal or hepatic vein(s) (UICC TNM staging system, sixth edition). Transcatheter arterial chemoembolization (TACE) was used in retrospective studies to improve the survival outcome of resected HCC. However, its beneficial effect on the survival outcomes of the Stage IIIA patients has not been evaluated. The present study is to evaluate if hepatectomy combining with adjuvant TACE for Stage IIIA HCC result in better long-term survival outcome when compared with hepatectomy alone. METHODS From January 2001 to March 2004, we conducted a prospective randomized trial in patients with Stage IIIA HCC (NCT00652587), recruiting 115 Stage IIIA HCC patients to undergo hepatectomy with adjuvant TACE (HT arm) or to undergo hepatectomy alone (HA arm) in our cancer center. Survival outcomes of the two arms were analyzed. RESULTS The demographic data were well matched between the two arms. There were no significant differences in the morbidity and in-hospital mortality between the two arms of patients. The most significant toxicities associated with adjuvant TACE were nausea/vomiting (54.4%) and transient hepatic toxicity (elevation of aminotransferase, 52.6%). Although there was no significant difference in the rate of recurrence between the two arms (50/57 vs. 56/58, P = 0.094), HT arm seemed to have more proportion of single lesion of recurrent HCC (chi (2) = 3.719, P = 0.054) and more proportion of potential curative therapy for recurrence (chi (2) = 4.456, P = 0.035). Until the time of censor, 92 patients had died. The 1-, 3-, and 5-year overall survival rates and median overall survival for HT arm were 80.7, 33.3, 22.8% and 23.0 months, respectively. The corresponding overall survival rates and median overall survival for HA arm were 56.5, 19.4, 17.5% and 14.0 months, respectively. The difference was significant (stratified log-rank test, P = 0.048). The 1-, 3-, and 5-year disease-free survival rates and median disease-free survival for HT arm were 29.7, 9.3, 9.3% and 6.0 months, respectively; correspondingly, for HA arm were 14.0, 3.5, 1.7% and 4.0 months, respectively (stratified log-rank test, P = 0.004). CONCLUSIONS For Stage IIIA HCC, hepatectomy with adjuvant TACE efficaciously and safely improved survival outcomes when compared with hepatectomy alone.
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Affiliation(s)
- Chong Zhong
- Department of Hepatobiliary Surgery, Cancer Center of Sun Yat-Sen University, Guangzhou, China
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Tanaka S, Mogushi K, Yasen M, Noguchi N, Kudo A, Kurokawa T, Nakamura N, Inazawa J, Tanaka H, Arii S. Surgical contribution to recurrence-free survival in patients with macrovascular-invasion-negative hepatocellular carcinoma. J Am Coll Surg 2009; 208:368-74. [PMID: 19317998 DOI: 10.1016/j.jamcollsurg.2008.10.031] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2008] [Revised: 10/09/2008] [Accepted: 10/29/2008] [Indexed: 02/08/2023]
Abstract
BACKGROUND Macroscopic vascular invasion (MVI) is a well-known indicator of recurrence of hepatocellular carcinoma (HCC) even after curative hepatectomy, but the clinicopathologic and molecular features of the recurrence remain unclear in MVI-negative HCC. STUDY DESIGN Two hundred seven consecutive patients with confirmed primary MVI-negative HCC were retrospectively assessed after curative resection, with special emphasis on the importance of anatomically systematized hepatectomy. HCC tissues were also analyzed for genome-wide gene expression profile of each tumor using a microarray technique. RESULTS Univariant analysis of HCC recurrence revealed multiple tumors (p < 0.001), moderate to poor differentiation (p = 0.044), Child-Pugh B/C (p = 0.047), alpha-fetoprotein elevation (p = 0.007), and nonanatomic hepatectomy (p = 0.010) as risk factors. According to Cox hazard multivariant analysis, multiple tumors (p = 0.002), alpha-fetoprotein elevation (p < 0.001), and nonanatomic hepatectomy (p = 0.002) were identified as independent factors of the recurrence. In the recurrent cases after anatomic hepatectomy for HCC, local recurrence was significantly infrequent compared with those after nonanatomic hepatectomy (p < 0.001). Network expression analysis using cDNA microarray revealed distinct signaling pathways of epithelial-mesenchymal transitions are associated with recurrence after anatomically systematized hepatectomy. CONCLUSIONS Anatomically systematized hepatectomy might contribute to recurrence-free survival of HCC patients of HCC without MVI. Local recurrence could be mostly averted by anatomic hepatectomy, although specific epithelial-mesenchymal transitions signaling might regulate the biologic aggressiveness of HCC.
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Affiliation(s)
- Shinji Tanaka
- Department of Hepato-Biliary-Pancreatic Surgery, Tokyo Medical and Dental University, Tokyo, Japan.
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Inoue Y, Hasegawa K, Ishizawa T, Aoki T, Sano K, Beck Y, Imamura H, Sugawara Y, Kokudo N, Makuuchi M. Is there any difference in survival according to the portal tumor thrombectomy method in patients with hepatocellular carcinoma? Surgery 2009; 145:9-19. [PMID: 19081470 DOI: 10.1016/j.surg.2008.09.005] [Citation(s) in RCA: 72] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2008] [Accepted: 09/15/2008] [Indexed: 12/13/2022]
Abstract
BACKGROUND Although portal venous tumor thrombus (PVTT) is regarded as an ominous prognostic factor in patients with hepatocellular carcinoma (HCC), the optimal treatment method for maximizing both safety and long-term outcome has not yet been discussed. We describe a surgical technique in which the venous wall is peeled off from the PVTT. METHODS In the peeling off (PO) technique, the portal venotomy was placed after adequate vascular control of portal flow. The PVTT was dissected from the portal venous wall and removed through the opening. Macroscopically residual PVTTs intruding into tiny branches were meticulously extracted. This procedure was compared with the en bloc resection of PVTT. Between 1995 and 2006, 49 patients underwent curative hepatic resections for HCC with macroscopic PVTT; these patients were classified according to whether the PO technique (n = 20) or the en bloc technique (n = 29) had been utilized. Both the short- and long-term results were compared between the 2 groups. RESULTS No mortalities occurred in either group. Both the 5-year overall survival and the recurrence-free survival rates of the PO group were comparable with those of the en bloc group (39% vs 41% [P = .90] and 23% vs 18% [P = .89], respectively). No local recurrences or regrowth of the PVTT occurred in either group. CONCLUSION Our procedure is useful for removing PVTT extending beyond the bifurcation or into other sectors that should be preserved in terms of liver function and enables a more conservative resection than an en bloc technique without sacrificing curability.
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Affiliation(s)
- Yosuke Inoue
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
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Lu ZH, Shen F, Yan ZL, Li J, Yang JH, Zong M, Shi LH, Wu MC. Treatment of portal vein tumor thrombus of hepatocellular carcinoma with percutaneous laser ablation. J Cancer Res Clin Oncol 2008; 135:783-9. [PMID: 19034515 DOI: 10.1007/s00432-008-0513-0] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2008] [Accepted: 10/30/2008] [Indexed: 02/07/2023]
Abstract
BACKGROUND Portal vein tumor thrombus (PVTT) is a common complication of hepatocellular carcinoma (HCC), and is associated with extremely poor prognosis. PATIENTS AND METHODS In this retrospective study, we first evaluate the application of percutaneous laser ablation as a treatment for PVTT due to advanced hepatocellular carcinoma. 108 patients (2002.7-2005.12) that have adequate liver function and be in reasonably good general condition were enrolled at Eastern hepatobiliary surgery hospital. The thrombus was ablated via an optic fiber placed in the guide needle with the guiding of ultrasound. In the follow-ups, the serial imaging and laboratory routines were examined and the overall clinical progress was measured at regular intervals until time of death. In the clinical assessment, survival time and factors affecting survival time were analyzed. The changes of laboratory test (alanine transaminase and alpha fetoprotein) and clinical manifestation (ascites and diarrhea) of the PVTT patients before and after laser ablation were observed. RESULTS Patency of the tumor-occluded portal vein branch is the only factor that affect the survival time, the longer the patency time, the longer the survival time. The long-term survivals of patients in our study are 55.56, 33.58 and 22.38% at 1, 2 and 3 years, respectively. Both laboratory test and clinical presentations were improved. Alphalpha fetoprotein in the positive patients decreased and alanine transaminase in the abnormal patients normalized at 1 month after the treatment. Ascites disappeared in 44.00% patients (11/25), and diarrhea ameliorated in 57.14% (12/21). CONCLUSION Laser ablation might be a novel and effective treatment for PVTT associated with advanced HCC.
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Affiliation(s)
- Zheng-Hua Lu
- Department of Ultraphonic Diagnosis, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
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Kamiyama T, Nakanishi K, Yokoo H, Tahara M, Nakagawa T, Kamachi H, Taguchi H, Shirato H, Matsushita M, Todo S. Efficacy of preoperative radiotherapy to portal vein tumor thrombus in the main trunk or first branch in patients with hepatocellular carcinoma. Int J Clin Oncol 2007; 12:363-8. [PMID: 17929118 DOI: 10.1007/s10147-007-0701-y] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2007] [Accepted: 06/26/2007] [Indexed: 02/05/2023]
Abstract
BACKGROUND The prognosis of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) in the main trunk or the first branch is very poor. METHODS Radiotherapy (RT) to PVTT was followed by hepatectomy within 2 weeks. The dose used was 30-36 Gy, in 10-12 fractions, for 15-20 days. The efficacy of preoperative RT to PVTT in the main trunk or first branch was evaluated by comparing results in patients who underwent hepatectomy (group R; n = 15) with preoperative RT and those without preoperative RT (group N; n = 28). RESULTS The 1-, 3-, and 5-year survival rates in group R were 86.2%, 43.5%, and 34.8%, respectively, while these values in group N were 39.0%, 13.1%, and 13.1%, respectively. The survival curve of group R was significantly better than that of group N (P = 0.0359). In group R, five (83.3%) of six patients whose tumor thrombus was completely necrosed (based on pathological examination) and whose follow-up period was over 2 years survived for more than 2 years. Female sex (P = 0.0066), multiple tumors (P = 0.0369), and absence of preoperative RT (P = 0.0359) were ranked as significant factors for a poor prognosis by univariate analysis. Multivariate analysis revealed absence of preoperative RT and female sex to be significant factors for a poor prognosis. CONCLUSION Preoperative RT to PVTT in the main trunk or first branch improved the prognosis of patients with HCC with PVTT, and could be a promising new modality in the treatment of these patients.
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Affiliation(s)
- Toshiya Kamiyama
- The Department of General Surgery, Graduate School of Medicine, Hokkaido University, North 5, West 7, Kita-ku, Sapporo 060-8638, Japan.
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Capussotti L, Ferrero A, Viganò L, Polastri R, Tabone M. Liver resection for HCC with cirrhosis: surgical perspectives out of EASL/AASLD guidelines. Eur J Surg Oncol 2007; 35:11-5. [PMID: 17689043 DOI: 10.1016/j.ejso.2007.06.005] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2007] [Accepted: 06/20/2007] [Indexed: 02/06/2023] Open
Abstract
EASL/AASLD guidelines clearly define indications for liver surgery for HCC: patients with single HCC and completely preserved liver function without portal hypertension. These guidelines exclude from operation many patients that could benefit from radical resection and that are daily scheduled for hepatectomy in surgical centers. Patients with large tumors or with portal vein thrombosis cannot be transplanted or treated by interstitial treatments. In selected cases liver resection may obtain good long-term outcomes, significantly better than non-curative therapies. In cases of multinodular HCC, liver transplantation is the treatment of choice within Milan criteria; patients beyond these limits can benefit from liver resection, especially if only two nodules are diagnosed: even if they have a worse prognosis, survival results after liver surgery are better than those reported after TACE or conservative treatments. EASL/AASLD guidelines excluded from operating patients with portal hypertension but data about this topic are not conclusive and further studies are necessary. Selected patients with mild portal hypertension could probably be scheduled for liver resection and, considering the shortage of donors, listing for transplantation could be avoided. In conclusion, guidelines for HCC treatment should consider good results of liver resection for advanced HCC, and indications for hepatectomy should be expanded in order not to exclude from radical therapy patients that could benefit from it.
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Affiliation(s)
- L Capussotti
- Department of Surgery, Ospedale Mauriziano Umberto I, Largo Turati 62, Torino, Italy.
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