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Feng X, Feng GY, Tao J, Ao YP, Wu XH, Qi SG, Shi ZR. Comparison of different adjuvant therapy regimen efficacies in patients with high risk of recurrence after radical resection of hepatocellular carcinoma. J Cancer Res Clin Oncol 2023; 149:10505-10518. [PMID: 37284841 DOI: 10.1007/s00432-023-04874-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Accepted: 05/19/2023] [Indexed: 06/08/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) has a high recurrence rate even after radical surgery. Postoperative adjuvant transhepatic arterial chemoembolization (PA-TACE), postoperative adjuvant hepatic arterial infusion chemotherapy (PA-HAIC), postoperative adjuvant radiotherapy (PA-RT), and postoperative adjuvant molecular targeted therapy have been demonstrated to be effective in reducing the postoperative recurrence rate. The present network meta-analysis was conducted to compare the effects of PA-TACE, PA-HAIC, PA-RT and postoperative adjuvant molecular targeted therapy on the overall survival (OS) and disease-free survival (DFS) in HCC patients after radical resection and to determine the optimal treatment strategy. METHODS Network meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Embase, Cochrane Library, and Web of Science were used to collect eligible studies up to December 25, 2022. Studies related to PA-TACE, PA-HAIC, and postoperative adjuvant molecular targeted therapy after radical HCC resection was included. The endpoints were OS and DFS, and the effect size was determined using hazard ratio with a 95% confidence interval. R software and "gemtc" package were employed to analyze the results. RESULTS A total of 38 studies involving 7079 patients with HCC after radical resection were ultimately enrolled to be analyzed. Four postoperative adjuvant therapy measures and two oncology indicators were evaluated. In this study, OS-related investigations validated that PA-Sorafenib and PA-RT markedly enhanced the OS rates in patients after radical resection when compared to PA-TACE and PA-HAIC. However, statistical analysis revealed no significant difference between PA-Sorafenib and PA-RT, as well as PA-TACE and PA-HAIC. In the DFS-related investigations, PA-RT demonstrated superior efficacy over PA-Sorafenib, PA-TACE, and PA-HAIC. Additionally, PA-Sorafenib displayed better efficacy than PA-TACE. Nevertheless, there was no statistical significance between PA-Sorafenib and PA-HAIC, as well as PA-TACE and PA-HAIC. We also performed a subgroup analysis of studies focusing on HCC complicated by microvascular invasion after radical resection. In terms of OS, both PA-RT and PA-Sorafenib demonstrated a noteworthy improvement over PA-TACE, whereas no statistical significance was detected between PA-RT and PA-Sorafenib. Likewise, for DFS, both PA-Sorafenib and PA-RT exhibited superior efficacy compared to PA-TACE. CONCLUSION In patients with HCC after radical resection and a high risk of recurrence, both PA-Sorafenib and PA-RT significantly improved OS and DFS when compared to PA-TACE and PA-HAIC. Notably, PA-RT exhibited superior efficacy over PA-Sorafenib, PA-TACE, and PA-HAIC in terms of DFS. Similarly, PA-Sorafenib appeared to be more effective than PA-TACE for DFS.
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Affiliation(s)
- Xu Feng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Guo-Ying Feng
- Department of Hepatobiliary Surgery, Daping Hospital, Army Medical University, Chongqing, China
| | - Jie Tao
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yu-Pei Ao
- Infection and Liver Disease Center, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xin-Hua Wu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Shi-Guai Qi
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Zheng-Rong Shi
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
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Zeng ZM, Mo N, Zeng J, Ma FC, Jiang YF, Huang HS, Liao XW, Zhu GZ, Ma J, Peng T. Advances in postoperative adjuvant therapy for primary liver cancer. World J Gastrointest Oncol 2022; 14:1604-1621. [PMID: 36187393 PMCID: PMC9516643 DOI: 10.4251/wjgo.v14.i9.1604] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 05/13/2022] [Accepted: 07/26/2022] [Indexed: 02/05/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a highly heterogeneous, invasive, and conventional chemotherapy-insensitive tumor with unique biological characteristics. The main methods for the radical treatment of HCC are surgical resection or liver transplantation. However, recurrence rates are as high as 50% and 70% at 3 and 5 years after liver resection, respectively, and even in Milan-eligible recipients, the recurrence rate is approximately 20% at 5 years after liver transplantation. Therefore, reducing the postoperative recurrence rate is key to improving the overall outcome of liver cancer. This review discusses the risk factors for recurrence in patients with HCC radical surgical resection and adjuvant treatment options that may reduce the risk of recurrence and improve overall survival, including local adjuvant therapy (e.g., transcatheter arterial chemoembolization), adjuvant systemic therapy (e.g., molecular targeted agents and immunotherapy), and other adjuvant therapies (e.g., antiviral and herbal therapy). Finally, potential research directions that may change the paradigm of adjuvant therapy for HCC are analyzed.
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Affiliation(s)
- Zhi-Ming Zeng
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Ning Mo
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Jie Zeng
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Fu-Chao Ma
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Yan-Feng Jiang
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Hua-Sheng Huang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Xi-Wen Liao
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Guang-Zhi Zhu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Jie Ma
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Tao Peng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
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Brown ZJ, Hewitt DB, Pawlik TM. Combination therapies plus transarterial chemoembolization in hepatocellular carcinoma: a snapshot of clinical trial progress. Expert Opin Investig Drugs 2021; 31:379-391. [PMID: 34788184 DOI: 10.1080/13543784.2022.2008355] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Unfortunately, some hepatocellular carcinoma (HCC) patients do not qualify for curative-intent treatments such as surgical resection or transplantation. Hence, locoregional treatments such as transarterial chemoembolization (TACE) remain instrumental in the treatment of HCC. Systemic therapy has improved over the past decade with the introduction of combination atezolizumab and bevacizumab as the new standard of care for advanced disease. These new therapies are currently under investigation in combination with TACE. AREA COVERED Combination therapies with TACE including systemic therapies, locoregional therapies, and immunotherapies are reviewed. EXPERT OPINION There has been limited progress in the management of advanced and intermediate HCC. Recent advances in the management of advanced disease with systemic therapy could be beneficial in combination with TACE for the treatment of intermediate stage disease. Immune based therapies are potentially beneficial in combination with TACE because TACE may produce increased antigen release and immune recognition.
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Affiliation(s)
- Zachary J Brown
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - D Brock Hewitt
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Timothy M Pawlik
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
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Sun Y, Zheng X, Yuan H, Chen G, Ouyang J, Liu J, Liu X, Xing X, Zhao B. Proteomic analyses reveal divergent ubiquitylation patterns in hepatocellula carcinoma cell lines with different metastasis potential. J Proteomics 2020; 225:103834. [PMID: 32454254 DOI: 10.1016/j.jprot.2020.103834] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2019] [Revised: 05/13/2020] [Accepted: 05/18/2020] [Indexed: 02/06/2023]
Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignant tumours, metastasis and recurrence remain the primary reasons for poor prognosis. Ubiquitination serves as a degradation mechanism of proteins, but it is involved in additional cellular processes including metastasis. Here, by using label-free quantification, double-glycine (di-Gly) antibody affinity purification and high-resolution liquid chromatography tandem mass spectrometry (LC-MS/MS), we investigated quantitative proteome, ubiquitylome, and the crosstalk between the two datasets in HCC cell lines with different metastasis potential to identify biomarkers associated with HCC metastasis. In total, 83 ubiquitinated proteins significantly and steadily changed their abundance according to their metastatic potential, and the participated biological processes of these ubiquitinated proteins were tightly associated with tumour metastasis. Further signaling pathway analysis revealed that the ribosome and proteasome were significantly over-activated in the highly metastatic cells. Furthermore, we analyzed the crosstalk between the whole proteome and the ubiquitylome, and further discussed the mechanism that how ubiquitination events affect HCC metastasis. Eventually, the ubiquitination of Ku80 was validated to be significantly down-regulated in the high-metastatic cells comparing with the low-metastatic cells. We believe that these findings will help us better understand the underlying molecular mechanisms of the metastasis of HCC. SIGNIFICANCE: In this manuscript, we used label free based proteomics combined with diglycine antibody (di-Gly) affinity purification approach to identify biomarkers associated with HCC recurrence/metastasis in in a serial HCC cell lines with increasing invasion and metastasis potential. And then, we analyzed the crosstalk between the whole proteome and the ubiquitylome. Eventually, the ubiquitination of Ku80 was confirm to be closely associated with invasion and migration of HCC cells. As far as we know, this is the first time to use quantitative proteomic approach to study the ubiquitylomics in HCC cell lines with increasing metastasis ability.
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Affiliation(s)
- Ying Sun
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China; School of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, People's Republic of China; Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, People's Republic of China
| | - Xiaoyuan Zheng
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China
| | - Hui Yuan
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China
| | - Geng Chen
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China
| | - Jiahe Ouyang
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China
| | - Jingfeng Liu
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China; School of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, People's Republic of China; Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, 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 350025, People's Republic of China; School of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, People's Republic of China; Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, People's Republic of China
| | - Xiaohua Xing
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China; The School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350004, People's Republic of China.
| | - Bixing Zhao
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China.
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Chen W, Ma T, Zhang J, Zhang X, Chen W, Shen Y, Bai X, Liang T. A systematic review and meta-analysis of adjuvant transarterial chemoembolization after curative resection for patients with hepatocellular carcinoma. HPB (Oxford) 2020; 22:795-808. [PMID: 31980307 DOI: 10.1016/j.hpb.2019.12.013] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2019] [Revised: 12/15/2019] [Accepted: 12/20/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND The aim of this study was to systematically evaluate and determine those patients with hepatocellular carcinoma (HCC) that would benefit from the administration of postoperative adjuvant transarterial chemoembolization (PA-TACE). METHODS PubMed, Embase and Cochrane Library were searched for randomized controlled trials (RCTs) and observational studies up to July 30, 2019. The outcome of Overall survival (OS) and disease-free survival (DFS) were extracted and converted to hazard ratios (HRs) with 95% confidence intervals (95%CIs). RESULTS A total of 40 studies (10 RCTs and 30 non-RCTs) involving 11,165 patients were included. Overall, PA-TACE was associated with an increased OS [HR, 0.71 (95% CI, 0.65-0.77); P < 0.001] and DFS [HR, 0.73 (95% CI, 0.66-0.80); P < 0.001]. Subgroup analysis in patients with microvascular invasion (MVI), tumor diameter >5 cm or multinodular tumors demonstrated that PA-TACE improved OS and DFS. In patients without MVI, PA-TACE showed no improvement in OS [HR, 1.14 (95% CI, 0.85-1.53); P = 0.370], and resulted in worse DFS than curative resection alone [HR, 1.20 (95% CI, 1.03-1.39); P = 0.002]. CONCLUSION This meta-analysis indicated that PA-TACE was beneficial in patients with HCC who were at high risk of postoperative recurrence including tumor diameter >5 cm, multinodular tumors and MVI-positive. In patients with tumor diameter ≤5 cm, single tumor or MVI-negative. PA-TACE does not appear to improve outcomes and may potentially promote postoperative recurrence in certain patients.
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Affiliation(s)
- Wen Chen
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou 310009, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang Province, China
| | - Tao Ma
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou 310009, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang Province, China
| | - Jian Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou 310009, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang Province, China
| | - Xiaozhen Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou 310009, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang Province, China
| | - Wei Chen
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou 310009, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang Province, China
| | - Yinan Shen
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou 310009, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang Province, China
| | - Xueli Bai
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou 310009, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang Province, China
| | - Tingbo Liang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou 310009, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang Province, China.
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Zou J, Li C, Chen Y, Chen R, Xue T, Xie X, Zhang L, Ren Z. Retrospective analysis of transcatheter arterial chemoembolization treatment for spontaneously ruptured hepatocellular carcinoma. Oncol Lett 2019; 18:6423-6430. [PMID: 31807165 PMCID: PMC6876292 DOI: 10.3892/ol.2019.11037] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2019] [Accepted: 09/13/2019] [Indexed: 12/26/2022] Open
Abstract
Spontaneous rupture is one of the complications of hepatocellular carcinoma (HCC) associated with a high mortality rate. Transcatheter arterial chemoembolization (TACE) has been widely used in patients with ruptured liver tumors. The aim of the present study was to evaluate the benefits and safety of conventional TACE and the disease prognosis following TACE and surgery with regard to the progression of spontaneously ruptured HCC. The clinical data of 70 patients diagnosed with spontaneous rupture of HCC were retrospectively reviewed. The majority of adverse reactions that occurred following treatment were Grade 2 or below. Grade 3/4 events occurred in 20 patients (14.3%), which included gastrointestinal hemorrhage, cardiac failure, pulmonary embolism, shock and recurrent tumor rupture. All of these patients recovered and were discharged following symptomatic and supportive treatment, with the exception of two cases of severe hemorrhagic shock and hepatic failure prior to TACE treatment. These patients did not survive during the period of hospitalization. Multivariate analysis identified that a maximum tumor size >10 cm and a high serum total bilirubin level >30 µmol/l were independent factors for determining overall patient survival rate. Additionally, the overall survival rates at 1, 6 and 12 months were 92.3, 53.8 and 46.2% in the TACE group and 100, 87.1 and 54.8% in the surgery group, respectively. The overall survival rates at 1 and 6 months following TACE were lower than those of the surgery group (P<0.05). However, the overall survival rates at 12 months were similar (P>0.05). Patients in the TACE group had a shorter hospital admission compared with those in the resection group (median 7 vs. 13 days; P<0.01). Therefore, the data demonstrated that conventional TACE therapy was safe and effective for the treatment of spontaneously ruptured HCC. In addition, this type of therapy conferred a similar long-term survival rate with that of open surgery.
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Affiliation(s)
- Jixue Zou
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
| | - Chao Li
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200433, P.R. China
| | - Yi Chen
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
| | - Rongxin Chen
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
| | - Tongchun Xue
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
| | - Xiaoying Xie
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
| | - Lan Zhang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
| | - Zhenggang Ren
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
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Wang L, Ke Q, Deng M, Huang X, Zeng J, Liu H, Yang Y, Zeng Y, Zhou W, Liu J. Adjuvant transarterial chemoembolization for patients with hepatocellular carcinoma after radical hepatectomy: a real world study. Scand J Gastroenterol 2019; 54:1403-1411. [PMID: 31686555 DOI: 10.1080/00365521.2019.1684986] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Revised: 09/11/2019] [Accepted: 10/21/2019] [Indexed: 02/06/2023]
Abstract
Objective: To investigate the clinical value of the adjuvant transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) after radical resection, and identify the potential beneficiaries.Methods: Patients were identified through the primary liver cancer big data (PLCBD) between 2012 and 2015. Overall survival (OS) between adjuvant TACE group and non-TACE was evaluated by Kaplan-Meier before and after propensity scoring match (PSM). Subgroup analysis was conducted stratified by risk factors.Results: A total of 2066 HCC patients receiving radical resection were identified. Patients with multiple tumors, tumor diameter >5 cm, satellite, and advanced stage were more likely to accept adjuvant TACE. Before PSM, the 1-, 3-, and 5-year OS rates in the TACE group and non-TACE group were 89%, 58%, 17%, and 88%, 53%, 13% (p = .43), respectively. While, the corresponding rates were 89%, 58%, 17%, and 86%, 49%, 11%, (p = .038), respectively after 1:1 PSM. In addition, patients were found to significantly benefit from adjuvant TACE if they had age ≥50 years, no cirrhosis, AFP ≤ 200 ng/ml, surgical margin <1 cm, tumor diameter >5 cm, no capsule, no satellite, or CN stage Ib/IIa (all p < .05), but patients with age < 50 years, tumor size ≤5 cm, or CN stage Ia were found to significantly benefit from radical resection in DFS (all p < .05).Conclusion: Currently, we concluded that not all of patients with HCC would benefit from adjuvant TACE. Patients with age ≥50 years, tumor size >5 cm, or CN stage Ib/IIa were strongly recommended to receive adjuvant TACE.
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Affiliation(s)
- Lei Wang
- Department of Radiation Oncology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, PR China
- Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, PR China
| | - Qiao Ke
- Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, PR China
| | - Manjun Deng
- Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, PR China
| | - Xin Huang
- Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, PR China
| | - Jianxing Zeng
- Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, PR China
| | - Hongzhi Liu
- Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, PR China
| | - Yuan Yang
- Department of Hepatopancreatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital of Secondary Military Medical University, Shanghai, PR China
| | - Yongyi Zeng
- Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, PR China
| | - Weiping Zhou
- Department of Hepatopancreatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital of Secondary Military Medical University, Shanghai, PR China
| | - Jingfeng Liu
- Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, PR China
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Akateh C, Black SM, Conteh L, Miller ED, Noonan A, Elliott E, Pawlik TM, Tsung A, Cloyd JM. Neoadjuvant and adjuvant treatment strategies for hepatocellular carcinoma. World J Gastroenterol 2019; 25:3704-3721. [PMID: 31391767 PMCID: PMC6676544 DOI: 10.3748/wjg.v25.i28.3704] [Citation(s) in RCA: 109] [Impact Index Per Article: 18.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Revised: 06/13/2019] [Accepted: 06/22/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common liver malignancy worldwide and a major cause of cancer-related mortality for which liver resection is an important curative-intent treatment option. However, many patients present with advanced disease and with underlying chronic liver disease and/or cirrhosis, limiting the proportion of patients who are surgical candidates. In addition, the development of recurrent or de novo cancers following surgical resection is common. These issues have led investigators to evaluate the benefit of neoadjuvant and adjuvant treatment strategies aimed at improving resectability rates and decreasing recurrence rates. While high-level evidence to guide treatment decision making is lacking, recent advances in locoregional and systemic therapies, including antiviral treatment and immunotherapy, raise the prospect of novel approaches that may improve the outcomes of patients with HCC. In this review, we evaluate the evidence for various neoadjuvant and adjuvant therapies and discuss opportunities for future clinical and translational research.
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Affiliation(s)
- Clifford Akateh
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Sylvester M Black
- Division of Transplant Surgery, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Lanla Conteh
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Eric D Miller
- Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Anne Noonan
- Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Eric Elliott
- Division of Diagnostic Radiology, Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Timothy M Pawlik
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Allan Tsung
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Jordan M Cloyd
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
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Liu H, Chen H, Wu X, Sun Y, Wang Y, Zeng Y, Chen G, Liu X, Xing X, Zhao B, Liu J. The serum proteomics tracking of hepatocellular carcinoma early recurrence following radical resection. Cancer Manag Res 2019; 11:2935-2946. [PMID: 31114342 PMCID: PMC6497822 DOI: 10.2147/cmar.s190561] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2018] [Accepted: 02/19/2019] [Indexed: 12/12/2022] Open
Abstract
Purpose: There is still lacking of highly sensitive and specific biomarkers for the prediction of hepatocellular carcinoma (HCC) early recurrence, which has hindered further improvement of the clinical outcomes. We aim to find highly sensitive and specific biomarkers for the prediction of HCC recurrence. Patients and methods: By using isobaric tags for relative and absolute quantitation (iTRAQ)-based multidimensional liquid chromatography-tandem mass spectrometry (2D LC-MS/MS) technique, we have quantitatively investigated and monitored the proteome alterations of a series of serum after radical resection during the follow-up of 4 HCC patients. Results: A total of 27 differentially abundant proteins (DAPs) in serum were identified to be closely associated with the early recurrence of HCC, and these DAPs were particularly concentrated within ERK1/2 and nuclear factor-κ beta signaling pathways, suggesting the dysregulation of these two pathways played an important role in the pathological process of HCC early recurrence. Further investigation of a cohort of patients confirmed that the high serum level of PGK1 was closely associated with HCC early recurrence and poor prognosis. In addition, the serum level of PGK1 could be complementary with AFP to further improve the sensitivity and specificity for predicting the relapse of HCC. Conclusion: PGK1 might be an independent factor for the recurrence of HCC. And the PGK1 could be complementary with AFP to further improve the sensitivity and specificity in prognostic prediction of HCC relapse.
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Affiliation(s)
- Hongzhi Liu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350007, People’s Republic of China
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou350025, People’s Republic of China
| | - Hui Chen
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350007, People’s Republic of China
| | - Xiaomo Wu
- Department of Biomedicine, University of Basel, Basel4056, Switzerland
- Dermatology Institute of Fuzhou, Dermatology Hospital of Fuzhou, Fuzhou350025, People’s Republic of China
| | - Ying Sun
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou350025, People’s Republic of China
| | - Yingchao Wang
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou350025, People’s Republic of China
| | - Yongyi Zeng
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350007, People’s Republic of China
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou350025, People’s Republic of China
| | - Geng Chen
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou350025, 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, Fuzhou350025, People’s Republic of China
| | - Xiaohua Xing
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou350025, People’s Republic of China
- The School of Basic Medical Sciences, Fujian Medical University, Fuzhou350004, People’s Republic of China
| | - Bixing Zhao
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou350025, People’s Republic of China
| | - Jingfeng Liu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350007, People’s Republic of China
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou350025, People’s Republic of China
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Liu S, Li H, Guo L, Zhang B, Zhou B, Zhang W, Zhou J, Fan J, Ye Q. Tumor Size Affects Efficacy of Adjuvant Transarterial Chemoembolization in Patients with Hepatocellular Carcinoma and Microvascular Invasion. Oncologist 2018; 24:513-520. [PMID: 30552155 DOI: 10.1634/theoncologist.2018-0305] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2018] [Accepted: 10/16/2018] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Patients with hepatocellular carcinoma (HCC) and microvascular invasion (mVI) have shown dismal postoperative prognosis; however, whether adjuvant transarterial chemoembolization (TACE) can improve their outcomes remains unclear. MATERIALS AND METHODS We retrospectively identified 549 eligible patients to form the crude cohort and adopted propensity score matching method to assemble another cohort of 444 patients with similar baseline characteristics. We assessed the effects of adjuvant TACE by stratified analyses and multivariate Cox analyses in two cohorts. RESULTS There was significant interaction between tumor size and adjuvant TACE with respect to overall survival (OS; p = .006 for interaction). In the matched cohort, patients who received adjuvant TACE showed higher rates of 5-year OS (72.4% vs. 50.9%, p = .005) and 5-year recurrence-free survival (50.5% vs. 36.4%, p = .003) in the tumor ≤5 cm subgroup, but not in the tumor >5 cm subgroup (32.3% vs. 24.9%, p = .350 and 18.8% vs. 19.7%, p = .180). The independent protective role of adjuvant TACE on OS was observed in patients with tumor ≤5 cm (adjusted odds ratio [OR] = 0.59, 95% confidence interval [CI] 0.36-0.97) but not in patients with tumor >5 cm (adjusted OR = 1.17, 95% CI 0.84-1.62). The effects of adjuvant TACE did not change materially while the analysis was performed in the crude cohort. CONCLUSION For patients with HCC and mVI, adjuvant TACE was associated with improved outcomes, but not for those with tumor >5 cm, according to the current protocol. IMPLICATIONS FOR PRACTICE The outcomes of patients with hepatocellular carcinoma and microvascular invasion who received adjuvant transarterial chemoembolization were inconsistent in this study. According to the current protocol, adjuvant transarterial chemoembolization was associated with improved prognosis in patients with microvascular invasion, except for those with tumor >5 cm. Multivariate Cox models confirmed adjuvant transarterial chemoembolization was an independent protective factor in the tumor ≤5 cm subgroup but not in the tumor >5 cm subgroup.
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Affiliation(s)
- Shuang Liu
- Department of Liver Surgery, Liver Cancer Institute and Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Fudan University, Shanghai, People's Republic of China
| | - Hui Li
- Department of Liver Surgery, Liver Cancer Institute and Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Fudan University, Shanghai, People's Republic of China
| | - Lei Guo
- Department of Liver Surgery, Liver Cancer Institute and Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Fudan University, Shanghai, People's Republic of China
| | - Bo Zhang
- Department of Liver Surgery, Liver Cancer Institute and Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Fudan University, Shanghai, People's Republic of China
| | - Binghai Zhou
- Department of Liver Surgery, Liver Cancer Institute and Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Fudan University, Shanghai, People's Republic of China
| | - Wentao Zhang
- Department of Liver Surgery, Liver Cancer Institute and Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Fudan University, Shanghai, People's Republic of China
| | - Jian Zhou
- Department of Liver Surgery, Liver Cancer Institute and Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Fudan University, Shanghai, People's Republic of China
| | - Jia Fan
- Department of Liver Surgery, Liver Cancer Institute and Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Fudan University, Shanghai, People's Republic of China
| | - Qinghai Ye
- Department of Liver Surgery, Liver Cancer Institute and Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Fudan University, Shanghai, People's Republic of China
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11
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Zhang C, Song Z, Yu G. High expression of Parkin predicts easier recurrence of patients with adjuvant transarterial chemoembolization. Biomark Med 2017; 11:823-834. [PMID: 28862485 DOI: 10.2217/bmm-2017-0129] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Aim: To investigate the clinical significance of E3 ubiquitin ligase Parkin in patients with adjuvant transarterial chemoembolization after curative resection of hepatocellular carcinoma. Methods: Parkin expression of hepatocellular carcinomas was detected and its correlation with clinicopathological factors was analyzed with χ2 test. The significance of Parkin in prognosis and recurrence was analyzed with log-rank test and the Cox-regression model. Results: High expression of Parkin could result in lower recurrence-free survival rate instead of overall survival rate. Larger tumor size, positive tumor recurrence, advanced T, N, M and TNM stage were significantly associated with poorer prognosis. Larger tumor size, advanced T and TNM stage could lead to higher recurrence. Conclusion: High Parkin expression could predict easier recurrence to patients with adjuvant transarterial chemoembolization.
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Affiliation(s)
- Changlie Zhang
- Department of Vascular Surgery, Linyi People's Hospital, Linyi, Shandong, PR China
| | - Zhihong Song
- Department of Oncology, Linyi People's Hospital, Linyi, Shandong, PR China
| | - Guangji Yu
- Department of Intervention, Linyi Cancer Hospital, Linyi, Shandong, PR China
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12
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Yu Y, Song J, Zhang R, Liu Z, Li Q, Shi Y, Chen Y, Chen J. Preoperative neutrophil-to-lymphocyte ratio and tumor-related factors to predict microvascular invasion in patients with hepatocellular carcinoma. Oncotarget 2017; 8:79722-79730. [PMID: 29108352 PMCID: PMC5668085 DOI: 10.18632/oncotarget.19178] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2017] [Accepted: 06/29/2017] [Indexed: 02/07/2023] Open
Abstract
Small hepatocellular carcinoma (HCC) is less invasive and has a better prognosis, but it still has a high recurrence rate. Microvascular invasion (MVI), as a poor prognostic indicator, is of great importance for treating of patients with HCC. The objective of the present study was to evaluate the predictive value of preoperative neutrophil-to-lymphocyte ratio and possible clinical parameters to MVI in patients with HCC. A total of 157 operable patients with HCC having a tumor diameter of less than or equal to 5 cm were enrolled in this study. The utility of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and other clinical parameters was evaluated using receiver operating characteristic curves. MVI was identified as an independent influencing factor for disease-free survival in patients with HCC who underwent curative resection, using the multivariate Cox proportional hazards regression model. The independent parameters associated with MVI were determined using logistic analysis. Multivariate analyses indicated that the neutrophil-to-lymphocyte ratio [hazard ratio, 1.705; 95% confidence interval, 0.467–6.232; P = 0.022)], platelet-to-lymphocyte ratio (hazard ratio, 1.048; 95% confidence interval, 1.006–1.092; P = 0.025), and a-fetoprotein (hazard ratio, 1.012; 95% confidence interval, 1.003–1.021; P = 0.007) were significantly associated with MVI independently. Therefore, this study concluded that the preoperative neutrophil-to-lymphocyte ratio and a-fetoprotein might serve as useful biomarkers for predicting MVI in patients with HCC.
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Affiliation(s)
- Yanlong Yu
- Department of General Surgery, Chifeng Municipal Hospital, Inner Mongolia Medical University institute of clinical, Chifeng 024000, Inner Mongolia Autonomous Region, China
| | - Jiuling Song
- Department of General Surgery, Chifeng Municipal Hospital, Inner Mongolia Medical University institute of clinical, Chifeng 024000, Inner Mongolia Autonomous Region, China
| | - Ran Zhang
- Department of General Surgery, Chifeng Municipal Hospital, Inner Mongolia Medical University institute of clinical, Chifeng 024000, Inner Mongolia Autonomous Region, China
| | - Zhonghua Liu
- Department of General Surgery, Chifeng Municipal Hospital, Inner Mongolia Medical University institute of clinical, Chifeng 024000, Inner Mongolia Autonomous Region, China
| | - Qiang Li
- Department of General Surgery, Chifeng Municipal Hospital, Inner Mongolia Medical University institute of clinical, Chifeng 024000, Inner Mongolia Autonomous Region, China
| | - Ying Shi
- Department of General Surgery, Chifeng Municipal Hospital, Inner Mongolia Medical University institute of clinical, Chifeng 024000, Inner Mongolia Autonomous Region, China
| | - Ying Chen
- Department of General Surgery, Chifeng Municipal Hospital, Inner Mongolia Medical University institute of clinical, Chifeng 024000, Inner Mongolia Autonomous Region, China
| | - Jinming Chen
- Department of General Surgery, Chifeng Municipal Hospital, Inner Mongolia Medical University institute of clinical, Chifeng 024000, Inner Mongolia Autonomous Region, China
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