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Jayabalan D, Dhakal S, Raguragavan A, Saxena A, Jeffrey GP, Calzadilla-Bertot L, Adams LA, Wallace MC. Hepatocellular Carcinoma and Health-Related Quality of Life: A Systematic Review of Outcomes From Systemic Therapies. Int J Hepatol 2025; 2025:1083642. [PMID: 40230581 PMCID: PMC11996279 DOI: 10.1155/ijh/1083642] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2025] [Accepted: 03/20/2025] [Indexed: 04/16/2025] Open
Abstract
Aim: Poor outcomes in advanced hepatocellular carcinoma (HCC) coupled with potential significant treatment side effects underpin a strong rationale to assess health-related quality of life (HRQOL) in those treated with systemic therapies. This study is aimed at quantifying the effect of systemic therapies on HRQOL outcomes in HCC patients when compared to baseline or placebo, other systemic therapies, and transarterial radioembolisation (TARE). Methods: In May 2024, two independent reviewers searched PubMed, EMBASE, and Google Scholar for studies comparing postsystemic therapy HRQOL scores in adult patients with HCC to baseline or placebo, other systemic therapies, or to TARE. Narrative synthesis was used to synthesise results. Risk of bias was assessed using RoB 2 and ROBINS-I. This review was structured according to PRISMA guidelines and was prospectively registered in the PROSPERO register (CRD42024521699). Results: Twenty-nine studies with 10,472 patients using eight HRQOL instruments were included. Compared to baseline, patients on atezolizumab/bevacizumab and sorafenib both experienced significant declines in HRQOL, and lenvatinib nonsignificantly decreased HRQOL. HRQOL remained unchanged in patients on pembrolizumab or nivolumab. Atezolizumab/bevacizumab and lenvatinib both significantly delayed HRQOL deterioration compared to sorafenib. Compared to TARE, atezolizumab/bevacizumab delayed time-to-deterioration in HRQOL, whereas sorafenib had significantly worse HRQOL. Conclusion: Despite worsening HRQOL outcomes compared to baseline, the first-line agents atezolizumab/bevacizumab and lenvatinib had superior HRQOL outcomes in comparison to sorafenib. Sorafenib significantly worsened HRQOL compared to TARE. As the majority of included studies included sorafenib, which has been largely superseded by newer therapies, further trials evaluating HRQOL with these newer therapies are required.
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Affiliation(s)
- Dujinthan Jayabalan
- Department of Hepatology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia
- Medical School, The University of Western Australia, Nedlands, Western Australia, Australia
| | - Sugam Dhakal
- Medical School, The University of Western Australia, Nedlands, Western Australia, Australia
| | - Aarohanan Raguragavan
- Medical School, The University of Western Australia, Nedlands, Western Australia, Australia
| | - Akshat Saxena
- Department of Cardiothoracic Surgery, Fiona Stanley Hospital, Murdoch, Western Australia, Australia
| | - Gary P. Jeffrey
- Department of Hepatology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia
- Medical School, The University of Western Australia, Nedlands, Western Australia, Australia
| | - Luis Calzadilla-Bertot
- Department of Hepatology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia
- Medical School, The University of Western Australia, Nedlands, Western Australia, Australia
| | - Leon A. Adams
- Department of Hepatology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia
- Medical School, The University of Western Australia, Nedlands, Western Australia, Australia
| | - Michael C. Wallace
- Department of Hepatology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia
- Medical School, The University of Western Australia, Nedlands, Western Australia, Australia
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Fu YY, Li WM, Cai HQ, Jiao Y. Landscape of transarterial chemoembolization represented interventional therapy for hepatocellular carcinoma. World J Gastrointest Surg 2024; 16:3903-3906. [PMID: 39734435 PMCID: PMC11650251 DOI: 10.4240/wjgs.v16.i12.3903] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Revised: 09/23/2024] [Accepted: 10/23/2024] [Indexed: 11/27/2024] Open
Abstract
This article discusses the article written by Tan et al. Transarterial chemoembolization (TACE) is one of the main treatment methods for advanced hepatocellular carcinoma (HCC). There are other vascular interventional therapies, including drug-eluting bead TACE, transarterial radioembolization, and hepatic arterial infusion chemotherapy. TACE combined with anti-angiogenesis therapy may improve tumor control and prolong progression free survival. The combination therapy of TACE and immunotherapy may improve the clinical efficacy of HCC. In future research, more basic and clinical studies are needed to explore the immunogenic intervention therapy.
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Affiliation(s)
- Yang-Yang Fu
- Department of The First Operation Room, The First Hospital of Jilin University, Changchun 130000, Jilin Province, China
| | - Wen-Mao Li
- Department of Rehabilitation, The Second Hospital of Jilin University, Changchun 130000, Jilin Province, China
| | - Hong-Qiao Cai
- Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
| | - Yan Jiao
- Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
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Zhang JB, Wei L, Tang H. Efficacy and safety of transcatheter arterial chemoembolization combined with sorafenib and sintilimab in the treatment of unresectable hepatocellular carcinoma. Am J Transl Res 2024; 16:7849-7858. [PMID: 39822508 PMCID: PMC11733392 DOI: 10.62347/kniv1276] [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: 02/22/2024] [Accepted: 11/05/2024] [Indexed: 01/19/2025]
Abstract
OBJECTIVE To investigate the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with sorafenib and sintilimab in the treatment of unresectable hepatocellular carcinoma (HCC). METHOD This study retrospectively analyzed the clinical data from 50 patients with unresectable HCC treated at Yunhe County People's Hospital of Zhejiang Province from January 2023 to December 2023. The patients were divided into two groups according to treatment regimen: a control group (n=20) treated with TACE alone, and a combination group (n=30) treated with TACE combined with sorafenib and sintilimab. Baseline data, changes in hematological parameters before and after treatment, objective response rate (ORR), disease control rate (DCR), and prognosis were compared between the two groups. Besides, the progression-free survival (PFS) and overall survival (OS) time were also compared between the two groups. RESULT The combination group demonstrated significantly lower AFP levels compared to the control group (789.44±23.55 ng/l vs. 1244.65±36.85 ng/l, P<0.05). The ORR and DCR of the combination group were notably higher than those of the control group (56.67% vs. 25.00%, P<0.05; 83.33% vs. 55.00%, P<0.05, respectively). The median PFS and OS of the combined group were significantly longer than those of the control group (12.86 months vs. 5.72 months, P=0.007; 15.63 months vs. 7.05 months, P=0.001, respectively). Moreover, there were no significant differences in grade 1-2 adverse events between the two groups, while the incidence of grade 3 adverse events was significantly lower in the combination group compared to the control group (P<0.05). CONCLUSION Our results suggest that the combination of TACE with sorafenib and sintilimab is a feasible treatment option for patients with unresectable HCC, with high efficacy and reasonable safety.
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Affiliation(s)
- Jian-Bo Zhang
- General Surgery II, Yunhe County People’s HospitalLishui 323000, Zhejiang, China
| | - Liu Wei
- Department of Intervention, Lishui People’s HospitalLishui 323000, Zhejiang, China
| | - Hui Tang
- General Surgery II, Yunhe County People’s HospitalLishui 323000, Zhejiang, China
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Zhu ZY, Qian Z, Qin ZQ, Xie B, Wei JZ, Yang PP, Yuan M. Effectiveness and safety of sequential transarterial chemoembolization and microwave ablation for subphrenic hepatocellular carcinoma: A comprehensive evaluation. World J Gastrointest Oncol 2024; 16:2941-2951. [PMID: 39072162 PMCID: PMC11271768 DOI: 10.4251/wjgo.v16.i7.2941] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2024] [Revised: 04/11/2024] [Accepted: 05/27/2024] [Indexed: 07/12/2024] Open
Abstract
BACKGROUND Subphrenic carcinoma has been identified as a significant risk factor for the thermal ablation of intrahepatic tumors, resulting in a high rate of residual tumor recurrence. Some studies have proposed that combination treatment with transarterial chemoembolization (TACE) followed by radiofrequency ablation is both feasible and safe for tumors in the subphrenic region. However, research specifically examining the therapeutic outcomes of combination therapy using TACE and microwave ablation (TACE-MWA) in subphrenic tumors is lacking. AIM To evaluate the efficacy and safety of TACE-MWA in patients with subphrenic hepatocellular carcinoma (HCC). METHODS Between December 2017 and December 2021, 49 patients diagnosed with HCC ≤ 6 cm, who received TACE-MWA, were included in this retrospective cohort study. These patients were classified into subphrenic and non-subphrenic groups based on the distance between the diaphragm and the tumor margin. The rates of local tumor progression (LTP), progression-free survival (PFS), and overall survival (OS) were compared between the two groups. Complications were evaluated by using a grading system developed by the Society of Interventional Radiology. RESULTS After a median follow-up time of 38 mo, there were no significant differences in LTP between the subphrenic and non-subphrenic groups (27.3% and 22.2% at 5 years, respectively; P = 0.66), PFS (55.5% at 5 years in both groups; P = 0.91), and OS (85.0% and 90.9% in the subphrenic and non-subphrenic groups at 5 years; P = 0.57). However, a significantly higher rate of LTP was observed in subphrenic HCC > 3 cm compared to those ≤ 3 cm (P = 0.085). The dosage of iodized oil [hazard ratio (HR): 1.52; 95% confidence interval (CI): 1.11-2.08; P = 0.009] and multiple tumors (HR: 13.22; 95%CI: 1.62-107.51; P = 0.016) were independent prognostic factors for LTP. There were no significant differences in complication rates between the two groups (P = 0.549). CONCLUSION Combined TACE and MWA was practical and safe for managing subphrenic HCC. The efficacy and safety levels did not vary significantly when tumors outside the subphrenic region were treated.
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Affiliation(s)
- Zi-Yi Zhu
- Department of Interventional Radiology, The First Affiliated Hospital of Bengbu Medical University, Bengbu 233004, Anhui Province, China
| | - Zhen Qian
- Department of Interventional Radiology, The First Affiliated Hospital of Bengbu Medical University, Bengbu 233004, Anhui Province, China
| | - Zhong-Qiang Qin
- Department of Interventional Radiology, The First Affiliated Hospital of Bengbu Medical University, Bengbu 233004, Anhui Province, China
| | - Bo Xie
- Department of Interventional Radiology, The First Affiliated Hospital of Bengbu Medical University, Bengbu 233004, Anhui Province, China
| | - Jian-Zhu Wei
- Department of Interventional Radiology, The First Affiliated Hospital of Bengbu Medical University, Bengbu 233004, Anhui Province, China
| | - Pei-Pei Yang
- Department of Interventional Radiology, The First Affiliated Hospital of Bengbu Medical University, Bengbu 233004, Anhui Province, China
| | - Mu Yuan
- Department of Interventional Radiology, The First Affiliated Hospital of Bengbu Medical University, Bengbu 233004, Anhui Province, China
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Gao Y, Xu Y, Wang Y, Lu J, Guo JH. Clinical features and prognostic factors of patients with inoperable hepatocellular carcinoma treated with chemotherapy: a population-based study. J Gastrointest Oncol 2024; 15:1122-1140. [PMID: 38989427 PMCID: PMC11231877 DOI: 10.21037/jgo-24-298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Accepted: 06/07/2024] [Indexed: 07/12/2024] Open
Abstract
Background In inoperable hepatocellular carcinoma (HCC), chemotherapy is a common treatment strategy. However, there is a lack of reliable methods to predict the prognosis of patients with inoperable HCC after chemotherapy. Therefore, the aim of this study was to identify the clinical characteristics of patients with inoperable HCC and to establish and validate nomogram models for predicting the survival outcomes in this patient group following chemotherapy. Methods The data of patients diagnosed with HCC from the Surveillance, Epidemiology, and End Results (SEER) database were retrospectively collected. Logistic regression analyses were used to identify potential factors for inoperability in patients with HCC. Kaplan-Meier analyses were applied to evaluate the impact of chemotherapy on prognosis. Additionally, Cox regression analyses were performed to identify the potential risk factors associated with overall survival (OS) and cancer-specific survival (CSS) in patients with inoperable HCC treated with chemotherapy. Finally, we constructed prognostic nomograms for predicting the 1- and 3-year survival probabilities. Results A total of 3,519 operable patients with HCC and 4,656 patients with inoperable HCC were ultimately included in this study. Logistic regression analyses revealed a significant association between patient age, gender, race, tumor, node, metastasis (TNM) stage, tumor size, pretreatment alpha fetoprotein (AFP) levels, and marital status with inoperability. Moreover, Kaplan-Meier analyses revealed a significant improvement in both OS and CSS with the administration of chemotherapy. Moreover, 1,456 patients with inoperable HCC were enrolled in the training group and 631 patients with inoperable HCC were enrolled in the validation group to develop and validate the prognostic models. Cox regression models indicated that TNM stage, tumor size, and pretreatment AFP were independent risk factors for predicting OS and CSS in patients with inoperable HCC receiving chemotherapy. These factors were subsequently integrated into the predictive nomograms. Conclusions We preliminarily developed survival models with strong predictive capabilities for estimating survival probabilities in patients with HCC following chemotherapy. These models hold potential for clinical application and warrant further exploration through additional studies.
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Affiliation(s)
- Yang Gao
- Center of Interventional Radiology & Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
- Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, Nanjing, China
| | - Yihang Xu
- The First Clinical Medical College, Nanjing Medical University, Nanjing, China
| | - Yong Wang
- Center of Interventional Radiology & Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
- Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, Nanjing, China
| | - Jian Lu
- Center of Interventional Radiology & Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
- Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, Nanjing, China
| | - Jin-He Guo
- Center of Interventional Radiology & Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
- Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, Nanjing, China
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Zeng N, Wang Y, Wan Y, Wang H, Li N. The Antitumor Impact of Combining Hepatic Artery Ligation With Copper Chelators for Liver Cancer. Clin Med Insights Oncol 2023; 17:11795549231204612. [PMID: 38023286 PMCID: PMC10666691 DOI: 10.1177/11795549231204612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Accepted: 09/13/2023] [Indexed: 12/01/2023] Open
Abstract
Background Hepatocellular carcinoma (HCC) is one of the main cancer-related mortality worldwide. Thus, there is a constant search for improvement in treatment strategies to enhance the prognosis of this malignancy. The study aims to investigate the combined antitumor activity of ammonium tetrathiomolybdate (TM, copper chelator) combined with hepatic artery ligation (HAL) for liver cancer. Methods A total of 40 Sprague-Dawley (SD) rats bearing hepatic tumors were randomly divided into four groups: the control group without any treatment (control), HAL only (HAL), given TM by gavage (TM), and given TM combined with HAL (HAL + TM). The concentrations of serum copper were measured at the predetermined time points. Tumor growth rate, overall survival (OS), expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and microvessel density (MVD), as determined by immunohistochemical examination, were compared. Results HAL treatment transiently could elevate alanine transaminase (ALT) and aspartate transaminase (AST) but resumed to baseline within 1 week. Serum copper was significantly increased in tumor-bearing animals over time. The values of serum copper in the three treatment groups were significantly lower than those in the control group at different time points, with the lowest values observed in the TM group (P < .05). The average tumor size was 30.33 ± 2.58, 20.83 ± 2.93, 16.80 ± 3.84, and 10.88 ± 1.08 mm in the control, HAL, TM, and HAL + TM groups, respectively (HAL + TM vs other groups, all P < .05). In addition, the expression levels of HIF-1α, VEGF, and MVD were significantly lower in the HAL + TM group than those in the other groups (P < .05). The OS of rats in the combined groups was significantly prolonged combined to the other groups (P < .05), with survival time of 19.1 ± 0.64, 25.4 ± 1.24, 25.3 ± 1.78, and 29.9 ± 2.22 days in the control, HAL, TM, and HAL + TM groups, respectively. Conclusion These findings suggest that combined treatment with TM and HAL holds great potential for liver cancer treatment by reducing tumor hypoxia and angiogenesis. The observed results indicate that these combinations may offer a novel target and strategy for interventional therapy of liver cancer.
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Affiliation(s)
- Ni Zeng
- Center for Translational Medicine, Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Ye Wang
- School of Medicine, South China University of Technology, Guangzhou, China
| | - Yuan Wan
- Interventional Center, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Hongyu Wang
- Department of Interventional Therapy, Guangdong Provincial Hospital of Chinese Medicine and Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
| | - Nan Li
- Department of Interventional Radiology, Guangzhou First People’s Hospital, Guangzhou, China
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Yan J, Deng M, Li T, Dong C, Wang M, Kong S, Guo Y, Fan H. Efficacy and complications of transarterial chemoembolization alone or in combination with different protocols for hepatocellular carcinoma: A Bayesian network meta-analysis of randomized controlled trials. ILIVER 2023; 2:130-141. [DOI: 10.1016/j.iliver.2023.03.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/01/2023]
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Koza A, Bhogal RH, Fotiadis N, Mavroeidis VK. The Role of Ablative Techniques in the Management of Hepatocellular Carcinoma: Indications and Outcomes. Biomedicines 2023; 11:1062. [PMID: 37189680 PMCID: PMC10135821 DOI: 10.3390/biomedicines11041062] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Revised: 03/18/2023] [Accepted: 03/27/2023] [Indexed: 04/03/2023] Open
Abstract
The management of hepatocellular carcinoma (HCC) remains complex and will continue to rely on the multidisciplinary input of hepatologists, surgeons, radiologists, oncologists and radiotherapists. With the appropriate staging of patients and selection of suitable treatments, the outcomes for HCC are improving. Surgical treatments encompassing both liver resection and orthotopic liver transplantation (OLT) are the definitive curative-intent options. However, patient suitability, as well as organ availability, pose essential limitations. Consequently, non-surgical options, such as ablative techniques, play an increasingly important role, especially in small HCCs, where overall and disease-free survival can be comparable to surgical resection. Ablative techniques are globally recommended in recognised classification systems, showing increasingly promising results. Recent technical refinements, as well as the emerging use of robotic assistance, may expand the treatment paradigm to achieve improved oncological results. At present, in very early stage and early stage unresectable disease, percutaneous thermal ablation is considered the treatment of choice. Owing to their different features, various ablative techniques, including radiofrequency ablation, microwave ablation, cryotherapy ablation and irreversible electroporation, have been shown to confer different comparative advantages and applicability. We herein review the role of available ablative techniques in the current complex multidisciplinary management of HCC, with a main focus on the indications and outcomes, and discuss future perspectives.
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Affiliation(s)
- Asanda Koza
- Department of Interventional Radiology, The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK
| | - Ricky H. Bhogal
- Department of Academic Surgery, The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK
| | - Nicos Fotiadis
- Department of Interventional Radiology, The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK
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Sun H, Yang W, Zhou W, Zhou C, Liu S, Shi H, Tian W. Prognostic value of des-γ-carboxyprothrombin in patients with AFP-negative HCC treated with TACE. Oncol Lett 2022; 25:69. [PMID: 36644150 PMCID: PMC9827467 DOI: 10.3892/ol.2022.13655] [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: 05/06/2022] [Accepted: 09/13/2022] [Indexed: 12/30/2022] Open
Abstract
In patients with AFP-negative hepatocellular carcinoma (HCC), des-γ-carboxyprothrombin (DCP) is an important prognostic indicator for the preoperative assessment of transarterial chemoembolization (TACE). However, the association between the serum DCP levels and the degree of progression and prognosis of patients with AFP-negative HCC treated with TACE has not been thoroughly investigated to date, and the molecular mechanism is also unclear. The present study retrospectively analyzed the clinical data of 107 patients with AFP-negative HCC treated with TACE and divided them into two groups based on the median serum DCP levels. The association between DCP and the clinical characteristics of the patients was analyzed, and the survival data were analyzed using Kaplan-Meier curves and Cox regression models. The results demonstrated that the median follow-up time was 755 days (range, 64-1,556 days), and patients in the low-DCP group (n=11; 20.8%) had a lower mortality rate than those in the high-DCP group (n=20; 37.0%). Cox multivariate regression analysis suggested that preoperative lymph node metastasis [hazard ratio (HR), 3.903; 95% CI, 1.778-8.519; P=0.001] and DCP group (HR, 2.465; 95% CI, 1.038-5.854; P=0.041) were independent risk factors. Furthermore, the Gene Expression Omnibus database was utilized to screen differentially expressed mRNAs. Enrichment analyses were then performed, and a protein-protein interaction (PPI) network was constructed to identify hub genes. A total of 169 differentially expressed genes were screened. Enrichment analyses revealed that cancer-related and ribosomal pathways were significantly enriched. Furthermore, 10 hub genes were identified in the PPI network by counting the number of gene interactions, the majority of which belonged to the ribosomal protein (RPS) family, and the top three significant genes were RPS23, RPS11 and RPS3A. In patients with AFP-negative HCC, higher serum DCP levels were associated with poor prognosis after TACE. This may be associated with genes such as those belonging to the RPS family, which may contribute to future personalized therapy for this disease.
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Affiliation(s)
- Hanyao Sun
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Wei Yang
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Weizhong Zhou
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Chungao Zhou
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Sheng Liu
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Haibin Shi
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China,Correspondence to: Dr Haibin Shi or Dr Wei Tian, Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, P.R. China, E-mail: , E-mail:
| | - Wei Tian
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China,Correspondence to: Dr Haibin Shi or Dr Wei Tian, Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, P.R. China, E-mail: , E-mail:
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Transarterial chemoembolisation plus I125 seeds implantation for people with unresectable hepatocellular carcinoma. Cochrane Database Syst Rev 2022; 2022:CD015389. [PMCID: PMC9744102 DOI: 10.1002/14651858.cd015389] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the benefits and harms of transarterial chemoembolisation (TACE) plus I125 seeds implantation compared with TACE alone, regardless of chemotherapeutic drugs and vascular occlusive agents, for people with unresectable hepatocellular carcinoma.
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Comparison of the prognosis of BCLC stage A ruptured hepatocellular carcinoma patients after undergoing transarterial chemoembolization (TACE) or hepatectomy: a propensity score-matched landmark analysis. Surg Endosc 2022; 36:8992-9000. [PMID: 35920912 DOI: 10.1007/s00464-022-09351-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Accepted: 05/20/2022] [Indexed: 01/06/2023]
Abstract
BACKGROUND At present, the choice of treatment modalities for ruptured hepatocellular carcinoma patients in BCLC stage A remains controversial, and this study compared the overall survival of ruptured HCC patients undergoing TACE or hepatectomy. METHODS A total of 283 ruptured HCC patients treated at our liver surgery center were included in our study, of which 175 were treated with hepatectomy and 108 were treated with TACE. To reduce selection bias, we used a propensity score matching (PSM) model, which yielded a total of 88 pairs of patients. We used the Kaplan-Meier method to compare the long-term prognosis, and the Landmark method was used to compare the short-term and long-term prognoses of patients after PSM. Finally, we performed subgroup analysis according to whether it met the Milan criteria. RESULTS After PSM, in the hepatectomy group, the 1-, 3-, and 5 year OS rates were 73.4%, 45.4%, and 33.9%, respectively. In the TACE group, the 1-, 3-, and 5 year OS rates were 58.5%, 40.6%, and 23.2%, respectively. Within one year, the hepatectomy group had a better prognosis than the TACE group (P = 0.022), but there was no difference in long-term survival(P = 0.936). In the subgroup analysis, in patients who met the Milan criteria, the survival curve indicated that there was no statistically significant difference in the survival prognosis between the two groups (P = 0.294) HR = 1.56(0.68-3.59); in the patients beyond the Milan criteria, the survival time was 28.0 months (20.0-34.0) in patients who underwent hepatectomy and 18 months (9.8-26.2) in patients who underwent TACE, and the survival curve indicated a statistically significant difference (P = 0.043) HR = 1.57(1.01-2.43). CONCLUSION Our propensity score-matched study found that ruptured HCC patients treated by hepatectomy had a better short-term prognosis than those treated by TACE, but there was no difference in the long-term prognosis between the two treatment groups.
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Liu CH, Peng CM, Hwang JI, Liang PC, Chen PJ, Abi-Jaoudeh N, Giiang LH, Tyan YS. Phase I Dose-Escalation Study of Tirapazamine Chemoembolization for Unresectable Early- and Intermediate-Stage Hepatocellular Carcinoma. J Vasc Interv Radiol 2022; 33:926-933.e1. [PMID: 35504436 DOI: 10.1016/j.jvir.2022.04.031] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2021] [Revised: 04/03/2022] [Accepted: 04/21/2022] [Indexed: 11/16/2022] Open
Abstract
PURPOSE To investigate the safety of replacing doxorubicin with tirapazamine in conventional transarterial chemoembolization (TACE) in an Asian population with hepatocellular carcinoma (HCC), and to determine the optimal tirapazamine dose for phase II studies. MATERIALS AND METHODS This was a phase I, 3 + 3 dose-escalation study for patients with unresectable early- and intermediate-stage HCC who received 5, 10, or 20 mg/m2 of intra-arterial (IA) tirapazamine followed by ethiodized oil/gelatin sponge-based embolization. Key eligibilities included HCCs no more than 10 cm in diameter, prior embolization allowed, Eastern Cooperative Oncology Group performance status of 0 or 1, Child-Pugh score of 5-7, and platelet count of ≥60,000 μL. Dose-limiting toxicity (DLT) was defined as any grade 3 nonhematological or grade 4 hematological toxicity, with the exception of transient elevation of aminotransferase levels after the procedure. RESULTS Seventeen patients were enrolled, 59% of whom had progression from a prior HCC therapy and 35% of whom had progression or recurrence after TACE. All patients tolerated the tirapazamine TACE well without any DLT or serious adverse event. Using the modified Response Evaluation Criteria in Solid Tumors, the complete response (CR) rate was 47%, and the CR + partial response rate was 65%. The median duration of response was not reached. The median time to progression was 12.6 months (95% confidence interval, 5.1-not reached). The median overall survival was 29.3 months. The selected phase II dose was set at a fixed dose of 35 mg of IA tirapazamine. CONCLUSIONS IA tirapazamine with transarterial embolization was well tolerated and showed promising efficacy signals in intermediate-stage HCC, justifying pursuit of a phase II study.
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Affiliation(s)
- Chang-Hsien Liu
- Department of Medical Imaging, China Medical University Hsinchu Hospital and China Medical University, Hsinchu, Taiwan, Republic of China; Department of Radiology, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan, Republic of China; Institute of Nuclear Engineering and Science, National Tsing Hua University, Hsinchu, Taiwan, Republic of China.
| | - Cheng-Ming Peng
- Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan, Republic of China
| | - Jen-I Hwang
- Department of Radiology, Taichung Veteran General Hospital, and Department of Medical Imaging, Tungs' Taichung MetroHarbor Hospital, Taichung, Taiwan, Republic of China
| | - Po-Chin Liang
- Department of Medical Imaging, National Taiwan University Hospital Hsin-Chu Branch, and National Taiwan University Hospital, Taipei, Taiwan, Republic of China
| | - Pei-Jer Chen
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, Republic of China
| | - Nadine Abi-Jaoudeh
- Department of Radiology, University of California, Irvine Medical Center, Orange, California, USA
| | - Lung-Hui Giiang
- Department of Radiology, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan, Republic of China
| | - Yu-Shen Tyan
- Department of Radiology, Chung Shan Medical University Hospital, Taichung, Taiwan, Republic of China
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Aly A, Lingohr-Smith M, Lin J, Seal B. Locoregional therapy patterns and healthcare economic burden of patients with hepatocellular carcinoma in the USA. Hepat Oncol 2021; 8:HEP37. [PMID: 34408847 PMCID: PMC8369525 DOI: 10.2217/hep-2021-0001] [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: 01/28/2021] [Accepted: 03/24/2021] [Indexed: 11/23/2022] Open
Abstract
Aim: To examine the locoregional therapy (LRT) patterns and the healthcare economic burden of patients with hepatocellular carcinoma (HCC) in the USA. Patients & methods: Patients with newly diagnosed HCC were identified from the MarketScan® databases (1 July 2015–31 May 2018). The LRTs received and all-cause and HCC-related healthcare costs were measured. Results: Among 2101 patients with HCC, most received embolization therapy as their first LRT treatment (57.8%, n = 1215); 17.1% (n = 360) received ablative therapy and 8.7% (n = 182) radiation therapy; 16.4% (n = 344) received multiple LRTs. After patients received their first LRT treatment, total all-cause healthcare costs averaged $20,316 per patient per month; 70.7% ($14,359) were HCC related. Conclusion: Among newly diagnosed HCC patients treated with LRT in the USA, the economic burden is high.
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Affiliation(s)
- Abdalla Aly
- AstraZeneca Pharmaceuticals LP, US Medical Affairs: Evidence Generation, Gaithersburg, MD 20878, USA
| | | | - Jay Lin
- Novosys Health, Green Brook, NJ 08812, USA
| | - Brian Seal
- AstraZeneca Pharmaceuticals LP, US Medical Affairs: Evidence Generation, Gaithersburg, MD 20878, USA
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Bajwa R, Madoff DC, Kishore SA. Embolotherapy for Hepatic Oncology: Current Perspectives and Future Directions. DIGESTIVE DISEASE INTERVENTIONS 2020; 4:134-147. [PMID: 32832829 DOI: 10.1055/s-0040-1712146] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
AbstractPrimary and secondary liver cancers are a major cause of mortality worldwide. Transarterial liver-directed therapy, or embolotherapy, represents an important locoregional treatment strategy for primary and secondary liver tumors. Embolotherapeutic modalities include bland embolization (transarterial embolization), chemoembolization (transarterial chemoembolization), and radioembolization or selective internal radiotherapy. A brief technical overview of embolotherapeutic modalities as well as supportive evidence for the treatment of most common primary and secondary liver tumors will be discussed in this review. Several potential future applications, including synergy with systemic therapy, interventional theranostics, and artificial intelligence will also be reviewed briefly.
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Affiliation(s)
- Raazi Bajwa
- Memorial Sloan Kettering Cancer Center, Department of Radiology, Division of Interventional Radiology, New York, NY, USA
| | - David C Madoff
- Yale University School of Medicine, Department of Radiology and Biomedical Imaging, Division of Interventional Radiology, New Haven, CT, USA
| | - Sirish A Kishore
- Memorial Sloan Kettering Cancer Center, Department of Radiology, Division of Interventional Radiology New York, NY, USA
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15
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Kishore SA, Bajwa R, Madoff DC. Embolotherapeutic Strategies for Hepatocellular Carcinoma: 2020 Update. Cancers (Basel) 2020; 12:791. [PMID: 32224882 PMCID: PMC7226474 DOI: 10.3390/cancers12040791] [Citation(s) in RCA: 56] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2020] [Revised: 03/16/2020] [Accepted: 03/17/2020] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) represents a significant contributor to cancer-related morbidity and mortality with increasing incidence in both developing and developed countries. Embolotherapy as a locoregional therapeutic strategy consists of trans-arterial or "bland" embolization (TAE), trans-arterial chemoembolization (TACE), and selective internal radiotherapy (SIRT). Trans-catheter arterial therapies can be applied along all stages of HCC, either as an alternative or neoadjuvant to surgical resection/transplantation in very early and early stage HCC or as a palliative option for local disease control in unresectable and advanced stage HCC. In advanced stage HCC, SIRT did not demonstrate superiority in comparison to systemic treatment options in several recent large prospective trials, though for carefully selected patients, may confer improved tolerability with similar disease control rates. The latest embolotherapeutic techniques and literature as they pertain to the management of HCC, as well as future directions, are reviewed in this article.
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Affiliation(s)
- Sirish A. Kishore
- Department of Radiology, Division of Interventional Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA; (S.A.K.); (R.B.)
| | - Raazi Bajwa
- Department of Radiology, Division of Interventional Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA; (S.A.K.); (R.B.)
| | - David C. Madoff
- Department of Radiology and Biomedical Imaging, Section of Interventional Radiology, Yale School of Medicine, New Haven, CT 06520, USA
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Iezzi R, Pompili M, Rinninella E, Annicchiarico E, Garcovich M, Cerrito L, Ponziani F, De Gaetano A, Siciliano M, Basso M, Zocco MA, Rapaccini G, Posa A, Carchesio F, Biolato M, Giuliante F, Gasbarrini A, Manfredi R. TACE with degradable starch microspheres (DSM-TACE) as second-line treatment in HCC patients dismissing or ineligible for sorafenib. Eur Radiol 2019; 29:1285-1292. [PMID: 30171360 DOI: 10.1007/s00330-018-5692-8] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2018] [Revised: 07/17/2018] [Accepted: 07/31/2018] [Indexed: 02/06/2023]
Abstract
OBJECTIVES To date, there is no approved second-line treatment for patients dismissing sorafenib or ineligible for this treatment, so it would be useful to find an effective alternative treatment option. The aim of our study was to evaluate safety, feasibility and effectiveness of transarterial chemoembolisation with degradable starch microspheres (DSM-TACE) in the treatment of patients with advanced hepatocellular carcinoma (HCC) dismissing or ineligible for multikinase-inhibitor chemotherapy administration (sorafenib) due to unbearable side effects or clinical contraindications. METHODS Forty consecutive BCLC stage B or C patients (31 male; age, 70.6 ± 13.6 years), with intermediate or locally advanced HCC dismissing or ineligible for sorafenib administration, who underwent DSM-TACE treatment cycle via lobar approach were prospectively enrolled. Tumour response was evaluated on multidetector computed tomography based on mRECIST criteria. Primary endpoints were safety, tolerance and overall disease control (ODC); secondary endpoints were progression-free survival (PFS) and overall survival (OS). RESULTS Technical success was achieved in all patients. No intra/peri-procedural death/major complications occurred. No signs of liver failure or systemic toxicity were detected. At 1-year follow-up, ODC of 52.5% was registered. PFS was 6.4 months with a median OS of 11.3 months. CONCLUSIONS DSM-TACE is safe and effective as a second-line treatment in HCC patients dismissing or ineligible for sorafenib. KEY POINTS • DSM-TACE is safe and effective as second-line treatment in HCC patients dismissing or ineligible for sorafenib • DSM-TACE allows the temporary occlusion of the smaller arterial vessels, improving overall therapeutic effectiveness by reducing the immediate wash-out of the cytostatic agent • DSM-TACE also decreases the risk of systemic toxicity and post-embolic syndrome.
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Affiliation(s)
- Roberto Iezzi
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168, Rome, Italy.
| | - Maurizio Pompili
- Dipartimento di Gastroenterologia, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168, Rome, Italy
| | - Emanuele Rinninella
- Dipartimento di Gastroenterologia, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168, Rome, Italy
| | - Eleonora Annicchiarico
- Dipartimento di Gastroenterologia, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168, Rome, Italy
| | - Matteo Garcovich
- Dipartimento di Gastroenterologia, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168, Rome, Italy
| | - Lucia Cerrito
- Dipartimento di Gastroenterologia, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168, Rome, Italy
| | - Francesca Ponziani
- Dipartimento di Gastroenterologia, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168, Rome, Italy
| | - AnnaMaria De Gaetano
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168, Rome, Italy
| | - Massimo Siciliano
- Dipartimento di Gastroenterologia, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168, Rome, Italy
| | - Michele Basso
- Dipartimento di Oncologia, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168, Rome, Italy
| | - Maria Assunta Zocco
- Dipartimento di Gastroenterologia, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168, Rome, Italy
| | - GianLodovico Rapaccini
- Dipartimento di Gastroenterologia, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168, Rome, Italy
| | - Alessandro Posa
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168, Rome, Italy
| | - Francesca Carchesio
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168, Rome, Italy
| | - Marco Biolato
- Dipartimento di Gastroenterologia, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168, Rome, Italy
| | - Felice Giuliante
- Dipartimento di Chirurgia, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168, Rome, Italy
| | - Antonio Gasbarrini
- Dipartimento di Gastroenterologia, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168, Rome, Italy
| | - Riccardo Manfredi
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168, Rome, Italy
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Lu L, Zeng J, Wen Z, Tang C, Xu N, Cochrane Hepato‐Biliary Group. Transcatheter arterial chemoembolisation followed by three-dimensional conformal radiotherapy versus transcatheter arterial chemoembolisation alone for primary hepatocellular carcinoma in adults. Cochrane Database Syst Rev 2019; 2:CD012244. [PMID: 30776082 PMCID: PMC6378926 DOI: 10.1002/14651858.cd012244.pub2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Hepatocellular carcinoma, also called malignant hepatoma, is a primary malignancy of the liver. Despite regular surveillance conducted in high-risk populations, most people with hepatocellular carcinoma are diagnosed at an advanced stage. Consequently, only a minority of people with the disease are suitable for surgical resection when diagnosed. OBJECTIVES To compare the beneficial and harmful effects of transcatheter arterial chemoembolisation (TACE) followed by three-dimensional conformal radiotherapy (3-DCRT) versus TACE alone in adults with primary hepatocellular carcinoma, considered unsuitable for surgical resection. SEARCH METHODS We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and Conference Proceedings Citation Index - Science up to 31 May 2018. We checked reference lists for all included studies and related reviews for further relevant articles. SELECTION CRITERIA We included all randomised clinical trials comparing TACE followed by 3-DCRT versus TACE alone in people with primary hepatocellular carcinoma. DATA COLLECTION AND ANALYSIS We used standard methodological procedures as suggested by Cochrane. We presented the results of the fixed-effect model in the absence of statistical heterogeneity. Otherwise, we reported the results from the random-effects model meta-analysis. We assessed risk of bias of the included trials using bias risk domains and presented the review results incorporating the methodological quality of the trials using GRADE. Our main conclusions were based on the analysis up to three years' follow-up. MAIN RESULTS We identified eight randomised clinical trials (632 participants) that fulfilled our inclusion criteria. All eight trials were at high risk of bias, and we rated the evidence as low to very low certainty. The mean age ranged from 16 years to 78 years. The proportion of men ranged from 60% to 75% and the proportion of people with stage III primary hepatocellular carcinoma ranged from 22% to 85%. The median follow-up duration was 12 months (2 months to 38 months).TACE followed by 3-DCRT compared with TACE alone may have reduced all-cause mortality at three years' follow-up (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.73 to 0.88; 552 participants; 7 trials; low-certainty evidence). TACE followed by 3-DCRT compared with TACE alone may reduce the proportion of participants without tumour response (complete response plus partial response) (RR 0.49, 95% CI 0.39 to 0.61; 632 participants; 8 trials; low-certainty evidence). Data, from one trial on health-related quality of life, favoured the TACE followed by 3-DCRT group, but the provided data were ill-defined (very low-certainty evidence). None of the trials reported serious adverse events. The results on non-serious adverse events were as follows: TACE followed by 3-DCRT compared with TACE alone showed no difference in the results for proportion of participants with leukopenia (RR 1.12, 95% CI 0.92 to 1.34; 438 participants; 5 trials; very low-certainty evidence) and serum transaminases elevation (RR 1.67, 95% CI 0.66 to 4.27; 280 participants; 4 trials; very low-certainty evidence). However, the proportion of participants with total bilirubin elevation was larger in the TACE followed by 3-DCRT group than in the TACE alone group (RR 2.69, 95% CI 1.34 to 5.40; 172 participants; 2 trials; very low-certainty evidence). The rate of participants with serum alpha-fetoprotein (AFP) without decline or normalisation was significantly lower in the TACE followed by 3-DCRT group than in the TACE group, but these data were from one trial only (Chi² = 7.24, P = 0.007; very low-certainty evidence). AUTHORS' CONCLUSIONS TACE followed by 3-DCRT may be associated with lower all-cause mortality and increased tumour response, despite the increased toxicity expressed by a higher rise of total bilirubin. Our review findings should be considered with caution because of the methodological weaknesses in the included trials, resulting in low- to very low-certainty evidence. Data on serious adverse events and health-related quality of life are lacking. We are also very much uncertain in the results of the reported non-serious adverse events. High-quality trials are needed to assess further the role of TACE followed by 3-DCRT for unresectable hepatocellular carcinoma.
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Affiliation(s)
- Liming Lu
- Clinical Research Center, South China Research Center for Acupuncture and Moxibustion, Medical College of Acu‐Moxi and Rehabilitation, Guangzhou University of Chinese Medicine232 Waihuan Dong RoadGuangzhouGuangdongChina510006
| | - Jingchun Zeng
- Department of Acupuncture, the First Affiliated Hospital of Guangzhou University of Chinese Medicine12 Jichang RoadGuangzhouGuangzhouChina510405
| | - Zehuai Wen
- Guangdong Provincial Hospital of Chinese Medicine, the Second Affiliated Hospital, Guangzhou University of Chinese MedicineKey Unit of Methodology in Clinical ResearchNo 111 Dade RoadGuangzhouGuangdongChina510120
| | - Chunzhi Tang
- Clinical Research Center, South China Research Center for Acupuncture and Moxibustion, Medical College of Acu‐Moxi and Rehabilitation, Guangzhou University of Chinese Medicine232 Waihuan Dong RoadGuangzhouGuangdongChina510006
| | - Nenggui Xu
- Clinical Research Center, South China Research Center for Acupuncture and Moxibustion, Medical College of Acu‐Moxi and Rehabilitation, Guangzhou University of Chinese Medicine232 Waihuan Dong RoadGuangzhouGuangdongChina510006
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Liu Z, Peng Q, Li Y, Gao Y. Resveratrol enhances cisplatin-induced apoptosis in human hepatoma cells via glutamine metabolism inhibition. BMB Rep 2018. [PMID: 30103844 PMCID: PMC6177506 DOI: 10.5483/bmbrep.2018.51.9.114] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Cisplatin is one of the most effective chemotherapeutic drugs used in the treatment of HCC, but many patients will ultimately relapse with cisplatin-resistant disease. Used in combination with cisplatin, resveratrol has synergistic effect of increasing chemosensitivity of cisplatin in various cancer cells. However, the mechanisms of resveratrol enhancing cisplatin-induced toxicity have not been well characterized. Our study showed that resveratrol enhances cisplatin toxicity in human hepatoma cells via an apoptosis-dependent mechanism. Further studies reveal that resveratrol decreases the absorption of glutamine and glutathione content by reducing the expression of glutamine transporter ASCT2. Flow cytometric analyses demonstrate that resveratrol and cisplatin combined treatment leads to a significant increase in ROS production compared to resveratrol or cisplatin treated hepatoma cells alone. Phosphorylated H2AX (γH2AX) foci assay demonstrate that both resveratrol and cisplatin treatment result in a significant increase of γH2AX foci in hepatoma cells, and the resveratrol and cisplatin combined treatment results in much more γH2AX foci formation than either resveratrol or cisplatin treatment alone. Furthermore, our studies show that over-expression of ASCT2 can attenuate cisplatin-induced ROS production, γH2AX foci formation and apoptosis in human hepatoma cells. Collectively, our studies suggest resveratrol may sensitize human hepatoma cells to cisplatin chemotherapy via glutamine metabolism inhibition.
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Affiliation(s)
- Zhaoyuan Liu
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, Guangdong Province, China
| | - Qing Peng
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, Guangdong Province, China
| | - Yang Li
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, Guangdong Province, China
| | - Yi Gao
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, Guangdong Province; State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou 510515, China
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Wei Y, Dai F, Zhao T, Tao C, Wang L, Ye W, Zhao W. Transcatheter arterial chemoembolization monotherapy vs combined transcatheter arterial chemoembolization-percutaneous microwave coagulation therapy for massive hepatocellular carcinoma (≥10 cm). Cancer Manag Res 2018; 10:5273-5282. [PMID: 30464624 PMCID: PMC6219403 DOI: 10.2147/cmar.s172395] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Background The prognosis of massive hepatocellular carcinomas (MHCCs; ≥10 cm) remains worse. Purpose The aim of this study was to evaluate the clinical benefits of transcatheter arterial chemoembolization (TACE) or TACE combined with percutaneous microwave coagulation therapy (PMCT) and the long-term survival rate of MHCC patients treated with these techniques. Patients and methods A retrospective study was performed using data involving 102 MHCC patients admitted to the Second Hospital of Nanjing from September 2010 to August 2015. The median interval between treatments and overall survival (OS) was hierarchically analyzed using log-rank tests. Multivariate analysis was done using Cox regression model analysis. Results The median survival time of MHCC patients was 3 months (range, 1–10 months) in the palliative group, 3 months (range, 1–39 months) in the TACE group, and 7.5 months (range, 3–30 months) in the TACE–PMCT group (P=0.038). The 6-, 12-, and 18-month OS rates for MHCC patients were 15%, 0%, and 0% in the palliative group, 30%, 25.63%, and 17.97% in the TACE group, and 50%, 41.67%, and 16.67% in the TACE–PMCT group, respectively (P=0.0467). In addition, TACE sessions had positive correlation with the survival time of MHCC patients (rho = 0.462, P<0.001). TACE treatment more than three times (HR =0.145, P<0.001) was an independent predictor of the survival of MHCC patients, which was identified by the Cox regression model analysis. Conclusions These results indicated that TACE–PMCT treatment in MHCC patients had advantages in prolonging OS and improving liver function. Multiple TACE treatments might be a suitable treatment for the MHCC patients.
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Affiliation(s)
- Yanyan Wei
- Liver Disease Department, The Second Hospital of Nanjing, Medical School of Southeast University, Nanjing, China, ;
| | - Feng Dai
- Liver Disease Department, The Second Hospital of Nanjing, Medical School of Southeast University, Nanjing, China, ;
| | - Tianhui Zhao
- Liver Disease Department, The Second Hospital of Nanjing, Medical School of Southeast University, Nanjing, China, ;
| | - Chen Tao
- Liver Disease Department, The Second Hospital of Nanjing, Medical School of Southeast University, Nanjing, China, ;
| | - Lili Wang
- Liver Disease Department, The Second Hospital of Nanjing, Medical School of Southeast University, Nanjing, China, ;
| | - Wei Ye
- Liver Disease Department, The Second Hospital of Nanjing, Medical School of Southeast University, Nanjing, China, ;
| | - Wei Zhao
- Liver Disease Department, The Second Hospital of Nanjing, Medical School of Southeast University, Nanjing, China, ;
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Lin YL. Proton beam therapy in apneic oxygenation treatment of an unresectable hepatocellular carcinoma: A case report and review of literature. World J Hepatol 2018; 10:772-779. [PMID: 30386470 PMCID: PMC6206151 DOI: 10.4254/wjh.v10.i10.772] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2018] [Revised: 06/14/2018] [Accepted: 06/28/2018] [Indexed: 02/06/2023] Open
Abstract
Presented here is the clinical course of a 63-year-old patient with a central, large and unresectable hepatocellular carcinoma (HCC) with liver metastases and tumor invasion of the portal and hepatic veins. After the tumor had been diagnosed, the patient was immediately treated with proton beam therapy (PBT), at a total dose of 60 Gy (relative biological effectiveness) in 20 fractions administered within 4 wk. To manage the respiratory movements, at the Rinecker Proton Therapy Center, apneic oxygenation was given daily, under general anesthesia. The patient tolerated both the PBT and general anesthesia very well, and did now show any signs of acute or late toxicity. The treatment was followed by constant reductions in the tumor marker alpha-fetoprotein and the cholestatic parameters gamma-glutamyltransferase and alkaline phosphatase. The patient commenced an adjuvant treatment with sorafenib, given at 6-wk intervals, after the PBT. Follow-up with regular magnetic resonance imaging has continued for 40 mo so far, demonstrating remarkable shrinkage of the HCC (maximal diameter dropping from approximately 13 cm to 2 cm). To date, the patient remains free of tumor recurrence. PBT served as a safe and effective treatment method for an unresectable HCC with vascular invasion.
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Affiliation(s)
- Yi-Lan Lin
- Department of Radiation Oncology, Rinecker Proton Therapy Center, Munich 81371, Germany
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Feasibility and outcomes of percutaneous thermal ablation of hepatocellular carcinoma in a transplanted allograft. Abdom Radiol (NY) 2018; 43:1478-1481. [PMID: 28936550 DOI: 10.1007/s00261-017-1323-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE To examine the safety, feasibility, and oncologic control following percutaneous image-guided thermal ablation of hepatocellular carcinoma (HCC) in a transplanted allograft. MATERIALS AND METHODS Retrospective review was performed to identify patients who underwent liver transplantation for HCC and subsequently underwent percutaneous hepatic thermal ablation for recurrent HCC within the allograft between January 1st, 2000-September 1st, 2016. Eleven patients with hepatic allograft HCC underwent twelve percutaneous thermal ablation procedures to treat 16 lesions. Patient, procedural characteristics, and local oncologic efficacy were reviewed. Complications were characterized via the Common Terminology for Clinically Adverse Events nomenclature [CTCAE] v4.03). RESULTS Eleven transplant recipients underwent treatment of 16 HCC tumors in their allografts during 12 ablation sessions. Mean follow-up time was 25 months (range 2-96 months). Local oncologic control was achieved in 10 of 11 tumors (91%) with imaging follow-up. One patient (8%) with Roux-en-Y biliary reconstruction developed a major complication with hepatic abscess. CONCLUSION Thermal ablation of recurrent HCC in transplanted allografts can be accomplished safely with acceptable rates of local control for patients with duct-to-duct biliary reconstruction. Due to the high number of patients deemed surgically unresectable, the morbidity of surgical resection, the side effects of targeted therapies, and significant mortality associated with recurrences in the transplanted allograft, patients may benefit from percutaneous thermal ablative treatments. Further study is needed to assess the role of thermal ablation in allograft HCC recurrences as primary therapy or in a multimodality approach with emerging systemic therapies.
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Lin H, Fan X, He L, Zhou D. Methylation patterns of RASA3 associated with clinicopathological factors in hepatocellular carcinoma. J Cancer 2018; 9:2116-2122. [PMID: 29937930 PMCID: PMC6010675 DOI: 10.7150/jca.24567] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2017] [Accepted: 03/31/2018] [Indexed: 12/25/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the sixth most common tumor worldwide. The relationship between the gene methylation accumulation and HCC has been widely studied. In our study, we used the Sequenom EpiTYPER assay to investigate the methylation levels of the RASA3 in 164 HCC samples and paired adjacent non-cancerous tissues, and the association between methylation level and clinicopathological features. The methylation level of the RASA3 in HCC samples was found significantly lower than that in the adjacent non-cancerous tissues (P<0.0001). Moreover, the hypomethylation of RASA3 in HCC samples was connected with the presence of tumornecrosis (P=0.029) and alcohol intake (P=0.002). Furthermore, it was found that the expression of RASA3 was significantly decreased in tumor tissues (P=0.0053), which was also correlated with the methylation levels of RASA3 gene. Thus, RASA3 hypomethylation is a common feature in HCC, and may be a potential mechanism for HCC development, and serves as a useful biomarker for the early detection, especially in alcohol-associated HCCs.
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Affiliation(s)
- Hui Lin
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,Biomedical Research Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Xiaoxiao Fan
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,Biomedical Research Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - LiFeng He
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,Biomedical Research Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Daizhan Zhou
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,Biomedical Research Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China.,Present address: Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine; Institute of Medical Genetics, Tongji University, Shanghai, China
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23
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Zhu Q, Liu J, Tang J, Guo DL, Li Y, Duan R. Overexpression of long non-coding RNAs DUXAP9 and DUXAP10 is associated with prognosis in patients with hepatocellular carcinoma after hepatectomy. INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY 2018; 11:1407-1414. [PMID: 31938237 PMCID: PMC6958151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 12/08/2017] [Accepted: 01/17/2018] [Indexed: 06/10/2023]
Abstract
AIM Hepatocellular carcinoma (HCC) is a common and aggressive malignant tumor with an especially high prevalence in Asian populations. This study aimed to identify differentially expressed lncRNAs using expression microarray and to explore the association between differential expression of lncRNAs and prognosis of HCC. METHODS We retrospectively reviewed 63 patients with primary HCC that underwent a curative liver resection at the Department of General Surgery, Jingmen First People's Hospital. The expression level of lncRNAs DUXAP9 and DUXAP10 were detected by real-time PCR. Prognostic factors were evaluated using Kaplan-Meier curves and Cox proportional hazards models. RESULTS By microarray profiling of lncRNAs, 256 were found to be differentially expressed, including 162 upregulated and 94 downregulated (P<0.05, fold change >2). Two candidate lncRNAs were determined as targets in this study, including DUXAP9 (upregulated by 6.35 fold) and DUXAP10 (upregulated by 4.53 fold). DUXAP9 and DUXAP10 were downregulated in the normal liver cell lines Chang liver, HL7702, THLE-2, THLE-3, FL62891, and AML12, which were significantly lower than HCC cell lines SMMC-7721, Hep3B, HuH7, MHCC-97H, HCC-LM, and SK-Hep-1 (P<0.05). Overexpression of lncRNAs DUXAP9 and DUXAP10 were associated with decreasing OS rates, respectively (P=0.0263 and P=0.0285). Meanwhile, Overexpression of DUXAP9 and DUXAP10 was associated with decreasing PFS rates, respectively (P=0.0174 and P=0.0041). After adjusting for competing risk factors, we identified microvascular invasion (P=0.014), tumor size (P=0.026), and lncRNAs DUXAP9 (P=0.001) and DUXAP10 (P=0.036) expression levels as independent prognostic factors associated with prognosis of patients with HCC. CONCLUSIONS We found that lncRNAs DUXAP9 and DUXAP10 are expressed significantly higher in HCC tissues compared with non-tumorous tissues. Overexpression of DUXAP9 and DUXAP10 were independent risk factors associated with prognosis of patients with HCC.
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Affiliation(s)
- Qian Zhu
- Department of General Surgery, Jingmen First People's Hospital Jingmen, Hubei Province, China
| | - Jian Liu
- Department of General Surgery, Jingmen First People's Hospital Jingmen, Hubei Province, China
| | - Jie Tang
- Department of General Surgery, Jingmen First People's Hospital Jingmen, Hubei Province, China
| | - De-Liang Guo
- Department of General Surgery, Jingmen First People's Hospital Jingmen, Hubei Province, China
| | - Yun Li
- Department of General Surgery, Jingmen First People's Hospital Jingmen, Hubei Province, China
| | - Rui Duan
- Department of General Surgery, Jingmen First People's Hospital Jingmen, Hubei Province, China
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Yasui D, Murata S, Ueda T, Sugihara F, Onozawa S, Kawamoto C, Kumita S. Novel treatment strategy for advanced hepatocellular carcinoma: combination of conventional transcatheter arterial chemoembolization and modified method with portal vein occlusion for cases with arterioportal shunt: a preliminary study. Acta Radiol 2018. [PMID: 28651444 DOI: 10.1177/0284185117717762] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Background A novel strategy to combine conventional transcatheter arterial chemoembolization (TACE) and TACE during portal vein occlusion (TACE-PVO) in the presence of high-flow arterioportal shunt (APS) has been developed to treat hepatocellular carcinoma (HCC) with portal invasion. Purpose To evaluate the efficacy of this strategy. Material and Methods Twenty-five cases of HCC with portal invasion, treated between April 2006 and December 2015, were evaluated. Balloon occlusion of the portal venous outlet was performed in eight cases of high-flow APS when performing TACE. Conventional TACE was performed in the other 17 cases. The primary endpoint was overall survival. Adverse events and deterioration of liver function were also evaluated. Results The median survival time (MST) was 12 months. One-, two-, and three-year survival rates were 48.0%, 39.3%, and 26.2%, respectively. Subgroup analysis and multivariate analysis revealed the CLIP score as prognostic factor. MST was 2.5 months in the subgroup with CLIP score ≥4 and 26.0 months in the subgroup with CLIP score ≤3 (hazard ratio = 7.7, 95% confidence interval = 2.3-25.8). Transient elevations of the levels of transaminase and bilirubin were observed; however, deterioration of liver function was infrequent; upgrading of Child-Pugh class in 9.1% of cases. Conclusion A novel strategy, combining conventional TACE and TACE-PVO, is effective for HCC with portal invasion. The CLIP score may be useful for considering treatment indication.
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25
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Gao L, Zhang J, Ma T, Yao N, Gao M, Shan X, Ni Y, Shao H, Xu K. Improved therapeutic outcomes of thermal ablation on rat orthotopic liver allograft sarcoma models by radioiodinated hypericin induced necrosis targeted radiotherapy. Oncotarget 2018; 7:51450-51461. [PMID: 27285983 PMCID: PMC5239487 DOI: 10.18632/oncotarget.9848] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2015] [Accepted: 05/22/2016] [Indexed: 12/19/2022] Open
Abstract
Residual tumor resulting in tumor recurrence after various anticancer therapies is an unmet challenge in current clinical oncology. This study aimed to investigate the hypothesis that radioiodinated hypericin (131I-Hyp) may inhibit residual tumor recurrence after microwave ablation (MWA) on rat orthotopic liver allograft sarcoma models.Thirty Sprague-Dawley (SD) rats with hepatic tumors were divided into three groups: Group A received laparotomy MWA and sequential intravenous injection (i.v.) of 131I labelled hypericin (131I-Hyp) in a time interval of 24 h; Group B received only laparotomy MWA; Group C was a blank control. Tumor inhibitory effects were monitored with in vivo magnetic resonance imaging (MRI) and these findings were compared to histopathology data before (baseline, day 0) and 1, 4, and 8 days after MWA. In addition, biodistribution of 131I-Hyp was assessed with in vivo single-photon emission computed tomography-computed tomography (SPECT-CT) imaging, in vitro autoradiography, fluorescent microscopy, and gamma counting.A fast clearance of 131I-Hyp and increasing deposit in necrotic tumors appeared over time, with a significantly higher radioactivity than other organs (0.9169 ± 1.1138 % ID/g, P < 0.01) on day 9. Tumor growth was significantly slowed down in group A compared to group B and C according to MRI images and corresponding tumor doubling time (12.13 ± 1.99, 4.09 ± 0.97, 3.36 ± 0.72 days respectively). The crescent tagerability of 131I-Hyp to necrosis was visualized consistently by autoradiography and fluorescence microscopy.In conclusion, 131I-Hyp induced necrosis targeted radiotherapy improved therapeutic outcomes of MWA on rat orthotopic liver allograft sarcoma models.
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Affiliation(s)
- Long Gao
- Department of Radiology, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Jian Zhang
- Laboratory of Translational Medicine, Jiangsu Provincial Academy of Traditional Chinese Medicine, Nanjing, China
| | - Tengchuang Ma
- Department of Radiology, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Nan Yao
- Laboratory of Translational Medicine, Jiangsu Provincial Academy of Traditional Chinese Medicine, Nanjing, China
| | - Meng Gao
- Laboratory of Translational Medicine, Jiangsu Provincial Academy of Traditional Chinese Medicine, Nanjing, China
| | - Xin Shan
- Laboratory of Translational Medicine, Jiangsu Provincial Academy of Traditional Chinese Medicine, Nanjing, China
| | - Yicheng Ni
- Department of Imaging & Pathology, Theragnostic Laboratory, University of Leuven, Leuven, Belgium
| | - Haibo Shao
- Department of Radiology, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Ke Xu
- Department of Radiology, The First Affiliated Hospital of China Medical University, Shenyang, China
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26
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Zhao J, Zhang H, Wei L, Xie S, Suo Z. Comparing the long-term efficacy of standard and combined minimally invasive procedures for unresectable HCC: a mixed treatment comparison. Oncotarget 2017; 8:15101-15113. [PMID: 27835871 PMCID: PMC5362470 DOI: 10.18632/oncotarget.13145] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2016] [Accepted: 10/12/2016] [Indexed: 12/16/2022] Open
Abstract
A small proportion of hepatocellular carcinoma (HCC) patients are suitable for surgical resections and various minimally invasive procedures have been introduced as alternatives to surgical resections. However, the relative efficacy of minimally invasive procedures remains to be studied in the current literature. Several popular minimally invasive procedures (monotherapy or combined therapies) were selected for comparison and their relative long-term efficacy were determined by using the statistics of hazard ratio (HR) which evaluates the survival status of HCC patients in one, two, three and four years, respectively. Evidence were obtained from the current literature and synthesized by using the approach of conventional pairwise meta-analysis and network meta-analysis (NMA). Moreover, selected minimally invasive procedures were ranked according to their surface under the cumulative ranking curve (SUCRA) which was produced by NMA in conjunction with the Markov Chain Monte Carlo (MCMC) sampling method. HCC patients treated by combined minimally invasive procedures, particularly transcatheter arterial chemoembolization (TACE) + high intensity focused ultrasound (HIFU), TACE + radiofrequency ablation (RFA), TACE + radiotherapy (RT) and TACE + Sorafenib (SOR) exhibited a significant decrease in the HR compared to those with standard TACE (HR < 1). The combined minimally invasive procedure of TACE + HIFU appears to be the most preferable therapy. PEI seems to be less favorable than other minimally invasive procedures. Combined minimally invasive procedures may be more preferable than standard minimally invasive procedures. Percutaneous ethanol injection (PEI) may not provide adequate efficacy compared to other minimally invasive procedures for unresectable HCC patients.
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Affiliation(s)
- Jianghai Zhao
- Department of Gastroenterology, Huaihe Hospital of Henan University, Kaifeng, Henan, 475000, China
| | - Hui Zhang
- Department of Gastroenterology, Huaihe Hospital of Henan University, Kaifeng, Henan, 475000, China
| | - Lunshou Wei
- Department of Gastroenterology, Huaihe Hospital of Henan University, Kaifeng, Henan, 475000, China
| | - Shuping Xie
- Department of Gastroenterology, Huaihe Hospital of Henan University, Kaifeng, Henan, 475000, China
| | - Zhimin Suo
- Department of Gastroenterology, Huaihe Hospital of Henan University, Kaifeng, Henan, 475000, China
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Lv D, Wang Y, Zhang Y, Cui P, Xu Y. Downregulated long non-coding RNA DREH promotes cell proliferation in hepatitis B virus-associated hepatocellular carcinoma. Oncol Lett 2017; 14:2025-2032. [PMID: 28789433 PMCID: PMC5530050 DOI: 10.3892/ol.2017.6436] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2016] [Accepted: 03/23/2017] [Indexed: 02/06/2023] Open
Abstract
The hepatitis B virus X (HBx) protein has been characterized as an oncogene involved in epigenetic modifications during hepatocarcinogenesis; however, the underlying mechanisms are not entirely clear. Long non-coding RNAs (lncRNAs), a type of epigenetic regulator molecules, have also been demonstrated to serve crucial roles in carcinogenesis, including hepatocellular carcinoma (HCC). In the present study, a human lncRNA DREH was identified, which inhibits cell proliferation in vitro and in vivo, and acts as a tumor suppressor in HBx-mediated hepatocarcinogenesis. The study revealed that the expression of DREH was frequently downregulated in hepatitis B virus (HBV)-associated HCC tissues in comparison with adjacent non-cancerous hepatic tissues, and was inversely correlated with HBx mRNA expression in HBV-associated HCC. In addition, the levels of DREH were inversely correlated with hepatitis B surface antigen and tumor size in HCC tissues. The forced expression of HBx in liver cell lines resulted in a significant decrease in the expression of DREH. Furthermore, suppression of DREH expression promotes the proliferation of HCC cells in vitro and in vivo. In conclusion, the present findings support the role of HBx-downregulated lncRNA DREH in tumor suppression in HBV-associated HCC patients. This contributes to a better understanding of epigenetic aberration of deregulated lncRNAs by HBx and the potential development of lncRNA-based targeted approaches for the treatment of HBV-associated HCC.
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Affiliation(s)
- Dong Lv
- Gastroenterology Department, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China
| | - Yuan Wang
- Third Department of General Surgery, Peking University People's Hospital, Beijing 100044, P.R. China
| | - Ying Zhang
- Gastroenterology Department, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China
| | - Peilin Cui
- Gastroenterology Department, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China
| | - Youqing Xu
- Gastroenterology Department, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China
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Welch BT, Schmitz JJ, Atwell TD, McGauvran AM, Kurup AN, Callstrom MR, Schmit GD. Evaluation of infectious complications following percutaneous liver ablation in patients with bilioenteric anastomoses. Abdom Radiol (NY) 2017; 42:1579-1582. [PMID: 28111698 DOI: 10.1007/s00261-017-1051-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
PURPOSE Prior bilioenteric anastomosis (BEA) has been associated with elevated risk of abscess formation after thermal ablation of hepatic tumors. We assessed the incidence of hepatic abscess after thermal ablation in a BEA cohort treated with extended antibiotic regimens following ablation. MATERIALS AND METHODS Retrospective review was performed to identify patients with BEA who underwent percutaneous hepatic thermal ablation between January 1, 2003-September 1, 2016. Fifteen patients with BEA underwent 18 percutaneous thermal ablation procedures. Patient and procedural characteristics were reviewed, as well as the antibiotic regiment utilized post ablation. Complications were characterized via standardized nomenclature [Common Terminology for Clinically Adverse Events (CTCAE) v4.03]. RESULTS Fifteen patients with BEA underwent treatment of 49 liver lesions during 18 ablation sessions. Mean follow-up in these patients was 39 months (range 3-138 months). Two patients (11%) developed hepatic abscesses, both of which occurred within 45 days of the ablation procedure while the patients were still on extended prophylactic antibiotic therapy. No additional CTCAE clinically significant complications were observed. CONCLUSION Thermal ablation of hepatic tumors can be accomplished safely in patients with BEA. Long-term post-procedural antibiotics may mitigate the risk of hepatic abscess formation. Due to the high number of patients who are deemed surgically unresectable, patients with BEA may have limited alternate treatment modalities and percutaneous hepatic thermal ablative treatments warrant consideration.
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Affiliation(s)
- B T Welch
- Mayo Clinic Department of Radiology, 200 1st ST SW, Rochester, MN, 55905, USA.
| | - J J Schmitz
- Mayo Clinic Department of Radiology, 200 1st ST SW, Rochester, MN, 55905, USA
| | - T D Atwell
- Mayo Clinic Department of Radiology, 200 1st ST SW, Rochester, MN, 55905, USA
| | - A M McGauvran
- Mayo Clinic Department of Radiology, 200 1st ST SW, Rochester, MN, 55905, USA
| | - A N Kurup
- Mayo Clinic Department of Radiology, 200 1st ST SW, Rochester, MN, 55905, USA
| | - M R Callstrom
- Mayo Clinic Department of Radiology, 200 1st ST SW, Rochester, MN, 55905, USA
| | - G D Schmit
- Mayo Clinic Department of Radiology, 200 1st ST SW, Rochester, MN, 55905, USA
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Hu J, Maybody M, Cao G, Wang X, Chen H, Zhu X, Yang R, Wang X. Lipiodol retention pattern assessed by cone beam computed tomography during conventional transarterial chemoembolization of hepatocellular carcinoma: accuracy and correlation with response. Cancer Imaging 2016; 16:32. [PMID: 27716376 PMCID: PMC5048686 DOI: 10.1186/s40644-016-0090-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2016] [Accepted: 09/10/2016] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND To investigate accuracy of intraprocedural cone beam computed tomography (CBCT) compared to fluoroscopy for detection of lipiodol retention pattern during conventional transarterial chemoembolization (cTACE) of hepatocellular carcinoma (HCC) and its correlation with short-term response. METHODS Between September 2013 and July 2014, 29 patients with HCC underwent chemoembolization of 51 tumors (mean diameter 28.1 mm, range 10.0-136.3 mm). Lipiodol retention pattern was assessed by CBCT at the endpoint of cTACE compared by fluoroscopy. Depending on the pattern of tumor covered by lipiodol three classes were defined: complete (more than 90 %, no peripheral defects), moderate (50-90 %, some with or without peripheral defects), and poor (less than 50 %). Tumor response was assessed by modified Response Evaluation Criteria in Solid Tumors (mRECIST) based on follow-up contrast enhanced (CE) computed tomography (CT) or magnetic resonance imaging (MRI) obtained 4-6 weeks post-cTACE. Correlations between lipiodol retention patterns on CBCT and fluoroscopy as well as tumor response were assessed using multivariate logistic regression. RESULTS Of 51 hepatic tumors, 40 (78.4 %) had complete response (CR); 8 (15.7 %) had partial response (PR); 1 (2.0 %) had stable disease (SD); and 2 (3.9 %) had progressive disease (PD). The degree of lipiodol retention scored excellent, moderate, and poor, in fluoroscopic images vs CBCT images were 23 (45.1 %) vs 39 (76.5 %), 19 (37.3 %) vs 11 (21.6 %), and 9 (17.6 %) vs 1 (2.0 %), respectively. Lipiodol retention assessment with CBCT (Az = 0.75) is more accurate than fluoroscopy (Az = 0.54) in predicting target tumor response. Other than lipiodol retention pattern assessed with CBCT (p = 0.01), tumor size (p = 0.04) is an independent predictors of CR. CONCLUSION CBCT is more accurate than fluoroscopy in classification of lipiodol retention pattern in HCC tumors at the time of cTACE. CBCT could be used as a reliable intra precedural monitoring modality of cTACE.
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Affiliation(s)
- Jungang Hu
- Department of Interventional Radiology, Peking University Cancer Hospital & Institute, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing, 100142 China
| | - Majid Maybody
- Department of Radiology, Interventional Radiology Service, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, 10021 NY USA
| | - Guang Cao
- Department of Interventional Radiology, Peking University Cancer Hospital & Institute, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing, 100142 China
| | - Xiao Wang
- Department of Epidemiology and Biostatistics, Peking University Sixth Hospital, Beijing, 100191 China
| | - Hui Chen
- Department of Interventional Radiology, Peking University Cancer Hospital & Institute, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing, 100142 China
| | - Xu Zhu
- Department of Interventional Radiology, Peking University Cancer Hospital & Institute, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing, 100142 China
| | - Renjie Yang
- Department of Interventional Radiology, Peking University Cancer Hospital & Institute, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing, 100142 China
| | - Xiaodong Wang
- Department of Interventional Radiology, Peking University Cancer Hospital & Institute, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing, 100142 China
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Sugihara F, Murata S, Ueda T, Yasui D, Yamaguchi H, Miki I, Kawamoto C, Uchida E, Kumita SI. Haemodynamic changes in hepatocellular carcinoma and liver parenchyma under balloon occlusion of the hepatic artery. Eur Radiol 2016; 27:2474-2481. [PMID: 27678134 DOI: 10.1007/s00330-016-4573-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2016] [Revised: 07/05/2016] [Accepted: 08/22/2016] [Indexed: 11/26/2022]
Abstract
OBJECTIVES To investigate haemodynamic changes in hepatocellular carcinoma (HCC) and liver under hepatic artery occlusion. METHODS Thirty-eight HCC nodules in 25 patients were included. Computed tomography (CT) during hepatic arteriography (CTHA) with and without balloon occlusion of the hepatic artery was performed. CT attenuation and enhancement volume of HCC and liver with and without balloon occlusion were measured on CTHA. Influence of balloon position (segmental or subsegmental branch) was evaluated based on differences in HCC-to-liver attenuation ratio (H/L ratio) and enhancement volume of HCC and liver. RESULTS In the segmental group (n = 20), H/L ratio and enhancement volume of HCC and liver were significantly lower with balloon occlusion than without balloon occlusion. However, in the subsegmental group (n = 18), H/L ratio was significantly higher and liver enhancement volume was significantly lower with balloon occlusion; HCC enhancement volume was similar with and without balloon occlusion. Rate of change in H/L ratio and enhancement volume of HCC and liver were lower in the segmental group than in the subsegmental group. There were significantly more perfusion defects in HCC in the segmental group. CONCLUSIONS Hepatic artery occlusion causes haemodynamic changes in HCC and liver, especially with segmental occlusion. KEY POINTS • Hepatic artery occlusion causes haemodynamic changes in hepatocellular carcinoma and liver. • Segmental occlusion decreased rate of change in hepatocellular carcinoma-to-liver attenuation ratio. • Subsegmental occlusion increased rate of change in hepatocellular carcinoma-to-liver attenuation ratio. • Hepatic artery occlusion decreased enhancement volume of hepatocellular carcinoma and liver. • Hepatic artery occlusion causes perfusion defects in hepatocellular carcinoma.
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Affiliation(s)
- Fumie Sugihara
- Department of Radiology, Center for Advanced Medical Technology, Nippon Medical School, Tokyo, Japan
| | - Satoru Murata
- Department of Radiology, Center for Advanced Medical Technology, Nippon Medical School, Tokyo, Japan.
| | - Tatsuo Ueda
- Department of Radiology, Center for Advanced Medical Technology, Nippon Medical School, Tokyo, Japan
| | - Daisuke Yasui
- Department of Radiology, Center for Advanced Medical Technology, Nippon Medical School, Tokyo, Japan
| | - Hidenori Yamaguchi
- Department of Radiology, Center for Advanced Medical Technology, Nippon Medical School, Tokyo, Japan
| | - Izumi Miki
- Department of Radiology, Center for Advanced Medical Technology, Nippon Medical School, Tokyo, Japan
| | - Chiaki Kawamoto
- Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| | - Eiji Uchida
- Department of Surgery, Nippon Medical School, Tokyo, Japan
| | - Shin-Ichiro Kumita
- Department of Radiology, Center for Advanced Medical Technology, Nippon Medical School, Tokyo, Japan
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Li J, Liu F, Gupta S, Li C. Interventional Nanotheranostics of Pancreatic Ductal Adenocarcinoma. Am J Cancer Res 2016; 6:1393-402. [PMID: 27375787 PMCID: PMC4924507 DOI: 10.7150/thno.15122] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2016] [Accepted: 05/19/2016] [Indexed: 12/13/2022] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) accounts for over 90% of all pancreatic cancer. Nanoparticles (NPs) offer new opportunities for image-guided therapy owing to the unique physicochemical properties of the nanoscale effect and the multifunctional capabilities of NPs. However, major obstacles exist for NP-mediated cancer theranostics, especially in PDAC. The hypovascular nature of PDAC may impede the deposition of NPs into the tumor after systemic administration, and most NPs localize predominantly in the mononuclear phagocytic system, leading to a relatively poor tumor-to-surrounding-organ uptake ratio. Image guidance combined with minimally invasive interventional procedures may help circumvent these barriers to poor drug delivery of NPs in PDAC. Interventional treatments allow regional drug delivery, targeted vascular embolization, direct tumor ablation, and the possibility of disrupting the stromal barrier of PDAC. Interventional treatments also have potentially fewer complications, faster recovery, and lower cost compared with conventional therapies. This work is an overview of current image-guided interventional cancer nanotheranostics with specific attention given to their applications for the management of PDAC.
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32
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Lu L, Zeng J, Wen Z. Combination of three-dimensional conformal radiotherapy and transcatheter arterial chemoembolisation versus transcatheter arterial chemoembolisation for primary hepatocellular carcinoma. Hippokratia 2016. [DOI: 10.1002/14651858.cd012244] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Affiliation(s)
- Liming Lu
- Guangdong Provincial Hospital of Chinese Medicine; Key Unit of Methodology in Clinical Research; 111 Dade Road Guangzhou Guangdong China 510120
| | - Jingchun Zeng
- Guangzhou University of Chinese Medicine; 12 Jichang Road Guangzhou Guangzhou China 510405
| | - Zehuai Wen
- Guangdong Provincial Hospital of Chinese Medicine; Key Unit of Methodology in Clinical Research; 111 Dade Road Guangzhou Guangdong China 510120
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Bai H, Gao P, Gao H, Sun G, Dong C, Han J, Jiang G. Improvement of Survival Rate for Patients with Hepatocellular Carcinoma Using Transarterial Chemoembolization in Combination with Three-Dimensional Conformal Radiation Therapy: A Meta-Analysis. Med Sci Monit 2016; 22:1773-81. [PMID: 27228411 PMCID: PMC4915316 DOI: 10.12659/msm.895548] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Transarterial chemoembolization (TACE) has been used alone or in combination with three-dimensional conformal radiation therapy (3DCRT) for treating hepatocellular carcinoma (HCC). The overall survival rate of HCC patients undergoing both treatments, however, has not been systematically studied. The aim of this meta-analysis-based study was to evaluate the overall efficacy of the combined therapy or monotherapy, thereby providing information for clinical treatment. MATERIAL AND METHODS We searched Google Scholar, PubMed, and Chinese National Knowledge Infrastructure (CNKI) for eligible studies, and a total of 17 case-control studies (including HCC patients treated by TACE plus 3DCRT or TACE alone) were included to perform the meta-analysis. Based on the available data, we assessed the improvements of 1-year, 2-year, and 3-year survival rate for the combination therapy of TACE and 3DCRT or TACE alone. Furthermore, the analysis was also stratified by the tumor response: complete response (CR), partial response (PR), no response (NR) and progressive disease (PD). Statistical analysis was performed using STATA 12 (Stata Statistical Software: Release 12). RESULTS The results show that HCC patients receiving combination therapy have significantly increased overall survival rate when compared to those receiving TACE alone (1-year survival rate: OR=1.95, 95% CI 1.54-2.47, p=7.3×10^-8; 2-year survival rate: OR=1.87, 95% CI 1.49-2.34, p=1.6×10^-7; 3-year survival rate: OR=2.00, 95% CI 1.52-2.64, p=1.8×10^-6). CONCLUSIONS Assessment of tumor response demonstrates that the combination therapy can efficiently increase the tumor response rate (CR+PR: OR=2.29, 95% CI 1.70-3.08, p=1.1×10^-7), with a lower rate of subsequent tumor development (PD: OR=0.25, 95% CI 0.15-0.40, p=5.5×10^-8).
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Affiliation(s)
- Houqiao Bai
- Department of Internal Medicine, Maternity and Child Care, Weihai, Shandong, China (mainland)
| | - Peng Gao
- Department of Internal Medicine, Maternity and Child Care, Weihai, Shandong, China (mainland)
| | - Hao Gao
- Department of Imaging, Tumor Branch of Municipal Hospital, Weihai, Shandong, China (mainland)
| | - Guangxi Sun
- Department of Internal Medicine, Maternity and Child Care, Weihai, Shandong, China (mainland)
| | - Chonghai Dong
- Department of Internal Medicine, Maternity and Child Care, Weihai, Shandong, China (mainland)
| | - Jian Han
- Department of Bone Cancer, Yantaishan Hospital, Yantai, Shandong, China (mainland)
| | - Guosheng Jiang
- , Medical Sciences of Shandong, Jinan, Shandong, China (mainland)
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Di Fazio P, Waldegger P, Jabari S, Lingelbach S, Montalbano R, Ocker M, Slater EP, Bartsch DK, Illig R, Neureiter D, Wissniowski TT. Autophagy-related cell death by pan-histone deacetylase inhibition in liver cancer. Oncotarget 2016; 7:28998-29010. [PMID: 27058414 PMCID: PMC5045373 DOI: 10.18632/oncotarget.8585] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2015] [Accepted: 03/18/2016] [Indexed: 02/07/2023] Open
Abstract
Autophagy is a homeostatic, catabolic degradation process and cell fate essential regulatory mechanism. Protracted autophagy triggers cell death; its aberrant function is responsible for several malignancies. Panobinostat, a potent pan-deacetylase inhibitor, causes endoplasmic reticulum stress-induced cell death. The aim of this study was to investigate the role of autophagy in deacetylase inhibitor-triggered liver cancer cell death.HepG2 (p53wt) and Hep3B (p53 null) liver cancer cell lines were exposed to panobinostat. RT-qPCR and western blot confirmed autophagic factor modulation. Immuno-fluorescence, -precipitation and -histochemistry as well as transmission electron microscopy verified autophagosome formation. The cytotoxicity of panobinostat and autophagy modulators was detected using a real time cell viability assay.Panobinostat induced autophagy-related factor expression and aggregation. Map1LC3B and Beclin1 were significantly over-expressed in HepG2 xenografts in nude mice treated with panobinostat for 4 weeks. Subcellular distribution of Beclin1 increased with the appearance of autophagosomes-like aggregates. Cytosolic loss of p53, in HepG2, and p73, in Hep3B cells, and a corresponding gain of their nuclear level, together with modulation of DRAM1, were observed. Autophagosome aggregation was visible after 6 h of treatment. Treatment of cells stably expressing GFP-RFPtag Map1LC3B resulted in aggregation and a fluorescence switch, thus confirming autophagosome formation and maturation. Tamoxifen, an inducer of autophagy, caused only a block in cell proliferation; but in combination with panobinostat it resulted in cell death.Autophagy triggers cell demise in liver cancer. Its modulation by the combination of tamoxifen and panobinostat could be a new option for palliative treatment of hepatocellular carcinoma.
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Affiliation(s)
- Pietro Di Fazio
- Department of Visceral, Thoracic and Vascular Surgery, Philipps University of Marburg, Marburg, Germany
| | - Petra Waldegger
- Institute for Biomedical Aging Research, University of Innsbruck, Rennweg, Innsbruck, Austria
| | - Samir Jabari
- Institute for Anatomy I, University of Erlangen-Nurnberg, Erlangen, Germany
| | | | - Roberta Montalbano
- Department of Visceral, Thoracic and Vascular Surgery, Philipps University of Marburg, Marburg, Germany
| | - Matthias Ocker
- Institute for Surgical Research, Philipps University of Marburg, Marburg, Germany
- Experimental Medicine Oncology, Bayer Pharma AG, Berlin Germany
| | - Emily P. Slater
- Department of Visceral, Thoracic and Vascular Surgery, Philipps University of Marburg, Marburg, Germany
| | - Detlef K. Bartsch
- Department of Visceral, Thoracic and Vascular Surgery, Philipps University of Marburg, Marburg, Germany
| | - Romana Illig
- Institute of Pathology, Paracelsus Medical University/Salzburger Landeskliniken (SALK), Salzburg, Austria
| | - Daniel Neureiter
- Institute of Pathology, Paracelsus Medical University/Salzburger Landeskliniken (SALK), Salzburg, Austria
| | - Thaddeus T. Wissniowski
- Department of Gastroenterology and Endocrinology, Philipps University of Marburg, Marburg, Germany
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Shi Y, Zhai B. A Recent Advance in Image-Guided Locoregional Therapy for Hepatocellular Carcinoma. Gastrointest Tumors 2016; 3:90-102. [PMID: 27904861 DOI: 10.1159/000445888] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2016] [Accepted: 03/22/2016] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third most common cause of cancer-related deaths. Hepatic resection and liver transplantation are considered to be the preferred treatment for HCC. However, as novel therapeutic options such as image-guided locoregional therapies have emerged and been refined, the manner in which HCC is treated has changed dramatically compared with what it was considered just 2 decades earlier. SUMMARY This study reviews the current results of various image-guided locoregional therapies for treating HCC, especially focusing on thermal ablative and transarterial techniques. KEY MESSAGE Advances in image-guided locoregional therapies, including local ablative therapy and transarterial therapy, have led to a major breakthrough in the management of HCC. Both survival rates and cure rates of patients with HCC have improved markedly since the introduction of these techniques. PRACTICAL IMPLICATIONS Radiofrequency ablation is currently considered as an alternative to surgical resection for patients with early-stage HCC. A newer technique of ablation such as microwave ablation is increasingly being used, especially for large HCC. Transarterial chemoembolization has become a standard care for asymptomatic patients with multinodular tumors in intermediate-stage disease, and transarterial radioembolization has become the method of choice in HCC cases with portal vein thrombosis. Moreover, combination treatment modalities, such as thermal-based ablation combined with transarterial chemoembolization or 125I seed implant brachytherapy, may further broaden their clinical indications for HCC. Moreover, use of localized radiation in combination with thermal ablation has been reported to improve tumor control and long-term survival.
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Affiliation(s)
- Yaoping Shi
- Department of Interventional Oncology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Bo Zhai
- Department of Interventional Oncology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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Liang KH, Lin CL, Chen SF, Chiu CW, Yang PC, Chang ML, Lin CC, Sung KF, Yeh C, Hung CF, Chien RN, Yeh CT. GALNT14 genotype effectively predicts the therapeutic response in unresectable hepatocellular carcinoma treated with transcatheter arterial chemoembolization. Pharmacogenomics 2016; 17:353-66. [DOI: 10.2217/pgs.15.179] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Aim: Transcatheter arterial chemoembolization is currently the standard treatment in hepatocellular carcinoma patients with Barcelona Clinic Liver Cancer stage B. Genomic variants of GALNT14 were recently identified as effective predictors for chemotherapy responses in Barcelona Clinic Liver Cancer stage C patients. Methods: We investigated the prognosis predictive value of GALNT14 genotypes in 327 hepatocelluar carcinoma patients treated by transcatheter arterial chemoembolization. Result: Cox proportional hazards model analysis showed that the genotype ‘TT’ was associated with shorter time-to-response (multivariate p < 0.001), time-to-complete-response (p = 0.004) and longer time-to-tumor progression (p < 0.001), compared with the genotype ‘non-TT’. In patients with albumin <3.5 g/dl, genotype ‘TT’ was associated with longer overall survival (p = 0.027). Finally, genotype ‘TT’ correlated with higher cancer-to-noncancer ratios of GALNT14 protein levels, lower cancer-to-noncancer ratios of antiapoptotic cFLIP-S, and a clustered glycosylation pattern in the extracellular domain of death receptor 5. Conclusion: GALNT14 genotypes were significantly associated with clinical outcomes of transcatheter arterial chemoembolization. The differential status of extrinsic apoptotic signaling between cancerous and non-cancerous tissues might underlie the clinical association.
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Affiliation(s)
- Kung-Hao Liang
- Liver Research Center, Chang Gung Memorial Hospital, No. 5, Fu-Sing Street, Guishan Township, Taoyuan, Taiwan
- Molecular Medicine Research Center, Chang Gung University, No. 259, Wenhua 1st Rd, Guishan Dist, Taoyuan, Taiwan
| | - Chih-Lang Lin
- Liver Research Center, Chang Gung Memorial Hospital, No. 5, Fu-Sing Street, Guishan Township, Taoyuan, Taiwan
- Liver Research Unit, Keelung Chang Gung Memorial Hospital, No. 222, Maijin Road, Keelung, Taiwan
| | - Sung-Fang Chen
- Department of Chemistry, National Taiwan Normal University, No. 162, Section 1, Heping E Rd, Taipei, Taiwan
| | - Chih-Wei Chiu
- Department of Chemistry, National Taiwan Normal University, No. 162, Section 1, Heping E Rd, Taipei, Taiwan
| | - Pei-Ching Yang
- Liver Research Center, Chang Gung Memorial Hospital, No. 5, Fu-Sing Street, Guishan Township, Taoyuan, Taiwan
- Molecular Medicine Research Center, Chang Gung University, No. 259, Wenhua 1st Rd, Guishan Dist, Taoyuan, Taiwan
| | - Ming-Ling Chang
- Liver Research Center, Chang Gung Memorial Hospital, No. 5, Fu-Sing Street, Guishan Township, Taoyuan, Taiwan
| | - Chen-Chun Lin
- Liver Research Center, Chang Gung Memorial Hospital, No. 5, Fu-Sing Street, Guishan Township, Taoyuan, Taiwan
| | - Kai-Feng Sung
- Liver Research Center, Chang Gung Memorial Hospital, No. 5, Fu-Sing Street, Guishan Township, Taoyuan, Taiwan
| | - Cassandra Yeh
- Taipei American School, 800 Chung Shan North Road, Section 6, Taipei, Taiwan
| | - Chien-Fu Hung
- Department of Diagnostic Radiology, Chang Gung Memorial Hospital, Taipei, Taiwan
| | - Rong-Nan Chien
- Liver Research Unit, Keelung Chang Gung Memorial Hospital, No. 222, Maijin Road, Keelung, Taiwan
| | - Chau-Ting Yeh
- Liver Research Center, Chang Gung Memorial Hospital, No. 5, Fu-Sing Street, Guishan Township, Taoyuan, Taiwan
- Molecular Medicine Research Center, Chang Gung University, No. 259, Wenhua 1st Rd, Guishan Dist, Taoyuan, Taiwan
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A randomised controlled trial of meloxicam, a Cox-2 inhibitor, to prevent hepatocellular carcinoma recurrence after initial curative treatment. Hepatol Int 2016; 10:799-806. [PMID: 26846471 PMCID: PMC5003903 DOI: 10.1007/s12072-016-9704-y] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2015] [Accepted: 01/11/2016] [Indexed: 01/04/2023]
Abstract
Background Because the recurrence rate of hepatocellular carcinoma (HCC) is high, even after curative treatments such as hepatic resection and microwave ablation, chemopreventive agents that can effectively suppress HCC recurrence are required. Cyclooxygenase-2 (Cox-2) was recently found to be overexpressed in HCC. Therefore, Cox-2 inhibitors may offer a chemopreventive therapy for HCC. This randomised controlled trial (RCT) investigated the potential for meloxicam, a clinically used Cox-2 inhibitor, to prevent HCC recurrence after initial curative treatment. Methods A total of 232 consecutive patients underwent hepatic resection and/or microwave ablation as initial therapy for HCC at our institute between July 2008 and April 2011. Eight patients were excluded because of poor renal function, history of non-steroidal anti-inflammatory drug-related ulceration, or multiple cancers. The remaining 224 patients were randomised to a control group (n = 113) or a meloxicam group (n = 111). To patients in the meloxicam group, meloxicam was administered at 15 mg daily (5 mg three times a day) as long as possible. The overall survival (OS) and disease-free survival (DFS) rates were determined. Results The 1-, 3-, and 5-year OS rates of the meloxicam group were 95.4, 82.4, and 70.1 %, respectively. Those of the control group were 98.2, 85.1, and 71.5 %, respectively (p = 0.9549). The corresponding DFS rates of the meloxicam group were 89.2, 53.9, and 44.0 % and those of control group were 86.5, 57.0, and 43.4 %, respectively (p = 0.6722). In the OS and DFS of subsets including patients with hepatitis B or C virus infection, we could not find significant differences between the meloxicam and control groups. However, in the subgroup of analysis of patients without viral hepatitis (NBNC-HCC), significant differences were observed in the DFS between the meloxicam group (1-year DFS, 92.3 %; 3-year DFS, 75.8 %; 5-year DFS, 70.4 %) and control group (1-year DFS, 83.3 %; 3-year DFS, 48.1 %; 5-year DFS, not obtained) (p = 0.0211). Conclusion Administration of the Cox-2 inhibitor meloxicam may have a possibility to suppress HCC recurrence after initial curative treatments in patients with NBNC-HCC.
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Gao XL, Lin H, Zhao W, Hou YQ, Bao YL, Song ZB, Sun LG, Tian SY, Liu B, Li YX. JA, a new type of polyunsaturated fatty acid isolated from Juglans mandshurica Maxim, limits the survival and induces apoptosis of heptocarcinoma cells. Apoptosis 2015; 21:340-50. [DOI: 10.1007/s10495-015-1202-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
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Habib A, Desai K, Hickey R, Thornburg B, Lewandowski R, Salem R. Locoregional therapy of hepatocellular carcinoma. Clin Liver Dis 2015; 19:401-20. [PMID: 25921670 DOI: 10.1016/j.cld.2015.01.008] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Hepatocellular carcinoma can be treated using minimally invasive, image-guided, catheter-based or percutaneous techniques. Such procedures offer compelling clinical outcomes with a favorable side-effect profile in a population of patients who are poor candidates for surgical or systemic treatment. This article discusses key data regarding the effectiveness of locoregional therapies in treating these patients. Disease-specific treatment is discussed in the context of hepatocellular carcinoma, with additional data discussed in the context of transplantation. As rapid innovation occurs in the realm of oncology, interventional oncology represents a safe, effective alternative that continues to generate impressive data that could potentially change treatment paradigms.
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Affiliation(s)
- Ali Habib
- Section of Interventional Radiology, Division of Interventional Oncology, Department of Radiology, Northwestern University, Chicago, IL, USA
| | - Kush Desai
- Section of Interventional Radiology, Division of Interventional Oncology, Department of Radiology, Northwestern University, Chicago, IL, USA
| | - Ryan Hickey
- Section of Interventional Radiology, Division of Interventional Oncology, Department of Radiology, Northwestern University, Chicago, IL, USA
| | - Bartley Thornburg
- Section of Interventional Radiology, Division of Interventional Oncology, Department of Radiology, Northwestern University, Chicago, IL, USA
| | - Robert Lewandowski
- Section of Interventional Radiology, Division of Interventional Oncology, Department of Radiology, Northwestern University, Chicago, IL, USA
| | - Riad Salem
- Vascular and Interventional Radiology, Image-Guided Therapy, Section of Interventional Radiology, Division of Interventional Oncology, Department of Radiology, Northwestern University, 676 North St. Clair, Suite 800, Chicago, IL 60611, USA.
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Varbiro G. Enhancement of the Cytotoxic Effect of Anticancer Agent by Cytochrome c Functionalised Hybrid Nanoparticles in Hepatocellular Cancer Cells. ACTA ACUST UNITED AC 2014. [DOI: 10.15406/jnmr.2014.01.00010] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
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