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Pan S, Wo X, Zhu H, Xia F. Conventional and drug‑eluting bead transarterial chemoembolization in patients with inoperable intrahepatic cholangiocarcinoma: a meta‑analysis. Wideochir Inne Tech Maloinwazyjne 2024; 19:407-413. [PMID: 40123725 PMCID: PMC11927539 DOI: 10.20452/wiitm.2024.17906] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Revised: 10/31/2024] [Indexed: 03/25/2025] Open
Abstract
INTRODUCTION In patients with inoperable intrahepatic cholangiocarcinoma (ICC), both conventional transarterial chemoembolization (cTACE) and drug‑eluting bead TACE (DEB‑TACE) can be employed as therapeutic interventions. However, the relative advantages of these strategies remain to be clarified. AIM This meta‑analysis was performed to compare the safety and efficacy of DEB‑TACE and cTACE in the treatment of ICC. MATERIALS AND METHODS A comprehensive search of the Cochrane Library, PubMed, and Wanfang databases was conducted to identify publications that were pertinent to the present meta‑analysis. The primary outcome of interest was the overall survival (OS) rate. Secondary outcomes were progression‑free survival (PFS), disease control rate (DCR), objective response rate (ORR), and adverse event (AE) rate. Heterogeneity was evaluated using the I 2 statistic, while publication bias was assessed with the Egger test. RESULTS A total of 6 articles involving 283 and 178 patients who received cTACE and DEB‑TACE treatment, respectively, were included in this study. DEB‑TACE was superior to cTACE in terms of DCR (P = 0.004), PFS (P <0.001), and OS (P = 0.004), despite comparable pooled ORRs. No intergroup differences were observed with respect to AE occurrence. The ORR, DCR, and OS end points showed significant heterogeneity (I2 = 79%, I2 = 61%, and I2 = 95%, respectively). Additionally, the OS end point was subject to substantial publication bias (Egger test, P = 0.002). CONCLUSIONS DEB‑TACE was shown to be superior to cTACE with respect to efficacy, while the safety profile of these 2 interventions was similar. Consequently, DEB‑TACE offers additional value in the management of inoperable ICC.
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Affiliation(s)
- Su‑Rong Pan
- Department of Gastroenterology, Binzhou People’s Hospital, Binzhou, China
| | - Xue‑Wen Wo
- Department of Neurology, Binzhou People’s Hospital, Binzhou, China
| | - Hong‑Fang Zhu
- Department of Interventional Vascular Surgery, Binzhou People’s Hospital, Binzhou, China
| | - Feng‑Fei Xia
- Department of Gastroenterology, Binzhou People’s Hospital, Binzhou, China
- Department of Neurology, Binzhou People’s Hospital, Binzhou, China
- Department of Interventional Vascular Surgery, Binzhou People’s Hospital, Binzhou, China
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Collettini F, Andrašina T, Reimer P, Schima W, Stroszczynski C, Lamprecht Y, Auer TA, Rohan T, Wildgruber M, Gebauer B, Masthoff M. Degradable starch microspheres transarterial chemoembolization (DSM-TACE) in patients with unresectable hepatocellular carcinoma: results from the Prospective Multicenter Observational HepaStar Trial. Eur Radiol 2024:10.1007/s00330-024-11272-8. [PMID: 39702628 DOI: 10.1007/s00330-024-11272-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Revised: 10/10/2024] [Accepted: 11/06/2024] [Indexed: 12/21/2024]
Abstract
OBJECTIVES Despite increasing interest, prospective data on the use of degradable starch microsphere-transarterial chemoembolization (DSM-TACE) in the management of patients with unresectable HCC are still scarce. The objective of the HepaStar study was to collect prospective safety and effectiveness data in a prospective multicenter observational study. MATERIALS AND METHODS Between January 2017 and December 2022, consecutive participants with unresectable or recurrent HCC treated with DSM-TACE as standard of care at 6 participating centers in Europe were enrolled. Tumor response was evaluated according to the mRECIST criteria. Overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were assessed by using Kaplan-Meier analysis and Common Terminology Criteria for Adverse Events, version 5. Liver function deterioration was assessed by monitoring changes in liver blood tests during the follow-up. RESULTS Seventy-nine participants (median age, 69 years (IQR, 51-87 years); 67 men (85%)) were enrolled and treated. The median follow-up time was 18 months (IQR 9.5-38.0 months). The estimated median OS and PFS for the entire cohort was 32 months (CI, 95% 21-NaN) and 9 months (CI, 95% 7-NaN), respectively. Eleven (13.9%) participants experienced at least one grade 3 or 4 AE. The most frequent grade 3-4 AE was elevated bilirubin (2.2%, 5 of 79). Deterioration of bilirubin, AST, ALT, and albumin were observed in 24.1%, 23.7%, 19%, and 24% of participants, respectively. CONCLUSION DSM-TACE achieves promising survival in patients with unresectable or recurrent HCC. This technique shows a favorable safety profile both in terms of treatment-related AEs and liver function deterioration. KEY POINTS Question Although degradable starch microspheres transarterial chemoembolization is widely used in clinical practice across Europe, prospective data on its application in hepatocellular carcinoma patients remains limited. Findings Degradable starch microspheres transarterial chemoembolization results in promising survival rates, good tumor response rates, and low rates of treatment-related adverse events. Clinical relevance In patients with unresectable hepatocellular carcinoma, degradable starch microspheres transarterial chemoembolization represents a safe and effective alternative to more well-established chemoembolization techniques like conventional transarterial chemoembolization and drug-eluting beads transarterial chemoembolization.
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Affiliation(s)
- Federico Collettini
- Department of Radiology, Charité University Medicine Berlin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
- Berlin Institute of Health (BIH), Anna-Louisa-Karsch-Straße 2, 10178, Berlin, Germany.
| | - Tomáš Andrašina
- Department of Radiology and Nuclear Medicine, University Hospital Brno and Masaryk University, Jihlavská 340/20, 625 00, Brno, Czech Republic
| | - Peter Reimer
- Department of Radiology, Klinikum Karlsruhe, Moltkestraße 90, 76133, Karlsruhe, Germany
| | - Wolfgang Schima
- Department of Diagnostic and Interventional Radiology, Göttlicher Heiland Krankenhaus, Dornbacher Straße 20-30, 1170, Wien, Austria
| | - Christian Stroszczynski
- Department of Radiology, University Medical Center Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany
| | - Yasmina Lamprecht
- Department of Radiology, Charité University Medicine Berlin Berlin, Charitéplatz 1, 10117, Berlin, Germany
| | - Timo Alexander Auer
- Department of Radiology, Charité University Medicine Berlin Berlin, Charitéplatz 1, 10117, Berlin, Germany
- Berlin Institute of Health (BIH), Anna-Louisa-Karsch-Straße 2, 10178, Berlin, Germany
| | - Tomáš Rohan
- Department of Radiology and Nuclear Medicine, University Hospital Brno and Masaryk University, Jihlavská 340/20, 625 00, Brno, Czech Republic
| | - Moritz Wildgruber
- Department of Radiology, University Hospital, LMU Munich, Marchioninistraße 15, 81377, Munich, Germany
| | - Bernhard Gebauer
- Department of Radiology, Charité University Medicine Berlin Berlin, Charitéplatz 1, 10117, Berlin, Germany
| | - Max Masthoff
- Clinic of Radiology, University Hospital of Münster, Albert-Schweitzer Campus 1, 48149, Münster, Germany
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Qi JS, Zhao P, Zhao XB, Zhao YL, Guo YC. Small particle drug-eluting beads-transarterial chemoembolization combined with targeted therapy in the clinical treatment of unresectable liver cancer. World J Gastrointest Oncol 2024; 16:4157-4165. [DOI: 10.4251/wjgo.v16.i10.4157] [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: 06/05/2024] [Revised: 08/07/2024] [Accepted: 08/12/2024] [Indexed: 09/26/2024] Open
Abstract
BACKGROUND Liver cancer is a highly malignant tumor with significant clinical impact. Chemotherapy alone often yields suboptimal outcomes in both the short and long term, characterized by high rates of local recurrence and distant metastasis, leading to a poor long-term prognosis.
AIM To evaluate the clinical efficacy of small particle drug-eluting beads-transarterial chemoembolization (DEB-TACE) combined with targeted therapy for the treatment of unresectable liver cancer.
METHODS We analyzed clinical data from 74 patients with unresectable liver cancer admitted between January 2019 and December 2020. Based on the different treatment regimens administered, patients were divided into the control (36 patients receiving sorafenib alone) and joint (38 patients receiving small particle DEB-TACE combined with sorafenib) groups. We compared liver function indicators [alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), albumin (ALB)] and serum tumor markers [alpha fetoprotein (AFP)] before and after treatment in both groups. Short-term efficacy measures [complete response (CR), partial response, progression disease, stable disease, objective response rate (ORR), and disease control rate (DCR)] were assessed post-treatment. Long-term follow-up evaluated median overall survival (OS), progression-free survival (PFS), and adverse reaction rates between the two groups.
RESULTS One month post-treatment, the joint group demonstrated significantly higher rates of CR, ORR, and DCR compared to the control group (P < 0.05). Three days after treatment, the joint group showed elevated levels of ALT, AST, and TBIL but reduced levels of ALB and AFP compared to the control group (P < 0.05). The median OS was 18 months for the control group and 25 months for the joint group, while the median PFS was 15 months for the control group and 22 months for the joint group, with significant differences observed (log-rank: χ2 = 7.824, 6.861, respectively; P = 0.005, 0.009, respectively). The incidence of adverse reactions was not significantly different between the groups (P > 0.05).
CONCLUSION The combination of small particle DEB-TACE and sorafenib significantly improves both short- and long-term outcomes in the treatment of unresectable liver cancer while preserving liver function.
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Affiliation(s)
- Jing-Song Qi
- Department of Interventional, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453100, Henan Province, China
| | - Peng Zhao
- Department of Interventional, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453100, Henan Province, China
| | - Xiao-Bo Zhao
- Department of Interventional, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453100, Henan Province, China
| | - Yong-Li Zhao
- Department of Interventional, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453100, Henan Province, China
| | - Ying-Chang Guo
- Department of Interventional, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453100, Henan Province, China
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Li Z, Huang M, Li Y, Wang Y, Ma Y, Ma L, Jiang H, Ngai T, Tang J, Guo Q. Emulsion-Based Multi-Phase Integrated Microbeads with Inner Multi-Interface Structure Enable Dual-Modal Imaging for Precision Endovascular Embolization. Adv Healthc Mater 2024; 13:e2400281. [PMID: 39081117 DOI: 10.1002/adhm.202400281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Revised: 07/16/2024] [Indexed: 10/30/2024]
Abstract
Microsphere-based embolic agents have gained prominence in transarterial embolization (TAE) treatment, a critical minimally invasive therapy widely applied for a variety of diseases such as hypervascular tumors and acute bleeding. However, the development of microspheres with long-term, real-time, and repeated X-ray imaging as well as ultrasound imaging remains challenging. In this study, emulsion-based dual-modal imaging microbeads with a unique internal multi-interface structure is developed for TAE treatment. The embolic microbeads are fabricated from a solidified oil-in-water (O/W) emulsion composed of crosslinked CaAlg-based aqueous matrix and dispersed radiopaque iodinated oil (IO) droplets through a droplet-based microfluidic fabrication method. The CaAlg-IO microbeads exhibit superior X-ray imaging visibility due to the incorporation of exceptionally high iodine level up to 221 mgI mL-1, excellent ultrasound imaging capability attributed to the multi-interface structure of the O/W emulsion, great microcatheter deliverability thanks to their appropriate biomechanical properties and optimal microbead density, and extended drug release behavior owing to the biodegradation nature of the embolics. Such an embolic agent presents a promising emulsion-based platform to utilize multi-phased structures for improving endovascular embolization performance and assessment capabilities.
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Affiliation(s)
- Zhihua Li
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Guangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, 518055, P. R. China
| | - Man Huang
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Guangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, 518055, P. R. China
| | - Yingnan Li
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Guangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, 518055, P. R. China
| | - Yongchao Wang
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Guangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, 518055, P. R. China
| | - Yutao Ma
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Guangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, 518055, P. R. China
| | - Le Ma
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Guangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, 518055, P. R. China
| | - Hongliang Jiang
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Guangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, 518055, P. R. China
| | - To Ngai
- Department of Chemistry, Chinese University of Hong Kong, Shatin, N. T., Hong Kong, 999077, P. R. China
| | - Jianbo Tang
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Guangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, 518055, P. R. China
| | - Qiongyu Guo
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Guangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, 518055, P. R. China
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Ma Z, Li Q, Wang W, Deng Z. Transcription factor E2F4 facilitates SUMOylation to promote HCC progression through interaction with LIN9. Int J Oncol 2024; 65:98. [PMID: 39239750 PMCID: PMC11387118 DOI: 10.3892/ijo.2024.5686] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Accepted: 06/14/2024] [Indexed: 09/07/2024] Open
Abstract
SUMOylation plays a crucial role in numerous cellular biological and pathophysiological processes associated with human disease; however, the mechanisms regulating the genes involved in SUMOylation remain unclear. In the present study, E2F transcription factor 4 (E2F4) was identified as an E2F member related to hepatocellular carcinoma (HCC) progression by public database analysis. It was found that E2F4 promoted the proliferation and invasiveness of HCC cells via SUMOylation using Soft agar and Transwell migration assays. Mechanistically, it was demonstrated that E2F4 upregulated the transcript and protein expression levels of baculoviral IAP repeat containing 5, cell division cycle associated 8 and DNA topoisomerase II α using western blotting. Furthermore, the interaction between E2F4 with lin‑9 DREAM multi‑vulva class B core complex component (LIN9) was explored by co‑immunoprecipitation, immunofluorescence co‑localization and bimolecular fluorescence complementation assays. Moreover, it was demonstrated that E2F4 promoted the progression of HCC cells via LIN9. Rescue experiments revealed that LIN9 facilitated the SUMOylation and proliferation of HCC cells, which was prevented by knocking down E2F4 expression. In conclusion, the findings of the present study indicated that E2F4 plays a major role in the proliferation of HCC cells and may be a potential therapeutic target in the future.
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Affiliation(s)
- Zhenwei Ma
- Department of Hepatobiliary and Pancreatic Surgery, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan, Hubei 430064, P.R. China
| | - Qilan Li
- Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
| | - Wenjing Wang
- Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
| | - Zhengdong Deng
- Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
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Zhang JL, Yuan B, Zhang XW, Zhang H, Wang H, Wang XZ, Zhao HW. X-ray Opaque Polymer Drug-Eluting Beads Loaded with Iodized Oil: Preparation and In Vitro and In Vivo Evaluations. ACS OMEGA 2024; 9:31353-31358. [PMID: 39072120 PMCID: PMC11270547 DOI: 10.1021/acsomega.3c09368] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Revised: 04/19/2024] [Accepted: 07/04/2024] [Indexed: 07/30/2024]
Abstract
Drug-eluting microspheres are commonly used as a local drug delivery system for interventional therapy. However, current drug-eluting microspheres have poor X-ray visibility, which can hinder tracking and postembolization evaluation. In the current study, X-ray-visible poly(acrylic acid) drug-eluting beads loaded with iodized oil (IO-PAA-DEBs) ranging from 100-300 μm were prepared and evaluated both in vitro and in vivo. Iodized oil served as the radiopaque agent, and X-ray and computed tomography scanning confirmed that the microspheres exhibited excellent X-ray-visible properties. The drug-loading capacities of bleomycin hydrochloride, doxorubicin hydrochloride, and oxaliplatin were also investigated. IO-PAA-DEBs exhibited sustained drug release properties, accompanied by a cumulative drug release rate that reached approximately 60% after 120 h. In vitro and in vivo experiments revealed that IO-PAA-DEBs had good biocompatibility. Collectively, these results demonstrated that IO-PAA-DEBs could facilitate transarterial embolization and sustained drug delivery.
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Affiliation(s)
- Jin Long Zhang
- Capital
Medical University Affiliated Beijing Tongren Hospital Department
of Radiology, Beijing 100730, China
| | - Bing Yuan
- Department
of Interventional Radiology, Chinese PLA
General Hospital, Beijing 100853, P. R. China
| | | | - Heng Zhang
- Department
of Radiology, Chinese PLA General Hospital
Second Medical Center, Beijing 100853, China
| | - Hao Wang
- Shenyang
Pharmaceutical University, Shenyang 117004, China
| | - Xing Zhi Wang
- Shenyang
Pharmaceutical University, Shenyang 117004, China
| | - Hong Wei Zhao
- Capital
Medical University Affiliated Beijing Tongren Hospital Department
of Radiology, Beijing 100730, China
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Ma Y, Li Z, Luo Y, Chen Y, Ma L, Liu X, Xiao J, Huang M, Li Y, Jiang H, Wang M, Wang X, Li J, Kong J, Shi P, Yu H, Jiang X, Guo Q. Biodegradable Microembolics with Nanografted Polyanions Enable High-Efficiency Drug Loading and Sustained Deep-Tumor Drug Penetration for Locoregional Chemoembolization Treatment. ACS NANO 2024; 18:18211-18229. [PMID: 38946122 DOI: 10.1021/acsnano.4c00047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/02/2024]
Abstract
Transarterial chemoembolization (TACE), the mainstay treatment of unresectable primary liver cancer that primarily employs nondegradable drug-loaded embolic agents to achieve synergistic vascular embolization and locoregional chemotherapy effects, suffers from an inferior drug burst behavior lacking long-term drug release controllability that severely limits the TACE efficacy. Here we developed gelatin-based drug-eluting microembolics grafted with nanosized poly(acrylic acid) serving as a biodegradable ion-exchange platform that leverages a counterion condensation effect to achieve high-efficiency electrostatic drug loading with electropositive drugs such as doxorubicin (i.e., drug loading capacity >34 mg/mL, encapsulation efficiency >98%, and loading time <10 min) and an enzymatic surface-erosion degradation pattern (∼2 months) to offer sustained locoregional pharmacokinetics with long-lasting deep-tumor retention capability for TACE treatment. The microembolics demonstrated facile microcatheter deliverability in a healthy porcine liver embolization model, superior tumor-killing capacity in a rabbit VX2 liver cancer embolization model, and stabilized extravascular drug penetration depth (>3 mm for 3 months) in a rabbit ear embolization model. Importantly, the microembolics finally exhibited vessel remodeling-induced permanent embolization with minimal inflammation responses after complete degradation. Such a biodegradable ion-exchange drug carrier provides an effective and versatile strategy for enhancing long-term therapeutic responses of various local chemotherapy treatments.
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Affiliation(s)
- Yutao Ma
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Guangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China
- Department of Biomedical Engineering, City University of Hong Kong, Kowloon, Hong Kong SAR 999077, China
| | - Zhihua Li
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Guangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China
| | - Yucheng Luo
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Guangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China
| | - Yao Chen
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Guangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China
| | - Le Ma
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Guangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China
| | - Xiaoya Liu
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Guangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China
| | - Jingyu Xiao
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Guangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China
| | - Man Huang
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Guangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China
| | - Yingnan Li
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Guangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China
| | - Hongliang Jiang
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Guangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China
| | - Meijuan Wang
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Guangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China
| | - Xiaoqian Wang
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Guangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China
| | - Jiangtao Li
- Department of Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China
| | - Jian Kong
- Department of Interventional Radiology, First Affiliated Hospital of Southern University of Science and Technology, Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, Guangdong 518020, China
| | - Peng Shi
- Department of Biomedical Engineering, City University of Hong Kong, Kowloon, Hong Kong SAR 999077, China
- Shenzhen Research Institute, City University of Hong Kong, Shenzhen, Guangdong 518057, China
| | - Hanry Yu
- Mechanobiology Institute, National University of Singapore, 117411 Singapore
- Department of Physiology, Institute for Digital Medicine (WisDM), Yong Loo Lin School of Medicine, 117593 Singapore
- Singapore-MIT Alliance for Research and Technology, 138602 Singapore
| | - Xingyu Jiang
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Guangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China
| | - Qiongyu Guo
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Guangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China
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Zhang Z, Jiang N, Yin X, Xu A, Hao Y, Li H, Yang W, Mu K. Comparison of efficacy and safety of conventional transarterial chemoembolization and drug-eluting bead transarterial chemoembolization in unresectable intrahepatic cholangiocarcinoma: A multicenter retrospective cohort study. Eur J Radiol 2024; 176:111541. [PMID: 38843693 DOI: 10.1016/j.ejrad.2024.111541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Revised: 05/18/2024] [Accepted: 05/31/2024] [Indexed: 06/17/2024]
Abstract
PURPOSE The efficacy and safety of drug-eluting bead transarterial chemoembolization (DEB-TACE) and conventional TACE (c-TACE) in the treatment of patients with unresectable intrahepatic cholangiocarcinoma (ICC) remained controversial. Therefore, we aimed to compare the efficacy and safety between c-TACE and DEB-TACE among patients with ICC. METHOD Between June 10, 2016 and November 19, 2022, consecutive patients with pathological diagnoses of ICC were divided into the DEB-TACE group and the c-TACE group based on the type of TACE treatment they received. The Kaplan-Meier method and log-rank test were used to compare overall survival (OS) between the two groups. Propensity score matching (PSM) was used to balance the characteristics between the c-TACE group and the DEB-TACE group. RESULTS A total of 132 patients were included in this study, with 64 patients in the c-TACE group and 68 patients in the DEB-TACE group. The median OS for c-TACE and DEB-TACE was 5 and 12 months, respectively. The objective response rate (ORR) for c-TACE and DEB-TACE was 0 % and 66.2 %, respectively; the disease control rate (DCR) was 37.5 % and 91.2 %. There were no significant differences between c-TACE and DEB-TACE among adverse effects at 3 months after treatment (P > 0.05). The results remained consistent after PSM. The Cox regression demonstrated that the DEB-TACE was an independent protective factor for OS. CONCLUSIONS Patients in the DEB-TACE group had longer OS and higher ORR and DCR than those in the c-TACE group, but no significant difference was observed between the two groups regarding adverse effects.
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Affiliation(s)
- Ze Zhang
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China; School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, China
| | - Nan Jiang
- School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, China
| | - Xiaoxv Yin
- School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, China
| | - Anhui Xu
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China
| | - Yonghong Hao
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China
| | - Hualing Li
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China
| | - Wenhua Yang
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China
| | - Ketao Mu
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China.
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Wang Q, Zhu L, Sheng Q. Clinical research progress of callisperes ® of drug-loaded microsphere arterial chemoembolisation in the treatment of solid tumors. Discov Oncol 2024; 15:161. [PMID: 38739205 DOI: 10.1007/s12672-024-01030-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Accepted: 05/10/2024] [Indexed: 05/14/2024] Open
Abstract
The incidence and mortality of cancer is ever-increasing, which poses a significant challengesto human health and a substantial economic burden to patients. At present, chemotherapy is still a primary treatment for various cancers. However, chemotherapy kills tumors but also induces the related side effects, whichadversely impacting patient quality of life and exacerbating suffering. Therefore, there is an urgent need for new and effective treatments that can control tumor growth while reducing the side effects for patients. Arterial chemoembolization has been attracted much attentionwhich attributed to the advantage of ability to embolize tumor vessels to block blood and nutrition supplies. Thus, to achieve local tumor control, it has become an effective means of local tumor control and has been widely used in clinical practice. Despite its efficacy, conventional arterial chemoembolization techniques, limited by embolization materials, have been associated with incomplete embolization and suboptimal drug delivery outcomes. Gradually, researchers have shifted their attention to a new type of embolic material called CalliSperes® drug-eluting embolic bead (DEB). DEB can not only load high doses of drugs, but also has strong sustained drug release ability and good biocompatibility. The integration of DEBs with traditional arterial chemoembolization (DEB-TACE) promises targeted vascular embolization, mitigated tumor ischemia and hypoxia, and direct intravascular chemotherapy delivery. It can prevent cancer cell differentiation and accelerate their death, meanwhile, directly injecting chemotherapy drugs into the target blood vessels reduced the blood concentration of the whole body, thus reduced the toxic and side effects of chemotherapy. Furthermore, DEB-TACE's sustained drug release capability elevates local drug concentrations at the tumor site, amplifying its antitumor efficacy. Therefore, DEB-TACE has become a hot spot in clinical research worldwide. This review introduces the pathogenesis of solid tumors, the background of research and biological characteristics of DEB, and the action mechanism of DEB-TACE, as well as its clinical research in various solid tumors and future prospects. This review aims to provide new ideas for the treatment of DEB-TACE in various solid tumors.
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Affiliation(s)
- Qin Wang
- Department of Infectious Diseases, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China
| | - Lujian Zhu
- Department of Infectious Diseases, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China
| | - Qiyue Sheng
- Department of Infectious Diseases, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China.
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Wang M, Gao Y, Liu X, Li Z, Xiao J, Gao X, Gibson MI, Guo Q. Cirrhotic hepatocellular carcinoma-based decellularized liver cancer model for local chemoembolization evaluation. Acta Biomater 2024; 176:144-155. [PMID: 38244660 DOI: 10.1016/j.actbio.2024.01.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Revised: 01/02/2024] [Accepted: 01/15/2024] [Indexed: 01/22/2024]
Abstract
Transarterial chemoembolization (TACE) is a common treatment for unresectable intermediate stage hepatocellular carcinoma (HCC) and involves the combination of chemotherapy agents and embolic materials to target and block the blood supply to the tumor, leading to localized treatment. However, the selection of clinical chemoembolization agents remains limited, and the effectiveness of various agents is still under investigation. Meanwhile, replicating the complex vasculature and extracellular matrix (ECM) circumstances of HCC in in vitro models for evaluating embolic agents proves to be challenging. Herein, we developed a decellularized cancerous liver model with translucent appearance, a complicated hepatic vascular system and tissue-specific ECM for the evaluation of embolic agents. Inkpad oil and microparticles were used to illustrate different systems of vascular structures between healthy and HCC rats' livers. Quantitative analysis with AngioTool revealed significant differences in vessel density and lacunarity between the two groups. Proteomics showed higher secretion of collagens in the HCC rat liver models than in healthy livers. Utilizing this in vitro model, we investigated the impact of tumor-specific vascular structure and ECM composition on chemoembolization performance, the two key factors inaccessible by currently available drug release testing platforms. Our findings revealed that the presence of an aberrant vascular system and the distorted ECM within the model led to drug retention. This preclinical model holds great promise as a valuable tool for evaluating embolic agents and studying their performance in the tumor microenvironment. STATEMENT OF SIGNIFICANCE: Transarterial chemoembolization (TACE), which employs drug-eluting embolic agents to obstruct the tumor-feeding vessels while locally releasing chemotherapeutic drugs into the tumor, has become the first-line treatment of unresectable liver cancer over past two decades. Nevertheless, the advancement of effective drug-eluting embolic agents has been retarded due to the lack of appropriate in vitro models for assessing the local embolization and chemotherapy performances in TACE. Here we developed a cirrhotic hepatocellular carcinoma-based decellularized liver cancer model, which preserves the aberrant vasculatures and tumor-specific extracellular matrix of liver cancer, for TACE evaluation. This model incorporates a blood flow simulation component to assess the dynamics of drug release behaviors of chemoembolic agents within tumor-mimicking conditions, more accurately replicating the in vivo environment for the locoregional assessments as compared to conventional in vitro models.
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Affiliation(s)
- Meijuan Wang
- Department of Biomedical Engineering, Shenzhen Key Laboratory of Smart Healthcare Engineering, Guangdong Provincial Key Laboratory of Advanced Biomaterials, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China
| | - Yanan Gao
- Department of Biomedical Engineering, Shenzhen Key Laboratory of Smart Healthcare Engineering, Guangdong Provincial Key Laboratory of Advanced Biomaterials, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China; Department of Chemistry and Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK
| | - Xiaoya Liu
- Department of Biomedical Engineering, Shenzhen Key Laboratory of Smart Healthcare Engineering, Guangdong Provincial Key Laboratory of Advanced Biomaterials, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China
| | - Zhihua Li
- Department of Biomedical Engineering, Shenzhen Key Laboratory of Smart Healthcare Engineering, Guangdong Provincial Key Laboratory of Advanced Biomaterials, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China
| | - Jingyu Xiao
- Department of Biomedical Engineering, Shenzhen Key Laboratory of Smart Healthcare Engineering, Guangdong Provincial Key Laboratory of Advanced Biomaterials, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China
| | - Xu Gao
- Department of Biomedical Engineering, Shenzhen Key Laboratory of Smart Healthcare Engineering, Guangdong Provincial Key Laboratory of Advanced Biomaterials, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China
| | - Matthew I Gibson
- Department of Chemistry and Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK; Department of Chemistry, University of Manchester, Oxford Road, Manchester M13 9PL, UK; Manchester Institute of Biotechnology, University of Manchester, 131 Princess St, Manchester M1 7DN, UK
| | - Qiongyu Guo
- Department of Biomedical Engineering, Shenzhen Key Laboratory of Smart Healthcare Engineering, Guangdong Provincial Key Laboratory of Advanced Biomaterials, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China.
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Zhu HD, Li X, Sun JH, Zhu X, Liu ZY, Li HL, Lu J, Yan ZP, Shao GL, He XF, Chao M, Lu LG, Zhong BY, Li R, Zhang Q, Teng GJ. Transarterial Chemoembolization with Epirubicin-Loaded Microspheres for Hepatocellular Carcinoma: A Prospective, Single-Arm, Multicenter, Phase 2 Study (STOPPER Trial). Cardiovasc Intervent Radiol 2024; 47:325-336. [PMID: 38413420 PMCID: PMC10920424 DOI: 10.1007/s00270-024-03666-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2023] [Accepted: 01/16/2024] [Indexed: 02/29/2024]
Abstract
PURPOSE While the role of drug-eluting beads transarterial chemoembolization (DEB-TACE) for hepatocellular carcinoma (HCC) is established, questions regarding appropriate bead size for use in patients remain. This trial evaluated the effectiveness and safety of DEB-TACE using small-size (≤ 100 μm) microspheres loaded with epirubicin. MATERIALS AND METHODS This prospective, single-arm, multicenter study enrolled patients diagnosed with HCC who underwent DEB-TACE using 40 (range, 30-50), 75 (range, 60-90), or 100 (range, 75-125) μm epirubicin-loaded microspheres (TANDEM microspheres, Varian Medical). Bead size was at the discretion of treating physicians and based on tumor size and/or vascular structure. The primary outcome measure was 6-month objective response rate (ORR). Secondary outcome measures were 30-day and 3-month ORR, time to tumor progression and extrahepatic spread, proportion of progression-free survival and overall survival (OS) at one year, and incidence of treatment-associated adverse events. RESULTS Data from 108 patients from ten centers was analyzed. Six-month ORR was 73.3 and 71.3% based on European association for the study of the liver (EASL) and modified response evaluation criteria in solid tumors (mRECIST) criteria, respectively. Thirty-day ORR was 79.6% for both EASL and mRECIST criteria with 3-month ORR being 80.0 and 81.0%, respectively, for each criteria. One-year PPF and OS rate were 60.3 and 94.3%. There was a total of 30 SAEs reported to be likely to definitely associated with microsphere (n = 9), epirubicin (n = 9), or procedure (n = 12) with none resulting in death. CONCLUSION DEB-TACE using epirubicin-loaded small-sized (≤ 100 μm) microspheres demonstrates promising local tumor control and acceptable safety in patients with HCC. TRIAL REGISTRATION Clinicaltrials.gov NCT03113955; registered April 14, 2017. Trial Registration Clinicaltrials.gov NCT03113955; registered April 14, 2017. LEVEL OF EVIDENCE 2, Prospective, Non-randomized, Single-arm, study.
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Affiliation(s)
- Hai-Dong Zhu
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Medical School, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China
| | - Xiao Li
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jun-Hui Sun
- Division of Hepatobiliary and Pancreatic Surgery, Hepatobiliary and Pancreatic Interventional Treatment Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xu Zhu
- Interventional Therapy Department, Peking University Cancer Hospital and Institute, Beijing, China
| | - Zhao-Yu Liu
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Hai-Liang Li
- Department of Minimal-Invasive Intervention, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
| | - Jian Lu
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Medical School, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China
| | - Zhi-Ping Yan
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University Shanghai Institution of Medical Imaging, Fudan University, Shanghai, China
| | - Guo-Liang Shao
- Department of Intervention, The Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer, Chinese Academy of Sciences, Hangzhou, China
| | - Xiao-Feng He
- Division of Vascular and Interventional Radiology, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Min Chao
- Department of Radiology, Second Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou, China
| | - Li-Gong Lu
- Zhuhai Interventional Medical Center, Zhuhai Precision Medical Center, Zhuhai People's Hospital, Zhuhai Hospital Affiliated with Jinan University, Jinan University, Zhuhai, China
| | - Bin-Yan Zhong
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, China
| | - Rui Li
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Medical School, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China
| | - Qi Zhang
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Medical School, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China
| | - Gao-Jun Teng
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Medical School, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China.
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Cheng S, Hu G, Jin Z, Wang Z, Xue H. CT-based radiomics nomogram for prediction of survival after transarterial chemoembolization with drug-eluting beads in patients with hepatocellular carcinoma and portal vein tumor thrombus. Eur Radiol 2023; 33:8715-8726. [PMID: 37436507 DOI: 10.1007/s00330-023-09830-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Revised: 04/02/2023] [Accepted: 04/14/2023] [Indexed: 07/13/2023]
Abstract
OBJECTIVES To develop and validate a CT-based radiomics model for the prediction of the overall survival (OS) of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) treated with drug-eluting beads transarterial chemoembolization (DEB-TACE). METHODS Patients were retrospectively enrolled from two institutions for the constitution of training (n = 69) and validation (n = 31) cohorts with a median follow-up of 15 months. A total of 396 radiomics features were extracted from each baseline CT image. Features selected by variable importance and minimal depth were used for random survival forest model construction. The performance of the model was assessed using the concordance index (C-index), calibration curves, integrated discrimination index (IDI), net reclassification index (NRI), and decision curve analysis. RESULTS Type of PVTT and tumor number were proved to be significant clinical indicators for OS. Arterial phase images were used to extract radiomics features. Three radiomics features were selected for model construction. The C-index for the radiomics model was 0.759 in the training cohort and 0.730 in the validation cohort. To improve the predictive performance, clinical indicators were integrated into the radiomics model to form a combined model with a C-index of 0.814 in the training cohort and 0.792 in the validation cohort. The IDI was significant in both cohorts for the combined model versus the radiomics model in predicting 12-month OS. CONCLUSIONS Type of PVTT and tumor number affected the OS of HCC patients with PVTT treated with DEB-TACE. Moreover, the combined clinical-radiomics model had a satisfactory performance. CLINICAL RELEVANCE STATEMENT A CT-based radiomics nomogram, which consisted of 3 radiomics features and 2 clinical indicators, was recommended to predict 12-month overall survival of patients with hepatocellular carcinoma and portal vein tumor thrombus initially treated with drug-eluting beads transarterial chemoembolization. KEY POINTS • Type of portal vein tumor thrombus and tumor number were significant predictors of the OS. • Integrated discrimination index and net reclassification index provided a quantitative evaluation of the incremental impact added by new indicators for the radiomics model. • A nomogram based on a radiomics signature and clinical indicators showed satisfactory performance in predicting OS after DEB-TACE.
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Affiliation(s)
- Sihang Cheng
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Ge Hu
- Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Zhengyu Jin
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Zhiwei Wang
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China.
| | - Huadan Xue
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China.
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Du QQ, Liang M, Jiang B, Zhang M, Yu XL, Li X, Hao JH. Incidence and predictors of abdominal pain after transarterial chemoembolization of hepatocellular carcinoma: a single-center retrospective study. Eur J Oncol Nurs 2023; 66:102355. [PMID: 37524027 DOI: 10.1016/j.ejon.2023.102355] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Revised: 05/22/2023] [Accepted: 06/05/2023] [Indexed: 08/02/2023]
Abstract
PURPOSE To assess the incidence and predictive factors of abdominal pain following transarterial hepatic chemoembolization (TACE) in patients with hepatocellular carcinoma. METHODS In this single-center retrospective cohort study, abdominal pain was defined as a score of 4 or more within 72 h after TACE and requiring additional drug intervention. Patient, tumor characteristics, and technical factors associated with severe pain were identified using the decision tree and binary logistic regression model. RESULTS Of 220 patients who were included in the study, 126 (57.3%) had abdominal pain after 206 of 420 TACE procedures (49.0%). A predictive model built based on the logistic regression identified the drug-eluting bead TACE (DEB-TACE) (odds ratio [OR] = 3.340; 95% confidence interval [CI] 2.169-5.141), the number of tumors (OR = 2.235; 95% CI 1.060-4.713), embolization of both hepatic lobes (OR = 2.310; 95% CI 1.109-4.813), and concomitant extrahepatic artery embolism (OR = 2.654; 95% CI 1.227-5.739) as the independent predictors of severe abdominal pain. Similarly, the decision tree confirmed the DEB-TACE as the strongest predictor of subsequent performance, followed by the history of hepatectomy and the embolization in the right or both lobes. The area under the receiver operating characteristic curve (AUC) of the classification prediction effect of the two models was 0.706 for the logistic regression and 0.676 for the decision tree. Internal validation results show that the accuracy of logistic regression model prediction was 71.4%. CONCLUSION The model suggests that DEB-TACE and multiple treatment sites are predictors of abdominal pain after TACE in patients with hepatocellular carcinoma. It may help improve nursing management practices.
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Affiliation(s)
- Qian-Qian Du
- Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, Anhui, China; Department of Interventional Therapy, The Second Affiliated Hospital of Anhui Medical University, No. 678 Furong Road, Hefei, 230601, Anhui, China
| | - Min Liang
- Department of Interventional Therapy, The Second Affiliated Hospital of Anhui Medical University, No. 678 Furong Road, Hefei, 230601, Anhui, China
| | - Bo Jiang
- Department of Interventional Therapy, The Second Affiliated Hospital of Anhui Medical University, No. 678 Furong Road, Hefei, 230601, Anhui, China
| | - Miao Zhang
- Nursing Department, The Second Affiliated Hospital of Anhui Medical University, No. 678 Furong Road, Hefei, 230601, Anhui, China
| | - Xiao-Ling Yu
- Nursing Department, The Second Affiliated Hospital of Anhui Medical University, No. 678 Furong Road, Hefei, 230601, Anhui, China
| | - Xiao Li
- Department of Radiology, The Second Affiliated Hospital of Anhui Medical University, No. 678 Furong Road, Hefei, 230601, Anhui, China
| | - Jia-Hu Hao
- Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, Anhui, China.
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Zhang N, He XF, Niu XK. Mapping research trends of transarterial chemoembolization for hepatocellular carcinoma from 2012 to 2021: A bibliometric analysis. World J Methodol 2023; 13:345-358. [PMID: 37771871 PMCID: PMC10523245 DOI: 10.5662/wjm.v13.i4.345] [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: 06/08/2023] [Revised: 07/20/2023] [Accepted: 08/21/2023] [Indexed: 09/19/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the second leading cause of cancer-related deaths. Transcatheter arterial chemoembolization (TACE) is a therapy where drugs aimed to slow or halt tumor development are injected into the artery supplying for HCC tissues. A comprehensive analysis of all the articles on TACE for HCC can give us a general understanding of the progress in this field and provide guidance for future research. AIM To analyze and visualize scientific results and research trends in TACE treatment for HCC. METHODS The "Web of Science" database was used to identify articles regarding TACE for the treatment of HCC from 2012 to 2021. VOSviewer and CiteSpace were used to analyze the publications trends, collaboration between countries/insti-tutions/authors, and the co-occurrence of keywords, keyword bursts, and references. RESULTS A total of 5728 original articles on TACE for HCC were retrieved. Regarding the volume of publications, the total number of yearly publications showed a generally increasing trend. China had the highest number of articles, while the United States achieved the highest Hirsch index and highest number of citations. The Sun Yat-sen University in China was most prolific institution. The most active author was Park, J.W from South Korea. The Journal of Vascular and Interventional Radiology (234 articles) was the most productive journal. There is a growing trend toward international collaboration in TACE for HCC. Cluster networks of co-cited references suggested that practice guidelines and targeted therapies are an essential theme in this field. In addition, cluster analysis based on keyword co-occurrence identified the research topic "prediction of TACE treatment" as a hotspot, and propensity score matching can be used to help investigators conduct innovative studies in the future. CONCLUSION The results of our bibliometric analysis provide the latest trends and hot topics in TACE therapy for HCC.
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Affiliation(s)
- Na Zhang
- Department of General Practice, Affiliated Hospital of Chengdu University, Chengdu 610081, Sichuan Province, China
| | - Xiao-Feng He
- Department of Interventional Radiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Xiang-Ke Niu
- Department of Interventional Radiology, Affiliated Hospital of Chengdu University, Chengdu 610081, Sichuan Province, China
- Department of Interventional Radiology, Sichuan Cancer Hospital & Research Institute, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610041, Sichuan Province, China
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Lyu T, Wang J, Tong X, Mi T, An C, Zou Y. Efficacy and safety of CalliSpheres® Microsphere transcatheter-arterial chemoembolization versus conventional TACE in treating renal angiomyolipoma patients. J Cancer Res Ther 2023; 19:933-938. [PMID: 37675719 DOI: 10.4103/jcrt.jcrt_2135_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/08/2023]
Abstract
Objective Transcatheter-arterial chemoembolization (TACE) is a well-established interventional technique for various tumor treatments, whereas its application in renal angiomyolipoma (RAML) is seldom reported. Conventional TACE (cTACE) with bleomycin-lipiodol emulsion is effective and tolerable for RAML treatment. In this study, we aimed to further explore the efficacy and safety between bleomycin-loaded CalliSpheres® microsphere TACE (CSM-TACE) and cTACE in treating RAML patients. Methods We retrospectively analyzed the data of 54 RAML patients treated by CSM-TACE (n = 17) or cTACE (n = 37). Data on tumor size, tumor volume reduction ratio, patient percentage with tumor size reduction, white blood cells (WBCs), creatinine (Cre) after treatment, complications, and adverse events were retrieved. Results Tumor size (88.66 vs. 81.19 cm3, P = 0.970), patient percentage with tumor size reduction (12 [70.59%] vs. 30 [81.08%], P = 0.486) after treatment, WBCs (P = 0.114), Cre (P = 0.659), and change in Cre after treatment (P = 0.947) were not significantly different between groups, whereas tumor volume reduction ratio was slightly lower in the CSM-TACE group than in the cTACE group (12 ± 34% vs. 32 ± 31%, P = 0.047). The most common postoperative complication was a post-embolization syndrome, including fever, nausea, and abdominal pain, which occurred in 9 (52.94%) and 14 (37.84%) patients from the CSM-TACE and cTACE groups, respectively (P = 0.347). Conclusion CSM-TACE is effective in and well tolerated by RAML patients, implying its potential as an alternative therapy.
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Affiliation(s)
- Tianshi Lyu
- Department of Interventional and Vascular Surgery, Peking University First Hospital, Beijing, China
| | - Jian Wang
- Department of Interventional and Vascular Surgery, Peking University First Hospital, Beijing, China
| | - Xiaoqiang Tong
- Department of Interventional and Vascular Surgery, Peking University First Hospital, Beijing, China
| | - Tianai Mi
- Lianren Digital Health Technology Company, LTD, Beijing, China
| | - Chao An
- Lianren Digital Health Technology Company, LTD, Beijing, China
| | - Yinghua Zou
- Department of Interventional and Vascular Surgery, Peking University First Hospital, Beijing, China
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Xiao J, Yang D, Fang X, Liu X, Liu X, Ma L, Wang Z, Wu C, Guo Q. Near Infrared-Absorbing Nanoparticle-Mediated Endovascular Photothermal Precision Embolization of Tumor Feeding Vessels for Starvation Treatment. ACS Biomater Sci Eng 2023. [PMID: 37216621 DOI: 10.1021/acsbiomaterials.3c00287] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/24/2023]
Abstract
Photothermal therapy has attracted enormous attention as an efficient treatment modality in cancer ablation but still encounters a major bottleneck due to the limited penetration depth of light inside tissues. To overcome the challenge of deep tissue penetration, we present a strategy of endovascular photothermal precision embolization (EPPE), which employs an endovascular optical fiber to induce local embolization only in the entrance of feeding vessels through photothermal heating for the purpose of fully blocking the blood supply of the whole tumor. In EPPE, we apply a highly efficient and biocompatible photothermal agent, i.e., near-infrared (NIR)-light-absorbing diketopyrrolopyrrole-dithiophene-based nanoparticle, which exhibits a high cell-killing efficacy at a concentration of 200 μg/mL using 808 nm laser irradiation of 0.5 W/cm2 within 5 min in both 2D cell culture and a 3D tumor spheroid model. We verify the feasibility of EPPE in an ex vivo organ-structured recellularized liver model and further confirm the in vivo efficacy of the photothermal treatment in a rat liver model. The photothermal treatment combined with the embolization effect holds promise to serve as an effective starvation therapy to treat tumors of varying sizes and locations.
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Affiliation(s)
- Jingyu Xiao
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Guangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, 1088 Xueyuan Boulevard, Shenzhen, Guangdong 518055, China
| | - Dishuang Yang
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Guangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, 1088 Xueyuan Boulevard, Shenzhen, Guangdong 518055, China
| | - Xiaofeng Fang
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Guangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, 1088 Xueyuan Boulevard, Shenzhen, Guangdong 518055, China
| | - Xiaoya Liu
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Guangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, 1088 Xueyuan Boulevard, Shenzhen, Guangdong 518055, China
| | - Xuezhe Liu
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Guangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, 1088 Xueyuan Boulevard, Shenzhen, Guangdong 518055, China
| | - Le Ma
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Guangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, 1088 Xueyuan Boulevard, Shenzhen, Guangdong 518055, China
| | - Ziyan Wang
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Guangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, 1088 Xueyuan Boulevard, Shenzhen, Guangdong 518055, China
| | - Changfeng Wu
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Guangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, 1088 Xueyuan Boulevard, Shenzhen, Guangdong 518055, China
| | - Qiongyu Guo
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Guangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, 1088 Xueyuan Boulevard, Shenzhen, Guangdong 518055, China
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Wang HY, Cui XW, Zhang YH, Chen Y, Lu NN, Sheng SP, Gao WF, Yang XZ, Duan ZP. Comparison of NK cell subsets, receptors and functions induced by radiofrequency ablation and microwave ablation in HBV-associated primary hepatocellular carcinoma. Front Oncol 2023; 13:1048049. [PMID: 37205189 PMCID: PMC10185829 DOI: 10.3389/fonc.2023.1048049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Accepted: 04/05/2023] [Indexed: 05/21/2023] Open
Abstract
BACKGROUND Topical therapy has been shown to induce an immune response in patients with hepatocellular carcinoma (HCC). In this study, a prospective parallel group control experiment was conducted to compare the differences between radiofrequency ablation and microwave ablation in inducing the immune regulation of NK cells. METHODS Sixty patients with clinically and pathologically confirmed hepatitis B-associated hepatocellular carcinoma (HCC) were selected for thermal ablation. Patients were randomly assigned into the MWA group (n = 30) and the RFA group (n = 30). Patient's peripheral blood was isolated on days D0, D7, and month M1. NK cell subsets, receptors, and killing function were detected by flow cytometry and LDH. Student t test and rank sum test were used to compare the statistical differences between the RFA (radio frequency) and MWA (microwave) groups. The Kaplan-Meier curve and log-rank test were used to calculate the difference between the two survival curves. RESULTS Comparison of the frequency of CD3-CD56+ and CD3-CD56+CD16+ in NK cells between the RFA and WMA groups showed that there was no difference in the D0, D7, M1, D7-D0, M1-D0, and M1-D7 groups. The changes of the inhibitory NK cell receptor CD159A were significantly different at D7 (P<0.05). CD107a were compared between the RFA and WMA groups, indicating that CD107a changes induced by NK cells were significantly different at D7-D0 (P<0.05). Comparison of NK cell lysis activity of target K562 cells between the RFA and WMA groups showed that there was no difference at D0, D7, D7-D0. There was no difference in recurrence-free survival (RFS) between the RFA and WMA groups (P=0.11). CONCLUSIONS The difference between MWA and RFA-induced NK cell changes was mainly manifested in the inhibitory receptors CD159a and CD107a 1 week after surgery, with microwave-induced changes being more severe. Comparison of the NK cell lysis activity of the target K562 cells between the RFA and WMA groups showed that there was no difference in D0, D7, D7- D0. Survival analysis showed that these differences did not affect the recurrence-free survival (RFS) in the two groups.
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Affiliation(s)
- Hai-Yan Wang
- Beijing Youan Hospital, Capital Medical University, Beijing, China
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Song PW, Wang JL, Wang T, Zou HN, Liu YH. Creating and Testing a Model to Predict Postoperative Discomfort in Patients with Hepatocellular Carcinoma Receiving Transarterial Chemoembolisation. HEPATITIS MONTHLY 2023. [DOI: 10.5812/hepatmon-133918] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/07/2023]
Abstract
Background: Abdominal pain is a frequent adverse event in patients with hepatocellular carcinoma (HCC) after transarterial chemoembolisation (TACE). However, there remains uncertainty regarding the determinants of post-TACE pain. Objectives: We aimed to create and verify a prediction model for postoperative pain in patients with HCC after TACE treatment. Methods: This prospective study included all patients with HCC undergoing TACE in our hospital. According to the time of treatment, the dataset was divided into two cohorts (development and validation) in a 3: 2 ratio. After TACE, the participants used a visual analog scale to quantify their pain level at rest over a 24-hour period. The age, gender, tumor location, tumor size and number, medication administration route, and presence of portal vein tumor thrombosis (PVTT) were recorded in all patients. Results: In total, 137 (mean age: 60.3 ± 10.1 years; 78.1% male) and 91 (mean age: 61.1 ± 10.5 years; 73.6% male) patients were included in the development and validation cohorts, respectively. Furthermore, 46.0% and 39.6% of the patients experienced acute moderate to severe pain after TACE in the development and validation cohorts, respectively. The tumor location, the drug delivery method, and the presence of PVTT were independently associated with post-TACE pain, all of which were combined to develop a prediction model based on a logistic equation. The discrimination of this risk score was satisfactory in both the development (area under the curve (AUC): 0.693, 95% confidence interval (CI): 0.609 to 0.769, P < 0.001) and validation (AUC: 0.652, 95% CI: 0.544 to 0.748, P = 0.002) cohorts. There was no significant difference between the two cohorts (difference: 0.042, 95% CI: -0.081 to 0.164, P = 0.506). The risk score had good specificity for predicting post-TACE pain in both the development (83.8% (95% CI: 73.4% to 91.3%)) and validation (76.4% (95% CI: 63.0% to 86.8%)) cohorts. Conclusions: The presence of PVTT, the tumor location, and the drug administration method were risk factors for post-TACE discomfort. A prediction model based on these risk factors was useful for identifying patients who were vulnerable to post-TACE pain. However, further studies are required to validate these findings and optimize the model’s performance.
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Liu X, Wang X, Luo Y, Wang M, Chen Z, Han X, Zhou S, Wang J, Kong J, Yu H, Wang X, Tang X, Guo Q. A 3D Tumor-Mimicking In Vitro Drug Release Model of Locoregional Chemoembolization Using Deep Learning-Based Quantitative Analyses. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2023; 10:e2206195. [PMID: 36793129 PMCID: PMC10104640 DOI: 10.1002/advs.202206195] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Revised: 12/23/2022] [Indexed: 06/18/2023]
Abstract
Primary liver cancer, with the predominant form as hepatocellular carcinoma (HCC), remains a worldwide health problem due to its aggressive and lethal nature. Transarterial chemoembolization, the first-line treatment option of unresectable HCC that employs drug-loaded embolic agents to occlude tumor-feeding arteries and concomitantly delivers chemotherapeutic drugs into the tumor, is still under fierce debate in terms of the treatment parameters. The models that can produce in-depth knowledge of the overall intratumoral drug release behavior are lacking. This study engineers a 3D tumor-mimicking drug release model, which successfully overcomes the substantial limitations of conventional in vitro models through utilizing decellularized liver organ as a drug-testing platform that uniquely incorporates three key features, i.e., complex vasculature systems, drug-diffusible electronegative extracellular matrix, and controlled drug depletion. This drug release model combining with deep learning-based computational analyses for the first time permits quantitative evaluation of all important parameters associated with locoregional drug release, including endovascular embolization distribution, intravascular drug retention, and extravascular drug diffusion, and establishes long-term in vitro-in vivo correlations with in-human results up to 80 d. This model offers a versatile platform incorporating both tumor-specific drug diffusion and elimination settings for quantitative evaluation of spatiotemporal drug release kinetics within solid tumors.
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Affiliation(s)
- Xiaoya Liu
- Shenzhen Key Laboratory of Smart Healthcare EngineeringGuangdong Provincial Key Laboratory of Advanced BiomaterialsDepartment of Biomedical EngineeringSouthern University of Science and TechnologyShenzhenGuangdong518055P. R. China
- Department of PharmacyShenzhen Children's HospitalShenzhenGuangdong518026P. R. China
| | - Xueying Wang
- Department of Electronic and Electrical EngineeringSouthern University of Science and TechnologyShenzhenGuangdong518055P. R. China
| | - Yucheng Luo
- Shenzhen Key Laboratory of Smart Healthcare EngineeringGuangdong Provincial Key Laboratory of Advanced BiomaterialsDepartment of Biomedical EngineeringSouthern University of Science and TechnologyShenzhenGuangdong518055P. R. China
| | - Meijuan Wang
- Shenzhen Key Laboratory of Smart Healthcare EngineeringGuangdong Provincial Key Laboratory of Advanced BiomaterialsDepartment of Biomedical EngineeringSouthern University of Science and TechnologyShenzhenGuangdong518055P. R. China
| | - Zijian Chen
- Shenzhen Key Laboratory of Smart Healthcare EngineeringGuangdong Provincial Key Laboratory of Advanced BiomaterialsDepartment of Biomedical EngineeringSouthern University of Science and TechnologyShenzhenGuangdong518055P. R. China
| | - Xiaoyu Han
- Shenzhen Key Laboratory of Smart Healthcare EngineeringGuangdong Provincial Key Laboratory of Advanced BiomaterialsDepartment of Biomedical EngineeringSouthern University of Science and TechnologyShenzhenGuangdong518055P. R. China
| | - Sijia Zhou
- Department of MolecularCellular and Developmental Biology (MCD)Centre de Biologie Integrative (CBI)University of ToulouseCNRSUPSToulouse31062France
| | - Jiahao Wang
- Mechanobiology InstituteNational University of SingaporeSingapore117411Singapore
| | - Jian Kong
- Department of Interventional RadiologyFirst Affiliated Hospital of Southern University of Science and TechnologySecond Clinical Medical College of Jinan UniversityShenzhen People's HospitalShenzhenGuangdong518020P. R. China
| | - Hanry Yu
- Mechanobiology InstituteNational University of SingaporeSingapore117411Singapore
- Department of PhysiologyInstitute of Digital Medicineand Mechanobiology InstituteNational University of SingaporeSingapore117593Singapore
| | - Xiaobo Wang
- Department of MolecularCellular and Developmental Biology (MCD)Centre de Biologie Integrative (CBI)University of ToulouseCNRSUPSToulouse31062France
| | - Xiaoying Tang
- Department of Electronic and Electrical EngineeringSouthern University of Science and TechnologyShenzhenGuangdong518055P. R. China
- Jiaxing Research InstituteSouthern University of Science and TechnologyJiaxingZhejiang314000P. R. China
| | - Qiongyu Guo
- Shenzhen Key Laboratory of Smart Healthcare EngineeringGuangdong Provincial Key Laboratory of Advanced BiomaterialsDepartment of Biomedical EngineeringSouthern University of Science and TechnologyShenzhenGuangdong518055P. R. China
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Safety, Efficacy and Distribution of Doxorubicin Loaded Radiopaque Beads in Chemoembolization in Intermediate Stage Hepatocellular Carcinoma (HCC) with Correlation with Local Response. Cardiovasc Intervent Radiol 2023; 46:337-349. [PMID: 36653660 DOI: 10.1007/s00270-022-03346-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Accepted: 12/14/2022] [Indexed: 01/20/2023]
Abstract
PURPOSE The primary objectives of this study were to evaluate safety, and efficacy of Transarterial Chemoembolization (TACE) using doxorubicin-loaded radiopaque microspheres (DC Bead LUMI™) for the treatment of early and intermediate stage Hepatocellular Carcinoma (HCC) not amenable for curative treatments. Distribution of the microspheres was correlated with results post embolization. MATERIALS AND METHODS This was a prospective, single arm, open label study. The primary outcome measures were distribution of the radiopaque microspheres as showed by computerized tomography (CT) and local response measured by modified Response Evaluation Criteria (mRECIST) after Magnetic Resonance Imaging (MRI). Secondary measures were Time to Progression (TTP) and Overall Survival (OS). RESULTS Fifty patients were enrolled over 36 months. Median age was 69.0 years; mean sum of target lesions diameters was 78.6 ± 36.8 mm. There were no Grade 4 or 5 adverse events (AEs). At 6 months Complete Response (CR) (18%), Partial Response (PR) (62%), Objective Response OR (80%) and Stable Disease (SD) (20%) were recorded. Before embolization, Diffusion Weighted Imaging (DWI) showed high signal (restricted diffusion). Post procedure, patients with dense deposition (< 5 mm distance of microsphere aggregations) showed 100% absence of enhancement and no restriction in 30.6%. Median TTP was 8.3 months. TTP for patients with CR was 13.3 months and 7.2 and 5.6 for PR and SD, respectively. At 6 and 36 months, survival was 94% and 34%, respectively. CONCLUSION DC Bead LUMI™ is well tolerated and effective in early and intermediate stage HCC with maximal necrosis obtained in dense deposition in the target.
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Shi Z, Wang D, Kang T, Yi R, Cui L, Jiang H. Comparison of CalliSpheres ® microspheres drug-eluting beads and conventional transarterial chemoembolization in hepatocellular carcinoma patients: a randomized controlled trial. Radiol Oncol 2023; 57:70-79. [PMID: 36794998 PMCID: PMC10039469 DOI: 10.2478/raon-2023-0001] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Accepted: 11/08/2022] [Indexed: 02/17/2023] Open
Abstract
BACKGROUND This trial aimed to compare the outcomes of drug-eluting beads transarterial chemoembolization (DEB-TACE) with CalliSpheres® microspheres (CSM) and conventional transarterial chemoembolization cTACE in the treatment of patients with unresectable hepatocellular carcinoma (HCC). PATIENTS AND METHODS A total of 90 patients were divided into DEB-TACE group (n = 45) and cTACE group (n = 45). The treatment response, overall survival (OS), progression-free survival (PFS), and the safety were compared between the two groups. RESULTS The objective response rate (ORR) in the DEB-TACE group was significantly higher than that in cTACE group at 1, 3, and 6 months of follow-up (P = 0.031, P = 0.003, P = 0.002). The complete response (CR) in DEB-TACE group was significantly higher than that in cTACE group at 3 months (P = 0.036). Survival analysis revealed that, DEB-TACE group had better survival benefits than cTACE group (median OS: 534 days vs. 367 days, P = 0.027; median PFS: 352 days vs. 278 days P = 0.004). The degree of liver function injury was more serious in DEB-TACE group at 1 week, but was similar between the two groups at 1 month. DEB-TACE with CSM caused a high incidence of fever and a severe abdominal pain (P = 0.031, P = 0.037). CONCLUSIONS DEB-TACE with CSM showed better treatment response and survival benefits than cTACE group. Although a transient more severe liver damage, high incidence of fever and a severe abdominal pain occurred in the DEB-TACE group, it could be resolved through symptomatic treatment.
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Affiliation(s)
- Zhongxing Shi
- Department of Interventional Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Dongqing Wang
- Department of Interventional Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Tanrong Kang
- Department of Interventional Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Ru Yi
- Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Liming Cui
- Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Huijie Jiang
- Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
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Tao YX, Li HW, Luo JT, Li Y, Wei WB, Beijing Tongren Eye Center, Beijing Key Laboratory of Intraocular Tumor Diagnosis and Treatment, Beijing Ophthalmology＆Visual Sciences Key Lab, Medical Artificial Intelligence Research and Verification Key Laboratory of the Ministry of Industry and Information Technology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China, Beijing Tongren Eye Center, Beijing Key Laboratory of Intraocular Tumor Diagnosis and Treatment, Beijing Ophthalmology＆Visual Sciences Key Lab, Medical Artificial Intelligence Research and Verification Key Laboratory of the Ministry of Industry and Information Technology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China, Beijing Tongren Eye Center, Beijing Key Laboratory of Intraocular Tumor Diagnosis and Treatment, Beijing Ophthalmology＆Visual Sciences Key Lab, Medical Artificial Intelligence Research and Verification Key Laboratory of the Ministry of Industry and Information Technology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China. Regional chemotherapy for uveal melanoma liver metastases. Int J Ophthalmol 2023; 16:293-300. [PMID: 36816216 PMCID: PMC9922637 DOI: 10.18240/ijo.2023.02.18] [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: 11/04/2022] [Accepted: 12/26/2022] [Indexed: 02/05/2023] Open
Abstract
Chemotherapy remains an important approach for the treatment of liver metastases from uveal melanoma (UM). Compared with systemic chemotherapy, regional chemotherapy has similar efficacy and fewer systemic adverse effects. Regional chemotherapy for UM liver metastases includes hepatic artery infusion (HAI), transarterial chemoembolization (TACE), and isolated hepatic perfusion (IHP). In this review, we aim to examine the efficacy of regional chemotherapy and compare HAI, TACE, and IHP in terms of overall survival (OS). The three approaches showed no obvious difference in OS results.
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Wu S, Fan K, Yang Q, Chen Z, Hou Y, Zou Y, Cai W, Kang L. Smart nanoparticles and microbeads for interventional embolization therapy of liver cancer: state of the art. J Nanobiotechnology 2023; 21:42. [PMID: 36747202 PMCID: PMC9901004 DOI: 10.1186/s12951-023-01804-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Accepted: 02/01/2023] [Indexed: 02/08/2023] Open
Abstract
The process of transcatheter arterial chemoembolization is characterized by the ability to accurately deliver chemotherapy drugs with minimal systemic side effects and has become the standard treatment for unresectable intermediate hepatocellular carcinoma (HCC). However, this treatment option still has much room for improvement, one of which may be the introduction of nanomaterials, which exhibit unique functions and can be applied to in vivo tumor imaging and therapy. Several biodegradable and multifunctional nanomaterials and nanobeads have recently been developed and applied in the locoregional treatment of hepatocellular cancer. This review explores recent developments and findings in relation to micro-nano medicines in transarterial therapy for HCC, emerging strategies to improve the efficacy of delivering nano-based medicines, and expounding prospects for clinical applications of nanomaterials.
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Affiliation(s)
- Sitong Wu
- Department of Nuclear Medicine, Peking University First Hospital, Beijing, 100034, China
- Department of Interventional Radiology and Vascular Surgery, Peking University First Hospital, Beijing, 100034, China
| | - Kevin Fan
- Departments of Radiology and Medical Physics, University of Wisconsin, Madison, WI, 53705, USA
| | - Qi Yang
- Department of Nuclear Medicine, Peking University First Hospital, Beijing, 100034, China
| | - Zhao Chen
- Department of Nuclear Medicine, Peking University First Hospital, Beijing, 100034, China
| | - Yi Hou
- College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, 100029, China.
| | - Yinghua Zou
- Department of Interventional Radiology and Vascular Surgery, Peking University First Hospital, Beijing, 100034, China.
| | - Weibo Cai
- Departments of Radiology and Medical Physics, University of Wisconsin, Madison, WI, 53705, USA.
| | - Lei Kang
- Department of Nuclear Medicine, Peking University First Hospital, Beijing, 100034, China.
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Mosconi C, Cappelli A, Pettinato C, Cocozza MA, Vara G, Terzi E, Morelli MC, Lodi Rizzini E, Renzulli M, Modestino F, Serenari M, Bonfiglioli R, Calderoni L, Tabacchi E, Cescon M, Morganti AG, Trevisani F, Piscaglia F, Fanti S, Strigari L, Cucchetti A, Golfieri R. Improved Survival after Transarterial Radioembolisation for Hepatocellular Carcinoma Gives the Procedure Added Value. J Clin Med 2022; 11:jcm11247469. [PMID: 36556085 PMCID: PMC9781303 DOI: 10.3390/jcm11247469] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Revised: 12/09/2022] [Accepted: 12/13/2022] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Transarterial Radioembolisation (TARE) requires multidisciplinary experience and skill to be effective. The aim of this study was to identify determinants of survival in patients with hepatocellular carcinoma (HCC), focusing on learning curves, technical advancements, patient selection and subsequent therapies. METHODS From 2005 to 2020, 253 patients were treated. TARE results achieved in an initial period (2005-2011) were compared to those obtained in a more recent period (2012-2020). To isolate the effect of the treatment period, differences between the two periods were balanced using "entropy balance". RESULTS Of the 253 patients, 68 were treated before 2012 and 185 after 2012. In the second period, patients had an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 1 (p = 0.025) less frequently, less liver involvement (p = 0.006) and a lesser degree of vascular invasion (p = 0.019). The median overall survival (OS) of patients treated before 2012 was 11.2 months and that of patients treated beginning in 2012 was 25.7 months. After reweighting to isolate the effect of the treatment period, the median OS of patients before 2012 increased to 16 months. CONCLUSIONS Better patient selection, refinement of technique and adoption of personalised dosimetry improved survival after TARE. Conversely, sorafenib after TARE did not impact life expectancy.
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Affiliation(s)
- Cristina Mosconi
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Alberta Cappelli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Cinzia Pettinato
- Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | - Maria Adriana Cocozza
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
- Correspondence: ; Tel.: +39-051-6362-311
| | - Giulio Vara
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Eleonora Terzi
- Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Maria Cristina Morelli
- Division of Internal Medicine for the Treatment of Severe Organ Failure, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Elisa Lodi Rizzini
- Radiation Oncology, IRCCS Azienda Ospedaliero—Universitaria di Bologna, 40138 Bologna, Italy
| | - Matteo Renzulli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Francesco Modestino
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Matteo Serenari
- General Surgery and Transplantation Unit, IRCCS Azienda Ospedaliero—Universitaria di Bologna, 40138 Bologna, Italy
| | - Rachele Bonfiglioli
- Nuclear Medicine Unit, IRCCS, Azienda Ospedaliero—Universitaria di Bologna, 40138 Bologna, Italy
| | - Letizia Calderoni
- Nuclear Medicine Unit, IRCCS, Azienda Ospedaliero—Universitaria di Bologna, 40138 Bologna, Italy
| | - Elena Tabacchi
- Nuclear Medicine Unit, IRCCS, Azienda Ospedaliero—Universitaria di Bologna, 40138 Bologna, Italy
| | - Matteo Cescon
- General Surgery and Transplantation Unit, IRCCS Azienda Ospedaliero—Universitaria di Bologna, 40138 Bologna, Italy
| | | | - Franco Trevisani
- Department of Medical and Surgical Sciences, Semeiotica Medica, IRCCS Azienda Ospedaliero—Universitaria di Bologna, 40138 Bologna, Italy
| | - Fabio Piscaglia
- Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Stefano Fanti
- Nuclear Medicine Unit, IRCCS, Azienda Ospedaliero—Universitaria di Bologna, 40138 Bologna, Italy
| | - Lidia Strigari
- Department of Medical Physics, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Alessandro Cucchetti
- Department of Medical and Surgical Sciences—DIMEC, Alma Mater Studiorum—University of Bologna, 40138 Bologna, Italy
- Department of General Surgery, Morgagni—Pierantoni Hospital, 47121 Forlì, Italy
| | - Rita Golfieri
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
- Alma Mater Studiorum, Università Degli Studi Di Bologna, 40138 Bologna, Italy
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Ye T, Shao SH, Ji K, Yao SL. Evaluation of short-term effects of drug-loaded microspheres and traditional transcatheter arterial chemoembolization in the treatment of advanced liver cancer. World J Gastrointest Oncol 2022; 14:2367-2379. [PMID: 36568947 PMCID: PMC9782616 DOI: 10.4251/wjgo.v14.i12.2367] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 08/29/2022] [Accepted: 11/17/2022] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Liver cancer is a malignant tumor with high morbidity and mortality. Transcatheter arterial chemoembolization (TACE) is the main method for surgically unresectable liver cancer. In recent years, drug-loaded microspheres have been gradually applied in TACE technology. There are some controversies about the therapeutic effects of drug-loaded microspheres TACE (D-TACE) and traditional TACE.
AIM To explore the short-term efficacy of D-TACE and traditional TACE in the treatment of advanced liver cancer.
METHODS The clinical data of 73 patients with advanced liver cancer admitted to the First and Sixth Medical Centers of Chinese PLA General Hospital from January 2017 to October 2019 were retrospectively analyzed. Among them, 15 patients were treated with D-TACE, and 58 patients were treated with traditional TACE. Clinical baseline characteristics, perioperative laboratory indices, postoperative adverse reactions and postoperative complications were compared between the two groups.
RESULTS There was no statistical difference between the two groups for the postoperative response: The highest postoperative body temperature of the drug-loaded microsphere group was 38.0 ± 0.9℃ and the postoperative highest body temperature of the traditional TACE group was 38.3 ± 0.7℃ (t = -1.414, P = 0.162). For the 24 h postoperative nausea and vomiting after surgery in terms of scoring and postoperative pain scores, the traditional TACE group was higher than the drug-loaded microsphere group (χ2 = 14.33, P = 0.014; χ2 = 32.967, P = 0.000) and the two groups had significant statistical differences. The disease control rate at 3 mo after treatment in the drug-loaded microsphere group was 60% and the disease control rate at 3 mo after treatment in the traditional TACE group was 75.9% (χ2 = 4.091, P = 0.252). There was no statistical difference between the two groups of data. During the follow-up period, the number of interventional treatments received was once in the drug-loaded microsphere group and the traditional TACE group received an average of 1.48 treatments (χ2 = 10.444 P = 0.005). There was a statistical difference between the two groups.
CONCLUSION Compared with traditional TACE, D-TACE may have some advantages in the treatment of advanced hepatocellular carcinoma with a large tumor load in the short term, but the long-term clinical efficacy needs additional follow-up studies. In addition, compared with the traditional group, the patients in the drug-loaded microsphere group had better subjective tolerance and could reduce the number of interventional treatments. Therefore, D-TACE is worthy of clinical promotion.
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Affiliation(s)
- Ting Ye
- Department of Nuclear Medicine, First Medical Center, PLA General Hospital, Beijing 100039, China
| | - Shi-Han Shao
- Department of Hepatobiliary Surgery, The Sixth Medical Center, PLA General Hospital, Beijing 100048, China
| | - Kan Ji
- Department of Interventional Radiology, First Medical Center, PLA General Hospital, Beijing 100071, China
| | - Shu-Lin Yao
- Department of Nuclear Medicine, First Medical Center, PLA General Hospital, Beijing 100039, China
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Tümen D, Heumann P, Gülow K, Demirci CN, Cosma LS, Müller M, Kandulski A. Pathogenesis and Current Treatment Strategies of Hepatocellular Carcinoma. Biomedicines 2022; 10:3202. [PMID: 36551958 PMCID: PMC9775527 DOI: 10.3390/biomedicines10123202] [Citation(s) in RCA: 67] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 12/02/2022] [Accepted: 12/05/2022] [Indexed: 12/14/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the most frequent liver cancer with high lethality and low five-year survival rates leading to a substantial worldwide burden for healthcare systems. HCC initiation and progression are favored by different etiological risk factors including hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, non-/and alcoholic fatty liver disease (N/AFLD), and tobacco smoking. In molecular pathogenesis, endogenous alteration in genetics (TP53, TERT, CTNNB1, etc.), epigenetics (DNA-methylation, miRNA, lncRNA, etc.), and dysregulation of key signaling pathways (Wnt/β-catenin, JAK/STAT, etc.) strongly contribute to the development of HCC. The multitude and complexity of different pathomechanisms also reflect the difficulties in tailored medical therapy of HCC. Treatment options for HCC are strictly dependent on tumor staging and liver function, which are structured by the updated Barcelona Clinic Liver Cancer classification system. Surgical resection, local ablative techniques, and liver transplantation are valid and curative therapeutic options for early tumor stages. For multifocal and metastatic diseases, systemic therapy is recommended. While Sorafenib had been the standalone HCC first-line therapy for decades, recent developments had led to the approval of new treatment options as first-line as well as second-line treatment. Anti-PD-L1 directed combination therapies either with anti-VEGF directed agents or with anti-CTLA-4 active substances have been implemented as the new treatment standard in the first-line setting. However, data from clinical trials indicate different responses on specific therapeutic regimens depending on the underlying pathogenesis of hepatocellular cancer. Therefore, histopathological examinations have been re-emphasized by current international clinical guidelines in addition to the standardized radiological diagnosis using contrast-enhanced cross-sectional imaging. In this review, we emphasize the current knowledge on molecular pathogenesis of hepatocellular carcinoma. On this occasion, the treatment sequences for early and advanced tumor stages according to the recently updated Barcelona Clinic Liver Cancer classification system and the current algorithm of systemic therapy (first-, second-, and third-line treatment) are summarized. Furthermore, we discuss novel precautional and pre-therapeutic approaches including therapeutic vaccination, adoptive cell transfer, locoregional therapy enhancement, and non-coding RNA-based therapy as promising treatment options. These novel treatments may prolong overall survival rates in regard with quality of life and liver function as mainstay of HCC therapy.
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Affiliation(s)
| | | | | | | | | | | | - Arne Kandulski
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases University Hospital Regensburg Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany
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Rizzo A, Carloni R, Ricci AD, Cusmai A, Laforgia M, Calabrò C, Ungaro V, Oreste D, Sollitto M, Palmiotti G, Brandi G. Treatment-related adverse events of first-line immunotherapy versus sorafenib for advanced hepatocellular carcinoma: a meta-analysis. Expert Opin Drug Saf 2022; 22:323-329. [PMID: 36426773 DOI: 10.1080/14740338.2023.2152793] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Affiliation(s)
- Alessandro Rizzo
- Struttura Semplice Dipartimentale di Oncologia Medica per la Presa in Carico Globale del Paziente Oncologico “Don Tonino Bello”, I.R.C.C.S. Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco 65, 70124 Bari, Italy
| | - Riccardo Carloni
- Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni - 15, Bologna, Italy
| | - Angela Dalia Ricci
- Medical Oncology Unit, National Institute of Gastroenterology, “Saverio de Bellis” Research Hospital, Castellana Grotte, Italy
| | - Antonio Cusmai
- Struttura Semplice Dipartimentale di Oncologia Medica per la Presa in Carico Globale del Paziente Oncologico “Don Tonino Bello”, I.R.C.C.S. Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco 65, 70124 Bari, Italy
| | - Mariarita Laforgia
- S.C. Farmacia e U.Ma.C.A., Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Istituto Tumori Giovanni Paolo II-Bari, Bari, Italy
| | - Concetta Calabrò
- S.C. Farmacia e U.Ma.C.A., Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Istituto Tumori Giovanni Paolo II-Bari, Bari, Italy
| | - Valentina Ungaro
- S.C. Farmacia e U.Ma.C.A., Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Istituto Tumori Giovanni Paolo II-Bari, Bari, Italy
| | - Donato Oreste
- Radiology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Tumori Giovanni Paolo II, Bari, Italy
| | - Mario Sollitto
- Radiology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Tumori Giovanni Paolo II, Bari, Italy
| | - Gennaro Palmiotti
- Struttura Semplice Dipartimentale di Oncologia Medica per la Presa in Carico Globale del Paziente Oncologico “Don Tonino Bello”, I.R.C.C.S. Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco 65, 70124 Bari, Italy
| | - Giovanni Brandi
- Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni - 15, Bologna, Italy
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Jia W, Han Y, Mao X, Xu W, Zhang Y. Nanotechnology strategies for hepatocellular carcinoma diagnosis and treatment. RSC Adv 2022; 12:31068-31082. [PMID: 36349046 PMCID: PMC9621307 DOI: 10.1039/d2ra05127c] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Accepted: 10/20/2022] [Indexed: 10/10/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a common malignancy threatening human health, and existing diagnostic and therapeutic techniques are facing great challenges. In the last decade or so, nanotechnology has been developed and improved for tumor diagnosis and treatment. For example, nano-intravenous injections have been approved for malignant perivascular epithelioid cell tumors. This article provides a comprehensive review of the applications of nanotechnology in HCC in recent years: (I) in radiological imaging, magnetic resonance imaging (MRI), fluorescence imaging (FMI) and multimodality imaging. (II) For diagnostic applications in HCC serum markers. (III) As embolic agents in transarterial chemoembolization (TACE) or directly as therapeutic drugs. (IV) For application in photothermal therapy and photodynamic therapy. (V) As carriers of chemotherapeutic drugs, targeted drugs, and natural plant drugs. (VI) For application in gene and immunotherapy. Compared with the traditional methods for diagnosis and treatment of HCC, nanoparticles have high sensitivity, reduce drug toxicity and have a long duration of action, and can also be combined with photothermal and photodynamic multimodal combination therapy. These summaries provide insights for the further development of nanotechnology applications in HCC.
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Affiliation(s)
- WeiLu Jia
- Medical School, Southeast University Nanjing 210009 China
| | - YingHui Han
- Outpatient Department, The Second Affiliated Hospital of Nanjing Medical University Nanjing 210009 China
| | - XinYu Mao
- Hepatopancreatobiliary Center, The Second Affiliated Hospital of Nanjing Medical University Nanjing 210009 China
| | - WenJing Xu
- Medical School, Southeast University Nanjing 210009 China
| | - YeWei Zhang
- Hepatopancreatobiliary Center, The Second Affiliated Hospital of Nanjing Medical University Nanjing 210009 China
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Mossenta M, Busato D, Dal Bo M, Macor P, Toffoli G. Novel Nanotechnology Approaches to Overcome Drug Resistance in the Treatment of Hepatocellular Carcinoma: Glypican 3 as a Useful Target for Innovative Therapies. Int J Mol Sci 2022; 23:10038. [PMID: 36077433 PMCID: PMC9456072 DOI: 10.3390/ijms231710038] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Revised: 08/30/2022] [Accepted: 08/30/2022] [Indexed: 11/23/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the second most lethal tumor, with a 5-year survival rate of 18%. Early stage HCC is potentially treatable by therapies with curative intent, whereas chemoembolization/radioembolization and systemic therapies are the only therapeutic options for intermediate or advanced HCC. Drug resistance is a critical obstacle in the treatment of HCC that could be overcome by the use of targeted nanoparticle-based therapies directed towards specific tumor-associated antigens (TAAs) to improve drug delivery. Glypican 3 (GPC3) is a member of the glypican family, heparan sulfate proteoglycans bound to the cell surface via a glycosylphosphatidylinositol anchor. The high levels of GPC3 detected in HCC and the absence or very low levels in normal and non-malignant liver make GPC3 a promising TAA candidate for targeted nanoparticle-based therapies. The use of nanoparticles conjugated with anti-GPC3 agents may improve drug delivery, leading to a reduction in severe side effects caused by chemotherapy and increased drug release at the tumor site. In this review, we describe the main clinical features of HCC and the common treatment approaches. We propose the proteoglycan GPC3 as a useful TAA for targeted therapies. Finally, we describe nanotechnology approaches for anti-GPC3 drug delivery systems based on NPs for HCC treatment.
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Affiliation(s)
- Monica Mossenta
- Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy
- Department of Life Sciences, University of Trieste, 34127 Trieste, Italy
| | - Davide Busato
- Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy
- Department of Life Sciences, University of Trieste, 34127 Trieste, Italy
| | - Michele Dal Bo
- Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy
| | - Paolo Macor
- Department of Life Sciences, University of Trieste, 34127 Trieste, Italy
| | - Giuseppe Toffoli
- Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy
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Liu YS, Chang PY, Liang PC, Ou MC, Hwang JI, Chen CH. Safety and Efficacy of Drug-Eluting Beads Trans-Arterial Chemoembolization for Hepatocellular Carcinoma in Taiwan (SERENADE-T). J Hepatocell Carcinoma 2022; 9:811-821. [PMID: 35996398 PMCID: PMC9391935 DOI: 10.2147/jhc.s374555] [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: 05/13/2022] [Accepted: 08/09/2022] [Indexed: 01/27/2023] Open
Abstract
Purpose The aim of this retrospective study was to evaluate the safety and efficacy of patients with hepatocellular carcinoma treated with drug-eluting bead with doxorubicin transarterial chemoembolization (DEBDOX-TACE) in Taiwan. Patients and Methods We retrospectively investigated 630 hepatocellular carcinoma patients who underwent DEBDOX-TACE in multiple institutions from 2011 to 2016 in Taiwan. Tumor response was assessed per modified response evaluation criteria in solid tumors, overall survival, and safety. Results This study included 630 patients who underwent DEBDOX-TACE, participants’ mean age was 66 years, 68.1% males and 15.6% females. The mean doxorubicin dose administered via DEBDOX-TACE was 56 mg. Complete and partial response rates were 14.6% and 49.2%, respectively, with a disease control rate of 84.6%. The median overall survival was 29.2 months. The most common post-embolization symptom was abdominal pain (22.4%). No hepatic encephalopathy and no procedure-related death were found. Conclusion Real-world data from Taiwan demonstrated that DEBDOX-TACE for hepatocellular carcinoma can achieve high tumor response rate with low adverse events.
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Affiliation(s)
- Yi-Sheng Liu
- Department of Medical Imaging, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Pi-Yi Chang
- Department of Radiology, Taichung Veterans General Hospital, Taichung City, Taiwan
| | - Po-Chin Liang
- Department of Radiology, National Taiwan University Hospital, Taipei City, Taiwan
| | - Ming-Ching Ou
- Department of Diagnostic Radiology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Jen-I Hwang
- Department of Medical Imaging, Tungs' Taichung MetroHarbor Hospital, Taichung City, Taiwan.,Department of Radiology, School of Medicine, National Defense Medical Center, Taipei City, Taiwan
| | - Chien-Hung Chen
- Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Douliu City, Yunlin County, Taiwan.,Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei City, Taiwan
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Ghosh A, Gupta V, Al Khalifah A, Akhter NM. Transradial versus transfemoral arterial access in DEB-TACE for hepatocellular carcinoma. J Clin Imaging Sci 2022; 12:38. [PMID: 36128344 PMCID: PMC9479582 DOI: 10.25259/jcis_47_2022] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Accepted: 06/24/2022] [Indexed: 11/04/2022] Open
Abstract
Objectives
Transradial access has become increasingly popular in body interventional procedures but has not been ubiquitously adapted. This retrospective study compares the efficacy of this approach versus transfemoral access in hepatocellular carcinoma (HCC) patients who underwent drug-eluting bead transarterial chemoembolization (DEB-TACE).
Materials and Methods
A total of 130 HCC patients underwent 146 DEB-TACE procedures within our institution from June 2015 to May 2020. About 90 and 56 procedures were logged for the transradial and transfemoral cohorts, respectively. Peak skin dose, fluoroscopy time, administered contrast volume, total procedure time, and equipment cost data for each procedure were reviewed to evaluate for statistical differences between the two groups.
Results
All 146 cases were technically successful without major complications or access failures in either group. No statistical differences were present between the two access groups in regards to peak skin dose or fluoroscopy time. Transradial access recorded a significantly higher contrast volume (P < 0.05), and a significantly longer procedural time than transfemoral access (P < 0.01). However, transradial access also displayed a significantly lower procedural equipment cost (P < 0.01) between the two groups.
Conclusion
Transradial DEB-TACE has similar trends to transfemoral DEB-TACE in several pertinent radiation parameters and is also significantly more cost-efficacious. The results of this investigation suggest the consideration of transradial access whenever viable as an alternative to transfemoral access in the DEB-TACE treatment of HCC patients.
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Affiliation(s)
- Abheek Ghosh
- Department of Interventional Radiology, University of Maryland, Baltimore, Maryland, United States,
| | - Vikash Gupta
- Department of Interventional Radiology, University of Maryland, Baltimore, Maryland, United States,
| | - Abdullah Al Khalifah
- Department of Interventional Radiology, University of Maryland, Baltimore, Maryland, United States,
| | - Nabeel Mohsin Akhter
- Department of Interventional Radiology, University of Maryland, Baltimore, Maryland, United States,
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Silk T, Silk M, Wu J. Up to seven criteria in selection of systemic therapy for hepatocellular carcinoma. World J Gastroenterol 2022; 28:2561-2568. [PMID: 35949352 PMCID: PMC9254139 DOI: 10.3748/wjg.v28.i23.2561] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 03/25/2022] [Accepted: 04/30/2022] [Indexed: 02/06/2023] Open
Abstract
Barcelona clinic liver cancer (BCLC) intermediate stage hepatocellular carcinoma is a heterogenous disease. Transarterial chemoembolization is offered as the first line therapy in this disease stage. Recent advances in systemic therapy have markedly improved outcomes even in advanced stage disease. The use of systemic therapy in BCLC intermediate stage disease may now be of therapeutic benefit in selected patients. We will focus on "the up to seven" criteria and its utility in selecting systemic therapy.
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Affiliation(s)
- Tarik Silk
- Department of Internal Medicine, NYU Grossman School of Medicine, New York, NY 10016, United States
| | - Mikhail Silk
- Department of Interventional Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States
| | - Jennifer Wu
- Division of Hematology and Oncology, Perlmutter Cancer Center of NYU Langone Health, NYU School of Medicine, New York, NY 10016, United States
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Shang C, Ke M, Liu L, Wang C, Liu Y, Zheng X. Exosomes From Cancer-Associated Mesenchymal Stem Cells Transmit TMBIM6 to Promote the Malignant Behavior of Hepatocellular Carcinoma via Activating PI3K/AKT Pathway. Front Oncol 2022; 12:868726. [PMID: 35720012 PMCID: PMC9201337 DOI: 10.3389/fonc.2022.868726] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Accepted: 03/22/2022] [Indexed: 12/16/2022] Open
Abstract
Objective Cancer-associated mesenchymal stem cells (MSCs) regulate the progression of cancers through exosome-delivered components, while few studies are conducted on hepatocellular carcinoma (HCC). This study aimed to evaluate the effect of exosomes from HCC-associated MSCs (HCC-MSCs) on HCC cellular functions and the potential regulatory mechanism. Methods HCC cells (Huh7 and PLC) were cultured normally or co-cultured with HCC-MSCs, HCC-MSCs plus GW4869, or HCC-MSC-derived exosomes; then mRNA sequencing and RT-qPCR validation were conducted. Subsequently, candidate genes were sorted out and modified in HCC cells. Next, TMBIM6-modified HCC-MSCs were used to treat HCC cells. Results Both HCC-MSCs and their derived exosomes promoted proliferation, invasion, sphere formation ability but suppressed apoptosis in HCC cells (all p < 0.05); however, the effect of HCC-MSCs on these cellular functions was repressed by exosome inhibitor (GW4869). Subsequently, TMBIM6, EEF2, and PRDX1 were sorted out by mRNA sequencing and RT-qPCR validation as candidate genes implicated in the regulation of HCC cellular functions by HCC-MSC-derived exosomes. Among them, TMBIM6 had a potent effect (all p < 0.05), while EEF2 and PRDX1 had less effect on regulating HCC cell viability and invasion. Next, direct silencing TMBIM6 repressed viability, sphere formation, invasion, epithelial-mesenchymal transition (EMT), and PI3K/AKT pathway but promoted apoptosis in HCC cells; however, overexpressing TMBIM6 showed the opposite effect. Furthermore, incubating with exosomes from TMBIM6-modified HCC-MSCs presented a similar effect as direct TMBIM6 modification in HCC cells. Conclusion HCC-MSC-derived exosomes transmit TMBIM6 to promote malignant behavior via PI3K/AKT pathway in HCC.
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Affiliation(s)
- Chuzhi Shang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Mi Ke
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Lin Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Cong Wang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Yufang Liu
- Department of General Surgery, Shangzhou Regional Hospital, Shangluo, China
| | - Xin Zheng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
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Deng J, Wen F. Transarterial Chemoembolization Combined With Tyrosine Kinase Inhibitors for Intermediate-Stage Hepatocellular Carcinoma, What Else Can We Do? Front Oncol 2022; 12:824799. [PMID: 35425716 PMCID: PMC9001928 DOI: 10.3389/fonc.2022.824799] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Accepted: 03/01/2022] [Indexed: 12/12/2022] Open
Abstract
Transarterial chemoembolization (TACE) has been considered the standard treatment for intermediate-stage hepatocellular carcinoma (HCC). However, intermediate‐stage HCC is highly heterogeneous with a broad population with varying tumour burdens, liver function. This suggests that TACE monotherapy treatment might not be suitable for all patients with intermediate‐stage HCC. The administration of tyrosine kinase inhibitors (TKIs) has become an important treatment option for improving the prognosis of patients with advanced HCC. Over the years, several trials have been conducted to explore the effects of TACE combined with TKIs for intermediate-stage HCC. However, the clinical efficacy is still controversial, and its potential clinical utility needs to be confirmed. This review will focus on the recent progress of TACE combined TKIs for intermediate-stage HCC.
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Affiliation(s)
- Jun Deng
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Feng Wen
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, China
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Li B. Prophylactic Use of Antibiotics for Postsurgical Infection in c-TACE and DEB-TACE High-Risk Patients: A Case-Control Study. JOURNAL OF HEALTHCARE ENGINEERING 2022; 2022:6203817. [PMID: 35444783 PMCID: PMC9015880 DOI: 10.1155/2022/6203817] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Accepted: 03/02/2022] [Indexed: 11/17/2022]
Abstract
Objectives According to recent reports, prophylactic use of antibiotics is not always required in conventional transarterial chemoembolization (c-TACE). However, clinical evidence of prophylactic antibiotics in drug-eluting beads transarterial chemoembolization (DEB-TACE) to prevent postsurgical infection is limited. This study is aimed to evaluate the correlation between the preoperative prophylactic application of antibiotics and postoperative infection in c-TACE or DEB-TACE, especially in a population with a high risk for postsurgical infection. Methods In this retrospective study, TACE patients diagnosed with hepatic carcinoma (between January 2019 and May 2021) were examined. The case group was given 1.5 g cefuroxime sodium 0.5-1 hour before TACE, while there was no intervention in the control group. The outcomes analyzed were leukocyte count >9.5 × 109/L on the second day after the operation and the diagnosis of infection within one month after the operation. We applied univariate, multivariate logistic regression, trend analysis, and subgroup analysis to find potential risk factors and the necessity of prophylactic antibiotics. Results Among 142 eligible cases, 72 received antibiotics while 70 were kept as control, 113 cases were treated with c-TACE, and 29 were treated with DEB-TACE. Multivariate analysis showed that the increase in white blood cell count after the operation was related to diabetes (OR 5.112, 95% CI 1.229-21.264, p = 0.025). The occurrence of postoperative infection was negatively correlated with preoperative albumin value (＜25 g/L) (OR 153.118, 95% CI 1.631-14372.331, p = 0.030). Trend analysis showed that the risk of postoperative infection increased with a decrease in serum albumin level (P < 0.05). Subgroup analysis showed that there were no significant differences in the incidence of increased leukocyte count and postoperative infection between the prophylactic and nonprophylactic treatment groups, in the case of diabetes, preoperative albumin levels, and operation mode (P > 0.1). Conclusions Prophylactic antibiotic treatment before the c-TACE or DEB-TACE had no significant correlation with postoperative leukocyte increase and postoperative infection. Diabetes history and serum albumin levels were the prominent risk factors associated with an increase in postoperative leukocyte count and postoperative infection. Future large-scale studies and randomized-controlled trials are required to confirm and validate this association.
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Affiliation(s)
- Baojian Li
- Department of Pharmacy, Heping Hospital Affiliated to Changzhi Medical College, Changzhi 046000, Shanxi, China
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36
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Lyu T, Yao H, Wang J, Song L, Tong X, Zou Y. Treatment response, survival and safety profile of transarterial chemoembolization using different sizes of drug-eluting beads in hepatocellular carcinoma patients with portal vein tumor thrombus. Clin Res Hepatol Gastroenterol 2022; 46:101819. [PMID: 34619365 DOI: 10.1016/j.clinre.2021.101819] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Revised: 09/16/2021] [Accepted: 09/30/2021] [Indexed: 02/04/2023]
Abstract
BACKGROUND Different sized microspheres may affect the efficacy and safety of drug-eluting beads transarterial chemoembolization (DEB-TACE) in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT), but related data are lacking. Therefore, the current study aimed to investigate the treatment response, survival and safety of DEB-TACE using different sized microspheres in HCC patients with or without PVTT. METHODS Totally 90 HCC patients underwent DEB-TACE treatment were retrospectively enrolled (30 cases with PVTT and 60 cases without PVTT). According to the sizes of microspheres, patients were divided into 100-300 μm, 300-500 μm and 500-700 μm groups, respectively. RESULTS Disease control rate (DCR) was highest in 300-500 μm group (81.3%), followed by 500-700 μm group (50.0%), then the lowest in 100-300 μm group (12.5%) (P = 0.004); while objective response rate (ORR) was similar among three groups (P = 0.177) in patients with PVTT. Furthermore, overall survival (OS) (P = 0.513) and adverse events (all P>0.05) were similar among three groups in patients with PVTT. Besides, in patients without PVTT: ORR (P = 0.694), DCR (P = 0.591), OS (P = 0.816) were of no difference among three groups; but the fever incidence was highest in 300-500 μm group (65.0%), second high in 500-700 μm group (50.0%), then lowest in 100-300 μm group (25.0%) (P = 0.008), except for this, no difference of other adverse events among three groups was found (all P>0.05). CONCLUSION DEB-TACE using 300-500 μm microspheres (versus 100-300 μm or 500-700 μm microspheres) exhibits best treatment response without additional adverse events, indicating it might be the optimal choice for HCC patients with PVTT.
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Affiliation(s)
- Tianshi Lyu
- Department of Interventional and Vascular Surgery, Peking University First Hospital, Beijing, China
| | - Hang Yao
- Department of Interventional and Vascular Surgery, Peking University First Hospital, Beijing, China
| | - Jian Wang
- Department of Interventional and Vascular Surgery, Peking University First Hospital, Beijing, China
| | - Li Song
- Department of Interventional and Vascular Surgery, Peking University First Hospital, Beijing, China
| | - Xiaoqiang Tong
- Department of Interventional and Vascular Surgery, Peking University First Hospital, Beijing, China
| | - Yinghua Zou
- Department of Interventional and Vascular Surgery, Peking University First Hospital, Beijing, China.
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Malagari K, Denys A, Burrel M, Reig M, Brunet M, Duran R, Kiakidis T, Moschouris H, Sanduzzi-Zamparell M, Bruix J. POLYETHYLENE-GLYCOL DRUG-ELUTING EMBOLIC MICROSPHERES LOADED WITH DOXORUBICIN FOR THE TREATMENT OF HEPATOCELLULAR CARCINOMA: FEASIBILITY, SAFETY AND PHARMACOKINETIC STUDY. J Vasc Interv Radiol 2022; 33:752-761. [PMID: 35351630 DOI: 10.1016/j.jvir.2021.11.019] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Revised: 11/01/2021] [Accepted: 11/24/2021] [Indexed: 11/30/2022] Open
Abstract
PURPOSE Polyethylene-glycol drug-eluting microspheres (PEG-DEM) can be loaded to elute doxorubicin. This study evaluated the pharmacokinetic profile and safety of PEG-DEMs in the treatment of patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS This prospective, multicentre, dose escalation study enrolled 25 patients (68% men) with early or intermediate stage HCC and performance status of 0. Patients in cohort I were assigned to receive target doxorubicin doses of 75, 100, or 150 mg. Analyses were performed based on the specific dose of doxorubicin that patients received, since some patients received less than the assigned dose. Patients in cohort II received the maximum safe tested dose. Adverse events (AEs) were classified according to Common Terminology Criteria for Adverse Events v.4.03. Tumor response was evaluated every 3 months according to European Association for the Study of the Liver criteria and modified Response Evaluation Criteria in Solid Tumors. RESULTS The maximum tested safe dose of doxorubicin was 150 mg. For the groups that received ≤75, 75-100, and 101-150 mg, the Cmax were 286.7±220.1, 157.1±94.6 and 245.4±142.8 ng/mL, respectively; AUC0-24h were 421.7±221.2, 288.1±100.9 and 608.3±319.3 (ng x hours)/mL respectively, with almost complete clearance at 24 hours. There were no deaths within 30 days. The best objective response rate was 81% and the disease control rate was 91%. Median overall survival was 27.2 (95% CI, 17.5-n.e) months; median progression free survival was 9.8 (95% CI, 5.5-n.e.) months. CONCLUSION PEG-DEMs demonstrated a favorable safety profile with low systemic concentration of doxorubicin, and promising efficacy.
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Affiliation(s)
- Katerina Malagari
- National and Kapodistrian University of Athens, Medical School, Evgenidion Hospital, Greece
| | - Alban Denys
- Department of Diagnostic and Interventional Radiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Martha Burrel
- BCLC group. Liver Unit, Hospital Clínic-IDIBAPS, CIBEREHD, University of Barcelona, Spain
| | - Maria Reig
- BCLC group. Liver Unit, Hospital Clínic-IDIBAPS, CIBEREHD, University of Barcelona, Spain
| | - Mercé Brunet
- BCLC group. Liver Unit, Hospital Clínic-IDIBAPS, CIBEREHD, University of Barcelona, Spain; Laboratory of Pharmacology & Toxicology, Hospital Clínic of Barcelona, Spain
| | - Rafael Duran
- Department of Diagnostic and Interventional Radiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Theodoros Kiakidis
- National and Kapodistrian University of Athens, Medical School, Evgenidion Hospital, Greece
| | - Hippokratis Moschouris
- National and Kapodistrian University of Athens, Medical School, Evgenidion Hospital, Greece
| | | | - Jordi Bruix
- BCLC group. Liver Unit, Hospital Clínic-IDIBAPS, CIBEREHD, University of Barcelona, Spain
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Facciorusso A, Paolillo R, Tartaglia N, Ramai D, Mohan BP, Cotsoglou C, Chandan S, Ambrosi A, Bargellini I, Renzulli M, Sacco R. Efficacy of combined transarterial radioembolization and sorafenib in the treatment of hepatocarcinoma: A meta-analysis. Dig Liver Dis 2022; 54:316-323. [PMID: 34193367 DOI: 10.1016/j.dld.2021.06.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Revised: 06/04/2021] [Accepted: 06/07/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Adjuvant sorafenib may further enhance the efficacy of transarterial radioembolization for the treatment of hepatocellular carcinoma. AIMS To evaluate the efficacy and safety of radioembolization plus sorafenib in hepatocellular carcinoma patients. METHODS With a literature search through October 2020, we identified 9 studies (632 patients). Primary outcome was overall survival. Results were expressed as pooled median, odds ratio, or hazard ratio and 95% confidence intervals. RESULTS Pooled overall survival after radioembolization plus sorafenib was 10.79 months (95% confidence interval 9.19-12.39) and it was longer in Barcelona Clinic Liver Cancer (BCLC) B (14.47 months, 9.07-19.86) as compared to BCLC C patients (10.22 months, 7.53-12.9). No difference between combined therapy versus radioembolization alone was observed in terms of overall survival (hazard ratio 1.07, 0.89-1.30). Pooled median progression-free survival was 6.32 months (5.68-6.98), with 1-year progression-free survival pooled rate of 38.5% (12.7%-44.2%). No difference in progression-free survival (hazard ratio 0.94, 0.79-1.12) between the two treatments was observed. Pooled rate of severe adverse events was 48.9% (26.7%-71.2%), again with no difference between the two treatment regimens (odds ratio 1.52, 0.15-15.02). CONCLUSIONS The association of sorafenib does not seem to prolong survival nor delay disease progression in patients treated with radioembolization.
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Affiliation(s)
- Antonio Facciorusso
- Gastroenterology Unit, Department of Medical Sciences, University of Foggia, Foggia 71122, Italy.
| | - Rosa Paolillo
- Gastroenterology Unit, Department of Medical Sciences, University of Foggia, Foggia 71122, Italy
| | - Nicola Tartaglia
- Surgical Unit, Department of Medical Sciences, University of Foggia, Foggia 71122, Italy
| | - Daryl Ramai
- Gastroenterology and Hepatology, Brooklyn Hospital Center, Brooklyn, NY, United States
| | - Babu P Mohan
- Gastroenterology & Hepatology, University of Utah Health, Salt Lake City, UT, United States
| | | | - Saurabh Chandan
- Division of Gastroenterology, CHI Creighton University Medical Center, Omaha, NE, United States
| | - Antonio Ambrosi
- Surgical Unit, Department of Medical Sciences, University of Foggia, Foggia 71122, Italy
| | - Irene Bargellini
- Department of Interventional Radiology, Pisa University Hospital, Pisa 56124, Italy
| | - Matteo Renzulli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Rodolfo Sacco
- Gastroenterology Unit, Department of Medical Sciences, University of Foggia, Foggia 71122, Italy
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Mohr I, Vogeler M, Pfeiffenberger J, Sprengel SD, Klauss M, Radeleff B, Teufel A, Chang DH, Springfeld C, Longerich T, Merle U, Mehrabi A, Weiss KH, Mieth M. Clinical effects and safety of different transarterial chemoembolization methods for bridging and palliative treatments in hepatocellular carcinoma. J Cancer Res Clin Oncol 2022; 148:3163-3174. [PMID: 35076764 PMCID: PMC9508038 DOI: 10.1007/s00432-021-03900-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Accepted: 12/24/2021] [Indexed: 01/09/2023]
Abstract
Purpose We assessed and compared clinical effects and safety endpoints of three methods of transarterial chemoembolization (TACE), conventional (cTACE), with drug-eluting beads (DEB-TACE), and with degradable starch microspheres (DSM-TACE), used in patients with hepatocellular carcinoma (HCC) in the bridging to liver transplant (LT) and the palliative setting. Methods In our center, 148 patients with HCC underwent 492 completed TACE procedures between 2008 and 2017 (158 for bridging to LT; 334 for palliative treatment) which we analyzed retrospectively. Of these procedures, 348 were DEB-TACE, 60 cTACE, and 84 DSM-TACE. Results The cTACE procedure revealed a significantly longer period of hospitalization (p = 0.02), increased occurrence of nausea (p = 0.025), and rise in alanine transaminase (ALT) levels (p = 0.001), especially in the palliative setting. In the bridging to LT cohort, these clinical endpoints did not reach statistical significance. Conclusions The clinical safety of different TACE methods for HCC in both the palliative and the bridging to LT setting was equivalent. In the palliative setting, the cTACE procedure revealed an increased risk for adverse clinical effects such as nausea, elevation of ALT, and a prolonged period of hospitalization what might either be related to the systemic effects of the chemotherapeutic agent or to the differences in both collectives. Thus, further studies must be conducted on a larger number of TACE procedures to effectively explore the clinical side effects of the various TACE variants.
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Affiliation(s)
- Isabelle Mohr
- Internal Medicine IV, Department of Gastroenterology, Heidelberg University Hospital, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
| | - Marie Vogeler
- Internal Medicine IV, Department of Gastroenterology, Heidelberg University Hospital, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
| | - Jan Pfeiffenberger
- Internal Medicine IV, Department of Gastroenterology, Heidelberg University Hospital, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
| | | | - Miriam Klauss
- Department of Radiology, Heidelberg University Hospital, Heidelberg, Germany
| | - Boris Radeleff
- Department of Diagnostic and Interventional Radiology, Sana Klinikum Hof, Hof, Germany
| | - Andreas Teufel
- Department of Gastroenterology and Hepatology, Mannheim University Hospital, Mannheim, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
| | - De-Hua Chang
- Department of Radiology, Heidelberg University Hospital, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
| | - Christoph Springfeld
- Department of Medical Oncology, Heidelberg University Hospital, National Center for Tumor Diseases (NCT), Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
| | - Thomas Longerich
- Department of Pathology, Heidelberg University Hospital, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
| | - Uta Merle
- Internal Medicine IV, Department of Gastroenterology, Heidelberg University Hospital, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
| | - Arianeb Mehrabi
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, INF 110, 69120, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
| | - Karl Heinz Weiss
- Internal Medicine, Salem Hospital Heidelberg, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
| | - Markus Mieth
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, INF 110, 69120, Heidelberg, Germany.
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany.
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Ren Y, Guo Y, Chen L, Sun T, Zhang W, Sun B, Zhu L, Xiong F, Zheng C. Efficacy of Drug-Eluting Beads Transarterial Chemoembolization Plus Camrelizumab Compared With Conventional Transarterial Chemoembolization Plus Camrelizumab for Unresectable Hepatocellular Carcinoma. Cancer Control 2022; 29:10732748221076806. [PMID: 35343254 PMCID: PMC8958708 DOI: 10.1177/10732748221076806] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
Abstract
Objectives The purpose of this study was to compare the efficacy and safety of drug-eluting beads transarterial chemoembolization plus camrelizumab (D-TACE-C) with conventional transarterial chemoembolization plus camrelizumab (C-TACE-C) in the treatment of patients with unresectable hepatocellular carcinoma (HCC). Materials and Methods This was a retrospective study that evaluated the consecutive medical records of patients with unresectable HCC who had undergone D-TACE-C or C-TACE-C from April 2020 to August 2021. Efficacy of treatment was evaluated using tumor response, progression-free survival (PFS) and survival rates. The adverse events were recorded. Results A total of 54 patients were included in this study, including 27 patients who had received D-TACE-C treatment, and 27 patients who had received C-TACE-C treatment. The median PFS and DCR in the D-TACE-C group were significantly longer than those for the C-TACE-C group (PFS: 10 vs. 3 months, P=.017; DCR: 70.4% vs. 40.7%, P = .028). Cox regression analysis showed that D-TACE-C was the only protective factor for PFS. The 6-month and 12-month survival rates in D-TACE-C group and C-TACE-C group were 85.2% versus 79.4% (P = .646) and 65.2% versus 65.1% (P = .903), respectively. Reactive cutaneous capillary endothelial proliferation was the most common adverse event associated with the treatment. There was no significant difference in the adverse events related to TACE and camrelizumab between the two groups. No treatment-related deaths occurred in this study. Conclusions D-TACE-C is a safe and well-tolerated treatment, and may produce better PFS and tumor response in patients with unresectable HCC than C-TACE-C.
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Affiliation(s)
- Yanqiao Ren
- Department of Radiology, 36630Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Yusheng Guo
- Department of Radiology, 36630Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Lei Chen
- Department of Radiology, 36630Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Tao Sun
- Department of Radiology, 36630Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Weihua Zhang
- Department of Radiology, 36630Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Bo Sun
- Department of Radiology, 36630Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Licheng Zhu
- Department of Radiology, 36630Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Fu Xiong
- Department of Radiology, 36630Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Chuansheng Zheng
- Department of Radiology, 36630Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
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Mostafa N, Salem A, Mansour SZ, El-Sonbaty SM, Moawed FSM, Kandil EI. Rationale for Tailoring an Alternative Oncology Trial Using a Novel Gallium-Based Nanocomplex: Mechanistic Insights and Preclinical Challenges. Technol Cancer Res Treat 2022; 21:15330338221085376. [PMID: 35382635 PMCID: PMC8990695 DOI: 10.1177/15330338221085376] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Revised: 02/07/2022] [Accepted: 02/11/2022] [Indexed: 01/10/2023] Open
Abstract
Introduction: In the fight against cancer, cisplatin is most widely used as a clinical mainstay for the chemotherapy of various human cancers. Meanwhile, its cytotoxic profile, as well as drug resistance, limits its widespread application. The goal of precision medicine is to tailor an optimized therapeutic program based on the biology of the disease. Recently, nanotechnology has been demonstrated to be promising in this scenario. Objective: The current work provides a rationale for the design of an alternative oncology trial for the treatment of hepatocarcinogenesis using a novel eco-friendly nanocomplex, namely gallic acid-coated gallium nanoparticles. Moreover, the study tests whether the antineoplastic efficacy of gallic acid-coated gallium nanoparticles could be enhanced or not when it is administrated together with cisplatin. Methods: The work comprised a series of both in vitro and in vivo investigations. The in vivo therapeutic efficacy of such treatments, against diethylnitrosamine-induced hepatocarcinogenesis, was strictly evaluated by tracking target genes expressions, iron homeostasis, diverse biomarkers alterations, and lastly, routine paraclinical investigations were also assessed. Results: The in vitro biological evaluation of gallic acid-coated gallium nanoparticles in a HepG-2 cancer cell line established its superior cytotoxicity. Else more, the results of the in vivo experiment highlighted that gallic acid-coated gallium nanoparticles could diminish key hallmarks of cancer by ameliorating most of the investigated parameters. This was well-appreciated with the histopathological findings of the liver architectures of the treated groups. Conclusions: Our findings suggest that novel biogenic Ga-based nanocomplexes may potentially present new hope for the development of alternative liver cancer therapeutics, which should attract further scientific interest.
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Affiliation(s)
- Nihal Mostafa
- Department of Biochemistry, Faculty of Science, 247928Ain Shams University, Cairo, Egypt
| | - Ahmed Salem
- Department of Biochemistry, Faculty of Science, 247928Ain Shams University, Cairo, Egypt
| | - Somaya Z Mansour
- Radiation Biology, National Center for Radiation Research and Technology (NCRRT), 68892Atomic Energy Authority (AEA), Cairo, Egypt
| | - Sawsan M El-Sonbaty
- Radiation Microbiology, National Center for Radiation Research and Technology (NCRRT), 68892Atomic Energy Authority (AEA), Cairo, Egypt
| | - Fatma S M Moawed
- Health Radiation Research, National Center for Radiation Research and Technology (NCRRT), 68892Atomic Energy Authority (AEA), Cairo, Egypt
| | - Eman I Kandil
- Department of Biochemistry, Faculty of Science, 247928Ain Shams University, Cairo, Egypt
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Long Term Survival Analysis in a Cohort of 125 Patients with Hepatocellular Carcinoma Treated with Transarterial Chemoembolization Using Small Drug Eluting Beads. Cardiovasc Intervent Radiol 2021; 45:54-61. [PMID: 34820694 DOI: 10.1007/s00270-021-02991-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Accepted: 10/11/2021] [Indexed: 02/07/2023]
Abstract
PURPOSE Different types of drug-eluting beads have been proposed for hepatocellular carcinoma (HCC) treatment, but long-term results are not well known. We report safety, efficacy and long-term overall survival of HCC patients not amenable of curative therapies treated with transcatheter arterial chemoembolization (TACE) using drug-eluting beads sized 70-150 micron. MATERIALS AND METHODS This single-center retrospective study included 125 patients with Barcelona Clinic Liver Cancer stage A (80), B (45) and compensated cirrhosis. TACE was executed injecting drug-elutings microparticles loaded with 75 mg of Doxorubicine and was repeated in patients with partial response or stable disease after one month. Adverse events, response according to modified Response Evaluation Criteria in Solid Tumors and overall survival were assessed. RESULTS Chemoembolization with 70-150 micron beads revealed an objective response rate of 88% according to mRECIST criteria and complete response was 60%. After a median follow-up of 53.3 months, overall survival was 36.6 months. Data were censored at the date of liver transplantation in 35 patients. 33 on 125 patients (26,4%) experienced at least one adverse event. We recorded a total of 102 adverse events and 18 were of a high grade (G3-G4). 30 day mortality was 0%. CONCLUSION Chemoembolization with very small particles (70-150 µm) is an effective and safe treatment in unresectable HCC both as a primary therapy or as bridge to transplantation.
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43
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Razi M, Jianping G, Xu H, Ahmed MJ. Conventional versus drug-eluting bead transarterial chemoembolization: A better option for treatment of unresectable hepatocellular carcinoma. J Interv Med 2021; 4:11-14. [PMID: 34805941 PMCID: PMC8562211 DOI: 10.1016/j.jimed.2020.10.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Revised: 09/27/2020] [Accepted: 10/10/2020] [Indexed: 02/07/2023] Open
Abstract
Transarterial chemoembolization (TACE) is a minimally invasive procedure involving intra-arterial catheter-based chemotherapy to selectively administer high doses of cytotoxic drugs to the tumor bed along with ischemic necrosis induced by arterial embolization. Chemoembolization forms the essential core of management in patients with hepatocellular carcinoma (HCC) who are not suitable for curative therapies such as transplantation, resection, or percutaneous ablation. TACE of hepatic cancer(s) has proven to be helpful in achieving local tumor control, and has supported the ability to prevent tumor progression, prolong patient life, and manage patient symptoms. Recent data have demonstrated that, in patients with single-nodule HCC ≤3 cm without vascular invasion, the 5-year overall survival with TACE was found to be comparable with hepatic resection and radiofrequency ablation. Used for several years, Lipiodol continues to play a vital role as a tumor-seeking and radiopaque drug delivery vector in interventional oncology. Efforts have been made to enhance the administration of chemotherapeutic agents to tumors. Compared with conventional TACE, drug-eluting bead TACE is a fairly new drug delivery embolization technique that permits fixed dosing and has the ability to provide sustained release of anticancer agents over a period of time. The present review discusses the basic procedure of TACE and its properties, and the effectiveness of conventional and drug-eluting bead chemoembolization systems currently available or presently undergoing clinical evaluation.
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Affiliation(s)
- Murtuza Razi
- Department of Interventional Radiology, Nanjing Medical University Third School of Clinical Medicine, Nanjing First Hospital, Nanjing, Jiangsu, 210006, China
| | - Gu Jianping
- Department of Interventional Radiology, Nanjing Medical University Third School of Clinical Medicine, Nanjing First Hospital, Nanjing, Jiangsu, 210006, China
| | - He Xu
- Department of Interventional Radiology, Nanjing Medical University Third School of Clinical Medicine, Nanjing First Hospital, Nanjing, Jiangsu, 210006, China
| | - Mohammed Jameeluddin Ahmed
- Department of Interventional Radiology, Nanjing Medical University Third School of Clinical Medicine, Nanjing First Hospital, Nanjing, Jiangsu, 210006, China
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Isaac A, Mohamed SM, Ahmed OA, Hassan AGM, Rasmy HS. Amphiregulin as a novel diagnostic and prognostic biomarker of hepatocellular carcinoma before and after locoregional treatment. THE EGYPTIAN JOURNAL OF INTERNAL MEDICINE 2021. [DOI: 10.1186/s43162-021-00078-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
Abstract
Abstract
Background
Hepatocellular carcinoma is a highly prevalent tumor worldwide. Amphiregulin is a ligand of the epidermal growth factor receptor. Its elevation is linked to different inflammatory and neoplastic conditions. Therefore, amphiregulin may represent a potential diagnostic target in HCC, which has sparked interest as a potential predictor of diagnosis and progression of HCC. The current work was set out to evaluate amphiregulin as a possible diagnostic and prognostic biomarker for HCC on top of cirrhosis. Thirty adult patients with liver cirrhosis and HCC (HCC group) were randomly selected as candidates for locoregional therapies, either radiofrequency ablation or transarterial chemoembolization. A separate group of thirty liver cirrhosis patients served as controls (cirrhosis group). All patients underwent standard laboratory tests and abdominal ultrasounds. Alpha-fetoprotein and amphiregulin were measured twice at baseline and 1 month after the intervention.
Results
Baseline serum amphiregulin was significantly higher in the HCC group than in the cirrhosis group (23.2 ± 11.5 vs. 11.1 ± 7.1), with a p value < 0.001. Patients with multiple and larger focal lesions had greater levels of amphiregulin, with p values of 0.015 and 0.002, respectively. At 1 month following locoregional treatment, the amphiregulin level considerably declined compared with its baseline levels (from 23.2 ± 11.5 to 19.4 ± 10.9), with a p value of 0.012, while AFP showed an insignificant reduction. At follow-up, the level of serum amphiregulin was statistically significantly greater in recurrence cases than in remission cases (30.8 ± 14.1 vs. 17.2 ± 8.8), with a p value of 0.008, and the same was observed for AFP level.
At a cutoff ≥ 17 pg/mL, amphiregulin was a valuable marker in HCC detection with a sensitivity and specificity of 63.3% and 86.7%, respectively, while it has 60% sensitivity and 96% specificity in detecting possible tumor recurrence at a cutoff ≥ 29.7 pg/ml.
Conclusions
Amphiregulin may be a good diagnostic marker for HCC and a prognostic marker after locoregional therapies because its follow-up levels are useful in predicting possible tumor recurrence.
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Gao X, Chen Z, Chen Z, Liu X, Luo Y, Xiao J, Gao Y, Ma Y, Liu C, Leo HL, Yu H, Guo Q. Visualization and Evaluation of Chemoembolization on a 3D Decellularized Organ Scaffold. ACS Biomater Sci Eng 2021; 7:5642-5653. [PMID: 34735119 DOI: 10.1021/acsbiomaterials.1c01005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Transarterial chemoembolization (TACE) has emerged as the mainstay treatment for patients suffering from unresectable intermediate hepatocellular carcinoma and also holds the potential to treat other types of hypervascular cancers such as renal cell carcinoma. However, an in vitro model for evaluating both embolic performance and drug-release kinetics of the TACE embolic agents is still lacking since the current models greatly simplified the in vivo vascular systems as well as the extracellular matrices (ECM) in the organs. Here, we developed a decellularized organ model with preserved ECM and vasculatures as well as a translucent appearance to investigate chemoembolization performances of a clinically widely used embolic agent, i.e., a doxorubicin-loaded ethiodised oil (EO)-based emulsion. We, for the first time, utilized an ex vivo model to evaluate the liquid-based embolic agent in two organs, i.e., liver and kidneys. We found that the EO-based emulsion with enhanced stability by incorporating an emulsifier, i.e., hydrogenated castor oil-40 (HCO), showed an enhanced occlusion level and presented sustained drug release in the ex vivo liver model, suggesting an advantageous therapeutic effect for TACE treatment of hepatocellular carcinoma. In contrast, we observed that drug-release burst happened when applying the same therapy in the kidney model even with the HCO emulsifier, which may be explained by the presence of the specific renal vasculature and calyceal systems, indicating an unfavorable effect in the renal tumor treatment. Such an ex vivo model presents a promising template for chemoembolization evaluation before in vivo experiments for the development of novel embolic agents.
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Affiliation(s)
- Xu Gao
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China
| | - Zijian Chen
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China.,Department of Biomedical Engineering, National University of Singapore, Engineering Drive 3, Engineering Block 4, #04-08, 117583 Singapore
| | - Zhengchang Chen
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China
| | - Xiaoya Liu
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China
| | - Yucheng Luo
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China
| | - Jingyu Xiao
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China
| | - Yanan Gao
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China
| | - Yutao Ma
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China
| | - Chuang Liu
- Cryo-EM Center, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China
| | - Hwa Liang Leo
- Department of Biomedical Engineering, National University of Singapore, Engineering Drive 3, Engineering Block 4, #04-08, 117583 Singapore
| | - Hanry Yu
- Mechanobiology Institute, National University of Singapore, 117411 Singapore.,Institute of Bioengineering and Nanotechnology, Agency for Science, Technology and Research, 138669 Singapore.,Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 117593 Singapore.,Singapore-MIT Alliance for Research and Technology, 138602 Singapore
| | - Qiongyu Guo
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China
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Muhammad H, Tehreem A, Ting PS, Gurakar M, Li SY, Simsek C, Alqahtani SA, Kim AK, Kohli R, Gurakar A. Hepatocellular Carcinoma and the Role of Liver Transplantation: A Review. J Clin Transl Hepatol 2021; 9:738-748. [PMID: 34722189 PMCID: PMC8516838 DOI: 10.14218/jcth.2021.00125] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 05/01/2021] [Accepted: 05/18/2021] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer deaths worldwide and liver transplantation (LT) is the only potentially curative treatment. Over the years, Milan criteria has been used for patient selection. There is ongoing research in this field with introduction of new biomarkers for HCC that can help guide future treatment. Furthermore, newer therapies for downstaging of the tumor are being implemented to prevent dropout from the transplant list. In addition, combination therapies for better outcome are under investigation. Interestingly, the concept of living-donor LT and possible use of hepatitis C virus-positive donors has been implemented as an attempt to expand the organ pool. However, there is a conflict of opinion between different centers regarding its efficacy and data is scarce. The aim of this review article is to outline the various selection criteria for LT, discuss the outcomes of LT in HCC patients, and explore future directions of LT for HCC. Therefore, a comprehensive PubMed/MEDLINE review was conducted. To expand our search, references of the retrieved articles were also screened for additional data. After selecting the studies, the authors independently reviewed them to identify the relevant studies. After careful evaluation 120 studies relevant to out topic are cited in the manuscript. Three tables and two figures are also included. In conclusion LT for HCC has evolved over the years. With the introduction of several expanded criteria beyond Milan, the introduction of bridging therapies, such as transcatheter arterial chemoembolization and radiofrequency ablation, and the approval of newer systemic therapies, it is evident that there will be more LT recipients in the future. It is promising to see ongoing trials and the continuous evolution of protocols. Prospective studies are needed to guide the development of a pre-LT criteria that can ensure low HCC recurrence risk and is not overly stringent, clarify the role of LDLT, and determine the optimal bridging therapies to LT.
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Affiliation(s)
- Haris Muhammad
- Department of Internal Medicine, Greater Baltimore Medical Center, MD, USA
| | - Aniqa Tehreem
- Department of Internal Medicine, Sinai Hospital, Baltimore, MD, USA
| | - Peng-Sheng Ting
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Merve Gurakar
- Department of Medicine, Osler Residency Program, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | | | - Cem Simsek
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Saleh A. Alqahtani
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Amy K. Kim
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Ruhail Kohli
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Ahmet Gurakar
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- Correspondence to: Ahmet Gurakar, Section of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross Research Building, Suite 918 Baltimore, MD 21205, USA. ORCID: https://orcid.org/0000-0002-2221-9148. Tel: +1-410-614-3369, Fax: +1-443-683-8349, E-mail:
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Liu KC, Lv WF, Lu D, Hou CL, Xie J, Lu YH, Cao QS, Tan YL, Zhang YZ, Liu J. Initial Experience of Drug-Eluting Bead-Transcatheter Arterial Chemoembolization After Lipiodol-Based Transcatheter Arterial Chemoembolization Failure for Patients with Advanced Hepatocellular Carcinoma. Cancer Manag Res 2021; 13:7973-7980. [PMID: 34703317 PMCID: PMC8541737 DOI: 10.2147/cmar.s332571] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Accepted: 09/20/2021] [Indexed: 01/10/2023] Open
Abstract
Purpose To investigate the potential safety and efficacy of drug-eluting bead-transcatheter arterial chemoembolization (DEB-TACE) in treating TACE-refractory hepatocellular carcinoma (HCC). Methods We retrospectively evaluated the treatment outcomes of DEB-TACE for 41 HCC nodules in 30 patients who were refractory to conventional TACE (c-TACE) according to tumor response. The antitumor response was evaluated according to mRECIST criteria, and changes in alpha-fetoprotein (AFP), albumin-bilirubin score, the incidence of adverse events, and the time to disease progression were observed. Results The objective response rate and disease control rates were 60.98% and 95.12% at 4 weeks after DEB-TACE, 63.41% and 92.68% at 8 weeks, respectively. The median time of disease progression was 4.60 ± 0.23 months. The AFP of patients decreased continuously at 2–6 weeks after operation, and the AFP at 4 weeks was significantly lower than that at 2 weeks (P = 0.038). Adverse reactions were well tolerated, and no grade 4 adverse reactions were reported. The albumin-bilirubin score did not deteriorate within 6 weeks. Conclusion DEB-TACE has potential efficacy and safety after failure of c-TACE in patients with advanced liver cancer. Further studies are needed to confirm the efficacy of DEB-TACE treatment after failure of c-TACE.
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Affiliation(s)
- Kai-Cai Liu
- Infection Hospital, The First Affiliated Hospital of University of Science and Technology of China, Hefei, People's Republic of China
| | - Wei-Fu Lv
- Department of Interventional Radiology, The First Affiliated Hospital of University of Science and Technology of China, Hefei, People's Republic of China
| | - Dong Lu
- Department of Interventional Radiology, The First Affiliated Hospital of University of Science and Technology of China, Hefei, People's Republic of China
| | - Chang-Long Hou
- Department of Interventional Radiology, The First Affiliated Hospital of University of Science and Technology of China, Hefei, People's Republic of China
| | - Jun Xie
- Department of Interventional Radiology, Fuyang People's Hospital, Fuyang, People's Republic of China
| | - Yu-He Lu
- Department of Interventional Radiology, Chuzhou First People's Hospital, Chuzhou, People's Republic of China
| | - Qi-Sheng Cao
- Department of Interventional Radiology, Ma'anshan People's Hospital, Ma'anshan, People's Republic of China
| | - Yu-Lin Tan
- Department of Interventional Radiology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, People's Republic of China
| | - Ying-Zhan Zhang
- Department of Interventional Radiology, The Second Affiliated Hospital of Bengbu Medical College, Bengbu, People's Republic of China
| | - Jie Liu
- Department of Interventional Radiology, Yingshang People's Hospital, Fuyang, People's Republic of China
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Zhang J, Feng GA, Li Y, Wang W. Drug-eluting bead transarterial chemoembolization with medium-sized versus small-sized CalliSpheres microspheres in unresectable primary liver cancer. Asia Pac J Clin Oncol 2021; 18:388-393. [PMID: 34708554 PMCID: PMC9543937 DOI: 10.1111/ajco.13660] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Accepted: 07/29/2021] [Indexed: 12/01/2022]
Abstract
Purpose The optimal microparticle size for drug‐eluting beads transarterial chemoembolization (DEB‐TACE) remains unknown. This retrospective cohort study analyzed the efficacy and safety of CalliSpheres microsphere embolization in the treatment of unresectable hepatocellular carcinoma (HCC) to determine the influence of particle size on the results. Patients and methods Forty‐two patients with unresectable HCC were enrolled in this retrospective study from January 2018 to January 2020. Patients received DEB‐TACE with CalliSpheres of 100–300 μm (small‐size, n = 15) or 300–500 μm (medium‐size, n = 27). The tumor response was evaluated via enhanced CT or MRI at 1 month, 3 months, and 6 months after treatment, based on the Modified Response Evaluation Criteria in Solid Tumors. Adverse events after DEB‐TACE were recorded. Results Complete response, partial response, stable disease, and progressive disease were recorded in 20%, 20%, 33.3%, 26.7%, respectively, of patients in the small‐size group and 3.7%, 25.9%, 44.4%, 25.9% of patients in the medium‐size group, respectively. No significant difference was found between the two groups (p = 0.516). Major adverse events, including grade three liver toxicity (n = 4) and liver abscess (n = 3), occurred significantly more in the small‐size group, while none were reported in the medium size group (p < 0.05). Conclusion DEB‐TACE with medium‐size (300–500 μm) CalliSpheres microspheres had similar efficacy and a better safety profile than DEB‐TACE with small‐size (100–300 μm) CalliSpheres, indicating that medium‐size microspheres may be a better choice for unresectable primary liver cancer.
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Affiliation(s)
- Jiao Zhang
- Department of Health Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Guo-An Feng
- Department of Vascular Surgery, Juye County People' Hospital, Heze, Shandong Province, China
| | - Yuliang Li
- Department of Interventional Medicine, The Second Hospital, Cheeloo College of Medicine, Shandong University, Interventional Oncology Institute of Shandong University, Jinan, Shandong Province, China
| | - Wujie Wang
- Department of Interventional Medicine, The Second Hospital, Cheeloo College of Medicine, Shandong University, Interventional Oncology Institute of Shandong University, Jinan, Shandong Province, China
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Cao L, Zhu YQ, Wu ZX, Wang GX, Cheng HW. Engineering nanotheranostic strategies for liver cancer. World J Gastrointest Oncol 2021; 13:1213-1228. [PMID: 34721763 PMCID: PMC8529922 DOI: 10.4251/wjgo.v13.i10.1213] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Revised: 06/28/2021] [Accepted: 08/12/2021] [Indexed: 02/06/2023] Open
Abstract
The incidence and mortality of hepatocellular carcinoma have continued to increase over the last few years, and the medicine-based outlook of patients is poor. Given great ideas from the development of nanotechnology in medicine, especially the advantages in the treatments of liver cancer. Some engineering nanoparticles with active targeting, ligand modification, and passive targeting capacity achieve efficient drug delivery to tumor cells. In addition, the behavior of drug release is also applied to the drug loading nanosystem based on the tumor microenvironment. Considering clinical use of local treatment of liver cancer, in situ drug delivery of nanogels is also fully studied in orthotopic chemotherapy, radiotherapy, and ablation therapy. Furthermore, novel therapies including gene therapy, phototherapy, and immunotherapy are also applied as combined therapy for liver cancer. Engineering nonviral polymers to function as gene delivery vectors with increased efficiency and specificity, and strategies of co-delivery of therapeutic genes and drugs show great therapeutic effect against liver tumors, including drug-resistant tumors. Phototherapy is also applied in surgical procedures, chemotherapy, and immunotherapy. Combination strategies significantly enhance therapeutic effects and decrease side effects. Overall, the application of nanotechnology could bring a revolutionary change to the current treatment of liver cancer.
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Affiliation(s)
- Lei Cao
- Department of Pathology, Quanzhou Women's and Children's Hospital, Quanzhou 362000, Fujian Province, China
| | - Yu-Qin Zhu
- Department of Pathology, Quanzhou Women's and Children's Hospital, Quanzhou 362000, Fujian Province, China
| | - Zhi-Xian Wu
- Department of Hepatobiliary Disease, The 900th Hospital of the People’s Liberation Army Joint Service Support Force, Fuzhou 350025, Fujian Province, China
| | - Gao-Xiong Wang
- Department of Pathology, Quanzhou Women's and Children's Hospital, Quanzhou 362000, Fujian Province, China
| | - Hong-Wei Cheng
- School of Public Health, Xiamen University, Xiamen 361002, Fujian Province, China
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Kong D, Jiang T, Liu J, Jiang X, Liu B, Lou C, Zhao B, Carroll SL, Feng G. Chemoembolizing hepatocellular carcinoma with microsphere cored with arsenic trioxide microcrystal. Drug Deliv 2021; 27:1729-1740. [PMID: 33307843 PMCID: PMC7738295 DOI: 10.1080/10717544.2020.1856219] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Chemoembolization for hepatocellular carcinoma (HCC) is often suboptimal due to multiple involved signaling and lack of effective drugs. Arsenic trioxide (ATO) is a potent chemotherapeutic agent, which can target multiple signaling and have substantial efficacy on HCC. However, its usage is limited due to systemic toxicity. Using ATO-eluting beads/microspheres for chemoembolization can have locoregional drug delivery and avoid systemic exposure but will require high drug load, which has not been achieved due to low solubility of ATO. Through an innovative approach, we generated the transiently formed ATO microcrystals via micronization and stabilized these microcrystals by solvent exchange. By encapsulating ATO microcrystals, but not individual molecules, with poly(lactide-co-glycolic acid) (PLGA), we developed microspheres cored with extremely high dense ATO. The molar ratio between ATO and PLGA was 157.4:1 and drug load was 40.1%, which is 4–20 fold higher than that of reported ATO nano/microparticles. These microspheres sustainably induced reactive oxygen species, apoptosis, and cytotoxicity on HCC cells and reduced tumor growth by 80% via locoregional delivery. Chemoembolization on mice model showed that ATO-microcrystal loaded microspheres, but not ATO, inhibited HCC growth by 60–75%, which indicates ATO within these microspheres gains the chemoembolizing function via our innovative approach.
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Affiliation(s)
- Degang Kong
- Department of Hepatobiliary Surgery, The Second Hospital of Tianjin Medical University, Tianjin, China.,Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, USA
| | - Tao Jiang
- Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, USA.,Department of General Surgery, Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing, China
| | - Jian Liu
- Department of Ophthalmology, Medical University of South Carolina, Charleston, SC, USA
| | - Xinyi Jiang
- Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, China
| | - Bei Liu
- Department of Internal Medicine, Division of Hematology, The Ohio State University, Columbus, OH, USA
| | - Cheng Lou
- Department of Hepatobiliary Surgery, Third Central Hospital of Tianjin, Tianjin, China
| | - Baobing Zhao
- Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, China
| | - Steven L Carroll
- Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, USA
| | - Gong Feng
- Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, USA.,Department of Pathology and Laboratory Medicine Residency Program, Medical University of South Carolina, Charleston, SC, USA
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