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Xu X, Liu Y, Liu Y, Yu Y, Yang M, Lu L, Chan L, Liu B. Functional hydrogels for hepatocellular carcinoma: therapy, imaging, and in vitro model. J Nanobiotechnology 2024; 22:381. [PMID: 38951911 PMCID: PMC11218144 DOI: 10.1186/s12951-024-02547-9] [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: 10/09/2023] [Accepted: 05/13/2024] [Indexed: 07/03/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is among the most common malignancies worldwide and is characterized by high rates of morbidity and mortality, posing a serious threat to human health. Interventional embolization therapy is the main treatment against middle- and late-stage liver cancer, but its efficacy is limited by the performance of embolism, hence the new embolic materials have provided hope to the inoperable patients. Especially, hydrogel materials with high embolization strength, appropriate viscosity, reliable security and multifunctionality are widely used as embolic materials, and can improve the efficacy of interventional therapy. In this review, we have described the status of research on hydrogels and challenges in the field of HCC therapy. First, various preparation methods of hydrogels through different cross-linking methods are introduced, then the functions of hydrogels related to HCC are summarized, including different HCC therapies, various imaging techniques, in vitro 3D models, and the shortcomings and prospects of the proposed applications are discussed in relation to HCC. We hope that this review is informative for readers interested in multifunctional hydrogels and will help researchers develop more novel embolic materials for interventional therapy of HCC.
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Affiliation(s)
- Xiaoying Xu
- Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai Clinical Medical College of Jinan University (Zhuhai People's Hospital), Zhuhai, 519000, Guangdong, China
| | - Yu Liu
- Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai Clinical Medical College of Jinan University (Zhuhai People's Hospital), Zhuhai, 519000, Guangdong, China
| | - Yanyan Liu
- Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai Clinical Medical College of Jinan University (Zhuhai People's Hospital), Zhuhai, 519000, Guangdong, China
| | - Yahan Yu
- Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai Clinical Medical College of Jinan University (Zhuhai People's Hospital), Zhuhai, 519000, Guangdong, China
| | - Mingqi Yang
- Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai Clinical Medical College of Jinan University (Zhuhai People's Hospital), Zhuhai, 519000, Guangdong, China
| | - Ligong Lu
- Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai Clinical Medical College of Jinan University (Zhuhai People's Hospital), Zhuhai, 519000, Guangdong, China.
| | - Leung Chan
- Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai Clinical Medical College of Jinan University (Zhuhai People's Hospital), Zhuhai, 519000, Guangdong, China.
| | - Bing Liu
- Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai Clinical Medical College of Jinan University (Zhuhai People's Hospital), Zhuhai, 519000, Guangdong, China.
- Guangzhou First People's Hospital, the Second Affiliated Hospital, School of Medicine, South China University of Technology, 510006, Guangzhou, China.
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Wu CH, Ho MC, Chen CH, Liang JD, Huang KW, Cheng MF, Chang CK, Chang CH, Liang PC. Computed Tomography-Defined Sarcopenia in Outcomes of Patients with Unresectable Hepatocellular Carcinoma Undergoing Radioembolization: Assessment with Total Abdominal, Psoas, and Paraspinal Muscles. Liver Cancer 2023; 12:550-564. [PMID: 38058418 PMCID: PMC10697672 DOI: 10.1159/000529676] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Accepted: 01/29/2023] [Indexed: 12/08/2023] Open
Abstract
INTRODUCTION Sarcopenia is an adverse prognostic factor in patients with liver cirrhosis and hepatocellular carcinoma (HCC). Image-based sarcopenia assessment allows a standardized method to assess abdominal skeletal muscle. However, which is an index muscle for sarcopenia remains unclear. Therefore, we investigated whether sarcopenia defined according to different muscle groups with computed tomography (CT) scans can predict the prognosis of HCC after radioembolization. METHODS In this retrospective study, we analyzed patients who underwent radioembolization for unresectable HCC between January 2010 and December 2019. Before treatment, the total abdominal muscle (TAM), psoas muscle (PM), and paraspinal muscle (PS) areas were evaluated using a single CT slice at the third lumbar vertebra. In previous studies, sarcopenia was determined using the TAM, PM, and PS after stratifying by sex. Finally, we investigated each muscle-defined sarcopenia to decide whether or not it can serve as a prognostic factor for overall survival (OS). RESULTS We included 92 patients (74 men and 18 women). TAM, PM, and PS areas were significantly higher in the men than in the women (all p < 0.05). The patients with sarcopenia defined using PM, but not TAM and PS, exhibited significantly poorer OS than those without sarcopenia (median 15.3 vs. 23.8 months, p = 0.034, 0.821, and 0.341, respectively). After adjustment for clinical variables, such as body mass index, liver function, alpha-fetoprotein level, clinical staging, treatment response, and posttreatment curative therapy, PM-defined sarcopenia (hazard ratio: 1.899, 95% confidence interval: 1.087-3.315) remained an independent predictor for the poor OS. CONCLUSION CT-assessed sarcopenia defined using PM was an independent prognostic factor for the poorer prognosis of unresectable HCC after radioembolization.
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Affiliation(s)
- Chih-Horng Wu
- Departments of Medical Imaging and Radiology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
| | - Ming-Chih Ho
- Departments of Surgery, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan
- Center for Functional Image and Interventional Image, National Taiwan University, Taipei, Taiwan
- Department of Surgery, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan
| | - Chien-Hung Chen
- Departments of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin, Taiwan
| | - Ja-Der Liang
- Departments of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Kai-Wen Huang
- Department of Surgery and Graduate Institute of Clinical Medicine, National Taiwan University, Taipei, Taiwan
- Centre of Mini-invasive Interventional Oncology, National Taiwan University Hospital, Taipei, Taiwan
| | - Mei-Fang Cheng
- Departments of Nuclear Medicine and Radiology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
| | - Chih-Kai Chang
- Departments of Medical Imaging and Radiology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
| | - Chia-Hung Chang
- Departments of Medical Imaging and Radiology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
| | - Po-Chin Liang
- Departments of Medical Imaging and Radiology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
- Department of Medical Imaging, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan
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Garg T, Shrigiriwar A, Habibollahi P, Cristescu M, Liddell RP, Chapiro J, Inglis P, Camacho JC, Nezami N. Intraarterial Therapies for the Management of Hepatocellular Carcinoma. Cancers (Basel) 2022; 14:cancers14143351. [PMID: 35884412 PMCID: PMC9322128 DOI: 10.3390/cancers14143351] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Revised: 07/05/2022] [Accepted: 07/07/2022] [Indexed: 12/11/2022] Open
Abstract
Image-guided locoregional therapies play a crucial role in the management of patients with hepatocellular carcinoma (HCC). Transarterial therapies consist of a group of catheter-based treatments where embolic agents are delivered directly into the tumor via their supplying arteries. Some of the transarterial therapies available include bland embolization (TAE), transarterial chemoembolization (TACE), drug-eluting beads-transarterial chemoembolization (DEB-TACE), selective internal radioembolization therapy (SIRT), and hepatic artery infusion (HAI). This article provides a review of pre-procedural, intra-procedural, and post-procedural aspects of each therapy, along with a review of the literature. Newer embolotherapy options and future directions are also briefly discussed.
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Affiliation(s)
- Tushar Garg
- Division of Vascular and Interventional Radiology, Russell H Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; (T.G.); (R.P.L.)
| | - Apurva Shrigiriwar
- Division of Gastroenterology and Hepatology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA;
| | - Peiman Habibollahi
- Department of Interventional Radiology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;
| | - Mircea Cristescu
- Vascular and Interventional Radiology Division, Department of Radiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA;
| | - Robert P. Liddell
- Division of Vascular and Interventional Radiology, Russell H Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; (T.G.); (R.P.L.)
| | - Julius Chapiro
- Section of Vascular and Interventional Radiology, Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT 06510, USA;
| | - Peter Inglis
- Division of Vascular and Interventional Radiology, Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA;
| | - Juan C. Camacho
- Department of Clinical Sciences, College of Medicine, Florida State University, Tallahassee, FL 32306, USA;
- Vascular and Interventional Radiology, Radiology Associates of Florida, Sarasota, FL 34239, USA
| | - Nariman Nezami
- Division of Vascular and Interventional Radiology, Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA;
- Experimental Therapeutics Program, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD 21201, USA
- Correspondence:
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Du Y, Cortez A, Josefsson A, Zarisfi M, Krimins R, Liapi E, Nedrow JR. Preliminary evaluation of alpha-emitting radioembolization in animal models of hepatocellular carcinoma. PLoS One 2022; 17:e0261982. [PMID: 35061763 PMCID: PMC8782514 DOI: 10.1371/journal.pone.0261982] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Accepted: 12/14/2021] [Indexed: 12/03/2022] Open
Abstract
Hepatocellular carcinoma is the most common primary liver cancer and the fifth most frequently diagnosed cancer worldwide. Most patients with advanced disease are offered non-surgical palliative treatment options. This work explores the first alpha-particle emitting radioembolization for the treatment and monitoring of hepatic tumors. Furthermore, this works demonstrates the first in vivo simultaneous multiple-radionuclide SPECT-images of the complex decay chain of an [225Ac]Ac-labeled agent using a clinical SPECT system to monitor the temporal distribution. A DOTA chelator was modified with a lipophilic moiety and radiolabeled with the α-particle emitter Actinium-225. The resulting agent, [225Ac]Ac-DOTA-TDA, was emulsified in ethiodized oil and evaluated in vivo in mouse model and the VX2 rabbit technical model of liver cancer. SPECT imaging was performed to monitor distribution of the TAT agent and the free daughters. The [225Ac]Ac-DOTA-TDA emulsion was shown to retain within the HEP2G tumors and VX2 tumor, with minimal uptake within normal tissue. In the mouse model, significant improvements in overall survival were observed. SPECT-imaging was able to distinguish between the Actinium-225 agent (Francium-221) and the loss of the longer lived daughter, Bismuth-213. An α-particle emitting TARE agent is capable of targeting liver tumors with minimal accumulation in normal tissue, providing a potential therapeutic agent for the treatment of hepatocellular carcinoma as well as a variety of hepatic tumors. In addition, SPECT-imaging presented here supports the further development of imaging methodology and protocols that can be incorporated into the clinic to monitor Actinium-225-labeled agents.
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Affiliation(s)
- Yong Du
- Russell H. Morgan Department of Radiology & Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America
| | - Angel Cortez
- Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America
| | - Anders Josefsson
- Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America
| | - Mohammadreza Zarisfi
- Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America
| | - Rebecca Krimins
- Russell H. Morgan Department of Radiology & Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America
| | - Eleni Liapi
- Russell H. Morgan Department of Radiology & Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America
| | - Jessie R. Nedrow
- Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America
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Brown ZJ, Hewitt DB, Pawlik TM. Combination therapies plus transarterial chemoembolization in hepatocellular carcinoma: a snapshot of clinical trial progress. Expert Opin Investig Drugs 2021; 31:379-391. [PMID: 34788184 DOI: 10.1080/13543784.2022.2008355] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Unfortunately, some hepatocellular carcinoma (HCC) patients do not qualify for curative-intent treatments such as surgical resection or transplantation. Hence, locoregional treatments such as transarterial chemoembolization (TACE) remain instrumental in the treatment of HCC. Systemic therapy has improved over the past decade with the introduction of combination atezolizumab and bevacizumab as the new standard of care for advanced disease. These new therapies are currently under investigation in combination with TACE. AREA COVERED Combination therapies with TACE including systemic therapies, locoregional therapies, and immunotherapies are reviewed. EXPERT OPINION There has been limited progress in the management of advanced and intermediate HCC. Recent advances in the management of advanced disease with systemic therapy could be beneficial in combination with TACE for the treatment of intermediate stage disease. Immune based therapies are potentially beneficial in combination with TACE because TACE may produce increased antigen release and immune recognition.
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Affiliation(s)
- Zachary J Brown
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - D Brock Hewitt
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Timothy M Pawlik
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
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Delache O, Landreau A, Royer L, Petit A, Rousseau C, Rolland Y, Lalys F. A new software tool for planning interventional procedures in liver cancer. MINIM INVASIV THER 2021; 31:737-746. [PMID: 34355657 DOI: 10.1080/13645706.2021.1954953] [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: 10/20/2022]
Abstract
INTRODUCTION Intra-arterial therapy is an effective way of performing chemotherapy or radiation therapy in patients with primary liver cancer (i.e. hepatocellular carcinoma). Although this minimally invasive approach is now an established treatment option, support tools for pre-operative planning and intra-operative assistance might be helpful. MATERIAL AND METHODS We developed an approach for semi-automatic segmentation of computed tomography angiography images of the main arterial branches (required for access path to the treatment site), automatic segmentation of the liver, arterial and venous tree, and interactive segmentation of the tumors (required for procedure-specific planning). This approach was then integrated into a liver-specific workflow within EndoSize® solution, a planning software for endovascular procedures. The main branches extraction approach was qualitatively evaluated inside the software, while the automatic segmentation methods were quantitatively assessed. RESULTS Main branches extraction provides a success rate of 85% (i.e. all arteries correctly extracted) in a dataset of 172 patients. On public databases, a mean DICE of 0.91, 0.47 and 0.92 was obtained for liver, venous and arterial trees segmentation, respectively. CONCLUSIONS This pipeline is suitable for directly accessing the treatment site, giving anatomic measurements, and visualizing the hepatic trees, liver, and surrounding arteries during the pre-operative planning. ABBREVIATIONS HCC: hepatocellular carcinoma; TACE: transarterial chemoembolization; SIRT: selective internal radiation therapy; CT: computed tomography; CTA: computed tomography angiography; AMS: superior mesenteric artery; LGA: left gastric artery; RHA: right hepatic artery; LHA: left hepatic artery; rbHA: right branch of the hepatic artery; lbHA: left branch of the hepatic artery; GDA: gastroduodenal artery; VOI: volume of interest; SD: standard deviation; MICCAI: medical image computing and computer assisted interventions; MR: magnetic resonance.
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Affiliation(s)
- Ondine Delache
- Department of Interventional Radiology, Centre Eugène Marquis, Rennes, France
| | | | | | | | - Chloé Rousseau
- Department of Clinical Pharmacology - CIC Inserm 1414, Centre Hospitalier Universitaire de Rennes - Hôpital Pontchaillou, Rennes, France
| | - Yan Rolland
- Department of Interventional Radiology, Centre Eugène Marquis, Rennes, France
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Bouvry C, Ardisson V, Noiret N, Garin E, Lepareur N. Labeling of Hinokitiol with 90Y for Potential Radionuclide Therapy of Hepatocellular Carcinoma. Processes (Basel) 2021; 9:940. [DOI: 10.3390/pr9060940] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Hepatocellular carcinoma (HCC), the most common form of primary liver tumors, is the fifth cancer in the world in terms of incidence, and third in terms of mortality. Despite significant advances in the treatment of HCC, its prognosis remains bleak. Transarterial radioembolization with radiolabeled microspheres and Lipiodol has demonstrated significant effectiveness. Here we present a new, simple radiolabeling of Lipiodol with Yttrium-90, for the potential treatment of HCC.
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Affiliation(s)
- Christelle Bouvry
- Comprehensive Cancer Center Eugène Marquis, F-35042 Rennes, France
- CNRS, ISCR (Institut des Sciences Chimiques de Rennes)—UMR 6226, University Rennes, F-35000 Rennes, France
| | - Valérie Ardisson
- Comprehensive Cancer Center Eugène Marquis, F-35042 Rennes, France
| | - Nicolas Noiret
- ENSCR, CNRS, ISCR (Institut des Sciences Chimiques de Rennes)—UMR 6226, University Rennes, F-35000 Rennes, France
| | - Etienne Garin
- Comprehensive Cancer Center Eugène Marquis, F-35042 Rennes, France
- Inrae, Inserm, Institut NUMECAN (Nutrition, Métabolismes et Cancer)—UMR_A 1341, University Rennes, UMR_S 1241, F-35033 Rennes, France
| | - Nicolas Lepareur
- Comprehensive Cancer Center Eugène Marquis, F-35042 Rennes, France
- Inrae, Inserm, Institut NUMECAN (Nutrition, Métabolismes et Cancer)—UMR_A 1341, University Rennes, UMR_S 1241, F-35033 Rennes, France
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Benson AB, D'Angelica MI, Abbott DE, Anaya DA, Anders R, Are C, Bachini M, Borad M, Brown D, Burgoyne A, Chahal P, Chang DT, Cloyd J, Covey AM, Glazer ES, Goyal L, Hawkins WG, Iyer R, Jacob R, Kelley RK, Kim R, Levine M, Palta M, Park JO, Raman S, Reddy S, Sahai V, Schefter T, Singh G, Stein S, Vauthey JN, Venook AP, Yopp A, McMillian NR, Hochstetler C, Darlow SD. Hepatobiliary Cancers, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2021; 19:541-565. [PMID: 34030131 DOI: 10.6004/jnccn.2021.0022] [Citation(s) in RCA: 550] [Impact Index Per Article: 137.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
The NCCN Guidelines for Hepatobiliary Cancers focus on the screening, diagnosis, staging, treatment, and management of hepatocellular carcinoma (HCC), gallbladder cancer, and cancer of the bile ducts (intrahepatic and extrahepatic cholangiocarcinoma). Due to the multiple modalities that can be used to treat the disease and the complications that can arise from comorbid liver dysfunction, a multidisciplinary evaluation is essential for determining an optimal treatment strategy. A multidisciplinary team should include hepatologists, diagnostic radiologists, interventional radiologists, surgeons, medical oncologists, and pathologists with hepatobiliary cancer expertise. In addition to surgery, transplant, and intra-arterial therapies, there have been great advances in the systemic treatment of HCC. Until recently, sorafenib was the only systemic therapy option for patients with advanced HCC. In 2020, the combination of atezolizumab and bevacizumab became the first regimen to show superior survival to sorafenib, gaining it FDA approval as a new frontline standard regimen for unresectable or metastatic HCC. This article discusses the NCCN Guidelines recommendations for HCC.
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Affiliation(s)
- Al B Benson
- 1Robert H. Lurie Comprehensive Cancer Center of Northwestern University
| | | | | | | | - Robert Anders
- 5The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
| | | | | | | | | | | | - Prabhleen Chahal
- 11Case Comprehensive Cancer Center, University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute
| | | | - Jordan Cloyd
- 13The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute
| | | | - Evan S Glazer
- 14St. Jude Children's Research HospitalThe University of Tennessee Health Science Center
| | | | - William G Hawkins
- 16Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
| | | | | | - R Kate Kelley
- 19UCSF Helen Diller Family Comprehensive Cancer Center
| | - Robin Kim
- 20Huntsman Cancer Institute at the University of Utah
| | - Matthew Levine
- 21Abramson Cancer Center at the University of Pennsylvania
| | | | - James O Park
- 23Fred Hutchinson Cancer Research CenterSeattle Cancer Care Alliance
| | | | | | | | | | | | | | | | - Alan P Venook
- 19UCSF Helen Diller Family Comprehensive Cancer Center
| | - Adam Yopp
- 31UT Southwestern Simmons Comprehensive Cancer Center; and
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Qian Y, Liu Q, Li P, Han Y, Zhang J, Xu J, Sun J, Wu A, Song S, Lu W. Highly Tumor-Specific and Long-Acting Iodine-131 Microbeads for Enhanced Treatment of Hepatocellular Carcinoma with Low-Dose Radio-Chemoembolization. ACS NANO 2021; 15:2933-2946. [PMID: 33529007 DOI: 10.1021/acsnano.0c09122] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
Transarterial radioembolization (TARE) is considered the standard treatment for intermediate-stage hepatocellular carcinoma (HCC). Iodine-131 (131I)-labeled lipiodol TARE is an effective treatment for HCC but has been withdrawn due to its poor retention in tumor lesions and significant distribution in normal tissues with severe side effects. In this work, a highly tumor-specific 131I-TARE agent with long-time retention is developed by simply introducing tyrosine to poly(vinyl alcohol) (PVA) drug-eluting microbeads (Tyr-PVA-DEBs). The labeling efficiency of 131I-labeled microbeads remains above 85% in 50% serum for 31 days. Micro-single-photon emission computed tomography/computed tomography (μSPECT/CT) evidences that the 131I-labeled microbeads accumulate in the orthotopic N1S1 hepatoma of rats for 31 days following intra-arterial injection. The cumulative radiation dose per cubic centimeter of the tumor is at least 13 678-fold higher than that of normal tissues. The highly tumor-selective radiation of the 131I-labeled microbeads allows localized delivery of 345.04 ± 139.16 Gy to the tumor following a single injection dose as low as 0.2 mCi of 131I. Moreover, the 131I-labeled microbeads are loaded with doxorubicin hydrochloride (DOX) through the carboxy groups on tyrosine of the polymer. The 131I-DOX-loaded microbeads present a synergetic antitumor effect without recurrence in comparison with the microbeads labeled with 131I or loading DOX alone, attributed to the sensitization of DOX to 131I-induced ionizing radiation damage to DNA under the embolization-induced hypoxia. Our results demonstrate a high tumor retention of 131I-labeled embolic agent for low-dose transarterial radio-chemoembolization (TARCE) with a synergetic therapeutic effect on treating HCC, showing potential for clinical application.
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Affiliation(s)
- Yuyi Qian
- Minhang Hospital & School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education, & State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai 201199, China
| | - Qiufang Liu
- Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China
| | - Panli Li
- Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China
| | - Yaobao Han
- Center for Molecular Imaging and Nuclear Medicine, State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou 215123, China
| | - Jianping Zhang
- Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China
| | - Jiaojiao Xu
- Minhang Hospital & School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education, & State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai 201199, China
| | - Jingwen Sun
- Minhang Hospital & School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education, & State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai 201199, China
| | - Aihua Wu
- Minhang Hospital & School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education, & State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai 201199, China
| | - Shaoli Song
- Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China
| | - Wei Lu
- Minhang Hospital & School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education, & State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai 201199, China
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Li Y, Zhou F, Liu F, Wang M, Xing W. Experimental Study on Evaluation of Blood Supply Level and Embolization Ratio of Liver Cancer Based on I-Flow Software. Technol Cancer Res Treat 2020; 19:1533033820970665. [PMID: 33174500 PMCID: PMC7672766 DOI: 10.1177/1533033820970665] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
Objective: To confirm the feasibility and accuracy of the method for evaluating blood supply and embolization rate of liver cancer based on I-flow software through animal experiments and clinical study. Methods: Rabbits underwent selective angiography under different perfusion conditions in the same kidney. The blood supply level was evaluated by I-flow software method. The results were analyzed for coefficient of variation. Thirty patients with liver cancer who underwent selective hepatic artery embolization were enrolled. The mathematical methods and 3 diagnostic specialists were used to evaluate the preoperative blood supply level and embolization rate. The results were recorded and the results were tested for consistency. Results: Animal experiments confirmed that the blood supply level analysis method designed by the research team was consistent under different contrast conditions (including total contrast agent, contrast medium perfusion rate, and limiting pressure) (coefficient of variation: 8.55%). The mathematical calculation results of preoperative blood supply level and embolization ratio of liver cancer are consistent with the average value of visual judgment results of diagnostic experts. (Preoperative blood supply level: concordance coefficient = 0.284, P = 0.003; embolization ratio: concordance coefficient = 0.218, P = 0.011). Conclusion: Based on I-flow software, the mathematical calculation method designed by this research group can effectively estimate the preoperative blood supply level of liver cancer and the embolization rate of single vascular embolization treatment, which can provide reliable data support for embolization treatment of liver cancer.
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Affiliation(s)
- Yong Li
- Interventional Therapy Department, 74675Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Feifan Zhou
- College of Physics and Optoelectronic Engineering, Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, 47890Shenzhen University, Shenzhen, China
| | - Fang Liu
- Interventional Therapy Department, 74675Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Meng Wang
- College of Physics and Optoelectronic Engineering, Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, 47890Shenzhen University, Shenzhen, China
| | - Wenge Xing
- Interventional Therapy Department, 74675Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
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11
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Sgouros G, Bodei L, McDevitt MR, Nedrow JR. Radiopharmaceutical therapy in cancer: clinical advances and challenges. Nat Rev Drug Discov 2020; 19:589-608. [PMID: 32728208 PMCID: PMC7390460 DOI: 10.1038/s41573-020-0073-9] [Citation(s) in RCA: 484] [Impact Index Per Article: 96.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/08/2020] [Indexed: 12/25/2022]
Abstract
Radiopharmaceutical therapy (RPT) is emerging as a safe and effective targeted approach to treating many types of cancer. In RPT, radiation is systemically or locally delivered using pharmaceuticals that either bind preferentially to cancer cells or accumulate by physiological mechanisms. Almost all radionuclides used in RPT emit photons that can be imaged, enabling non-invasive visualization of the biodistribution of the therapeutic agent. Compared with almost all other systemic cancer treatment options, RPT has shown efficacy with minimal toxicity. With the recent FDA approval of several RPT agents, the remarkable potential of this treatment is now being recognized. This Review covers the fundamental properties, clinical development and associated challenges of RPT.
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Affiliation(s)
- George Sgouros
- Johns Hopkins University School of Medicine, Baltimore, MD, USA.
| | - Lisa Bodei
- Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | | | - Jessie R Nedrow
- Johns Hopkins University School of Medicine, Baltimore, MD, USA
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12
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Chagas AL, Mattos AAD, Carrilho FJ, Bittencourt PL, Vezozzo DCP, Horvat N, Rocha MDS, Alves VAF, Coral GP, Alvares-DA-Silva MR, Barros FMDR, Menezes MR, Monsignore LM, Coelho FF, Silva RFD, Silva RDCMA, Boin IDFSF, D Albuquerque LAC, Garcia JHP, Felga GEG, Moreira AM, Braghiroli MIFM, Hoff PMG, Mello VBD, Dottori MF, Branco TP, Schiavon LDL, Costa TDFA. BRAZILIAN SOCIETY OF HEPATOLOGY UPDATED RECOMMENDATIONS FOR DIAGNOSIS AND TREATMENT OF HEPATOCELLULAR CARCINOMA. ARQUIVOS DE GASTROENTEROLOGIA 2020; 57:1-20. [PMID: 32294682 DOI: 10.1590/s0004-2803.202000000-20] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Accepted: 12/19/2019] [Indexed: 02/06/2023]
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. The Brazilian Society of Hepatology (SBH) published in 2015 its first recommendations about the management of HCC. Since then, new data have emerged in the literature, prompting the governing board of SBH to sponsor a single-topic meeting in August 2018 in São Paulo. All the invited experts were asked to make a systematic review of the literature reviewing the management of HCC in subjects with cirrhosis. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of updated recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present manuscript is the final version of the reviewed manuscript containing the recommendations of SBH.
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Affiliation(s)
- Aline Lopes Chagas
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil
- Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil
| | - Angelo Alves de Mattos
- Universidade Federal de Ciências da Saúde de Porto Alegre e Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, RS, Brasil
| | - Flair José Carrilho
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil
- Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil
| | | | | | - Natally Horvat
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil
- Hospital Sírio-Libanês, São Paulo, SP, Brasil
| | - Manoel de Souza Rocha
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil
| | - Venâncio Avancini Ferreira Alves
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil
- Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil
| | - Gabriela Perdomo Coral
- Universidade Federal de Ciências da Saúde de Porto Alegre e Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, RS, Brasil
| | | | | | - Marcos Roberto Menezes
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil
- Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil
- Hospital Sírio-Libanês, São Paulo, SP, Brasil
| | - Lucas Moretti Monsignore
- Universidade de São Paulo, Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, São Paulo, SP, Brasil
| | | | - Renato Ferreira da Silva
- Faculdade de Medicina de São José do Rio Preto (FAMERP) e Hospital de Base de São José do Rio Preto (FUNFARME), São José do Rio Preto, SP, Brasil
| | - Rita de Cássia Martins Alves Silva
- Faculdade de Medicina de São José do Rio Preto (FAMERP) e Hospital de Base de São José do Rio Preto (FUNFARME), São José do Rio Preto, SP, Brasil
| | | | | | | | | | - Airton Mota Moreira
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil
- Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil
| | | | - Paulo Marcelo Gehm Hoff
- Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil
| | | | | | - Tiago Pugliese Branco
- Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil
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13
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Shao W, Li C, Tang J, Song J, Li Z, Sun J, Xu Y, Zheng Z, Cao J, Zhang L. Efficacy And Safety Of Raltitrexed Plus Oxaliplatin-Based Transarterial Chemoembolization In Patients With Unresectable Hepatocellular Carcinoma. Cancer Manag Res 2019; 11:9863-9869. [PMID: 31819623 PMCID: PMC6875237 DOI: 10.2147/cmar.s217524] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2019] [Accepted: 10/22/2019] [Indexed: 12/12/2022] Open
Abstract
Objective To evaluate the efficacy and safety of raltitrexed plus oxaliplatin-based transarterial chemoembolization (TACE) in patients with unresectable hepatocellular carcinoma (HCC). Methods A total of 123 patients with unresectable HCC were recruited into the prospective cohort study. Raltitrexed plus oxaliplatin-based TACE was performed according to the traditional method at monthly intervals and was repeated for up to 4 cycles if no disease progression or intolerable toxicity occurred. The primary efficacy endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS) and tumor response rate. The Cox proportional-hazards regression model was used to assess the independent prognostic factors of OS. Adverse events were also observed. Results The median OS time and PFS were 623 days (95% CI: 461, 785) and 338 days (95% CI: 302, 704), respectively. The disease control rate was 95.5% (118/123). The Cox proportional-hazards regression model indicated that age, ECOG performance status and response to TACE as independent prognostic factors of OS. No treatment-related mortality occurred within 30 days of treatment procedure. The most common complications included postembolization syndrome, liver dysfunction and hematological toxicity. Grade 3 pain, transglutaminase abnormality and thrombocytopenia were observed in 16 (13%), 15 (12.2%) and 3 (2.4%) patients, respectively. No grade 4 adverse events were observed. Conclusion Raltitrexed plus oxaliplatin-based TACE led to high tumor response rate and promising PFS and OS, and was considered safe and tolerable in patients with unresectable HCC.
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Affiliation(s)
- Wenbo Shao
- Department of Surgical Oncology (Interventional Therapy), Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, People's Republic of China
| | - Caixia Li
- Department of Interventional Radiology, Qilu Hospital of Shandong University, Jinan, People's Republic of China
| | - Jun Tang
- Department of Interventional Radiology, Shandong Medical Imaging Research Institute, Jinan, People's Republic of China
| | - Jinlong Song
- Department of Surgical Oncology (Interventional Therapy), Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, People's Republic of China
| | - Zixiang Li
- Department of Interventional Radiology, Affiliated Hospital of Qingdao University, Qingdao, People's Republic of China
| | - Jize Sun
- Department of Interventional Radiology, Qingdao Central Hospital, Qingdao, People's Republic of China
| | - Yili Xu
- Department of Interventional Radiology, 960 Hospital of People's Liberation Army, Tai'an, People's Republic of China
| | - Zhaomin Zheng
- Department of Interventional Radiology, Qianfoshan Hospital of Shandong Province, Jinan, People's Republic of China
| | - Jingqin Cao
- Department of Interventional Radiology, People's Hospital of Jining City, Jining, People's Republic of China
| | - Lei Zhang
- Department of Interventional Radiology, Shandong Medical Imaging Research Institute, Jinan, People's Republic of China
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Hulin A, Stocco J, Bouattour M. Clinical Pharmacokinetics and Pharmacodynamics of Transarterial Chemoembolization and Targeted Therapies in Hepatocellular Carcinoma. Clin Pharmacokinet 2019; 58:983-1014. [PMID: 31093928 DOI: 10.1007/s40262-019-00740-w] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The management of hepatocellular carcinoma (HCC) is based on a multidisciplinary decision tree. Treatment includes loco-regional therapy, mainly transarterial chemoembolization, for intermediate-stage HCC and systemic therapy with oral tyrosine kinase inhibitors (TKIs) for advanced HCC. Transarterial chemoembolization involves hepatic intra-arterial infusion with either conventional procedure or drug-eluting-beads. The aim of the loco-regional procedure is to deliver treatment as close as possible to the tumor both to embolize the tumor area and to enhance efficacy and minimize systemic toxicity of the anticancer drug. Pharmacokinetic studies applied to transarterial chemoembolization are rare and pharmacodynamic studies even rarer. However, all available studies lead to the same conclusions: use of the transarterial route lowers systemic exposure to the cytotoxic drug and leads to much higher tumor drug concentrations than does a similar dose via the intravenous route. However, reproducibility of the procedure remains a major problem, and no consensus exists regarding the choice of anticancer drug and its dosage. Systemic therapy with TKIs is based on sorafenib and lenvatinib as first-line treatment and regorafenib and cabozantinib as second-line treatment. Clinical use of TKIs is challenging because of their complex pharmacokinetics, with high liver metabolism yielding both active metabolites and their common toxicities. Changes in liver function over time with the progression of HCC adds further complexity to the use of TKIs. The challenges posed by TKIs and the HCC disease process means monitoring of TKIs is required to improve clinical management. To date, only partial data supporting sorafenib monitoring is available. Results from further pharmacokinetic/pharmacodynamic studies of these four TKIs are eagerly awaited and are expected to permit such monitoring and the development of consensus guidelines.
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Affiliation(s)
- Anne Hulin
- APHP, Laboratory of Pharmacology, GH Henri Mondor, EA7375, University Paris Est Creteil, 94010, Creteil, France
| | - Jeanick Stocco
- APHP, HUPNVS, Department of Clinical Pharmacy and Pharmacology, Beaujon University Hospital, 92110, Clichy, France
| | - Mohamed Bouattour
- APHP, HUPNVS, Department of Digestive Oncology, Beaujon University Hospital, 92110, Clichy, France.
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15
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Triarico S, Maurizi P, Mastrangelo S, Attinà G, Capozza MA, Ruggiero A. Improving the Brain Delivery of Chemotherapeutic Drugs in Childhood Brain Tumors. Cancers (Basel) 2019; 11:824. [PMID: 31200562 PMCID: PMC6627959 DOI: 10.3390/cancers11060824] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Revised: 05/27/2019] [Accepted: 06/11/2019] [Indexed: 12/20/2022] Open
Abstract
The central nervous system (CNS) may be considered as a sanctuary site, protected from systemic chemotherapy by the meninges, the cerebrospinal fluid (CSF) and the blood-brain barrier (BBB). Consequently, parenchymal and CSF exposure of most antineoplastic agents following intravenous (IV) administration is lower than systemic exposure. In this review, we describe the different strategies developed to improve delivery of antineoplastic agents into the brain in primary and metastatic CNS tumors. We observed that several methods, such as BBB disruption (BBBD), intra-arterial (IA) and intracavitary chemotherapy, are not routinely used because of their invasiveness and potentially serious adverse effects. Conversely, intrathecal (IT) chemotherapy has been safely and widely practiced in the treatment of pediatric primary and metastatic tumors, replacing the neurotoxic cranial irradiation for the treatment of childhood lymphoma and acute lymphoblastic leukemia (ALL). IT chemotherapy may be achieved through lumbar puncture (LP) or across the Ommaya intraventricular reservoir, which are both described in this review. Additionally, we overviewed pharmacokinetics and toxic aspects of the main IT antineoplastic drugs employed for primary or metastatic childhood CNS tumors (such as methotrexate, cytosine arabinoside, hydrocortisone), with a concise focus on new and less used IT antineoplastic agents.
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Affiliation(s)
- Silvia Triarico
- Pediatric Oncology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Sacro Cuore, 00168 Rome, Italy.
| | - Palma Maurizi
- Pediatric Oncology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Sacro Cuore, 00168 Rome, Italy.
| | - Stefano Mastrangelo
- Pediatric Oncology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Sacro Cuore, 00168 Rome, Italy.
| | - Giorgio Attinà
- Pediatric Oncology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Sacro Cuore, 00168 Rome, Italy.
| | - Michele Antonio Capozza
- Pediatric Oncology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Sacro Cuore, 00168 Rome, Italy.
| | - Antonio Ruggiero
- Pediatric Oncology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Sacro Cuore, 00168 Rome, Italy.
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16
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Woodard LE, Dennis CL, Borchers JA, Attaluri A, Velarde E, Dawidczyk C, Searson PC, Pomper MG, Ivkov R. Nanoparticle architecture preserves magnetic properties during coating to enable robust multi-modal functionality. Sci Rep 2018; 8:12706. [PMID: 30139940 PMCID: PMC6107675 DOI: 10.1038/s41598-018-29711-0] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2018] [Accepted: 07/17/2018] [Indexed: 11/09/2022] Open
Abstract
Magnetic iron oxide nanoparticles (MIONs) have established a niche as a nanomedicine platform for diagnosis and therapy, but they present a challenging surface for ligand functionalization which limits their applications. On the other hand, coating MIONs with another material such as gold to enhance these attachments introduces other complications. Incomplete coating may expose portions of the iron oxide core, or the coating process may alter their magnetic properties. We describe synthesis and characterization of iron oxide/silica/gold core-shell nanoparticles to elucidate the effects of a silica-gold coating process and its impact on the resulting performance. In particular, small angle neutron scattering reveals silica intercalates between iron oxide crystallites that form the dense core, likely preserving the magnetic properties while enabling formation of a continuous gold shell. The synthesized silica-gold-coated MIONs demonstrate magnetic heating properties consistent with the original iron oxide core, with added x-ray contrast for imaging and laser heating.
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Affiliation(s)
- Lauren E Woodard
- Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, 21218, USA
| | - Cindi L Dennis
- Material Measurement Laboratory, NIST, Gaithersburg, MD, 20899-8550, USA
| | - Julie A Borchers
- NIST Center for Neutron Research, NIST, Gaithersburg, MD, 20899-6102, USA
| | - Anilchandra Attaluri
- Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA
- Department of Mechanical Engineering, School of Science, Engineering, and Technology, Pennsylvania State University, Harrisburg,Middletown, PA, 17057, USA
| | - Esteban Velarde
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA
| | - Charlene Dawidczyk
- Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, 21218, USA
| | - Peter C Searson
- Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, 21218, USA
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA
- Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA
| | - Martin G Pomper
- Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, 21218, USA
- Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA
- Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA
- Division of Cancer Imaging Research, Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA
| | - Robert Ivkov
- Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, 21218, USA.
- NIST Center for Neutron Research, NIST, Gaithersburg, MD, 20899-6102, USA.
- Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA.
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17
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Li S, Qin Y, Wang X, Yang X. Bubble growth in cylindrically-shaped optical absorbers during photo-mediated ultrasound therapy. Phys Med Biol 2018; 63:125017. [PMID: 29794345 DOI: 10.1088/1361-6560/aac7bc] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
Photo-mediated ultrasound therapy (PUT) is a non-invasive, agent-free technique to shut down microvessels with high precision by promoting cavitation activity precisely in the targeted microvessels. PUT is based on the photoacoustic (PA) cavitation generated through concurrently applied nanosecond laser pulses and ultrasound bursts. In this study, a PA cavitation model is employed to understand the enhanced cavitation activity during PUT, with full consideration of the optical absorption of blood vessels. Bubble size evolution in cylindrically-shaped optical absorbers (vessels) due to rectified diffusion is simulated. Results show that the ultrasound pressure required for bubble growth decreases dramatically with the increased laser fluence. At a relatively low ultrasound driving pressure, bubble equilibrium radius increases rapidly due to concurrently applied nanosecond laser pulses and ultrasound bursts, resulting in a transition from inertial cavitation to stable cavitation. This inertial to stable transition is verified by the experimentally measured results on 0.76 mm silicone tubes filled with human whole blood with 0.5 MHz ultrasound at 0.243 MPa. This study demonstrated the potential to induce stable bubbles in blood vessels by PUT non-invasively.
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Affiliation(s)
- Shuying Li
- Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, United States of America. These two authors contribute equally to the work
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18
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Benson AB, D'Angelica MI, Abbott DE, Abrams TA, Alberts SR, Saenz DA, Are C, Brown DB, Chang DT, Covey AM, Hawkins W, Iyer R, Jacob R, Karachristos A, Kelley RK, Kim R, Palta M, Park JO, Sahai V, Schefter T, Schmidt C, Sicklick JK, Singh G, Sohal D, Stein S, Tian GG, Vauthey JN, Venook AP, Zhu AX, Hoffmann KG, Darlow S. NCCN Guidelines Insights: Hepatobiliary Cancers, Version 1.2017. J Natl Compr Canc Netw 2017; 15:563-573. [PMID: 28476736 DOI: 10.6004/jnccn.2017.0059] [Citation(s) in RCA: 252] [Impact Index Per Article: 31.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The NCCN Guidelines for Hepatobiliary Cancers provide treatment recommendations for cancers of the liver, gallbladder, and bile ducts. The NCCN Hepatobiliary Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding locoregional therapy for treatment of patients with hepatocellular carcinoma.
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Affiliation(s)
- Al B Benson
- Robert H. Lurie Comprehensive Cancer Center of Northwestern University
| | | | | | | | | | | | | | | | | | | | - William Hawkins
- Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
| | | | - Rojymon Jacob
- University of Alabama at Birmingham Comprehensive Cancer Center
| | | | - R Kate Kelley
- UCSF Helen Diller Family Comprehensive Cancer Center
| | - Robin Kim
- Huntsman Cancer Institute at the University of Utah
| | | | - James O Park
- Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance
| | | | | | - Carl Schmidt
- The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute
| | | | | | - Davendra Sohal
- Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute
| | | | - G Gary Tian
- St. Jude Children’s Research Hospital/The University of Tennessee Health Science Center
| | | | - Alan P Venook
- UCSF Helen Diller Family Comprehensive Cancer Center
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Ultrasound-guided percutaneous microwave ablation assisted by three-dimensional visualization operative treatment planning system and percutaneous transhepatic cholangial drainage with intraductal chilled saline perfusion for larger hepatic hilum hepatocellular (D ≥ 3 cm): preliminary results. Oncotarget 2017; 8:79742-79749. [PMID: 29108354 PMCID: PMC5668087 DOI: 10.18632/oncotarget.19275] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2016] [Accepted: 06/02/2017] [Indexed: 01/05/2023] Open
Abstract
To assess the clinical efficiency of ultrasound-guided percutaneous microwave ablation (US-PMWA) assisted by three-dimensional (3D) visualization operative treatment planning system and percutaneous transhepatic cholangial drainage with intraductal chilled saline perfusion (PTCD-ICSP) for larger hepatic hilum hepatocellular carcinoma (HH-HCC) (D ≥ 3 cm). The combination therapy was performed in 14 patients from Sep 2011 to May 2017. The major outcomes for assessment were biliary duct complications, local tumor recurrence, distant recurrence and overall survival rates. Median follow-up period was 26 months. The series of 3D visualization operative treatment planning, PTCD-ICSP and US-PMWA were successfully performed and complete ablation was achieved in all cases. The mean session for one tumor was 1.0 ± 0.4. The mean ablation time for per tumor was 1805 ± 567s. The saline volume used for the PTCD-ICSP was 250-450 ml per session. The 1-, 2-, and 3-year local tumor recurrence rates were 7.1%, 14.3%, and 35.7%, the 1-, 2-, and 3-year distant recurrence rates were 0%, 14.3%, and 28.6%, and 1-, 2-, and 3-year overall survival rates were 100%, 92.9%, and 71.4%, respectively. No severe complications related to ablation occurred. Conclusions US-PMWA assisted by 3D visualization operative treatment planning system and PTCD-ICSP appears to be a safe, effective and innovative technique for management for larger HH-HCCs, which improved the prognosis.
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Luo SH, Song SL, Zheng CS, Li WY, Wang Y, Xia XW, Feng GS. Embolic effects of Bletilla striata microspheres in renal artery and transplanted VX2 liver tumor model in rabbits. Chin J Integr Med 2017; 25:431-438. [PMID: 28497394 DOI: 10.1007/s11655-017-2953-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2016] [Indexed: 01/14/2023]
Abstract
OBJECTIVES To evaluate the characteristics of Bletilla striata microspheres (BSMs) and its effects as an embolic agent in a rabbit model. METHODS BSMs were prepared with an emulsification-cool condensation-chemical cross-linking method. The characteristics of BSMs in vitro were observed. Embolization experiments were performed in renal artery of rabbit and in a rabbit liver VX2 carcinoma model. Seventy-two New Zealand rabbits were divided into 2 groups, and the right renal artery was embolized with BSMs (200 μm in diameter) in the experimental group and with polyvinyl alcohol (PVA) of the same size in the control group. The pathological findings were examined with hematoxylin-eosin and Masson stainings. Liver and renal functions were tested before and after embolization. VX2 tumor was transplanted in 15 New Zealand rabbits, which were randomly divided into 3 groups (n=5). Group A were treated with saline, group B with a mixture of doxorubicin and lipiodol, and group C with hepatic arterial infusion of BSMs (200 μm in diameter). Tumor growth rate was evaluated by magnetic resonance imaging scan. Apoptosis-related factors (bax, bcl-2) and tumor vascular endothelial cell growth factor (VEGF) were evaluated through immunohistochemical staining. RESULTS The characteristics of BSMs in vitro were in full compliance with the requirements for use in interventional procedures. In the renal artery embolization experiment, after BSMs intervention, it was more difficult to form collateral circulation than that with PVAs, and the kidney manifested atrophy and calcification. There were no significant difference of liver and renal functions in rabbits between groups. In the liver VX2 carcinoma embolization experiment, compared with group A, the growth rate of VX2 liver tumor and Bcl-2 levels was reduced, while apoptosis index, Bax, and VEGF were increased in group B (P<0.05). There were no significant difference between groups B and C (P>0.05). CONCLUSIONS The characteristics of BSMs in vitro and in vivo meet the requirements for its use as an embolic agent in interventional approaches.
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Affiliation(s)
- Shi-Hua Luo
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Song-Lin Song
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Chuan-Sheng Zheng
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
| | - Wei-Yong Li
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Yong Wang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Xiang-Wen Xia
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Gan-Sheng Feng
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
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Hu Z, Zhang H, Mordovanakis A, Paulus YM, Liu Q, Wang X, Yang X. High-precision, non-invasive anti-microvascular approach via concurrent ultrasound and laser irradiation. Sci Rep 2017; 7:40243. [PMID: 28074839 PMCID: PMC5225605 DOI: 10.1038/srep40243] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2016] [Accepted: 12/05/2016] [Indexed: 11/09/2022] Open
Abstract
Antivascular therapy represents a proven strategy to treat angiogenesis. By applying synchronized ultrasound bursts and nanosecond laser irradiation, we developed a novel, selective, non-invasive, localized antivascular method, termed photo-mediated ultrasound therapy (PUT). PUT takes advantage of the high native optical contrast among biological tissues and can treat microvessels without causing collateral damage to the surrounding tissue. In a chicken yolk sac membrane model, under the same ultrasound parameters (1 MHz at 0.45 MPa and 10 Hz with 10% duty cycle), PUT with 4 mJ/cm2 and 6 mJ/cm2 laser fluence induced 51% (p = 0.001) and 37% (p = 0.018) vessel diameter reductions respectively. With 8 mJ/cm2 laser fluence, PUT would yield vessel disruption (90%, p < 0.01). Selectivity of PUT was demonstrated by utilizing laser wavelengths at 578 nm or 650 nm, where PUT selectively shrank veins or occluded arteries. In a rabbit ear model, PUT induced a 68.5% reduction in blood perfusion after 7 days (p < 0.001) without damaging the surrounding cells. In vitro experiments in human blood suggested that cavitation may play a role in PUT. In conclusion, PUT holds significant promise as a novel non-invasive antivascular method with the capability to precisely target blood vessels.
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Affiliation(s)
- Zizhong Hu
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.,Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, USA.,Department of Ophthalmology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China
| | - Haonan Zhang
- Department of Radiology, University of Michigan, Ann Arbor, MI, USA.,Institute of Acoustics, Tongji University, Shanghai, P.R. China
| | - Aghapi Mordovanakis
- Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, USA
| | - Yannis M Paulus
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.,Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, USA
| | - Qinghuai Liu
- Department of Ophthalmology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China
| | - Xueding Wang
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.,Department of Radiology, University of Michigan, Ann Arbor, MI, USA
| | - Xinmai Yang
- Bioengineering Research Center and Department of Mechanical Engineering, University of Kansas, Lawrence, KS, USA
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22
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Kouri BE, Abrams RA, Al-Refaie WB, Azad N, Farrell J, Gaba RC, Gervais DA, Gipson MG, Kolbeck KJ, Marshalleck FE, Pinchot JW, Small W, Ray CE, Hohenwalter EJ. ACR Appropriateness Criteria Radiologic Management of Hepatic Malignancy. J Am Coll Radiol 2016; 13:265-73. [PMID: 26944037 DOI: 10.1016/j.jacr.2015.12.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2015] [Accepted: 12/04/2015] [Indexed: 12/18/2022]
Abstract
Management of primary and secondary hepatic malignancy is a complex problem. Achieving optimal care for this challenging population often requires the involvement of multiple medical and surgical disciplines. Because of the wide variety of potential therapies, treatment protocols for various malignancies continue to evolve. Consequently, development of appropriate therapeutic algorithms necessitates consideration of medical options, such as systemic chemotherapy; surgical options, such as resection or transplantation; and loco-regional therapies, such as thermal ablation and transarterial embolization techniques. This article provides a review of treatment strategies for the three most common subtypes of hepatic malignancy treated with loco-regional therapies: hepatocellular carcinoma, neuroendocrine metastases, and colorectal metastases. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every three years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
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Affiliation(s)
- Brian E Kouri
- Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina.
| | | | - Waddah B Al-Refaie
- Georgetown University Hospital, Washington, District of Columbia, American College of Surgeons
| | - Nilofer Azad
- Sidney Kimmel Cancer Center at Johns Hopkins University, Baltimore, Maryland, American Society of Clinical Oncology
| | - James Farrell
- Interventional Endoscopy and Pancreatic Diseases, New Haven, Connecticut, American Gastroenterological Association
| | - Ron C Gaba
- University of Illinois Hospital, Chicago, Illinois
| | | | - Matthew G Gipson
- University of Colorado, Anschutz Medical Campus, Aurora, Colorado
| | | | | | | | - William Small
- Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois
| | - Charles E Ray
- University of Illinois Hospital and Health Science System, Chicago, Illinois
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23
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Carrilho FJ, Mattos AAD, Vianey AF, Vezozzo DCP, Marinho F, Souto FJ, Cotrim HP, Coelho HSM, Silva I, Garcia JHP, Kikuchi L, Lofego P, Andraus W, Strauss E, Silva G, Altikes I, Medeiros JE, Bittencourt PL, Parise ER. Brazilian society of hepatology recommendations for the diagnosis and treatment of hepatocellular carcinoma. ARQUIVOS DE GASTROENTEROLOGIA 2016; 52 Suppl 1:2-14. [PMID: 26959803 DOI: 10.1590/s0004-28032015000500001] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Hepatocellular carcinoma is a malignancy of global importance and is associated with a high rate of mortality. Recent advances in the diagnosis and treatment of this disease make it imperative to update the recommendations on the management of the disease. In order to draw evidence-based recommendations concering the diagnosis and management of hepatocellular carcinoma, the Brazilian Society of Hepatology has sponsored a single-topic meeting in João Pessoa (PB). All the invited pannelists were asked to make a systematic review of the literature and to present topics related to the risk factors for its development, methods of screening, radiological diagnosis, staging systems, curative and palliative treatments and hepatocellular carcinoma in noncirrhotic liver. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of those recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present paper is the final version of the reviewed manuscript containing the recommendations of the Brazilian Society of Hepatology.
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Affiliation(s)
| | | | | | | | - Fábio Marinho
- Hospital Português de Beneficiência, Recife, PE, Brazil
| | | | | | | | - Ivonete Silva
- Faculdade de Medicina, Universidade Federal de São Paulo, SP, Brazil
| | | | - Luciana Kikuchi
- Faculdade de Medicina, Universidade de São Paulo, SP, Brazil
| | - Patricia Lofego
- Faculdade de Medicina, Universidade Federal do Espírito Santo, ES, Brazil
| | | | - Edna Strauss
- Faculdade de Medicina, Universidade de São Paulo, SP, Brazil
| | | | | | | | | | - Edison R Parise
- Faculdade de Medicina, Universidade Federal de São Paulo, SP, Brazil
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24
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Youssef MM, Tolba MF, Badawy NN, Liu AW, El-Ahwany E, Khalifa AE, Zada S, Abdel-Naim AB. Novel combination of sorafenib and biochanin-A synergistically enhances the anti-proliferative and pro-apoptotic effects on hepatocellular carcinoma cells. Sci Rep 2016; 6:30717. [PMID: 27470322 PMCID: PMC4965826 DOI: 10.1038/srep30717] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2015] [Accepted: 07/06/2016] [Indexed: 02/08/2023] Open
Abstract
Sorafenib (SOR) is the first-line treatment for hepatocellular carcinoma (HCC). However, its use is hindered by the recently expressed safety concerns. One approach for reducing SOR toxicity is to use lower doses in combination with other less toxic agents. Biochanin-A (Bio-A), a promising isoflavone, showed selective toxicity to liver cancer cells. We postulated that combining SOR and Bio-A could be synergistically toxic towards HCC cells. We further evaluated the underlying mechanism. Cytotoxicity assay was performed to determine the IC50 of Bio-A and SOR in HepG2, SNU-449 and Huh-7 cells. Then, combination index in HepG2 was evaluated using Calcusyn showing that the concurrent treatment with lower concentrations of SOR and Bio-A synergistically inhibited cell growth. Our combination induced significant arrest in pre-G and G0/G1 cell cycle phases and decrease in cyclin D1 protein level. Concomitantly, SOR/Bio-A reduced Bcl-2/Bax ratio. Furthermore, this co-treatment significantly increased caspase-3 & -9 apoptotic markers, while decreased anti-apoptotic and proliferative markers; survivin and Ki-67, respectively. Active caspase-3 in HepG2, SNU-449 and Huh-7 confirmed our synergism hypothesis. This study introduces a novel combination, where Bio-A synergistically enhanced the anti-proliferative and apoptotic effects of SOR in HCC cells, which could serve as a potential effective regimen for treatment.
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Affiliation(s)
- Mohieldin M Youssef
- The American University in Cairo, New Cairo, 11835 Egypt.,Okinawa Institute of Science and Technology Graduate University, OIST, Okinawa, 904-0495 Japan
| | - Mai F Tolba
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Ain-Shams University, Cairo, 11566 Egypt
| | - Noha N Badawy
- The American University in Cairo, New Cairo, 11835 Egypt
| | - Andrew W Liu
- Okinawa Institute of Science and Technology Graduate University, OIST, Okinawa, 904-0495 Japan
| | - Eman El-Ahwany
- Immunology Department, Theodor-Bilharz Research Institute (TBRI), Giza, 12411 Egypt
| | - Amani E Khalifa
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Ain-Shams University, Cairo, 11566 Egypt
| | - Suher Zada
- The American University in Cairo, New Cairo, 11835 Egypt
| | - Ashraf B Abdel-Naim
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Ain-Shams University, Cairo, 11566 Egypt
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Attaluri A, Seshadri M, Mirpour S, Wabler M, Marinho T, Furqan M, Zhou H, De Paoli S, Gruettner C, Gilson W, DeWeese T, Garcia M, Ivkov R, Liapi E. Image-guided thermal therapy with a dual-contrast magnetic nanoparticle formulation: A feasibility study. Int J Hyperthermia 2016; 32:543-57. [PMID: 27151045 DOI: 10.3109/02656736.2016.1159737] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
Abstract
PURPOSE/OBJECTIVE The aim of this study was to develop and investigate the properties of a magnetic iron oxide nanoparticle-ethiodised oil formulation for image-guided thermal therapy of liver cancer. MATERIALS AND METHODS The formulation comprises bionised nano-ferrite (BNF) nanoparticles suspended in ethiodised oil, emulsified with polysorbate 20 (BNF-lip). Nanoparticle size was measured via photon correlation spectroscopy and transmission electron microscopy. In vivo thermal therapy capability was tested in two groups of male Foxn1(nu) mice bearing subcutaneous HepG2 xenograft tumours. Group I (n = 12) was used to screen conditions for group II (n = 48). In group II, mice received one of BNF-lip (n = 18), BNF alone (n = 16), or PBS (n = 14), followed by alternating magnetic field (AMF) hyperthermia, with either varied duration (15 or 20 min) or amplitude (0, 16, 20, or 24 kA/m). Image-guided fluoroscopic intra-arterial injection of BNF-lip was tested in New Zealand white rabbits (n = 10), bearing liver VX2 tumours. The animals were subsequently imaged with CT and 3 T MRI, up to 7 days post-injection. The tumours were histopathologically evaluated for distribution of BNF-lip. RESULTS The BNF showed larger aggregate diameters when suspended in BNF-lip, compared to clear solution. The BNF-lip formulation produced maximum tumour temperatures with AMF >20 kA/m and showed positive X-ray visibility and substantial shortening of T1 and T2 relaxation time, with sustained intratumoural retention up to 7 days post-injection. On pathology, intratumoural BNF-lip distribution correlated well with CT imaging of intratumoural BNF-lip distribution. CONCLUSION The BNF-lip formulation has favourable thermal and dual imaging capabilities for image-guided thermal therapy of liver cancer, suggesting further exploration for clinical applications.
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Affiliation(s)
- Anilchandra Attaluri
- a Department of Radiation Oncology and Molecular Radiation Sciences , Johns Hopkins University School of Medicine , Baltimore , Maryland
| | - Madhav Seshadri
- a Department of Radiation Oncology and Molecular Radiation Sciences , Johns Hopkins University School of Medicine , Baltimore , Maryland
| | - Sahar Mirpour
- b Department of Radiology and Radiological Sciences , Johns Hopkins Hospital , Baltimore , Maryland
| | - Michele Wabler
- a Department of Radiation Oncology and Molecular Radiation Sciences , Johns Hopkins University School of Medicine , Baltimore , Maryland
| | - Thomas Marinho
- a Department of Radiation Oncology and Molecular Radiation Sciences , Johns Hopkins University School of Medicine , Baltimore , Maryland
| | - Muhammad Furqan
- a Department of Radiation Oncology and Molecular Radiation Sciences , Johns Hopkins University School of Medicine , Baltimore , Maryland
| | - Haoming Zhou
- a Department of Radiation Oncology and Molecular Radiation Sciences , Johns Hopkins University School of Medicine , Baltimore , Maryland
| | - Silvia De Paoli
- c Center for Biological Evaluation and Research , Food and Drug Administration , Bethesda , Maryland , USA
| | | | - Wesley Gilson
- e Siemens Healthcare Solutions, Inc. , Baltimore , Maryland , USA
| | - Theodore DeWeese
- a Department of Radiation Oncology and Molecular Radiation Sciences , Johns Hopkins University School of Medicine , Baltimore , Maryland
| | - Monica Garcia
- a Department of Radiation Oncology and Molecular Radiation Sciences , Johns Hopkins University School of Medicine , Baltimore , Maryland ;,f Department of Genetics and Morphology , Institute of Biological Sciences, University of Brasilia , Brazil
| | - Robert Ivkov
- a Department of Radiation Oncology and Molecular Radiation Sciences , Johns Hopkins University School of Medicine , Baltimore , Maryland ;,g Department of Oncology , Johns Hopkins University School of Medicine , Baltimore , Maryland ;,h Institute for NanoBioTechnology, Johns Hopkins University , Baltimore , Maryland ;,i Department of Materials Science and Engineering , Johns Hopkins University , Baltimore , Maryland , USA
| | - Eleni Liapi
- b Department of Radiology and Radiological Sciences , Johns Hopkins Hospital , Baltimore , Maryland
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26
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Jeon MJ, Gordon AC, Larson AC, Chung JW, Kim YI, Kim DH. Transcatheter intra-arterial infusion of doxorubicin loaded porous magnetic nano-clusters with iodinated oil for the treatment of liver cancer. Biomaterials 2016; 88:25-33. [PMID: 26938029 PMCID: PMC4792762 DOI: 10.1016/j.biomaterials.2016.02.021] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2016] [Revised: 02/13/2016] [Accepted: 02/17/2016] [Indexed: 12/11/2022]
Abstract
A promising strategy for liver cancer treatment is to deliver chemotherapeutic agents with multifunctional carriers into the tumor tissue via intra-arterial (IA) transcatheter infusion. These carriers should release drugs within the target tissue for prolonged periods and permit intra-procedural multi-modal imaging of selective tumor delivery. This targeted transcatheter delivery approach is enabled via the arterial blood supply to liver tumors and utilized in current clinical practice which is called chemoembolization or radioembolization. During our study, we developed Doxorubicin (Dox) loaded porous magnetic nano-clusters (Dox-pMNCs). The porous structure and carboxylic groups on the MNCs achieved high-drug loading efficiency and sustained drug release, along with magnetic properties resulting in high MRI T2-weighted image contrast. Dox-pMNC within iodinated oil, Dox-pMNCs, and Dox within iodinated oil were infused via hepatic arteries to target liver tumors in a rabbit model. MRI and histological evaluations revealed that the long-term drug release and retention of Dox-pMNCs within iodinated oil induced significantly enhanced liver cancer cell death.
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Affiliation(s)
- Min Jeong Jeon
- Department of Radiology, Seoul National University Hospital, Seoul, South Korea
| | - Andrew C Gordon
- Department of Radiology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA; Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA
| | - Andrew C Larson
- Department of Radiology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA; Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, USA; Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA; Department of Electrical Engineering and Computer Science, Evanston, IL, USA; International Institute of Nanotechnology (IIN), Northwestern University, Evanston, IL, USA
| | - Jin Wook Chung
- Department of Radiology, Seoul National University Hospital, Seoul, South Korea
| | - Young Il Kim
- Department of Radiology, Seoul National University Hospital, Seoul, South Korea; Department of Radiology, Sheikh Khalifa Specialty Hospital, Ras Al Khaimah, United Arab Emirates.
| | - Dong-Hyun Kim
- Department of Radiology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA; Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, USA.
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Lee VHF, Leung DK, Luk MY, Tong CC, Law MW, Ng SC, Wong KK, Poon RT, Kwong DL, Leung TW. Yttrium-90 radioembolization for advanced inoperable hepatocellular carcinoma. Onco Targets Ther 2015; 8:3457-64. [PMID: 26640386 PMCID: PMC4662370 DOI: 10.2147/ott.s92473] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Advanced inoperable hepatocellular carcinoma (HCC) conferring a grave prognosis may benefit from yttrium-90 ((90)Y) radioembolization. METHODS Thirty patients with advanced inoperable HCC including those with any lesion >8 cm in maximal diameter or multiple bi-lobar lesions (totally more than five lesions), or portal vein thrombosis treated with radioembolization were reviewed. Treatment efficacy and safety were evaluated. Univariate and multivariate analyses were performed for identifying potential prognostic factors. RESULTS After a median follow-up of 18.3 months, the response rate was 30.0%, and the disease control rate was 50.0%. Median overall progression-free survival (PFS) and overall survival (OS) were 3.3 months and 13.2 months, respectively. Longer median PFS was noted in those who had transarterial chemoembolization before radioembolization (7.3 months vs 3.1 months; P=0.021) and duration of alfafeto protein (AFP) response ≥6 months (11.8 months vs 3.0 months; P<0.001). Longer median OS was also revealed in those without portal vein thrombosis (17.1 months vs 4.4 months; P=0.015) and those whose duration of AFP response was ≥6 months (21.2 months vs 8.6 months; P=0.001). Seventeen patients (56.7%) developed treatment-related complications including five (16.7%) grade 3 events. Multivariate analysis revealed that treatment responders (P=0.001) and duration of AFP response ≥6 months (P=0.006) were prognostic of PFS, whereas the absence of portal vein invasion (P=0.025), treatment responders (P=0.010), and duration of AFP response ≥6 months (P=0.001) were prognostic of OS. CONCLUSION (90)Y radioembolization is an alternative treatment with a promising outcome for poor-risk advanced inoperable HCC.
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Affiliation(s)
- Victor Ho-Fun Lee
- Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
| | - Dennis Kc Leung
- Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
| | - Mai-Yee Luk
- Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
| | - Chi-Chung Tong
- Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
| | - Martin Wm Law
- Department of Nuclear Medicine, The University of Hong Kong, Hong Kong
| | - Sherry Cy Ng
- Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
| | - Ka-Kin Wong
- Department of Radiology, Queen Mary Hospital, The University of Hong Kong, Hong Kong
| | - Ronnie Tp Poon
- Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
| | - Dora Lw Kwong
- Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
| | - To-Wai Leung
- Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
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Yu SJ, Kim YJ. Effective treatment strategies other than sorafenib for the patients with advanced hepatocellular carcinoma invading portal vein. World J Hepatol 2015; 7:1553-1561. [PMID: 26085914 PMCID: PMC4462693 DOI: 10.4254/wjh.v7.i11.1553] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2014] [Revised: 02/12/2015] [Accepted: 04/14/2015] [Indexed: 02/06/2023] Open
Abstract
Patients with hepatocellular carcinoma (HCC) accompanying portal vein tumor thrombosis (PVTT) have relatively few therapeutic options and an extremely poor prognosis. These patients are classified into barcelona clinic liver cancer stage C and sorafenib is suggested as the standard therapy of care. However, overall survival (OS) gain from sorafenib is unsatisfactory and better treatment modalities are urgently required. Therefore, we critically appraised recent data for the various treatment strategies for patients with HCC accompanying PVTT. In suitable patients, even surgical resection can be considered a potentially curative strategy. Transarterial chemoembolization (TACE) can be performed effectively and safely in a carefully chosen population of patients with reserved liver function and sufficient collateral blood flow nearby the blocked portal vein. A recent meta-analysis demonstrated that TACE achieved a substantial improvement of OS in HCC patients accompanying PVTT compared with best supportive care. In addition, transarterial radioembolization (TARE) using yttrium-90 microspheres achieves quality-of-life advantages and is as effective as TACE. A large proportion of HCC patients accompanying PVTT are considered to be proper for TARE. Moreover, TACE or TARE achieved comparable outcomes to sorafenib in recent studies and it was also reported that the combination of radiotherapy with TACE achieved a survival gain compared to sorafenib in HCC patients accompanying PVTT. Surgical resection-based multimodal treatments, transarterial approaches including TACE and TARE, and TACE-based appropriate combination strategies may improve OS of HCC patients accompanying PVTT.
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30
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Warren KE. Novel therapeutic delivery approaches in development for pediatric gliomas. CNS Oncol 2015; 2:427-35. [PMID: 24511389 DOI: 10.2217/cns.13.37] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Pediatric gliomas are a heterogeneous group of diseases, ranging from relatively benign pilocytic astrocytomas with >90% 5-year survival, to glioblastomas and diffuse intrinsic pontine gliomas with <20% 5-year survival. Chemotherapy plays an important role in the management of these tumors, particularly in low-grade gliomas, but many high-grade tumors are resistant to chemotherapy. A major obstacle and contributor to this resistance is the blood–brain barrier, which protects the CNS by limiting entry of potential toxins, including chemotherapeutic agents. Several novel delivery approaches that circumvent the blood–brain barrier have been developed, including some currently in clinical trials. This review describes several of these novel approaches to improve delivery of chemotherapeutic agents to their site of action at the tumor, in attempts to improve their efficacy and the prognosis of children with this disease.
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31
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Laake AM, Liappis AP, Guy E, Kerr G, Benator DA. Tuberculosis reactivation in hepatocellular carcinoma: association with transarterial chemoembolization. Infect Dis (Lond) 2015; 47:267-70. [PMID: 25688446 DOI: 10.3109/00365548.2014.989540] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
Transarterial chemoembolization (TACE) is an important therapeutic option for patients with hepatocellular carcinoma (HCC). We discuss five patients with HCC and tuberculosis (TB) reactivation following TACE. Screening patients for latent TB infection at diagnosis of cirrhosis or HCC should be considered because of the immunosuppression inherent in both the diseases and their treatments.
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Affiliation(s)
- Ann M Laake
- From the Infectious Diseases Section, Medical Service, Veterans Affairs Medical Center , Washington, DC , USA
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Firouznia K, Ghanaati H, Alavian SM, Azadeh P, Nasiri Toosi M, Haj Mirzaian A, Najafi S, Shakiba M, Jalali AH. Transcatheter arterial chemoembolization therapy for patients with unresectable hepatocellular carcinoma. HEPATITIS MONTHLY 2014; 14:e25792. [PMID: 25737732 PMCID: PMC4329238 DOI: 10.5812/hepatmon.25792] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/03/2014] [Accepted: 12/17/2014] [Indexed: 02/08/2023]
Abstract
BACKGROUND Although transcatheter arterial chemoembolization (TACE) has been widely used as a palliative treatment for unresectable hepatocellular carcinoma (HCC), its actual efficacy and prognostic usefulness have not been clarified in past studies. OBJECTIVES The aim of the study is to investigate the efficacy, complications, and prognostic factors of the TACE in unresectable HCC patients. PATIENTS AND METHODS Thirty-two patients with unresectable HCC were treated with TACE. The procedure was performed with a combination of Lipiodol, doxorubicin, and cytomycin followed by gelatin-sponge particles embolization. CT-scan imaging and liver function tests (AST, ALT, ALP, BIL, and PT) were performed before and after the TACE. All patients were followed-up for 6-months. RESULTS Of all patients, 1 and 11 patients respectively, exhibited a complete response (CR) and a partial response (PR) (response rate, CR+PR, 44%). Data have shown that tumor size, number of lesions and number of involved segments are significantly reduced after the TACE performance (P < 0.05). No significant clinical adverse effect was observed in patients after the intervention. Also, liver function tests including AST, ALT, ALP, BIL, and PT did not significantly differ before and after the intervention (P > 0.05). The 6-month cumulative survival rates of the 32 patients were 78.1 %, respectively. Univariate analysis showed that survival correlated significantly with the following factors: tumor size; ≥ 8 cm versus < 8 cm (P < 0.010), serum ALP level; < 300 versus ≥ 300 (P < 0.043), and number of liver involved segments; < 2 versus ≥ 2 (P < 0.020). CONCLUSIONS We showed that in treatment of patients with unresectable hepatocellular carcinoma, TACE significantly improved the disease and the overall survival rate. Also, we introduce the tumor size, serum ALP level, and number of liver involved segments as prognostic factors of the procedure. Finally, TACE can be recommended as the initial treatment for unresectable HCC patients.
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Affiliation(s)
- Kavous Firouznia
- Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Sciences, Tehran, IR Iran
| | - Hossein Ghanaati
- Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Sciences, Tehran, IR Iran
- Corresponding Author: Hossein Ghanaati, Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Sciences, Tehran, IR Iran. Tel: +98-2166581516, Fax: +98-2166581578, E-mail:
| | - Seyed Moayed Alavian
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences, Tehran, IR Iran
| | - Payam Azadeh
- Department of Radiation Oncology, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran
| | - Mohsen Nasiri Toosi
- Internal Medicine Department, Imam-Khomeini Hospital, Tehran University of Medical Sciences (TUMS), Tehran, IR Iran
| | - Arya Haj Mirzaian
- Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Sciences, Tehran, IR Iran
| | - Safa Najafi
- Tehran University of Medical Sciences, Tehran, IR Iran
| | - Madjid Shakiba
- Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Sciences, Tehran, IR Iran
| | - Amir Hossein Jalali
- Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Sciences, Tehran, IR Iran
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White JA, Redden DT, Bryant MK, Dorn D, Saddekni S, Aal AKA, Zarzour J, Bolus D, Smith JK, Gray S, Eckhoff DE, DuBay DA. Predictors of repeat transarterial chemoembolization in the treatment of hepatocellular carcinoma. HPB (Oxford) 2014; 16:1095-101. [PMID: 25158123 PMCID: PMC4253333 DOI: 10.1111/hpb.12313] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2014] [Accepted: 06/05/2014] [Indexed: 12/12/2022]
Abstract
OBJECTIVES Repeat transarterial chemoembolization (TACE) is a common intervention performed for hepatocellular carcinoma (HCC). The aim of this study was to identify predictors of the need for repeat TACE. METHODS Between 2008 and 2012, data on patient and tumour variables were collected for 262 patients treated with a first TACE procedure for HCC. The decision to perform repeat TACE procedures was made at the completion of the first TACE or after follow-up imaging demonstrated the subtotal treatment of HCC tumours. RESULTS Repeat TACE was performed in 67 of 262 (25.6%) patients. Necrosis of HCC, measured after the first TACE, was lower in patients who subsequently received repeat TACE (P = 0.042). On multivariable analysis, total tumour diameter of >5 cm [odds ratio (OR) 2.76, 95% confidence interval (CI) 1.45-5.25; P = 0.002] and increasing age (OR 1.04/year, 95% CI 1.00-1.07; P = 0.030) were predictive of the need for repeat TACE. Measures of liver function and TACE approach (selective versus non-selective) were not predictive of repeat TACE. Median survival did not differ significantly between patients who did (median survival: 21.1 months) and did not (median survival: 26.1 months) receive a repeat TACE procedure (P = 0.574). CONCLUSIONS The requirement for repeat TACE is associated with older age, increased HCC tumour burden and subtotal TACE-induced HCC necrosis. Importantly, repeat TACE was not associated with reduced survival.
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Affiliation(s)
- Jared A White
- Department of Liver Transplant and Hepatobiliary Surgery, University of Alabama at BirminghamBirmingham, AL, USA
| | - David T Redden
- Biostatistics Department, School of Public Health, University of Alabama at BirminghamBirmingham, AL, USA
| | - Mary Kate Bryant
- Department of Liver Transplant and Hepatobiliary Surgery, University of Alabama at BirminghamBirmingham, AL, USA
| | - David Dorn
- Department of Liver Transplant and Hepatobiliary Surgery, University of Alabama at BirminghamBirmingham, AL, USA
| | - Souheil Saddekni
- Interventional Oncology, Department of Radiology, University of Alabama at BirminghamBirmingham, AL, USA
| | - Ahmed Kamel Abdel Aal
- Interventional Oncology, Department of Radiology, University of Alabama at BirminghamBirmingham, AL, USA
| | - Jessica Zarzour
- Diagnostic Body Radiology, Department of Radiology, University of Alabama at BirminghamBirmingham, AL, USA
| | - David Bolus
- Diagnostic Body Radiology, Department of Radiology, University of Alabama at BirminghamBirmingham, AL, USA
| | - J Kevin Smith
- Diagnostic Body Radiology, Department of Radiology, University of Alabama at BirminghamBirmingham, AL, USA
| | - Stephen Gray
- Department of Liver Transplant and Hepatobiliary Surgery, University of Alabama at BirminghamBirmingham, AL, USA
| | - Devin E Eckhoff
- Department of Liver Transplant and Hepatobiliary Surgery, University of Alabama at BirminghamBirmingham, AL, USA
| | - Derek A DuBay
- Department of Liver Transplant and Hepatobiliary Surgery, University of Alabama at BirminghamBirmingham, AL, USA,Correspondence Derek A. DuBay, Department of Liver Transplant and Hepatobiliary Surgery, University of Alabama at Birmingham, 701 ZRB, 1530 Third Avenue South, Birmingham, AL 35294-0007, USA. Tel: + 1 205 996 5970. Fax: + 1 205 996 9037. E-mail:
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Lopez A, Noiret N, Garin E, Lepareur N. Mixed-ligand complexes of yttrium-90 dialkyldithiocarbamates with 1,10-phenanthroline as a possible agent for therapy of hepatocellular carcinoma. Appl Radiat Isot 2014; 94:241-246. [PMID: 25238135 DOI: 10.1016/j.apradiso.2014.08.015] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2014] [Revised: 08/16/2014] [Accepted: 08/26/2014] [Indexed: 11/28/2022]
Abstract
Yttrium-90 is a radioelement which has found wide use in targeted radionuclide therapy because of its attractive physical and chemical properties. Radioembolisation of hepatocellular carcinoma with radiolabelled Lipiodol is a method of choice. We have synthesised a series of alkyldithiocarbamate yttrium complexes, easily extracted into Lipiodol due to their high lipophilicity. Among the prepared series, a new radioconjugate, which is stable over an extended period of time, has been prepared, and could represent a potential treatment procedure for hepatocellular carcinoma.
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Affiliation(s)
- A Lopez
- Centre Eugène Marquis, INSERM UMR-S 991, Avenue de la Bataille Flandres-Dunkerque, CS 44229, F-35042 Rennes, France; ENSCR, CNRS UMR 6226, 11, Allée de Beaulieu, CS 50837, F-35708 Rennes, France
| | - N Noiret
- ENSCR, CNRS UMR 6226, 11, Allée de Beaulieu, CS 50837, F-35708 Rennes, France; Université Européenne de Bretagne, F-35000 Rennes, France
| | - E Garin
- Centre Eugène Marquis, INSERM UMR-S 991, Avenue de la Bataille Flandres-Dunkerque, CS 44229, F-35042 Rennes, France; Université Européenne de Bretagne, F-35000 Rennes, France
| | - N Lepareur
- Centre Eugène Marquis, INSERM UMR-S 991, Avenue de la Bataille Flandres-Dunkerque, CS 44229, F-35042 Rennes, France; Université Européenne de Bretagne, F-35000 Rennes, France.
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She WH, Cheung TT, Yau TCC, Chan ACY, Chok KSH, Chu FSK, Liu RKY, Poon RTP, Chan SC, Fan ST, Lo CM. Survival analysis of transarterial radioembolization with yttrium-90 for hepatocellular carcinoma patients with HBV infection. Hepatobiliary Surg Nutr 2014; 3:185-193. [PMID: 25202695 PMCID: PMC4141294 DOI: 10.3978/j.issn.2304-3881.2014.07.09] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2014] [Accepted: 07/22/2014] [Indexed: 12/13/2022]
Abstract
INTRODUCTION For patients with resectable hepatocellular carcinoma (HCC), hepatectomy remains one of the best treatment options to provide long-term survival. However, more than 50% of the patients have unresectable disease upon diagnosis even though there are no distant metastases. Transarterial chemoembolization (TACE) is a well-established treatment option that offers a palliative survival benefit for this group of patients. A better treatment for unresectable HCC has been sought after. There is some evidence that transarterial radioembolization (TARE) with the agent yttrium-90 produces encouraging outcomes, especially in patients with portal vein tumor thrombus. This study aims to analyze the outcomes of TARE at our center. METHODS From August 2009 to April 2013, 16 patients underwent TARE at our center. Sixteen patients with similar tumor characteristics were selected to undergo TACE alone for comparison. A retrospective analysis of the prospectively collected data of the patients was conducted. Only patients with newly diagnosed primary tumors were included in this study. RESULTS The median survival for patients having TARE was 19.9 versus 14.0 months in the TACE group (P=0.615). There was no difference in terms of tumor response according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) (P=0.632). The 1-, 2- and 3-year survival rates in the TARE group were 80.0%, 30.5% and 20.3% respectively. The 1-year survival in the TACE group was 58.3% (P=0.615). For patients who had major vascular invasion (eight in each group), the 1- and 2-year survival rates in the TARE group were 62.5% and 15.6% respectively, while the 1-year survival in the TACE group was 35.0% (P=0.664). CONCLUSIONS The two groups showed similar results in terms of tumor response and overall survival benefit. TARE might provide a survival benefit for patients with major vessel invasion.
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Dudeck O. Safety and efficacy of target vessel catheterization with the new steerable microcatheter Direxion compared with a standard microcatheter: a prospective, preclinical trial. Cardiovasc Intervent Radiol 2014; 37:1041-6. [PMID: 24849303 DOI: 10.1007/s00270-014-0918-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2014] [Accepted: 04/09/2014] [Indexed: 11/28/2022]
Abstract
PURPOSE To assess the potential of a steerable microcatheter in a comparative preclinical trial. METHODS A total of 100 small target vessels of the lower limbs with a maximum diameter of 3 mm were prospectively randomized to catheterize with either the preshaped torqueable Direxion™ (J tip shape; Boston Scientific, Natick, MA) or a similarly steam-shaped Renegade™ microcatheter (Boston Scientific) in a porcine model. Catheterization was first performed in combination with a microguidewire and afterwards without. RESULTS No significant differences were found for the mean vessel diameter in the Direxion (1.53 ± 0.44 mm; n = 50) or Renegade (1.62 ± 0.43 mm; n = 50; p = 0.35) group. Guidewire-assisted catheterization was successful in all target vessels, whereas access was achieved in most cases with the guidewire alone. However, when it became necessary to steer the Direxion actively, this was regarded as key to obtain vessel access in three of four target vessels (75 %). Vessel catheterization without guidewire was significantly more successful with the Direxion (88 %; n = 44) compared with the Renegade (32 %; n = 16; p < 0.0001). In addition, this catheterization technique was also significantly faster with the Direxion compared with guidewire-assisted vessel catheterization with the Renegade (16.1 ± 14.4 sec compared with 27.1 ± 24.7 sec; p = 0.011). CONCLUSIONS The Direxion microcatheter demonstrated unique steerability characteristics, which makes it a promising new tool especially for complex coaxial endovascular procedures.
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Affiliation(s)
- Oliver Dudeck
- Department of Radiology and Nuclear Medicine, University of Magdeburg, Magdeburg, Germany,
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Chen J, Sheu AY, Li W, Zhang Z, Kim DH, Lewandowski RJ, Omary RA, Shea LD, Larson AC. Poly(lactide-co-glycolide) microspheres for MRI-monitored transcatheter delivery of sorafenib to liver tumors. J Control Release 2014; 184:10-7. [PMID: 24727059 DOI: 10.1016/j.jconrel.2014.04.008] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2013] [Revised: 01/25/2014] [Accepted: 04/02/2014] [Indexed: 12/13/2022]
Abstract
The multi-kinase inhibitor (MKI) sorafenib can be an effective palliative therapy for patients with hepatocellular carcinoma (HCC). However, patient tolerance is often poor due to common systemic side effects following oral administration. Local transcatheter delivery of sorafenib to liver tumors has the potential to reduce systemic toxicities while increasing the dose delivered to targeted tumors. We developed sorafenib-eluting PLG microspheres for delivery by intra-hepatic transcatheter infusion in an orthotropic rodent HCC model. The particles also encapsulated iron-oxide nanoparticles permitting magnetic resonance imaging (MRI) of intra-hepatic biodistributions. The PLG microspheres (diameter≈1μm) were loaded with 18.6% (w/w) sorafenib and 0.54% (w/w) ferrofluid and 65.2% of the sorafenib was released within 72h of media exposure. In vitro studies demonstrated significant reductions in HCC cell proliferation with increasing doses of the sorafenib-eluting microspheres, where the estimated IC50 was a 29μg/mL dose of microspheres. During in vivo studies, MRI permitted intra-procedural visualization of intra-hepatic microsphere delivery. At 72h after microsphere infusion, microvessel density was significantly reduced in tumors treated with the sorafenib-eluting microspheres compared to both sham control tumors (by 35%) and controls (by 30%). These PLG microspheres offer the potential to increase the efficacy of molecularly targeted MKI therapies while reducing systemic exposures via selective catheter-directed delivery to HCC.
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Affiliation(s)
- Jeane Chen
- Department of Chemical & Biological Engineering, Northwestern University, Evanston, IL, USA; Department of Radiology, Northwestern University, Chicago, IL, USA
| | - Alexander Y Sheu
- Department of Radiology, Northwestern University, Chicago, IL, USA
| | - Weiguo Li
- Department of Radiology, Northwestern University, Chicago, IL, USA
| | - Zhuoli Zhang
- Department of Radiology, Northwestern University, Chicago, IL, USA; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA
| | - Dong-Hyun Kim
- Department of Radiology, Northwestern University, Chicago, IL, USA
| | - Robert J Lewandowski
- Department of Radiology, Northwestern University, Chicago, IL, USA; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA
| | - Reed A Omary
- Department of Radiology, Northwestern University, Chicago, IL, USA; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA; Department of Biomedical Engineering, Northwestern University, Chicago, IL, USA
| | - Lonnie D Shea
- Department of Chemical & Biological Engineering, Northwestern University, Evanston, IL, USA; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA
| | - Andrew C Larson
- Department of Radiology, Northwestern University, Chicago, IL, USA; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA; Department of Biomedical Engineering, Northwestern University, Chicago, IL, USA; Department of Electrical Engineering and Computer Science, Evanston, IL, USA.
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MRI-monitored transcatheter intra-arterial delivery of SPIO-labeled natural killer cells to hepatocellular carcinoma: preclinical studies in a rodent model. Invest Radiol 2014; 48:492-9. [PMID: 23249649 DOI: 10.1097/rli.0b013e31827994e5] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
OBJECTIVES The objective of this study was to test the hypotheses that intra-arterial infusion allows for targeted natural killer (NK) lymphocyte delivery to hepatocellular carcinoma (HCC) and that iron oxide labeling allows for quantitative visualization of intra-arterial NK delivery with magnetic resonance imaging (MRI). MATERIALS AND METHODS Experiments received approval from the institutional animal care and use committee. NK-92MI cells were labeled with superparamagnetic iron oxide (SPIO) nanoparticles. Cell viability, labeling efficacy, and cell phantom imaging studies were performed. Eighteen rats were each implanted with HCC tumors. Catheter was placed in proper hepatic artery for either NK lymphocyte (12 rats) or saline (6 rats) infusion. For the 6 rats, MRI T2* measurements for tumor and normal liver were compared before and after the NK infusion and correlated with histologic measurements. Prussian blue staining was used for labeled NK identification. The remaining rats survived for 8 days after the infusion to compare tumor size changes in the rats that received NK cell (6 rats) or saline (6 rats) infusions. Spearman correlation coefficients and t tests were calculated for statistical analyses. RESULTS Increasing SPIO incubation concentration decreased cell viability. Labeling efficacy mean (SD) was 88.0% (3.1%) across samples. The spatial extent of T2*-weighted contrast and R2* relaxivity values increased for cell phantom samples incubated with increasing SPIO concentrations. T2* measurements decreased in the tumor and normal liver tissues after the NK infusion (P < 0.001); ΔT2* was greater in the tumors than in the normal liver tissue (P < 0.001). Histologic measurements demonstrated increased NK delivery to the tumor compared with the normal liver (P < 0.001). ΔT2* was well correlated with histologic NK measurements (ρ = 0.70). Changes in tumor diameter 8 days after the infusion were significantly different between those rats that received NK cell infusions (-2.49 [0.86] mm) and those that received sham saline infusion (5.23 [0.66] mm). CONCLUSIONS Intra-arterial infusion permitted selective delivery of NK cells to HCC. Transcatheter delivery of SPIO-labeled NK cells can be quantitatively visualized with MRI. Transcatheter NK cell delivery limited tumor size progression compared with controls.
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SISTA AKHILESHK, MADOFF DAVIDC. Interventional management of hepatocellular carcinoma. CLINICAL INTERVENTIONAL ONCOLOGY 2014:76-87. [DOI: 10.1016/b978-1-4557-1221-2.00017-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Enriquez J, Javadi S, Murthy R, Ensor J, Mahvash A, Abdelsalam ME, Madoff DC, Wallace MJ, Avritscher R. Gastroduodenal artery recanalization after transcatheter fibered coil embolization for prevention of hepaticoenteric flow: incidence and predisposing technical factors in 142 patients. Acta Radiol 2013; 54:790-4. [PMID: 23535183 DOI: 10.1177/0284185113481696] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
BACKGROUND Prophylactic occlusion of extrahepatic vessels prior to radioembolization or chemotherapy infusion is an effective method to prevent gastrointestinal complications. Unfortunately, vascular recanalization can occur. PURPOSE To retrospectively determine the rate and technical factors associated with gastroduodenal artery (GDA) recanalization after transcatheter occlusion with fibered coils. MATERIAL AND METHODS Patients with hepatic malignancy who underwent fibered coil occlusion of the GDA origin for radioembolization or hepatic arterial chemotherapy infusion with at least one subsequent hepatic angiogram between March 2006 and January 2011 were included. One hundred and forty-two patients (men, 71; women, 71) met study criteria. Hepatic arteriograms were reviewed to determine the frequency of arterial recanalization. Additional parameters included: patients' demographics, GDA diameter, length of coil pack, distance between GDA origin and most cephalad coil, persistent flow at the conclusion of the initial GDA occlusion procedure, platelet count, and international normalized ratio (INR). Chi-square test and pooled t-test were used to compare the two groups. Prospective multivariate analysis was performed with a logistic regression model. RESULTS Twenty-nine of 142 patients (20.4%) experienced GDA recanalization. The distance between the GDA origin and most cephalad coil was significantly greater in the recanalization group than in the non-recanalization group (9.6 mm vs. 12.6 mm, P = 0.01). A prospective multivariate analysis established that the further the coil was from the origin the more likely the GDA was to recanalize. The two groups did not differ on the basis of any other factors examined. CONCLUSION GDA origin recanalization after fibered coil occlusion is common. The distance between the GDA origin and most cephalad coil appears to be a predisposing factor for recanalization. Familiarity with this phenomenon is beneficial to reduce the likelihood of gastrointestinal tract complications during hepatic locoregional therapy.
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Affiliation(s)
- Jose Enriquez
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX
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Idée JM, Guiu B. Use of Lipiodol as a drug-delivery system for transcatheter arterial chemoembolization of hepatocellular carcinoma: a review. Crit Rev Oncol Hematol 2013; 88:530-49. [PMID: 23921081 DOI: 10.1016/j.critrevonc.2013.07.003] [Citation(s) in RCA: 153] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2013] [Revised: 06/05/2013] [Accepted: 07/09/2013] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC) remains a major public health problem. Transarterial chemoembolization (TACE) is recognized as the standard of care for patients with unresectable, asymptomatic, noninvasive and multinodular HCC. This procedure is based on percutaneous administration of a cytotoxic drug emulsified with Lipiodol followed by embolization of the tumour-feeding arteries. The standard procedure involves Lipiodol, an oily contrast medium which consists of a mixture of long-chain di-iodinated ethyl esters of poppy seed fatty acids. The aim of this review is to discuss the physical properties, tumour uptake behaviour and drug delivery effects of Lipiodol, the parameters influencing tumour uptake and future prospects. Lipiodol has a unique place in TACE as it combines three specific characteristics: drug delivery, transient and plastic embolization and radiopacity properties. Substantial heterogeneity in the physicochemical characteristics of Lipiodol/cytotoxic agent emulsions might reduce the efficacy of this procedure and justifies the current interest in Lipiodol for drug delivery.
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Affiliation(s)
- Jean-Marc Idée
- Guerbet, Research and Innovation Division, BP 57400, 95943 Roissy-Charles de Gaulle cedex, France.
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Kouri BE, Funaki BS, Ray CE, Abou-Alfa GK, Burke CT, Darcy MD, Fidelman N, Greene FL, Harrison SA, Kinney TB, Kostelic JK, Lorenz JM, Nair AV, Nemcek AA, Owens CA, Saad WEA, Vatakencherry G. ACR Appropriateness Criteria radiologic management of hepatic malignancy. J Am Coll Radiol 2013. [PMID: 23206650 DOI: 10.1016/j.jacr.2012.09.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Management of hepatic malignancy is a challenging clinical problem involving several different medical and surgical disciplines. Because of the wide variety of potential therapies, treatment protocols for various malignancies continue to evolve. Consequently, development of appropriate therapeutic algorithms necessitates consideration of medical options, such as systemic chemotherapy; surgical options, such as resection or transplantation; and locoregional therapies, such as thermal ablation and transarterial embolization. The authors discuss treatment strategies for the 3 most common subtypes of hepatic malignancy treated with locoregional therapies: hepatocellular carcinoma, neuroendocrine metastases, and colorectal metastases. The ACR Appropriateness Criteria(®) are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
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Affiliation(s)
- Brian E Kouri
- Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina, USA.
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Ganapathy-Kanniappan S, Kunjithapatham R, Geschwind JF. Glyceraldehyde-3-phosphate dehydrogenase: a promising target for molecular therapy in hepatocellular carcinoma. Oncotarget 2013; 3:940-53. [PMID: 22964488 PMCID: PMC3660062 DOI: 10.18632/oncotarget.623] [Citation(s) in RCA: 72] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most highly lethal malignancies ranking as the third leading-cause of cancer-related death worldwide. Although surgical resection and transplantation are effective curative therapies, very few patients qualify for such treatments due to the advanced stage of the disease at diagnosis. In this context, loco-regional therapies provide a viable therapeutic alternative with minimal systemic toxicity. However, as chemoresistance and tumor recurrence negatively impact the success of therapy resulting in poorer patient outcomes it is imperative to identify new molecular target(s) in cancer cells that could be effectively targeted by novel agents. Recent research has demonstrated that proliferation in HCC is associated with increased glucose metabolism. The glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a multifunctional protein primarily recognized for its role in glucose metabolism, has already been shown to affect the proliferative potential of cancer cells. In human HCC, the increased expression of GAPDH is invariably associated with enhanced glycolytic capacity facilitating tumor progression. Though it is not yet known whether GAPDH up-regulation contributes to tumorigenesis sensu stricto, emerging evidence points to the existence of a link between GAPDH up-regulation and the promotion of survival mechanisms in cancer cells as well as chemoresistance. The involvement of GAPDH in several hepatocarcinogenic mechanisms (e.g. viral hepatitis, metabolic alterations) and its sensitivity to a new class of prospective anticancer agents prompted us to review the current understanding of the therapeutic potential of targeting GAPDH in HCC.
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Lau WY, Sangro B, Chen PJ, Cheng SQ, Chow P, Lee RC, Leung T, Han KH, Poon RTP. Treatment for hepatocellular carcinoma with portal vein tumor thrombosis: the emerging role for radioembolization using yttrium-90. Oncology 2013; 84:311-8. [PMID: 23615394 DOI: 10.1159/000348325] [Citation(s) in RCA: 125] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2012] [Accepted: 01/18/2013] [Indexed: 12/13/2022]
Abstract
BACKGROUND/PURPOSE Patients with hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) have an extremely poor prognosis and relatively few treatment options. METHOD During a consensus meeting, experts met to examine the published data for HCC treatment strategies in patients with PVTT. RESULTS Many treatment guidelines consider the presence of PVTT a contraindication to partial hepatectomy or liver transplantation. Transarterial chemoembolization (TACE) is associated with an increased risk of ischemic necrosis of liver and of treatment-related death in patients with PVTT, and is, therefore, limited to a select group of patients with good hepatic function and adequate collateral circulation around the occluded portal vein. Systemic sorafenib results in survival benefit in patients regardless of the presence of PVTT. However, side effects are common, and there are no effects on time-to-symptom progression or quality of life. Transarterial radioembolization (TARE) with yttrium-90 microspheres is emerging as a valuable strategy. A wider range of patients with PVTT are suitable for this procedure compared to TACE. TARE is as effective as TACE in HCC and has quality-of-life advantages. CONCLUSION In patients with HCC with PVTT, medical evidence suggests that TARE is a good choice of treatment.
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Affiliation(s)
- Wan-Yee Lau
- Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, SAR, China.
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Abstract
Image-guided drug delivery provides a means for treating a variety of diseases with minimal systemic involvement while concurrently monitoring treatment efficacy. These therapies are particularly useful to the field of interventional oncology, where elevation of tumor drug levels, reduction of systemic side effects and post-therapy assessment are essential. This review highlights three such image-guided procedures: transarterial chemoembolization, drug-eluting implants and convection-enhanced delivery. Advancements in medical imaging technology have resulted in a growing number of new applications, including image-guided drug delivery. This minimally invasive approach provides a comprehensive answer to many challenges with local drug delivery. Future evolution of imaging devices, image-acquisition techniques and multifunctional delivery agents will lead to a paradigm shift in patient care.
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Phase II study of chemoembolization with drug-eluting beads in patients with hepatic neuroendocrine metastases: high incidence of biliary injury. Cardiovasc Intervent Radiol 2012; 36:449-59. [PMID: 22722717 DOI: 10.1007/s00270-012-0424-y] [Citation(s) in RCA: 73] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/29/2012] [Accepted: 04/26/2012] [Indexed: 01/26/2023]
Abstract
PURPOSE To evaluate safety in an interim analysis of transarterial chemoembolization (TACE) with doxorubicin-eluting beads (DEB) in 13 patients with hepatic metastases from neuroendocrine tumors (NETs) as part of a phase II trial. METHODS Institutional Review Board approval and informed consent were obtained. Thirteen patients completed preliminary safety analysis. Their mean age was 65 years, Eastern Cooperative Oncology Group status was 0/1, tumor burden range was 4-75 %, and mean targeted tumor size was 5.9 cm. Up to four DEB-TACE sessions (100-300 μm beads loaded with ≤100 mg doxorubicin) within 6 months were allowed. Tumor response was assessed by magnetic resonance imaging 1 month after treatment using contrast-enhancement [European Association for the Study of the Liver (EASL) and size Response Evaluation Criteria in Solid Tumors (RECIST)] criteria. Safety was assessed by National Cancer Institute Common Terminology Criteria. RESULTS DEB-TACE was successfully performed in all 13 patients. At 1 month follow-up, there was a mean 12 % decrease in tumor size (p < 0.0003) and a 56 % decrease in tumor enhancement (p < 0.0001). By EASL criteria, the targeted lesion objective response rate was 78 %. Grade 3 to 4 toxicities were fatigue (23 %), increased alanine amino transferase (15 %), hyperglycemia (15 %), and abdominal pain (8 %). Seven patients developed bilomas (54 %); all of these patients had multiple small (<4 cm) lesions. Subsequently, four underwent percutaneous drainage, three for abscess formation and one for symptoms related to mass effect. CONCLUSIONS Although biloma and liver abscess are known risks after TACE, the high incidence in our study population was unexpected and forced interruption of the trial. Although this occurred in a small group of patients, we have changed our technique and patient selection as a result of these findings, thus allowing resumption of the trial.
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Electroporation-mediated transcatheter arterial chemoembolization in the rabbit VX2 liver tumor model. Invest Radiol 2012; 47:116-20. [PMID: 21934518 DOI: 10.1097/rli.0b013e31822e57cc] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
RATIONALE AND OBJECTIVES Electropermeabilization involves the application of electrical pulses to increase cell membrane permeability. The purpose of our study was to demonstrate the potential to use electroporation-mediated transcatheter arterial chemoembolization (E-TACE) approaches to increase liver tumor drug uptake while using magnetic resonance imaging (MRI) for intraprocedural optimization of these procedures. METHODS Fourteen VX2 tumors were grown in the left hepatic lobes of 8 rabbits. Two tumors were grown in each of 6 rabbits (1 tumor serving as E-TACE-treated tumor and the other as nonelectroporated control), and solitary larger tumors were grown in 2 rabbits (half of the tumor treated with E-TACE, remaining half serving as control). Each rabbit was selectively catheterized under digital subtraction angiography guidance. Baseline MRI was performed to generate tumor contrast enhancement curves following catheter-directed infusion of gadopentetate dimeglumine to estimate the proper time delay between subsequent bolus infusion of cisplatin and application of electrical pulses (electrodes were used to deliver 8, 100-μs, 1300-V pulses at the selected delay interval postinfusion). Three hours after E-TACE, rabbits were euthanized, and tumors were sectioned for inductively coupled plasma mass spectroscopy measurements of platinum concentration (serving as reference standard of cisplatin uptake levels). RESULTS Inductively coupled plasma mass spectroscopy results demonstrated significantly increased cisplatin uptake in E-TACE-treated tumor tissues, increases of 6.0 ± 3.3-fold compared with transcatheter infusion alone (P = 0.017). CONCLUSIONS Our findings suggest that our E-TACE approach may significantly increase liver tumor drug uptake after targeted transcatheter infusion. MRI measurements permitted intraprocedural guidance during these catheter-directed E-TACE procedures.
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Waly Raphael S, Yangde Z, YuXiang C. Hepatocellular carcinoma: focus on different aspects of management. ISRN ONCOLOGY 2012; 2012:421673. [PMID: 22655206 PMCID: PMC3359687 DOI: 10.5402/2012/421673] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/08/2012] [Accepted: 03/04/2012] [Indexed: 12/12/2022]
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third cause of cancer-related mortality worldwide. Its incidence is clearly arising comprised by the prevalence of major risk factors mainly hepatitis B and hepatitis C. The population at risk is composed of chronic liver patients at the stage of extensive fibrosis or cirrhosis. The monitoring programs of this population have allowed early detection of disease management to promote a radical therapy. Understanding the carcinogenic process and the mastery of the staging systems remain essential keys in diagnosis and treatment of HCC. Recent advances in diagnosis and new treatments have made important impacts on the disease by increasing survival rates and improving quality of life for HCC patients. This paper outlines the different management aspects of HCC which include epidemiology, prevention, carcinogenesis, staging systems, diagnosis, surveillance, and the treatment.
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Affiliation(s)
- Sene Waly Raphael
- National Hepatobiliary and Enteric Surgery Research Center of Ministry of Health, Central South University, Changsha, Hunan 410008, China
| | - Zhang Yangde
- National Hepatobiliary and Enteric Surgery Research Center of Ministry of Health, Central South University, Changsha, Hunan 410008, China
| | - Chen YuXiang
- National Hepatobiliary and Enteric Surgery Research Center of Ministry of Health, Central South University, Changsha, Hunan 410008, China
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Ganapathy-Kanniappan S, Kunjithapatham R, Torbenson MS, Rao PP, Carson KA, Buijs M, Vali M, Geschwind JFH. Human hepatocellular carcinoma in a mouse model: assessment of tumor response to percutaneous ablation by using glyceraldehyde-3-phosphate dehydrogenase antagonists. Radiology 2012; 262:834-45. [PMID: 22357885 DOI: 10.1148/radiol.11111569] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
PURPOSE To characterize tumor response to percutaneous injection of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) antagonists in a mouse model of human hepatocellular carcinoma (HCC). MATERIALS AND METHODS Animal experiments were approved by the Johns Hopkins University Animal Care and Use Committee. Luciferase (luc) gene-expressing Hep3B tumor-bearing athymic nude mice were randomly divided into four groups of six mice each. Tumor-specific GAPDH inhibition was achieved by using percutaneous injection of GAPDH antagonists-3-bromopyruvate (3-BrPA) or GAPDH-specific short hairpin RNA (shRNA). Tumor response to treatment was assessed by using bioluminescence imaging and analysis of GAPDH function and apoptotic markers (caspase-3, caspase-9, and positive staining for terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphospate nick end labeling). HCC samples from 34 patients were obtained from the Johns Hopkins tumor bank, as approved by the Institutional Review Board, for GAPDH expression analysis. Statistical analysis was performed by using a two-sample t test or Spearman rank correlation coefficient. RESULTS In vitro, 3-BrPA affected Hep3B cell viability (half maximal inhibitory concentration = 0.15 mmol/L), and GAPDH shRNA suppressed (45.5%) colony formation. In vivo, percutaneous injection of GAPDH antagonists into luc-Hep3B tumors decreased bioluminescence imaging signal and viability (3-BrPA, P < .0001; GAPDH shRNA, P = .03). The 3-BrPA treatment primarily inhibited GAPDH activity (74.5%) compared with its expression (34.3%), whereas GAPDH shRNA inhibited both activity (60.6%) and expression (44.4%). Targeted inhibition of GAPDH by using 3-BrPA or shRNA induced apoptosis. HCC samples from patients demonstrated a strong correlation between GAPDH upregulation and the proto-oncogene c-jun expression (r = 0.543, P = .003). CONCLUSION Percutaneous injection of GAPDH antagonists induces apoptosis and blocks Hep3B tumor progression, which demonstrates the therapeutic potential of targeting GAPDH in human HCC.
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Affiliation(s)
- Shanmugasundaram Ganapathy-Kanniappan
- Russell H Morgan Department of Radiology and Radiological Sciences and Department of Pathology, Johns Hopkins University School of Medicine, 600 N Wolfe St, Blalock 545, Baltimore, MD 21287, USA
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Kneuertz PJ, Cosgrove DP, Cameron AM, Kamel IR, Geschwind JFH, Herman JM, Pawlik TM. Multidisciplinary management of recurrent hepatocellular carcinoma following liver transplantation. J Gastrointest Surg 2012; 16:874-81. [PMID: 21975686 PMCID: PMC3541014 DOI: 10.1007/s11605-011-1710-8] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2011] [Accepted: 09/20/2011] [Indexed: 01/31/2023]
Abstract
INTRODUCTION Tumor recurrence remains a main limitation to the long-term survival of patients following liver transplantation for hepatocellular carcinoma (HCC). While the majority of patients recur in the first two years after transplantation, late recurrence is not infrequent. DISCUSSION Most common sites of recurrence in order of decreasing frequency are liver graft, lung, bone, abdominal lymph nodes, adrenal glands and peritoneum. Reported five-year survival after surgical resection ranges from 27-88%. Few patients, however, are candidates for surgical resection. Other therapeutic options for recurrent HCC include systemic therapy, intra-arterial therapy, or radiation therapy. Although systemic molecular targeted therapy is generally tolerated with very few interactions with immunosuppressive medications, there is only modest success regarding prolongation of survival. Utilization of radiation therapy for extrahepatic recurrences similarly has minimal impact on overall survival, but may effectively in palliate symptoms. While late recurrence is associated with a more favorable prognosis than early recurrences, prognosis is still poor. CONCLUSION Late recurrence of HCC following transplantation should be borne in mind even after many years from transplant. Surgical salvage, when feasible, remains a viable treatment option in select patients with a chance for long-term survival. A multi-disciplinary approach is critical as different therapeutic modalities have a role in treating recurrent HCC following transplant.
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Affiliation(s)
- Peter J. Kneuertz
- Department of Surgery, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - David P. Cosgrove
- Department of Medical Oncology, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Andrew M. Cameron
- Department of Surgery, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Ihab R. Kamel
- Department of Radiology, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Jean-Francois H. Geschwind
- Department of Interventional Radiolog, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Joseph M. Herman
- Department of Radiation Oncology, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Timothy M. Pawlik
- Department of Surgery, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
- Department of Medical Oncology, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
- Johns Hopkins Medicine Liver Tumor Center Multi-Disciplinary Clinic, Center for Surgical Trials and Outcomes Research, Johns Hopkins Hospital, 600 N. Wolfe Street, Harvey 611, Baltimore, MD 21287, USA,
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