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Ron C. Gaba - One of the best experts on this subject based on the ideXlab platform.

  • Mechanism of Action, Pharmacokinetics, Efficacy, and Safety of Transarterial Therapies Using Ethiodized Oil: Preclinical Review in Liver Cancer Models.
    Journal of vascular and interventional radiology : JVIR, 2017
    Co-Authors: Ron C. Gaba, Regina M. Schwind, Sébastien Ballet
    Abstract:

    To systematically review mechanism of action, pharmacokinetics (PKs), efficacy, and safety of Ethiodized Oil-based locoregional therapy (LRT) for liver cancer in preclinical models. A MEDLINE search was performed from 1988 to 2016. Search terms included hepatocellular carcinoma (HCC), HCC, liver-cell carcinoma, liver, hepatic, hepatocarcinoma, transarterial or chemoembolization, TACE, animal, Lipiodol, Ethiodol, iodized Oil, and/or poppy-seed Oil. Inclusion criteria were: publication in a peer-reviewed journal, an accepted animal model, and PK/safety/efficacy data reported. Exclusion criteria were: inadequate PK, safety, or efficacy data; anticancer drug name/dose not available; and article not in English. Outcomes included intratumoral anticancer drug uptake, PKs, tolerance, tumor response, and survival. Of 102 identified articles, 49 (49%) met the inclusion criteria. Seventeen, 35, and 2 articles used rat, rabbit, and pig models. Mechanism of action was investigated in 11 articles. Eleven articles reported drug uptake, PK, and tolerance data, showing 0.5%-9.5% of injected chemotherapy dose in tumor. Tumor-to-liver drug distribution ratios were 2-157. Toxicology data across 6 articles showed transient liver laboratory level elevations 1 day after LRT. There was no noteworthy liver or extrahepatic histologic damage. Nine articles reported tumor response, with 0%-30% viable tumor and -10% to -38% tumor growth at 7 days after LRT. Two articles reported survival, showing significantly longer survival after LRT vs untreated controls (56/60 d vs 33/28 d). Several articles described Ethiodized Oil mixed with radiopharmaceutical (n = 7), antiangiogenic (n = 6), gene (n = 6), nanoembolic (n = 5), immune (n = 2), or other novel (n = 1) agents. Animal studies show preferential tumor uptake of anticancer agent, good hepatic/systemic tolerance, high tumor response, and enhanced survival after Ethiodized Oil-based LRT. Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.

  • mechanism of action pharmacokinetics efficacy and safety of transarterial therapies using Ethiodized Oil preclinical review in liver cancer models
    Journal of Vascular and Interventional Radiology, 2017
    Co-Authors: Ron C. Gaba, Regina M. Schwind, Sébastien Ballet
    Abstract:

    Abstract Purpose To systematically review mechanism of action, pharmacokinetics (PKs), efficacy, and safety of Ethiodized Oil–based locoregional therapy (LRT) for liver cancer in preclinical models. Materials and Methods A MEDLINE search was performed from 1988 to 2016. Search terms included hepatocellular carcinoma (HCC), HCC, liver-cell carcinoma, liver, hepatic, hepatocarcinoma, transarterial or chemoembolization, TACE, animal, Lipiodol, Ethiodol, iodized Oil, and/or poppy-seed Oil. Inclusion criteria were: publication in a peer-reviewed journal, an accepted animal model, and PK/safety/efficacy data reported. Exclusion criteria were: inadequate PK, safety, or efficacy data; anticancer drug name/dose not available; and article not in English. Outcomes included intratumoral anticancer drug uptake, PKs, tolerance, tumor response, and survival. Results Of 102 identified articles, 49 (49%) met the inclusion criteria. Seventeen, 35, and 2 articles used rat, rabbit, and pig models. Mechanism of action was investigated in 11 articles. Eleven articles reported drug uptake, PK, and tolerance data, showing 0.5%–9.5% of injected chemotherapy dose in tumor. Tumor-to-liver drug distribution ratios were 2–157. Toxicology data across 6 articles showed transient liver laboratory level elevations 1 day after LRT. There was no noteworthy liver or extrahepatic histologic damage. Nine articles reported tumor response, with 0%–30% viable tumor and –10% to –38% tumor growth at 7 days after LRT. Two articles reported survival, showing significantly longer survival after LRT vs untreated controls (56/60 d vs 33/28 d). Several articles described Ethiodized Oil mixed with radiopharmaceutical (n = 7), antiangiogenic (n = 6), gene (n = 6), nanoembolic (n = 5), immune (n = 2), or other novel (n = 1) agents. Conclusions Animal studies show preferential tumor uptake of anticancer agent, good hepatic/systemic tolerance, high tumor response, and enhanced survival after Ethiodized Oil–based LRT.

  • Pharmacokinetic study of conventional sorafenib chemoembolization in a rabbit VX2 liver tumor model.
    Diagnostic and Interventional Radiology, 2015
    Co-Authors: Ahmad Parvinian, Leigh C. Casadaban, Zane Hauck, Richard B Van Breemen, Ron C. Gaba
    Abstract:

    PURPOSE: Use of oral sorafenib, an antiangiogenic chemotherapeutic agent for hepatocellular carcinoma (HCC), is limited by an unfavorable side effect profile. Transarterial chemoembolization (TACE) employs targeted intravascular drug administration, and has potential as a novel sorafenib delivery method to increase tumoral concentrations and reduce systemic levels. This study aimed to discern the pharmacokinetics of sorafenib TACE in a rabbit VX2 liver tumor model. METHODS: A 3 mg/kg dose of sorafenib Ethiodized Oil emulsion was delivered via an arterial catheter to VX2 liver tumors in seven New Zealand white rabbits. Following TACE, serum sorafenib levels were measured at days 0, 1, 2, 3, 7, 10, and 14 until the time of sacrifice, after which rabbit livers were harvested for analysis of sorafenib concentrations within treated tumors and normal liver. Liquid chromatography tandem mass spectrometry was used for drug quantification. RESULTS: Sorafenib uptake within liver tumor and nontumorous liver tissue peaked at mean 3.53 and 0.75 μg/mL, respectively, immediately post-procedure (5:1 tumor to normal tissue drug uptake ratio), before decreasing with a 10-18 hour half-life. Serum sorafenib levels peaked immediately after TACE at a mean value of 58.58 μg/mL before normalizing with a 5.2-hour half-life, suggesting early drug washout from liver into the systemic circulation. Hepatic lab parameters showed transient increase 24 hours post-TACE with subsequent resolution. CONCLUSION: While targeted transarterial delivery of sorafenib Ethiodized Oil emulsion shows preferential tumor uptake compared to normal liver, systemic washout occurs with a short half-life, resulting in high circulating drug levels.

  • cerebral embolization of Ethiodized Oil following intranodal lymphangiography
    Seminars in Interventional Radiology, 2015
    Co-Authors: Arman Sheybani, Ron C. Gaba, Jeet Minocha
    Abstract:

    Intranodal lymphangiography (IL) has supplanted pedal lymphangiography (PL) as an easier and more practical approach to opacifying lymphatic vessels for interventional radiologists treating refractory chyle leaks. As more interventional radiologists—many of who are not trained in or have not performed PL—incorporate IL into their practice, it is imperative that they be familiar with the risks of lymphangiography, including pulmonary and systemic embolization of Oily contrast material. Herein, the authors report a devastating case of cerebral embolization of Ethiodized Oil following IL and review the literature regarding systemic embolization following lymphangiography.

  • Transarterial Sorafenib Chemoembolization: Preliminary Study of Technical Feasibility in a Rabbit Model
    Journal of vascular and interventional radiology : JVIR, 2013
    Co-Authors: Ron C. Gaba, Ahmad Parvinian, Richard B. Van Breemen, Felix Y. Yap, Elizabeth M. Martinez, Grace Guzman, Nishant Kumar
    Abstract:

    Purpose Sorafenib is an anti-angiogenic agent associated with increased overall survival in patients with unresectable hepatocellular carcinoma. However, adverse effects (diarrhea and hand-foot syndrome) of this oral agent limit compliance, and other routes of sorafenib delivery have not been explored. Sorafenib infusion from a transarterial approach may impart high intrahepatic drug concentrations to reduce the angiogenic cascade stimulated by chemoembolization hypoxia, while potentially decreasing systemic side effects. Herein, we tested the feasibility of transarterial hepatic delivery of a lipid-emulsified preparation of sorafenib using a rabbit model. Materials and Methods The left hepatic lobes of 5 New Zealand white rabbits (mean weight 2.7±0.2 kg) were treated with chemoembolization using sorafenib and Ethiodized Oil emulsion, followed by immediate sacrifice. Post-procedure non-contrast computed tomography (CT) scan was used to evaluate intrahepatic chemotherapy mixture distribution. Liquid chromatography tandem mass spectrometry (LC-MS/MS) was then used to directly measure sorafenib concentration in treated liver tissue. Histopathologic assessment of treated left lobes was performed to identify any immediate toxic effects of the sorafenib solution. Results Lobar sorafenib chemoembolization was successfully performed in all cases via the left hepatic artery. Mean 6.4±3.8 mg sorafenib and 0.85±0.7 mL Ethiodized Oil was injected. CT confirmed targeted left hepatic lobe sorafenib emulsion delivery in all cases. Corresponding LC-MS/MS analysis yielded mean sorafenib concentration of 20.62±8.55 mcg/mL in treated left lobe samples (n=5), almost five times greater than typical therapeutic drug levels (4.65 mcg/mL) achieved with oral sorafenib systemic therapy. Histopathologic assessment showed only mild or moderate non-specific ballooning degeneration in zone 3 hepatocytes without tissue necrosis. Conclusion Targeted transarterial sorafenib delivery is feasible and results in higher tissue drug levels than systemic sorafenib therapy, without immediate tissue toxicity. Future studies should aim to determine the utility of sorafenib chemoembolization in reducing hypoxia-induced vasculogenesis in liver tumors.

Lawrence V. Hofmann - One of the best experts on this subject based on the ideXlab platform.

  • superselective chemoembolization of hcc comparison of short term safety and efficacy between drug eluting lc beads quadraspheres and conventional Ethiodized Oil emulsion
    Radiology, 2016
    Co-Authors: Feng Duan, Gloria L. Hwang, Lawrence V. Hofmann, Ellen Q Wang, Marnix G E H Lam, M Abdelmaksoud, John D Louie, N Kothary, William T Kuo, Daniel Y. Sze
    Abstract:

    Doxorubicin-delivering LC Beads, QuadraSpheres, and Ethiodized Oil emulsions appear to be equivalent in efficacy and toxicity when used for superselective transcatheter arterial chemoembolization with C-arm cone-beam CT guidance in patients with hepatocellular carcinoma.

  • Superselective Chemoembolization of HCC: Comparison of Short-term Safety and Efficacy between Drug-eluting LC Beads, QuadraSpheres, and Conventional Ethiodized Oil Emulsion.
    Radiology, 2015
    Co-Authors: Feng Duan, Gloria L. Hwang, Nishita Kothary, Lawrence V. Hofmann, Ellen Q Wang, Marnix G E H Lam, M Abdelmaksoud, John D Louie, William T Kuo, Daniel Y. Sze
    Abstract:

    To study the comparative short-term safety and efficacy of transcatheter arterial chemoembolization (TACE) with drug-eluting LC Beads loaded with doxorubicin (DEBDOX), doxorubicin-eluting QuadraSpheres (hqTACE), and conventional TACE using Ethiodized Oil for superselective C-arm computed tomography (CT)-guided treatment of hepatocellular carcinoma (HCC) after the onset of drug shortages. From March 2010 to March 2011, 166 patients with HCC were treated with 232 superselective TACE procedures using C-arm cone-beam CT at one institution. Patients underwent treatment depending on the availability of materials after the onset of drug shortages. Conventional TACE with doxorubicin, cisplatin, and Ethiodol was performed for 159 procedures, DEBDOX TACE was performed for 47, and hqTACE was performed for 26. Toxicity and objective response were compared at 3 months after treatment. Data were stratified for the high-risk population (Child-Pugh class B, performance status 1, bilobar disease, and/or post-resection recurrence) and initial versus repeat treatment. Kruskal-Wallis H test, Mann-Whitney U test, and Fisher exact test were used to compare the groups, with Bonferroni correction where needed. Whole liver response rates trended higher for conventional TACE (conventional TACE, 65.4%; DEBDOX, 63.8%; hqTACE, 53.8%) (P = .085). Only minor trends for differences in toxicity were observed between the three groups. Low-risk patients had higher whole liver (P = .001) and treated lesion (P = .007) response rates when treated with conventional TACE, but no significant differences were seen for DEBDOX and hqTACE. Treatment-naive patients also had higher whole liver (P = .012) and treated lesion (P = .056) response rates. No advantages for drug-eluting microspheres were found. Within statistical power limitations, overall toxicity and efficacy were equivalent in patients treated with LC Beads, QuadraSpheres, or Ethiodized Oil emulsions, including in high-risk patients, when performed superselectively with cone-beam C-arm CT guidance. © RSNA, 2015.

  • in vitro design and characterization of the nonviral gene delivery vector iopamidol protamine Ethiodized Oil reagent
    Journal of Vascular and Interventional Radiology, 2011
    Co-Authors: Luke J. Higgins, Gloria L. Hwang, Jarrett Rosenberg, R.h. Katzenberg, Nishita Kothary, Daniel Y. Sze, Lawrence V. Hofmann
    Abstract:

    Abstract Purpose To demonstrate cellular selectivity toward hepatoma cells and compare the efficiency of gene delivery of a novel nonviral vector of iopamidol, protamine, and Ethiodized Oil reagents (VIPER). Materials and Methods Rat hepatocellular carcinoma (HCC) cells were transfected in triplicate under varying conditions by using firefly luciferase as a reporter gene. Conditions included variations of a protamine:DNA (P:D) complex (20:1, 50:1, 100:1, 200:1 mass ratios), iopamidol (0%, 10%, 33%), and Ethiodized Oil (0%, 1%, 2%, 4%, 8%, and 16%). The conditions affording efficient gene transfer and ease of translation to in vivo studies were selected for cell line comparison (HCC cells vs hepatocytes). Adenoviral transduction was compared with nonviral vector transfection. Results At low concentrations, Ethiodized Oil increased transfection efficiency regardless of P:D mass ratio. However, high concentrations resulted in significant attenuation. Unexpectedly, the addition of iopamidol to P:D complexes markedly improved transfection efficiency. When using an optimal P:D, iopamidol, and Ethiodized Oil solution, DNA transfection of normal liver and tumor cells showed significant selectivity for tumor cells. In the context of hepatoma cells, transfection efficiency with the nonviral vector was better than 10 4 pfu adenovirus. Conclusions The development and characterization of the VIPER system provides a possible alternative to viral gene therapy of HCC.

  • In vitro design and characterization of the nonviral gene delivery vector iopamidol, protamine, Ethiodized Oil reagent.
    Journal of vascular and interventional radiology : JVIR, 2011
    Co-Authors: Luke J. Higgins, Gloria L. Hwang, Jarrett Rosenberg, R.h. Katzenberg, Nishita Kothary, Daniel Y. Sze, Lawrence V. Hofmann
    Abstract:

    To demonstrate cellular selectivity toward hepatoma cells and compare the efficiency of gene delivery of a novel nonviral vector of iopamidol, protamine, and Ethiodized Oil reagents (VIPER). Rat hepatocellular carcinoma (HCC) cells were transfected in triplicate under varying conditions by using firefly luciferase as a reporter gene. Conditions included variations of a protamine:DNA (P:D) complex (20:1, 50:1, 100:1, 200:1 mass ratios), iopamidol (0%, 10%, 33%), and Ethiodized Oil (0%, 1%, 2%, 4%, 8%, and 16%). The conditions affording efficient gene transfer and ease of translation to in vivo studies were selected for cell line comparison (HCC cells vs hepatocytes). Adenoviral transduction was compared with nonviral vector transfection. At low concentrations, Ethiodized Oil increased transfection efficiency regardless of P:D mass ratio. However, high concentrations resulted in significant attenuation. Unexpectedly, the addition of iopamidol to P:D complexes markedly improved transfection efficiency. When using an optimal P:D, iopamidol, and Ethiodized Oil solution, DNA transfection of normal liver and tumor cells showed significant selectivity for tumor cells. In the context of hepatoma cells, transfection efficiency with the nonviral vector was better than 10(4) pfu adenovirus. The development and characterization of the VIPER system provides a possible alternative to viral gene therapy of HCC. Copyright © 2011 SIR. Published by Elsevier Inc. All rights reserved.

Kenneth C. Wright - One of the best experts on this subject based on the ideXlab platform.

  • Pure Ethiodized Oil-based transcatheter ablative therapy in normal rabbit kidneys and kidneys inoculated with VX-2 carcinoma.
    Cardiovascular and interventional radiology, 2011
    Co-Authors: Andras Konya, L. Clifton Stephens, Kenneth C. Wright
    Abstract:

    Purpose To evaluate the efficacy of ablation with selective arterial injection of pure Ethiodized Oil followed by arterial occlusion with 9:1 ethanol–Ethiodol mixture (EEM) and cOil placement in normal rabbit kidneys and kidneys inoculated with VX-2 carcinoma.

  • pure Ethiodized Oil as a capillary embolic agent with and without ethanol ethiodol mixture in the rabbit kidney embolic efficacy and temporal histopathologic findings
    Journal of Vascular and Interventional Radiology, 2010
    Co-Authors: Andras Konya, Clifton L Stephens, Kenneth C. Wright
    Abstract:

    Purpose To determine the extent of ablation and the temporal histopathologic findings associated with selective arterial injection of pure Ethiodol in the normal rabbit kidney, with or without arterial occlusion of the main renal artery. Materials and Methods In 19 rabbits, 27 kidneys were embolized by injecting 0.6 mL of pure Ethiodol into the main renal artery to achieve capillary stasis. A 9:1 ethanol-Ethiodized Oil mixture was then injected into 17 of the 27 kidneys until complete arterial stasis was accomplished. Macro- and microscopic evaluation was performed 10 minutes to 6 weeks and 60 minutes to 1 week, respectively, for kidneys with and without arterial occlusion. Results Ethiodol followed by ethanol-Ethiodol mixture (mean ± standard deviation, 0.37 mL ± 0.03) caused complete and permanent arterial stasis in all 17 kidneys. Thrombosis of the large arteries occurred initially. Ischemic coagulative necrosis of renal tubules and damage to glomeruli were detected 2 hours after embolization. Within 24 hours, the glomeruli and most tubules of the cortex and medulla were necrotic. Without arterial occlusion, the arteriocapillary bed of the kidneys was completely patent, with normal contrast medium excretion. Ethiodol was observed in glomeruli and interstitial capillaries from 60 minutes to 1 week and caused mild acute glomerulitis from day 1. The lesions were confined to the glomeruli, and no significant parenchymal changes were observed. Conclusions In the rabbit, selective arterial injection of pure Ethiodol produces complete renal ablation within 24 hours if prompt and permanent occlusion of the arterial compartment guarantees its permanent capillary retention.

  • Pure Ethiodized Oil as a capillary embolic agent with and without ethanol-ethiodol mixture in the rabbit kidney: embolic efficacy and temporal histopathologic findings.
    Journal of vascular and interventional radiology : JVIR, 2010
    Co-Authors: Andras Konya, L. Clifton Stephens, Kenneth C. Wright
    Abstract:

    To determine the extent of ablation and the temporal histopathologic findings associated with selective arterial injection of pure Ethiodol in the normal rabbit kidney, with or without arterial occlusion of the main renal artery. In 19 rabbits, 27 kidneys were embolized by injecting 0.6 mL of pure Ethiodol into the main renal artery to achieve capillary stasis. A 9:1 ethanol-Ethiodized Oil mixture was then injected into 17 of the 27 kidneys until complete arterial stasis was accomplished. Macro- and microscopic evaluation was performed 10 minutes to 6 weeks and 60 minutes to 1 week, respectively, for kidneys with and without arterial occlusion. Ethiodol followed by ethanol-Ethiodol mixture (mean +/- standard deviation, 0.37 mL +/- 0.03) caused complete and permanent arterial stasis in all 17 kidneys. Thrombosis of the large arteries occurred initially. Ischemic coagulative necrosis of renal tubules and damage to glomeruli were detected 2 hours after embolization. Within 24 hours, the glomeruli and most tubules of the cortex and medulla were necrotic. Without arterial occlusion, the arteriocapillary bed of the kidneys was completely patent, with normal contrast medium excretion. Ethiodol was observed in glomeruli and interstitial capillaries from 60 minutes to 1 week and caused mild acute glomerulitis from day 1. The lesions were confined to the glomeruli, and no significant parenchymal changes were observed. In the rabbit, selective arterial injection of pure Ethiodol produces complete renal ablation within 24 hours if prompt and permanent occlusion of the arterial compartment guarantees its permanent capillary retention. Copyright 2010 SIR. Published by Elsevier Inc. All rights reserved.

  • Ethiodized Oil ethanol capillary embolization in rabbit kidneys temporal histopathologic findings
    Radiology, 2004
    Co-Authors: Andras Konya, Carolyn S Van Pelt, Kenneth C. Wright
    Abstract:

    PURPOSE: To determine the temporal histopathologic findings associated with selective arterial injection of a 1:1 Ethiodized Oil–ethanol mixture (EEM) in normal rabbit kidney followed by administration of pure ethanol into the main renal artery. MATERIALS AND METHODS: In five rabbits, the EEM was injected sequentially into each segmental renal artery of the right kidney until capillary stasis occurred. Pure ethanol was then injected into the main renal artery to achieve complete arterial stasis. Before sacrifice, the left kidney in each animal was acutely (ie, with a short follow-up period) embolized by using the same technique. The 10 kidneys of the five rabbits were evaluated microscopically at 1 (n = 3), 1½ (n = 1), and 3 hours (n = 1) and 1 (n = 1), 3 (n = 1), 5 (n = 1), 7 (n = 1), and 14 days (n = 1) after embolization. RESULTS: Injection of the EEM (mean volume, 0.46 mL ± 0.14 [SD]) followed by ethanol alone (mean volume, 0.25 mL ± 0.09) led to complete stasis in all kidneys. There was no recanaliza...

  • Ethiodized Oil-ethanol capillary embolization in rabbit kidneys: temporal histopathologic findings.
    Radiology, 2004
    Co-Authors: Andras Konya, Carolyn S Van Pelt, Kenneth C. Wright
    Abstract:

    To determine the temporal histopathologic findings associated with selective arterial injection of a 1:1 Ethiodized Oil-ethanol mixture (EEM) in normal rabbit kidney followed by administration of pure ethanol into the main renal artery. In five rabbits, the EEM was injected sequentially into each segmental renal artery of the right kidney until capillary stasis occurred. Pure ethanol was then injected into the main renal artery to achieve complete arterial stasis. Before sacrifice, the left kidney in each animal was acutely (ie, with a short follow-up period) embolized by using the same technique. The 10 kidneys of the five rabbits were evaluated microscopically at 1 (n = 3), 1(1/2) (n = 1), and 3 hours (n = 1) and 1 (n = 1), 3 (n = 1), 5 (n = 1), 7 (n = 1), and 14 days (n = 1) after embolization. Injection of the EEM (mean volume, 0.46 mL +/- 0.14 [SD]) followed by ethanol alone (mean volume, 0.25 mL +/- 0.09) led to complete stasis in all kidneys. There was no recanalization in the chronically (ie, with a longer follow-up period) embolized kidneys. Microscopically, uniform distribution of the EEM was evident in all slices at all time points. From 1 to 3 hours, sloughing of endothelium, formation of thrombi, and deposition of eosinophilic material along the renal, interlobar, and arcuate arteries were observed, without evidence of parenchymal damage. Within 24 hours, complete coagulative necrosis of the entire kidney occurred as a result of an occluding thrombus in the main renal artery. Analysis at subsequent time points revealed liquefaction of necrotic tissue and replacement with granulation tissue. In the rabbit, selective renal arterial injection of EEM followed by administration of ethanol produces vascular endothelial damage initiating thrombosis that results in renal infarction and ablation within 24 hours. Copyright RSNA, 2004

Daniel Y. Sze - One of the best experts on this subject based on the ideXlab platform.

  • superselective chemoembolization of hcc comparison of short term safety and efficacy between drug eluting lc beads quadraspheres and conventional Ethiodized Oil emulsion
    Radiology, 2016
    Co-Authors: Feng Duan, Gloria L. Hwang, Lawrence V. Hofmann, Ellen Q Wang, Marnix G E H Lam, M Abdelmaksoud, John D Louie, N Kothary, William T Kuo, Daniel Y. Sze
    Abstract:

    Doxorubicin-delivering LC Beads, QuadraSpheres, and Ethiodized Oil emulsions appear to be equivalent in efficacy and toxicity when used for superselective transcatheter arterial chemoembolization with C-arm cone-beam CT guidance in patients with hepatocellular carcinoma.

  • Superselective Chemoembolization of HCC: Comparison of Short-term Safety and Efficacy between Drug-eluting LC Beads, QuadraSpheres, and Conventional Ethiodized Oil Emulsion.
    Radiology, 2015
    Co-Authors: Feng Duan, Gloria L. Hwang, Nishita Kothary, Lawrence V. Hofmann, Ellen Q Wang, Marnix G E H Lam, M Abdelmaksoud, John D Louie, William T Kuo, Daniel Y. Sze
    Abstract:

    To study the comparative short-term safety and efficacy of transcatheter arterial chemoembolization (TACE) with drug-eluting LC Beads loaded with doxorubicin (DEBDOX), doxorubicin-eluting QuadraSpheres (hqTACE), and conventional TACE using Ethiodized Oil for superselective C-arm computed tomography (CT)-guided treatment of hepatocellular carcinoma (HCC) after the onset of drug shortages. From March 2010 to March 2011, 166 patients with HCC were treated with 232 superselective TACE procedures using C-arm cone-beam CT at one institution. Patients underwent treatment depending on the availability of materials after the onset of drug shortages. Conventional TACE with doxorubicin, cisplatin, and Ethiodol was performed for 159 procedures, DEBDOX TACE was performed for 47, and hqTACE was performed for 26. Toxicity and objective response were compared at 3 months after treatment. Data were stratified for the high-risk population (Child-Pugh class B, performance status 1, bilobar disease, and/or post-resection recurrence) and initial versus repeat treatment. Kruskal-Wallis H test, Mann-Whitney U test, and Fisher exact test were used to compare the groups, with Bonferroni correction where needed. Whole liver response rates trended higher for conventional TACE (conventional TACE, 65.4%; DEBDOX, 63.8%; hqTACE, 53.8%) (P = .085). Only minor trends for differences in toxicity were observed between the three groups. Low-risk patients had higher whole liver (P = .001) and treated lesion (P = .007) response rates when treated with conventional TACE, but no significant differences were seen for DEBDOX and hqTACE. Treatment-naive patients also had higher whole liver (P = .012) and treated lesion (P = .056) response rates. No advantages for drug-eluting microspheres were found. Within statistical power limitations, overall toxicity and efficacy were equivalent in patients treated with LC Beads, QuadraSpheres, or Ethiodized Oil emulsions, including in high-risk patients, when performed superselectively with cone-beam C-arm CT guidance. © RSNA, 2015.

  • in vitro design and characterization of the nonviral gene delivery vector iopamidol protamine Ethiodized Oil reagent
    Journal of Vascular and Interventional Radiology, 2011
    Co-Authors: Luke J. Higgins, Gloria L. Hwang, Jarrett Rosenberg, R.h. Katzenberg, Nishita Kothary, Daniel Y. Sze, Lawrence V. Hofmann
    Abstract:

    Abstract Purpose To demonstrate cellular selectivity toward hepatoma cells and compare the efficiency of gene delivery of a novel nonviral vector of iopamidol, protamine, and Ethiodized Oil reagents (VIPER). Materials and Methods Rat hepatocellular carcinoma (HCC) cells were transfected in triplicate under varying conditions by using firefly luciferase as a reporter gene. Conditions included variations of a protamine:DNA (P:D) complex (20:1, 50:1, 100:1, 200:1 mass ratios), iopamidol (0%, 10%, 33%), and Ethiodized Oil (0%, 1%, 2%, 4%, 8%, and 16%). The conditions affording efficient gene transfer and ease of translation to in vivo studies were selected for cell line comparison (HCC cells vs hepatocytes). Adenoviral transduction was compared with nonviral vector transfection. Results At low concentrations, Ethiodized Oil increased transfection efficiency regardless of P:D mass ratio. However, high concentrations resulted in significant attenuation. Unexpectedly, the addition of iopamidol to P:D complexes markedly improved transfection efficiency. When using an optimal P:D, iopamidol, and Ethiodized Oil solution, DNA transfection of normal liver and tumor cells showed significant selectivity for tumor cells. In the context of hepatoma cells, transfection efficiency with the nonviral vector was better than 10 4 pfu adenovirus. Conclusions The development and characterization of the VIPER system provides a possible alternative to viral gene therapy of HCC.

  • In vitro design and characterization of the nonviral gene delivery vector iopamidol, protamine, Ethiodized Oil reagent.
    Journal of vascular and interventional radiology : JVIR, 2011
    Co-Authors: Luke J. Higgins, Gloria L. Hwang, Jarrett Rosenberg, R.h. Katzenberg, Nishita Kothary, Daniel Y. Sze, Lawrence V. Hofmann
    Abstract:

    To demonstrate cellular selectivity toward hepatoma cells and compare the efficiency of gene delivery of a novel nonviral vector of iopamidol, protamine, and Ethiodized Oil reagents (VIPER). Rat hepatocellular carcinoma (HCC) cells were transfected in triplicate under varying conditions by using firefly luciferase as a reporter gene. Conditions included variations of a protamine:DNA (P:D) complex (20:1, 50:1, 100:1, 200:1 mass ratios), iopamidol (0%, 10%, 33%), and Ethiodized Oil (0%, 1%, 2%, 4%, 8%, and 16%). The conditions affording efficient gene transfer and ease of translation to in vivo studies were selected for cell line comparison (HCC cells vs hepatocytes). Adenoviral transduction was compared with nonviral vector transfection. At low concentrations, Ethiodized Oil increased transfection efficiency regardless of P:D mass ratio. However, high concentrations resulted in significant attenuation. Unexpectedly, the addition of iopamidol to P:D complexes markedly improved transfection efficiency. When using an optimal P:D, iopamidol, and Ethiodized Oil solution, DNA transfection of normal liver and tumor cells showed significant selectivity for tumor cells. In the context of hepatoma cells, transfection efficiency with the nonviral vector was better than 10(4) pfu adenovirus. The development and characterization of the VIPER system provides a possible alternative to viral gene therapy of HCC. Copyright © 2011 SIR. Published by Elsevier Inc. All rights reserved.

Melvin E. Clouse - One of the best experts on this subject based on the ideXlab platform.

  • Targeting of different Ethiodized Oil-doxorubicin mixtures to hypovascular hepatic metastases with intraarterial and intraportal injections.
    Journal of vascular and interventional radiology : JVIR, 1996
    Co-Authors: Osman Cay, Jonathan B. Kruskal, Peter Thomas, Melvin E. Clouse
    Abstract:

    Purpose The distribution of different Ethiodized Oil-doxorubicin mixtures within and around hypovascular liver metastases in athymic nude mice was compared following either intraarterial or intraportal injections. Materials and Methods Six different mixtures of doxorubicin and Ethiodized Oil in water-soluble contrast material, shaken for 5, 10,15, and 30 minutes, respectively, were prepared and the size of the Oil droplets in the mixtures evaluated. Intraarterial and intraportal injections of mixtures shaken for 10 and 15 minutes were performed in mice bearing hypovascular hepatic colorectal metastases. In vivo video microscopy was used to evaluate microvascular flow and the biodistribution and the size of the Oil droplets within and around the tumors. Results Oil droplets smaller than 20 μm in diameter were taken up by tumor nodules. There was no significant difference in Oil droplet accumulation within the tumor between intraarterial and intraportal injections. Oil droplets larger than 20 μm occluded small and medium portal branches. The optimum combination was 0.1 mL of Ethiodized Oil in 2 mL of diatrizoate sodium meglumine (Renografin-76) shaken for 15 minutes at 800 rpm, which formed droplets smaller than 20 μm (92%). Conclusion Avascular regions of hepatic metastases may be embolized with Ethiodized Oil–anticancer drug mixtures containing Oil droplets smaller than 20 μm. Since these droplets penetrate to the tumor interstitium with either intraarterial or intraportal injections, chemoembolization via the arterial route seems preferable for treatment of unresectable hypovascular hepatic metastases since it is easier to perform. The conclusions drawn from this study are limited to the animal model for experimental hypovascular hepatic metastases.

  • chemoembolization for hepatocellular carcinoma epinephrine followed by a doxorubicin Ethiodized Oil emulsion and gelatin sponge powder
    Journal of Vascular and Interventional Radiology, 1993
    Co-Authors: Melvin E. Clouse, Jonathan B. Kruskal, K R Stokes, Laura J. Perry, Keith Stuart, Imad Nasser
    Abstract:

    Purpose This study evaluates chemoembolization (CE) of the liver with minimal vasoconstriction followed by selective intraarterial delivery of an emulsion of iopamidol, doxorubicin, and Ethiodized Oil and temporary occlusion of hepatic artery with gelatin sponge powder in patients with hepatocellular carcinoma. Patients and Methods Since 1988, 30 patients with nonresectable hepatocellular carcinoma underwent CE with the above protocol. Intraarterial epinephrine (0.5–1 μg diluted in 10 mL of saline) was rapidly injected directly into the proper hepatic artery or selectively into the right or left hepatic arteries and was followed by 40–60 mg of doxorubicin dissolved in 10 mL of iopamidol and emulsified in 20 mL of Ethiodized Oil. The chemoembolic mixture was injected at the rate of arterial flow. Liver function and clotting parameters were monitored three times a day until there was a downward trend toward preembolic levels. Computed tomography (CT) was performed immediately after embolization and at 1–3-month intervals. Embolization was repeated when CT demonstrated recurrent or progressive disease. Results Disease recurred or progressed in 11 patients at 2–17 months after embolization. CE was repeated in four patients; one individual underwent three embolizations. Re-embolization was performed up to 14 months after initial embolization (median, 10 months). Five patients (16.7%) died within 1 month of embolization. Ten patients died at 3–33 months after CE. Two of these patients died of cirrhosis at 6 and 14 months, without evidence of recurrent tumor. Fifteen patients remain alive 5–28 months after CE. Kaplan-Meier estimation of probability of survival curves demonstrates a median survival of 14 months. Sixty-one percent of patients were alive at 1 year and 36% at 2 years after the procedure. Conclusion CE with use of the above technique is effective for palliating inoperable hepatocellular carcinoma. It causes a significant prolongation of survival over the expected 18–24 weeks in untreated patients; this may occur because high doses of chemotherapeutic agents are delivered and come in contact with the tumor for a longer period, followed by ischemia brought about by temporary arterial occlusion.

  • Chemoembolization for Hepatocellular Carcinoma: Epinephrine Followed by a Doxorubicin–Ethiodized Oil Emulsion and Gelatin Sponge Powder☆
    Journal of vascular and interventional radiology : JVIR, 1993
    Co-Authors: Melvin E. Clouse, Jonathan B. Kruskal, K R Stokes, Laura J. Perry, Keith Stuart, Imad Nasser
    Abstract:

    This study evaluates chemoembolization (CE) of the liver with minimal vasoconstriction followed by selective intraarterial delivery of an emulsion of iopamidol, doxorubicin, and Ethiodized Oil and temporary occlusion of hepatic artery with gelatin sponge powder in patients with hepatocellular carcinoma. Since 1988, 30 patients with nonresectable hepatocellular carcinoma underwent CE with the above protocol. Intraarterial epinephrine (0.5-1 microgram diluted in 10 mL of saline) was rapidly injected directly into the proper hepatic artery or selectively into the right or left hepatic arteries and was followed by 40-60 mg of doxorubicin dissolved in 10 mL of iopamidol and emulsified in 20 mL of Ethiodized Oil. The chemoembolic mixture was injected at the rate of arterial flow. Liver function and clotting parameters were monitored three times a day until there was a downward trend toward preembolic levels. Computed tomography (CT) was performed immediately after embolization and at 1-3-month intervals. Embolization was repeated when CT demonstrated recurrent or progressive disease. Disease recurred or progressed in 11 patients at 2-17 months after embolization. CE was repeated in four patients; one individual underwent three embolizations. Re-embolization was performed up to 14 months after initial embolization (median, 10 months). Five patients (16.7%) died within 1 month of embolization. Ten patients died at 3-33 months after CE. Two of these patients died of cirrhosis at 6 and 14 months, without evidence of recurrent tumor. Fifteen patients remain alive 5-28 months after CE. Kaplan-Meier estimation of probability of survival curves demonstrates a median survival of 14 months. Sixty-one percent of patients were alive at 1 year and 36% at 2 years after the procedure. CE with use of the above technique is effective for palliating inoperable hepatocellular carcinoma. It causes a significant prolongation of survival over the expected 18-24 weeks in untreated patients; this may occur because high doses of chemotherapeutic agents are delivered and come in contact with the tumor for a longer period, followed by ischemia brought about by temporary arterial occlusion.

  • In Vivo and in Vitro Analysis of the Effectiveness of Doxorubicin Combined with Temporary Arterial Occlusion in Liver Tumors
    Journal of vascular and interventional radiology : JVIR, 1993
    Co-Authors: Jonathan B. Kruskal, K R Stokes, Lynn Hlatky, Philip Hahnfeldt, Kenichi Teramoto, Melvin E. Clouse
    Abstract:

    Purpose The authors evaluated the effects of daunomycin (daunoru-bicin)—an analogue of doxorubicin—Ethiodized Oil, and arterial occlusion on an in vitro hepatoma analogue and on in vivo rat liver tumors. Materials and Methods A human Sk hepatoma cell monolayer sandwich system was used to determine uptake of 3 H-daunomycin under normoxic/hypoxic conditions with use of autoradiography. Fluorescence microscopy was used to evaluate the biodistribution of doxorubicin in cell cultures (human Sk hepatoma and colon carcinoma). Microvascular flow adjacent to and within liver tumors and the intrahepatic effects of doxorubicin and Ethiodized Oil were studied with in vivo video microscopy on exteriorized rat livers containing peripheral hepatomas. Results Increased uptake of 3 H-daunomycin by hepatoma cells occurred under hypoxic conditions. Intrahepatic arterial administration of Ethiodized Oil caused temporary occlusion of peripheral sinusoids following passage through arterioportal anastomoses. Tumors received portal venous and neovascular blood supply and Ethiodized Oil occluded but did not enter the narrow neovasculature perfusing the tumors. Conclusion Hypoxia increases uptake of 3 H-daunomycin by human Sk hepatoma and colon carcinoma cell cultures. Selective hepatic arterial occlusion (and perhaps the resultant hypoxia) may facilitate increased uptake of doxorubicin analogues into liver tumors. Hepatomas receive both arterial and portal venous blood supply, and Ethiodized Oil reaches the tumor via arterioportal anastomoses that perfuse the tumor periphery.

  • Hepatic Arterial Chemoembolization for Metastatic Endocrine Tumors
    Journal of vascular and interventional radiology : JVIR, 1993
    Co-Authors: K R Stokes, Keith Stuart, Melvin E. Clouse
    Abstract:

    In patients with hepatic metastases from endocrine tumors, the safety and effectiveness of chemoembolization with Ethiodized Oil was determined and compared with those of embolization with particulate matter alone. Twenty patients with hepatic islet cell or carcinoid tumor metastases were treated with selective hepatic artery injection of doxorubicin and iopamidol emulsified in Ethiodized Oil, followed by gelatin foam powder embolization. In 16 patients with hormonally active tumors, hormone secretion decreased 90% (range, 69%-98%) in 10 days, with relief of symptoms in all patients. Average tumor size decrease was 84%; average hospitalization was 8 days. Seventeen patients are alive 6-27 months after embolization, and all are asymptomatic. Three patients died within 1 year after embolization of progressive disease outside the liver. Chemoembolization with doxorubicin emulsified in Ethiodized Oil and iopamidol is effective in the treatment of hepatic metastases from endocrine tumors. This technique appears to result in less morbidity than particulate embolization alone.