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Efficacy and safety of hepatic arterial embolization compared to portal vein embolization for the preoperative induction of liver hypertrophy: results of animal experiments in swine
JVIR
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Scientific Session
Monday
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S73
Radiology, University Medical Center HamburgEppendorf, Hamburg, Germany; 2Department of General, Visceral-, Thoracic-, Transplantation- and Pediatric Surgery, University Medical Center Schleswig-Holstein, Kiel, Germany; 3Surgical Centre Schleswig-Holstein, Neumuenster, Germany; 4Institute for Hematopathology Hamburg, Hamburg, Germany; 5Münster University Hospital, Münster, Germany
4:33 PM
Purpose: Segmental hepatic arterial embolization has been proposed as an alternative to portal vein embolization to induce segmental hypertrophy of a future liver remnant after major resection. The purpose was to compare efficacy and safety of both techniques in a mini-pig model. Materials and Methods: A total of 29 mini-pigs were either subject to hepatic arterial embolization (AE-group, n¼12), portal vein embolization (PVE-group, n¼11), or a sham operation (SO-group, n¼6). In the AE-group 75% of the hepatic arterial flow was excluded by NBCA-embolization. In the PVE-group 75% of the portal vein were embolized in similar technique. Sham operation included laparotomy with mobilization of the liver and preparation of the duodenal ligament. The animals were sacrificed after 4 weeks. Analyzed data were growth and atrophy of the liver lobes, laboratory data, arteriography and portography controls after 4 weeks, and histopathology. Results: In the PVE-group 2 animals were excluded due to technical problems. In the AE-group 4 animals were excluded after technical problems and an earlier sacrificed related to post-interventional complications. The PVE-group demonstrated a significant increase of the liver-to-body weight index in the non-embolized lobe compared to the AE- and SO-group (po0.05). Portography 28 days after PVE days showed slow refilling of the portal branches by collateral vessels; arteriography follow-up in the AE-group showed a only slight recanalization by neocollaterals. However, after extended arterial embolization necrotic and inflammatory alterations as well as abscess formations of the liver and bile duct parenchyma were observed. Conclusion: Portal vein embolization is a safe and effective technique to induce segmental hypertrophy. In comparison, arterial embolization showed no significant hypertrophy of the non-embolized liver lobe, resulted in extended necrotic inflammatory damage of the liver in several cases and should not be the favored technique for embolization to induce segmental hypertrophy.
Abstract No. 153
Cell killing efficacy of combined electroporation and drug delivery of NVP-BEZ235 Y. Qiao1, J. Zhao2, P. Lee3,1, J. Jody Vykoukal4, M.J. Wallace1, C. Li2, S. Gupta1, M.P. Melancon1; 1 Interventional Radiology, University of Texas M.D. Anderson Cancer Center, Houston, TX; 2Cancer Systems Imaging, University of Texas M.D. Anderson Cancer Center, Houston, TX; 3SUNY Upstate Medical University, Syracuse, NY; 4Translational Molecular Pathology, University of Texas M.D. Anderson Cancer Center, Houston, TX Purpose: To test the effectiveness of electroporation in enhancing the drug delivery of a novel PI3K/mTOR inhibitor, NVP-BEZ235, for increased cell killing in vitro. Materials and Methods: The half maximal inhibitory concentration (IC50) of NVP-BEZ235 (Novartis Pharma AG) was tested against various cell lines (U87, HN5, HEK293, MiaPaca2-Luc-GFP, Hep3B, and N1S1). When the IC50 values were determined, this concentration was used in combination with electroporation (EP) using ECM 830 (BTX Harvard Apparatus) at varying field strengths. Furthermore, the effect of time at which the drug was added in relation to cell viability was also investigated. Standard MTS Assay (Promega) was used to determine the cell viability. Results: The IC50 values of cell lines treated with NVP-BEZ235 ranged from 16.91 nM to 112.8 nM, with HEK293 and Hep3B as the lowest and highest values, respectively. Optimization of EP parameters showed that at 1000 V/cm, more than 50% cell death occurred with Panc1 and HepG2, but a higher power of 1600 V/cm is needed for Hep3B and MiaPaca2-Luc-GFP. EP with drug delivery for Hep3B resulted in a significant decrease in cell viability (10.25 ⫾ 0.01) as compared to either EP (18.65 ⫾ 0.03) or NVP-BEZ235 (33.86 ⫾ 0.01) alone with p-values o0.01. The combination therapy is especially effective when NVP-BEZ235 is administered immediately after (3.71⫾ 0.01) or 1.5 minutes before (4.08 ⫾ 0.02) electroporation. Conclusion: Enhancement of drug uptake through electroporation is a key mechanism for increased cell death, which may benefit electrochemotherapy and numerous applications that employ electroporation for cell permeabilization.
4:42 PM
Abstract No. 154
Efficacy and safety of hepatic arterial embolization compared to portal vein embolization for the preoperative induction of liver hypertrophy: results of animal experiments in swine A. Koops1, N. Heits2, L. Müller3, S. Koops4, J. Herrmann1, G. Adam1, C. Wilms5; 1Diagnostic and Interventional
4:51 PM
Abstract No. 155
Photoacoustic ultrasound-guided real-time imaging of thermochemical ablation in ex vivo porcine liver L. Shea1, K.L. Dextraze2, T. Mitchham2, J. Gray2, R. Bouchard2, E. Cressman2; 1University of Illinois College of Medicine, Champaign, IL; 2MD Anderson Cancer Center, Houston, TX Purpose: (1) Assess feasibility of using photoacoustic ultrasound-guided imaging as method for monitoring thermochemical ablation; (2) Observe thermochemical ablation in real time to gain insight as to mechanism of action
MONDAY: Scientific Sessions
the delivery of M-Dox into cell nuclei, as compared to electroporation or M-Dox alone. Conclusion: Electroporation enhanced intracellular delivery of M-Dox in hepatocellular xenograft model. Such enhanced delivery could be utilized to improve the anti-tumor effect of irreversible electroporation.
’
Scientific Session
Monday
’
S73
Radiology, University Medical Center HamburgEppendorf, Hamburg, Germany; 2Department of General, Visceral-, Thoracic-, Transplantation- and Pediatric Surgery, University Medical Center Schleswig-Holstein, Kiel, Germany; 3Surgical Centre Schleswig-Holstein, Neumuenster, Germany; 4Institute for Hematopathology Hamburg, Hamburg, Germany; 5Münster University Hospital, Münster, Germany
4:33 PM
Purpose: Segmental hepatic arterial embolization has been proposed as an alternative to portal vein embolization to induce segmental hypertrophy of a future liver remnant after major resection. The purpose was to compare efficacy and safety of both techniques in a mini-pig model. Materials and Methods: A total of 29 mini-pigs were either subject to hepatic arterial embolization (AE-group, n¼12), portal vein embolization (PVE-group, n¼11), or a sham operation (SO-group, n¼6). In the AE-group 75% of the hepatic arterial flow was excluded by NBCA-embolization. In the PVE-group 75% of the portal vein were embolized in similar technique. Sham operation included laparotomy with mobilization of the liver and preparation of the duodenal ligament. The animals were sacrificed after 4 weeks. Analyzed data were growth and atrophy of the liver lobes, laboratory data, arteriography and portography controls after 4 weeks, and histopathology. Results: In the PVE-group 2 animals were excluded due to technical problems. In the AE-group 4 animals were excluded after technical problems and an earlier sacrificed related to post-interventional complications. The PVE-group demonstrated a significant increase of the liver-to-body weight index in the non-embolized lobe compared to the AE- and SO-group (po0.05). Portography 28 days after PVE days showed slow refilling of the portal branches by collateral vessels; arteriography follow-up in the AE-group showed a only slight recanalization by neocollaterals. However, after extended arterial embolization necrotic and inflammatory alterations as well as abscess formations of the liver and bile duct parenchyma were observed. Conclusion: Portal vein embolization is a safe and effective technique to induce segmental hypertrophy. In comparison, arterial embolization showed no significant hypertrophy of the non-embolized liver lobe, resulted in extended necrotic inflammatory damage of the liver in several cases and should not be the favored technique for embolization to induce segmental hypertrophy.
Abstract No. 153
Cell killing efficacy of combined electroporation and drug delivery of NVP-BEZ235 Y. Qiao1, J. Zhao2, P. Lee3,1, J. Jody Vykoukal4, M.J. Wallace1, C. Li2, S. Gupta1, M.P. Melancon1; 1 Interventional Radiology, University of Texas M.D. Anderson Cancer Center, Houston, TX; 2Cancer Systems Imaging, University of Texas M.D. Anderson Cancer Center, Houston, TX; 3SUNY Upstate Medical University, Syracuse, NY; 4Translational Molecular Pathology, University of Texas M.D. Anderson Cancer Center, Houston, TX Purpose: To test the effectiveness of electroporation in enhancing the drug delivery of a novel PI3K/mTOR inhibitor, NVP-BEZ235, for increased cell killing in vitro. Materials and Methods: The half maximal inhibitory concentration (IC50) of NVP-BEZ235 (Novartis Pharma AG) was tested against various cell lines (U87, HN5, HEK293, MiaPaca2-Luc-GFP, Hep3B, and N1S1). When the IC50 values were determined, this concentration was used in combination with electroporation (EP) using ECM 830 (BTX Harvard Apparatus) at varying field strengths. Furthermore, the effect of time at which the drug was added in relation to cell viability was also investigated. Standard MTS Assay (Promega) was used to determine the cell viability. Results: The IC50 values of cell lines treated with NVP-BEZ235 ranged from 16.91 nM to 112.8 nM, with HEK293 and Hep3B as the lowest and highest values, respectively. Optimization of EP parameters showed that at 1000 V/cm, more than 50% cell death occurred with Panc1 and HepG2, but a higher power of 1600 V/cm is needed for Hep3B and MiaPaca2-Luc-GFP. EP with drug delivery for Hep3B resulted in a significant decrease in cell viability (10.25 ⫾ 0.01) as compared to either EP (18.65 ⫾ 0.03) or NVP-BEZ235 (33.86 ⫾ 0.01) alone with p-values o0.01. The combination therapy is especially effective when NVP-BEZ235 is administered immediately after (3.71⫾ 0.01) or 1.5 minutes before (4.08 ⫾ 0.02) electroporation. Conclusion: Enhancement of drug uptake through electroporation is a key mechanism for increased cell death, which may benefit electrochemotherapy and numerous applications that employ electroporation for cell permeabilization.
4:42 PM
Abstract No. 154
Efficacy and safety of hepatic arterial embolization compared to portal vein embolization for the preoperative induction of liver hypertrophy: results of animal experiments in swine A. Koops1, N. Heits2, L. Müller3, S. Koops4, J. Herrmann1, G. Adam1, C. Wilms5; 1Diagnostic and Interventional
4:51 PM
Abstract No. 155
Photoacoustic ultrasound-guided real-time imaging of thermochemical ablation in ex vivo porcine liver L. Shea1, K.L. Dextraze2, T. Mitchham2, J. Gray2, R. Bouchard2, E. Cressman2; 1University of Illinois College of Medicine, Champaign, IL; 2MD Anderson Cancer Center, Houston, TX Purpose: (1) Assess feasibility of using photoacoustic ultrasound-guided imaging as method for monitoring thermochemical ablation; (2) Observe thermochemical ablation in real time to gain insight as to mechanism of action
MONDAY: Scientific Sessions
the delivery of M-Dox into cell nuclei, as compared to electroporation or M-Dox alone. Conclusion: Electroporation enhanced intracellular delivery of M-Dox in hepatocellular xenograft model. Such enhanced delivery could be utilized to improve the anti-tumor effect of irreversible electroporation.