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The Accumulation and Effects of Liposomal Doxorubicin in Tissues Treated by Radiofrequency Ablation and Irreversible Electroporation in Liver: In Vivo Experimental Study on Porcine Models

  • Tomáš Andrašina
  • Josef Jaroš
  • Tomáš JůzaEmail author
  • Tomáš Rohan
  • Dalibor Červinka
  • Michal Crha
  • Vlastimil Válek
  • Nahum S. Goldberg
Laboratory Investigation

Abstract

Purpose

To compare the accumulation and effect of liposomal doxorubicin in liver tissue treated by radiofrequency ablation (RFA) and irreversible electroporation (IRE) in in vivo porcine models.

Materials and Methods

Sixteen RFA and 16 IRE procedures were performed in healthy liver of two groups of three pigs. Multi-tined RFA parameters included: 100 W, target temperature 105°C for 7 min. 100 IRE pulses were delivered using two monopolar electrodes at 2250 V, 1 Hz, for 100 µsec. For each group, two pigs received 50 mg liposomal doxorubicin (0.5 mg/kg) as a drip infusion during ablation procedure, with one pig serving as control. Samples were harvested from the central and peripheral zones of the ablation at 24 and 72 h. Immunohistochemical analysis to evaluate the degree of cellular stress, DNA damage, and degree of apoptosis was performed. These and the ablation sizes were compared. Doxorubicin concentrations were also analyzed using fluorescence photometry of homogenized tissue.

Results

RFA treatment zones created with concomitant administration of doxorubicin at 24 h were significantly larger than controls (2.5 ± 0.3 cm vs. 2.2 ± 0.2 cm; p = 0.04). By contrast, IRE treatment zones were negatively influenced by chemotherapy (2.2 ± 0.4 cm vs. 2.6 ± 0.4 cm; p = 0.05). At 24 h, doxorubicin concentrations in peripheral and central zones of RFA were significantly increased in comparison with untreated parenchyma (0.431 ± 0.078 µg/g and 0.314 ± 0.055 µg/g vs. 0.18 ± 0.012 µg/g; p < 0.05). Doxorubicin concentrations in IRE zones were not significantly different from untreated liver (0.191 ± 0.049 µg/g and 0.210 ± 0.049 µg/g vs. 0.18 ± 0.012 µg/g).

Conclusions

Whereas there is an increased accumulation of periprocedural doxorubicin and an associated increase in ablation zone following RFA, a contrary effect is noted with IRE. These discrepant findings suggest that different mechanisms and synergies will need to be considered in order to select optimal adjuvants for different classes of ablation devices.

Keywords

Liposomal doxorubicin Radiofrequency ablation Irreversible electroporation 

Notes

Acknowledgments

This study was supported by Ministry of Health of the Czech Republic, Grant No. 15-32484a, and supported by funds from the Faculty of Medicine MU to junior researcher Tomáš Andrašina.

Compliance with Ethical Standards

Conflict of interest

Author Nahum S. Goldberg is a consultant to Angiodynamics, Inc. and Cosman Medical Inc.

Ethical Approval

All applicable international, national, and institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

Informed Consent

For this type of study, informed consent is not required.

Consent for Publication

For this type of study, consent for publication is not required.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2019

Authors and Affiliations

  • Tomáš Andrašina
    • 1
  • Josef Jaroš
    • 2
  • Tomáš Jůza
    • 1
    Email author
  • Tomáš Rohan
    • 1
  • Dalibor Červinka
    • 3
  • Michal Crha
    • 4
  • Vlastimil Válek
    • 1
  • Nahum S. Goldberg
    • 5
  1. 1.Faculty of Medicine, Department of Radiology and Nuclear MedicineUniversity Hospital Brno and Masaryk UniversityBrnoCzech Republic
  2. 2.Faculty of Medicine, Department of Histology and EmbryologyMasaryk UniversityBrnoCzech Republic
  3. 3.Faculty of Electrical Engineering and Communication, Department of Power Electrical and Electronic EngineeringBrno University of TechnologyBrnoCzech Republic
  4. 4.Faculty of Veterinary Medicine, Department of Surgery and Orthopedics, Small Animal ClinicUniversity of Veterinary and Pharmaceutical Sciences BrnoBrnoCzech Republic
  5. 5.Hadassah Hebrew University Medical CenterJerusalemIsrael

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