The Accumulation and Effects of Liposomal Doxorubicin in Tissues Treated by Radiofrequency Ablation and Irreversible Electroporation in Liver: In Vivo ... View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-02-13

AUTHORS

Tomáš Andrašina, Josef Jaroš, Tomáš Jůza, Tomáš Rohan, Dalibor Červinka, Michal Crha, Vlastimil Válek, Nahum S. Goldberg

ABSTRACT

PurposeTo 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 MethodsSixteen 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.ResultsRFA 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).ConclusionsWhereas 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. More... »

PAGES

751-762

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00270-019-02175-z

DOI

http://dx.doi.org/10.1007/s00270-019-02175-z

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1112097570

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30761413


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89 materials
90 mechanism
91 min. 100 IRE pulses
92 model
93 monopolar electrodes
94 optimal adjuvants
95 order
96 parameters
97 parenchyma
98 peripheral zone
99 periprocedural doxorubicin
100 photometry
101 pigs
102 porcine model
103 procedure
104 pulses
105 radiofrequency ablation
106 samples
107 size
108 stress
109 study
110 synergy
111 temperature 105
112 tissue
113 treatment zone
114 untreated liver
115 untreated parenchyma
116 vivo experimental studies
117 vivo porcine model
118 zone
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