Andrašina Tomáš, Jaroš Josef, Jůza Tomáš, Rohan Tomáš, Červinka Dalibor, Crha Michal, Válek Vlastimil, Goldberg Nahum S
Faculty of Medicine, Department of Radiology and Nuclear Medicine, University Hospital Brno and Masaryk University, Brno, Czech Republic.
Faculty of Medicine, Department of Histology and Embryology, Masaryk University, Brno, Czech Republic.
Cardiovasc Intervent Radiol. 2019 May;42(5):751-762. doi: 10.1007/s00270-019-02175-z. Epub 2019 Feb 13.
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.
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.
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).
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.
在体内猪模型中比较脂质体阿霉素在经射频消融（RFA）和不可逆电穿孔（IRE）治疗的肝组织中的蓄积情况及效果。
在两组各三头猪的健康肝脏上分别进行16次RFA和16次IRE手术。多针RFA参数包括：100瓦，目标温度105°C，持续7分钟。使用两个单极电极以2250伏、1赫兹、100微秒的参数施加100次IRE脉冲。每组中，两只猪在消融过程中接受50毫克脂质体阿霉素（0.5毫克/千克）静脉滴注，一只猪作为对照。在24小时和72小时从消融的中央和周边区域采集样本。进行免疫组织化学分析以评估细胞应激程度、DNA损伤程度和凋亡程度。将这些结果与消融大小进行比较。还使用匀浆组织的荧光光度法分析阿霉素浓度。
在24小时时，同时给予阿霉素的RFA治疗区域明显大于对照组（2.5±0.3厘米对2.2±0.2厘米；p = 0.04）。相比之下，IRE治疗区域受到化疗的负面影响（2.2±0.4厘米对2.6±0.4厘米；p = 0.05）。在24小时时，与未处理的实质组织相比，RFA周边和中央区域的阿霉素浓度显著增加（0.431±0.078微克/克和0.
