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.

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.

[PERCUTANEOUS TREATMENT OF SMALL RENAL TUMORS BY THERMAL ABLATION].

INTRODUCTION: Kidney cancer accounts for approximately 2-3 % of all types of cancers. Renal tumors prevalence and especially the prevalence of small renal tumors, is on the rise. About half of the tumors currently diagnosed are smaller than 4 cm. Minimally invasive methods of radiofrequency ablation technology were recently developed for the treatment of small renal tumors and are characterized by reducing the surgical and anesthetic risk. The ablation is performed with a percutaneous approach guided by ultrasound, CT or MRI. We reviewed the results of this treatment. METHODS: A total of 75 patients with a mean age of 69.5 years (27 - 90) were treated using RF during the period 2007-2014. The average tumor diameter was 28.4 mm (11-58 mm); 40 tumors were exophytic and 30 were central. Monitoring protocol after treatment included imaging after 1, 3, 6, 12 months subsequent to treatment and later annually; median follow-up time was 21 months (1 - 97). RESULTS: Evidence of tumor recurrence was observed in 9 patients (11.4%); 8 were treated successfully by another RF session. Cases in which recurrence was observed were characterized by a tumor larger than 30 mm (5/9) and adjacent to renal cysts (3/9); 5 of the lesions were central (endophytic) (P=0.5). One patient died due to metastatic RCC and a metastatic disease developed in two additional patients who died of other causes. CONCLUSIONS: It is possible to destroy most of the small renal tumors by RF ablation. When the tumor size is up to 30 mm, a 94% long-term cure may be reached. In the event of renewed growth of the tumor, the treatment can be repeated with good results. In light of short-term experience, it is recommended to limit this treatment to older patients, with a short life expectancy or when anesthetic risks prohibit surgery.