BACKGROUND: Continuing research ex vivo and in vivo with animal models is performed to advance the oncological safety of radiofrequency ablation (RFA) of liver tumors. In these experiments, frequently imaging modalities (e.g. MRI or CT) or macro-morp

Purpose: Clinical data indicate that the drug density on drug-coated balloons (DCBs) might have a role on treatment effect and durability. The aim of the current study was to investigate inhibition of neointimal formation and potential adverse effects after treatment with a novel double-dose DCB in swine. Material and methods: A four-week study was performed in peripheral arteries of 12 domestic pigs after vessel injury and stent implantation. The novel double-dose DCB with 6-µg paclitaxel (Ptx)/mm² balloon surface (1 × 6) was compared to a standard DCB with 3.5 µg Ptx/mm² (3.5) and uncoated balloons (POBA). Potential adverse effects were stimulated by using three fully overlapping DCBs with 6 µg Ptx/mm² each (3 × 6). Quantitative angiography, histomorphometry and histopathological analyses were performed. Results: Higher paclitaxel doses per square millimeter of treated arteries were associated with reduced late lumen loss (LLL) in quantitative angiography 4 weeks after treatment (POBA: 0.91 ± 0.75 mm; 3.5: 0.45 ± 0.53 mm; 1 × 6: 0.21 ± 0.41 mm; 3 × 6: − 0.38 ± 0.65 mm). In histomorphometry, maximal neointimal thickness and neointimal area were the lowest for the 1 × 6 group (0.15 ± 0.06 mm/1.5 ± 0.4 mm²), followed by 3 × 6 (0.20 ± 0.07 mm/1.8 ± 0.4 mm²), 3.5 (0.22 ± 0.12 mm/2.2 ± 1.1 mm²) and POBA (0.30 ± 0.07 mm/3.2 ± 0.7 mm²). Downstream tissue showed histopathological changes in all groups including POBA, in larger number and different quality (e.g., edema, inflammation, vessel wall necrosis, vasculitis and perivasculitis) in the 3 × 6 group, which did not cause clinical or functional abnormalities throughout the study. Conclusion: Treatment with the double-dose DCB (6 µg Ptx/mm²) tended to increase inhibition of in-stent neointimal formation and to diminish LLL after peripheral intervention in the porcine model compared to a market-approved DCB with 3.5 µg Ptx/mm².

Background: Drug penetration into the deeper arterial wall of heavily calcified lesions is one of the limitations of drug-coated balloons and drug-eluting stents in vascular interventions. The Temporary Spur Stent (TSS) system is characterized by a self-expanding nitinol stent that is uniformly covered in radialspikes, which, when coated, should allow a deeper penetration and longer retention of the drug into the diseased artery walls by penetrating through the calcified plaques. Materials and Methods and Results: Uncoated TSS and paclitaxel (PTX)-coated TSS systems have been deployed in porcine peripheral arteries. Four weeks after the deployment of uncoated TSS systems, no adverse vascular remodeling or neointimal formation in the treated vessel segments were noticed. PTX-coated TSS systems transferred 9%±7% of the drug that was on the device to the targeted vessel area (196±163 ng PTX/mg arterial tissue) and the addition of the fluorescent dye Nile red to the coating showed that the spikes promote the transfer of the coating to the deeper layers of the vessel wall. The PTX-coated TSS systems showed a significant reduction in neointimal proliferation compared to the uncoated TSS systems: quantitative angiography showed a vessel diameter stenosis of 37.2%±11.0% and 16.4%±8.8% 4 weeks after the treatment with uncoated and PTX-coated TSS systems, respectively. Conclusion: The treatment with the TSS system was well tolerated and the spikesfacilitate the transfer of the coating into deeper layers of the vessel wall. Moreover, the PTX-coated TSS systems effectively inhibit neointimal proliferation.

Background: Drug coated balloons (DCB) with paclitaxel (Ptx) dose of 2–3.5 μg/mm² balloon surface inhibit restenosis with different effectiveness and duration of success. A clinical dose finding study is not known for any of the currently marketed products. The aim of the present preclinical trial was to investigate a novel DCB coated with 6 μg Ptx/mm² in a porcine model. Methods and results: The current study investigated a DCB with a novel, modified iopromide based matrix with 6 μg Ptx/mm². Drug transfer to the vessel wall of peripheral arteries was compared with a dose of 3 μg Ptx/mm² and two fully overlapping DCB with 3 μg Ptx/mm², each. Ptx concentration in the vessel wall after drug transfer was about twice as high for balloons with 6 μg/mm² (1957±1472 μg/g) and two overlapping DCB with 3 μg Ptx/mm², each (1287±619 μg/g) compared to a single balloon with 3 μg Ptx/mm², (787±738 μg/g), with statistical significant differences for 1x6 μg/mm² vs. 1x3 μg/mm² (p = 0.017) but not for 2x3 μg/mm² vs. 1x3 μg/mm² (p = 0.184) and 1x6 μg/mm² vs. 2x3 μg/mm² (p = 0.178). The proportion of residual Ptx on balloon after treatment was similar for all groups between 6±1% and 10±3% of dose on balloon. Conclusion: The dose of 6 μg Ptx/mm² was successfully as well as reproducibly coated on conventional balloon catheters. Increased Ptx on balloons resulted in increased drug concentration in the vessel wall. A single balloon with 6 μg Ptx/mm² seems to provide double dose compared to 3 μg Ptx/mm², facilitates the procedure, and may reduce medico-economic cost compared to the use of two standard DCB.

Thermal ablation offers a minimally invasive alternative in the treatment of hepatic tumours. Several types of ablation are utilised with different methods and indications. However, to this day, ablation size remains limited due to the formation of a central non-conductive boundary layer. In thermal ablation, this boundary layer is formed by carbonisation. Our goal was to prevent or delay carbonisation, and subsequently increase ablation size. We used bovine liver to compare ablation diameter and volume, created by a stand-alone laser applicator, with those created when utilising a spacer between laser applicator and hepatic tissue. Two spacer variants were developed: one with a closed circulation of cooling fluid and one with an open circulation into hepatic tissue. We found that the presence of a spacer significantly increased ablation volume up to 75.3 cm³, an increase of a factor of 3.19 (closed spacer) and 3.02 (open spacer) when compared to the stand-alone applicator. Statistical significance between spacer variants was also present, with the closed spacer producing a significantly larger ablation volume (p < 0.001, M_Diff = 3.053, 95% CI[1.612, 4.493]) and diameter (p < 0.001, M_Diff = 4.467, 95% CI[2.648, 6.285]) than the open spacer. We conclude that the presence of a spacer has the potential to increase ablation size.