Radiofrequency ablation: effect of tumor- and organ-specific pharmacologic modulation of arterial and portal venous blood flow on coagulation diameter in an N1-S1 tumor model

Abstract

Purpose: To investigate inherent differences in vasculature of tumors versus normal parenchyma and efficacy of radiofrequency (RF) ablation with glucagon, adenosine, and a combination of the two compared with normal saline solution (NS) controls in an N1-S1 tumor model implanted in Sprague-Dawley rat livers.

Materials and methods: A total of 17 tumors were established in the left lobes of rats. Tumor perfusion relative to surrounding liver parenchyma was evaluated with contrast-enhanced ultrasound with intermittent-bolus technique before and after administration of glucagon, adenosine, a combination of the two, or NS. Tumors were ablated with a 22-gauge RF probe with 1 cm of exposed tip at 80 °C for 2 min. Tumor size, zone of necrosis, and viable tumor were measured in tumors after 2,3,5-triphenyltetrazolium chloride staining. Results were compared with degree of tumor perfusion.

Results: The normalized tumor perfusion ratio did not significantly change with administration of NS (1.38% ± 3.93). Vasomodulation resulted in significant decreases in normalized tumor perfusion ratio: 66.22% ± 24.57 (P < .01) with glucagon, 71.45% ± 22.72 (P < .01) with adenosine, and 74.98% ± 16.58 (P < .01) with glucagon plus adenosine. After tumor ablation, there was an increase in size of the ablated area by 100%-165% in the three treatment groups compared with NS controls. Differences among treatment groups were not statistically significant.

Conclusions: Tumor blood flow may be significantly altered by using systemic injection of appropriate medications. This tumor- and organ-specific approach to tumor vasomodulation may be used to enhance current therapeutic options.

Figure 1

Representative method of assessing relative tumor perfusion prior to (above) and following Adenosine + Glucagon (AD+GN) (below). Circle 1 within tumor and cicle 2 within normal liver. Graphs show decrease in ratio of A β in tumor versus A β in liver reflecting relative tumor hypoperfusion following vasomodulation with AD+GN.

Figure 2

Post-ablation Tumors stained with 2% TTC. Dash line reflects border of ablated tumor. Solid line indicates border of viable tumor. NS = normal saline. AD = adenosine. GN = glucagon.

Figure 3

Graph simultaneously comparing vasomodulation agents and normal saline (NS) control compared with area of ablation (cm²) (left y-axis) and change in relative tumor perfusion ratio (%) (right y-axis). AD = adenosine. GN = glucagon.