Abstract
Ethanol ablation, the injection of ethanol to induce necrosis, was originally used to treat hepatocellular carcinoma, with survival rates comparable to surgery. However, efficacy is limited due to leakage into surrounding tissue. To reduce leakage, we previously reported incorporating ethyl cellulose (EC) with ethanol as this mixture forms a gel when injected into tissue. To further develop EC-ethanol injection as an ablative therapy, the present study evaluates the extent to which salient injection parameters govern the injected fluid distribution. Utilizing ex vivo swine liver, injection parameters (infusion rate, EC%, infusion volume) were examined with fluorescein added to each solution. After injection, tissue samples were frozen, sectioned, and imaged. While leakage was higher for ethanol and 3%EC-ethanol at a rate of 10mL/hr compared to 1mL/hr, leakage remained low for 6%EC-ethanol regardless of infusion rate. The impact of infusion volume and pressure were also investigated first in tissue-mimicking surrogates and then in tissue. Results indicated that there is a critical infusion pressure beyond which crack formation occurs leading to fluid leakage. At a rate of 10mL/hr, a volume of 50μL remained below the critical pressure. Although increasing the infusion rate increases stress on the tissue and the risk of crack formation, injections of 6%EC-ethanol were localized regardless of infusion rate. To further limit leakage, multiple low-volume infusions may be employed. These results, and the experimental framework developed to obtain them, can inform optimizing EC-ethanol to treat a range of medical conditions.
Highlights
A BLATION–MINIMALLY-INVASIVE destruction of diseased tissue without removal from the body [1]–has the potential to be an effective treatment for many medical conditions and could be an effective adjunct or alternative to surgery
The addition of ethyl cellulose (EC) increased the localization of an injected ethanol solution into ex vivo swine liver tissue
At the fluid infusion rates investigated here, the formation of cracks within the tissue could lead to substantial fluid leakage away from the injection site; EC formed a gel that may have occluded these cracks and reduced fluid leakage
Summary
A BLATION–MINIMALLY-INVASIVE destruction of diseased tissue without removal from the body [1]–has the potential to be an effective treatment for many medical conditions and could be an effective adjunct or alternative to surgery. Ethanol ablation is the direct injection of pure ethanol into tissue to induce cell death. Ethanol ablation was originally used in the treatment of inoperable hepatocellular carcinoma, with 5-year survival rates comparable to surgical resection [8]. Ethanol ablation involves injection of a high volume (often equal to or greater than the tumor volume) of pure ethanol at a high infusion rate (≥100 mL/hr) [8], [13]. That rate can cause fracturing of the tissue and lead to ethanol leakage out of the target region, incomplete distribution within the tumor, and damage to surrounding tissue. Fluid leakage during ethanol ablation of hepatocellular carcinomas is well-documented, which results in vascular and bile duct injuries [14], coagulation necrosis outside of the target region of interest [15], and incomplete tumor coverage [6]
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