Understanding factors governing distribution volume of ethyl cellulose-ethanol to optimize ablative therapy in the liver

OBJECTIVE: Ethanol ablation, the injection of ethanol to induce necrosis, was originally used to treat hepatocellular carcinoma, with survival rates comparable to surgery. However, efficacy has been 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 in tissue. METHODS: 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. RESULTS: While leakage was higher for ethanol and 3%EC-ethanol at a rate of 10 mL/hr compared to 1 mL/hr, the non-depot volume did not increase for 6%EC-ethanol. 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 10 mL/hr, a volume of 50 muL remained below the critical pressure. CONCLUSIONS: 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. SIGNIFICANCE: These results, and the experimental framework developed to obtain them, can inform optimizing EC-ethanol to treat a range of medical conditions.