ethyl-cellulose and Liver-Neoplasms

Ethanol provides a rapid, low-cost ablative solution for liver tumors with a small technological footprint but suffers from uncontrolled diffusion in target tissue, limiting treatment precision and accuracy. Incorporating the gel-forming polymer ethyl cellulose to ethanol localizes the distribution. The purpose of this study was to establish a non-invasive methodology based on CT imaging to quantitatively determine the relationship between the delivery parameters of the EC-ethanol formulation, its distribution, and the corresponding necrotic volume. The relationship of radiodensity to ethanol concentration was characterized with water-ethanol surrogates. Ex vivo EC-ethanol ablations were performed to optimize the formulation (n = 6). In vivo ablations were performed to compare the optimal EC-ethanol formulation to pure ethanol (n = 6). Ablations were monitored with CT and ethanol distribution volume was quantified. Livers were removed, sectioned and stained with NADH-diaphorase to determine the ablative extent, and a detailed time-course histological study was performed to assess the wound healing process. CT imaging of ethanol-water surrogates demonstrated the ethanol concentration-radiodensity relationship is approximately linear. A concentration of 12% EC in ethanol created the largest distribution volume, more than eight-fold that of pure ethanol, ex vivo. In vivo, 12% EC-ethanol was superior to pure ethanol, yielding a distribution volume three-fold greater and an ablation zone six-fold greater than pure ethanol. Finally, a time course histological evaluation of the liver post-ablation with 12% EC-ethanol and pure ethanol revealed that while both induce coagulative necrosis and similar tissue responses at 1-4 weeks post-ablation, 12% EC-ethanol yielded a larger ablation zone. The current study demonstrates the suitability of CT imaging to determine distribution volume and concentration of ethanol in tissue. The distribution volume of EC-ethanol is nearly equivalent to the resultant necrotic volume and increases distribution and necrosis compared to pure ethanol.

Topics: Animals; Catheter Ablation; Cellulose; Ethanol; Female; Liver; Liver Neoplasms; Male; Models, Animal; Necrosis; Rats; Rats, Inbred F344

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 10 mL/hr compared to 1 mL/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 10 mL/hr, a volume of 50 μL 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.

Topics: Animals; Carcinoma, Hepatocellular; Catheter Ablation; Cellulose; Ethanol; Liver Neoplasms; Swine

Anti-tumor activity of cisplatin-capsulated microspheres with ethylcellulose (CDDPmc) was studied in Wistar rat bearing transplantable hepatocellular cancer. Seven days after inoculation into the rat's liver, normal saline, conventional cisplatin, placebo ethylcellulose microsphere and CDDPmc at comparable doses were infused into the proper hepatic artery. The results indicated that the rats treated with CDDPmc had a significantly slower tumor growth, more extensive tumor necrosis and longer survival as compared with the three other groups. It is suggested that the tumoricidal effect of arterial chemoembolization with CDDPmc be superior to arterial chemotherapy or embolization alone in the treatment of liver cancer.

Topics: Animals; Carcinoma, Hepatocellular; Cellulose; Cisplatin; Embolization, Therapeutic; Infusions, Intra-Arterial; Liver Neoplasms; Male; Microspheres; Neoplasm Transplantation; Rats; Rats, Inbred Strains; Tumor Cells, Cultured