Imaging and Pathologic Evaluation of Cryoablation of Woodchuck (Marmota monax) Hepatocellular Carcinoma

We characterized cryoablation as a mode of clinical intervention in adult woodchucks with hepatocellular carcinoma (HCC). Woodchucks (n = 4) were infected with woodchuck hepatitis virus at birth and developed LI-RADS-5 hypervascular HCC. At 21 mo of age, they underwent ultrasound (US), contrast-enhanced CT (CECT) imaging, and US-guided subtotal cryoablation (IcePearl 2.1 CX, Galil, BTG) of their largest tumor (Mean HCC volume of 49 +/- 9 cm(3)). Cryoablation was performed using two 10-min freeze cycles, each followed by an 8-min thaw cycle. The first woodchuck developed significant hemorrhage after the procedure and was euthanized. In the other 3 woodchucks, the probe track was cauterized and all 3 completed the study. Fourteen days after ablation, CECT was performed, and woodchucks were euthanized. Explanted tumors were sectioned using subject-specific, 3D-printed cutting molds. Initial tumor volume, the size of the cryoablation ice ball, gross pathology and hematoxylin and eosin-stained tissue sections were evaluated. On US, the edges of the solid ice balls were echogenic with dense acoustic shadowing and average dimensions of 3.1 +/- 0.5 x 2.1 +/- 0.4 cm and cross-sectional area of 4.7 +/- 1.0 cm(2). On day 14 after cryoablation, CECT of the 3 woodchucks showed devascularized hypo-attenuating cryolesions with dimensions of 2.8 +/- 0.3 x 2.6 +/- 0.4 x 2.93 +/- 0.7 cm and a cross-sectional area of 5.8 +/- 1.2 cm(2). Histopathologic evaluation showed hemorrhagic necrosis with a central amorphous region of coagulative necrosis surrounded by a rim of karyorrhectic debris. A rim of approximately 2.5 mm of coagulative necrosis and fibrous connective tissue clearly demarcated the cryolesion from adjacent HCC. Partial cryoablation of tumors produced coagulative necrosis with well-defined ablation margins at 14 d. Cauterization appeared to prevent hemorrhage after cryoablation of hypervascular tumors. Our findings indicate that woodchucks with HCC may provide a predictive preclinical model for investigating ablative modalities and developing new combination therapies.

Automated summary

In this study, cryoablation was characterized as a clinical intervention mode for adult woodchucks with hepatocellular carcinoma (HCC). The results showed that cryoablation was effective in causing necrosis and removing tumors in woodchucks with HCC.