Intrahepatic Transneedle Inoculation of VX2 Particles for Obtaining a Solitary Hepatic Tumor in an Animal Model

Cho, Jin Han; Choi, Jong Cheol; Shin, Tae Beom; Park, Byeong Ho

Abstract

PURPOSE
The purpose of this study was to develop a large animal (rabbit) model which has a proper solitary intrahepatic tumor with lower leakage rates through less traumatic methods. Consequently, we evaluated tumor progression following the intrahepatic inoculation of VX2 cells into New Zealand white rabbits to acquire baseline data on the progression of a VX2 tumor.
MATERIALS AND METHODS
Twenty New Zealand white rabbits, each weighting 2.5-3 kg, were selected for this study. A 1 mm3 VX2 tumor fragment was created and then minced to enable the particles to pass through a 21 G needle mounting in a tuberculin syringe with 0.1 ml of normal saline. The minced VX2 tumor particles were injected into the subcapsular parenchyma of the left hepatic lobe. A 21 G needle was used to avoid penetrating large hepatic vessels. In order to prevent hemorrhage or leakage of the VX2 tumor cells through the injection route, a purse-string suture around the puncture site was made using black silk 4-0. The tumor particles were then injected through the center of the suture. While removing the needle, the suture was tightened to prevent hemorrhage or leakage of the VX2 tumor cells through the injection route. Finally, the injection site was covered with a Surgicel(R) patch. The inoculated intrahepatic VX2 tumors were then imaged with a 16 channel multidetector CT every week for the duration of the study. The CT images covered from the lung apex to the pelvic floor. Two radiologists evaluated the size, location, and peritoneal seeding of the tumors as well as metastasis of other organs. Three rabbits were sacrificed at random beginning in the second week, and this process continued on a weekly basis for the duration of the study. The CT images and pathologic findings for the sacrificed rabbits were correlated.
RESULTS
The inoculated intrahepatic VX2 tumors were not visible in the first week. By the second week 66.7% were visible on CT images and by the third week all tumors were visible. Of the twenty rabbits, three (15%) had tumor growth both in the liver and the peritoneal cavity, suggesting tumor leakage from the injection site into the peritoneal cavity. The remaining rabbits (n=17) had successful inoculation in the liver parenchyma as a solitary mass. Three of twenty rabbits (15%) showed tumor regression after successful inoculation. Tumor metastasis in extratumoral regions, including the liver and peritoneal seeding, increased beginning in the fourth week and more than 12x103 mm3 in volume after the initial inoculation of the VX2 tumors.
CONCLUSION
This new technique using innoculated intrahepatic VX2 tumor particles seems to be a simple and effective method for obtaining a solitary hepatic tumor in animal models. Results of this study suggest that a solitary intrahepatic tumor model without metastasis can be maintained. However, the evaluation of any therapeutic effects or any planned intervention should not occur until the fourth week following innoculation or less than 12x103 mm3 in volume after the inoculation of the VX2 tumor. The second highlighted section does not seem to fir with the rest of the sentence. Consider rephrasing the last part of the sentence.