Relative Initial Weight Is Associated with Improved Survival without Altering Tumor Latency in a Translational Rat Model of Diethylnitrosamine-Induced Hepatocellular Carcinoma and Transarterial Embolization

Abstract

Purpose To test the hypotheses that greater initial body weight is associated with a relative improvement in survival with diminished fibrosis in a diethylnitrosamine (DEN)-induced rat model of HCC and that TAE (TAE) via femoral artery access decreases procedure times compared to carotid artery access. Materials and Methods 138 male Wistar rats were administered 0.01% DEN in water ad libitum for 12 weeks. Rats received weekly T2-MRI to detect HCC. Upon development of ≥5mm tumors, rats underwent selective TAE via carotid or femoral artery catheterization under fluoroscopic guidance. Rats were retrospectively categorized into 3 groups (<300g, 300-400g, >400g) based on initial weight for analyses of survival, tumor latency, and fibrosis. Site of access was compared relative to procedural outcomes of success, mortality, and time. Results No significant differences in tumor latency were related to weight group (p=0.310). Rats weighing <300g had shorter survival time than both larger groups (mean=88d vs. 108d, p<0.0001) and more severe fibrosis (<300g median=4.0, 300-400g median=1.5, >400g median=1.0; p=0.015). No significant difference was found in peri-procedural mortality based on access site; however, procedure times were shorter via a femoral approach (mean=71+/-23min vs. 127+/-24min; p<0.0001). Conclusion Greater initial body weight resulted in improved survival without prolonging tumor latency for rats with DEN-induced HCCs and was associated with less severe fibrosis. A femoral approach for TAE in this model resulted in decreased procedure time. These modifications provide a translational animal model of HCC and TAE that may be suited for short-term survival studies.

B-mode ultrasound for the assessment of hepatic fibrosis: a quantitative multiparametric analysis for a radiomics approach

“…In this study, quantitative ultrasound features changed with verifiable progression of rats’ chronic liver disease and hepatic fibrogenesis. Specifically, DEN uniformly led to reduction in the weight gain of DEN-exposed rats, consistent with previous observations of this model 26 and created progressive hepatic fibrosis verified by histologic evaluation. The four computer-extracted features studied in the B-mode US images (echointensity, HRI, heterogeneity, and anisotropy) consistently increased over time as hepatic disease progressed.…”

Functional Genetic Screening Enables Theranostic Molecular Imaging in Cancer

“…Induction of autochthonous hepatocellular carcinomas in male Wistar rats was performed as described previously with diethylnitrosamine (8). One week prior to completion of the diethylnitrosamine exposure, rats underwent MRI screening approximately twice per week with T 2 -weighted MRI [Field of view: 70 mm  70 mm, grid size: 256  256, slice thickness: 2 mm, Repetition time (TR) minimum: 1.4 s (respiratory gated), Echo time (TE): 59.1 ms, and minimum averages: 4) using an Agilent 4.7T 40 cm horizontal bore MR Spectrometer with a 25 gauss/cm gradient tube interfaced to an Agilent DirectDrive console (9).…”

Three-Dimensional Augmented Reality Visualization Informs Locoregional Therapy in a Translational Model of Hepatocellular Carcinoma

“…This study was approved by University of Pennsylvania Institutional Animal Welfare & Use Committee. The induction of cirrhosis and HCC in rats using DEN and TAE via right common femoral artery access were previously described [10,11]. All rats developed tumors, the majority of which appeared within 2 weeks of completing the DEN diet.…”