Ultrasound Tumor Size Assessment, Histology and Serum Enzyme Analysis in a Rat Model of Colorectal Liver Cancer

Abstract

During tumor development, tissue necrosis appears as a natural phenomenon directly associated with an increase in tumor size. The aim of this study was to assess the use of ultrasound (US) for predicting natural tumor necrosis in a rat liver implant model of colorectal cancer. To achieve this goal, we sought to establish a correlation between US-measured tumor volume, serum enzyme levels and histopathological findings, particularly those regarding necrosis phenomena in liver implants. Under US guidance, CC531 colorectal cancer cells were injected into the left liver lobe of WAG/RijHsd rats. Twenty-eight days after cell inoculation, tumor volume was measured by US, and rats were sacrificed to obtain samples of tumor tissue as well as blood serum. In hematoxylin and eosin-stained tumor samples, the percentage of tumor that was necrotic was estimated. The association between percentage tumor necrosis and US-measured tumor volume was assessed by univariate logistic regression analysis, and a linear regression equation was obtained. Serum enzyme levels did not differ significantly between tumor-bearing and tumor-free rats. Tumor implants appeared as well-defined hyper-echoic regions with a mean volume of 0.61 ± 0.39 mL and tumor necrosis percentage of 8.6 ± 7.7%. Linear regression analysis revealed a very strong relationship (Pearson correlation coefficient r = 0.911) between US-measured tumor volume and tumor necrosis percentage; the regression equation was tumor necrosis percentage = 21 × US-measured tumor volume (in mL) - 3.1. The study found US to be a useful tool in animal-based trials. Tumors inside the liver (ranging in volume from 0.24-1.37 mL) can be observed by US, and moreover, US-measured tumor volume on day 28 can be used to estimate tumor necrosis occurring as the natural evolution of tumor implants.

Keywords: Intrahepatic injection; Orthotopic tumor model; Tumor volume assessment; Ultrasound-guided injection.