Feature of fast progression has brought great challenge for selecting the optimal time for starting therapy

In this study, two commonly used inoculation methods including VX2 cell suspension and VX2 tissue fragment were used to establish animal models. In our study, the tumor grew rapidly after implantation with a quick increase of the diameter and volume, leading to a shortened time span that was suitable for treatment. The animal model would have to be abandoned if the optimal intervention time was missed. The tumors derived from VX2 cell suspension and VX2 tissue fragment showed different growth behaviors. The tumors of the cell suspension group grew faster than those of the tissue fragment group. For animals inoculated using the tissue fragment method, the therapy starting point should be later than the one of animals inoculated using the cell suspension method. The rate of tumor visualization on CT scans on day 14 after implantation was low. On day 7, the visualization rate on plain and contrast-enhanced CT scans was 12.5% and 53.13%, respectively. CT scans did not reliably detect the tumors at very early period after implantation. The blood supply of human HCC comes from the portal vein at its very early stage. As the tumor grows the blood supply becomes progressively arterialized. The low visualization rate of CT scans may be due to the portal vein supply of the early-stage VX2 liver tumors or the improper enhanced phase used in CT enhanced scans. It is reported that the visualization rate of MRI scans was low at 1 week after implantation. the visualization rate of tumor on plain and contrast-enhanced MRI scans was 57.25% and 37.5%, respectively. Metastases and ascites were not observed on day 7 in both groups. On day 14, one case in the cell suspension group showed intra-hepatic and pulmonary metastases. We considered that the multiple metastases may be due to dissemination though blood vessels which were broken during VX2 cell suspension injection. This is also mentioned in previous literature. On day 21, metastases and ascites were observed in eight animals of the cell suspension group on CT scans. On day 28, most animals in the cell suspension group showed metastases and ascites. In the tissue fragment group, intra-hepatic metastases were only observed in one case on day 28. The average survival time of untreated animals was longer than 35 days. These results suggest that metastases and ascites might appear on approximately day 21 and 28, respectively in the cell suspension group and the tissue fragment group. Compared with the animals in the cell suspension group, the animals in the tissue fragment group indicated a longer survival time and a later occurrence of metastases and ascites. Three reasons may contribute to the difference. Firstly, the tumors in the cell suspension group grew more fastly than those in the tissue fragment group, suggesting a more rapid disease progression; secondly, the way of tumor tissue implantation might influence its biological behavior.

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