Abstract
Purpose Limited treatment options exist for patients with malignant biliary obstruction caused by pancreaticobiliary cancer. The aim of this study was to validate the feasibility of using intrabiliary radiofrequency hyperthermia (RFH) to enhance local chemotherapy administration to cholangiocarcinoma. Materials and Methods GFP/lentivirus-transduced human cholangiocarcinoma cells (Mz-ChA-1) were treated with various concentrations of gemcitabine and the half maximal inhibitory concentration (IC50) was determined. For in vitro evaluation, Mz-ChA-1 cells were cultured in four-chamber slides and treated by using (a) 20-min RFH at approximately 42 degrees celsius plus 500-mM gemcitabine; (b) 20-min RFH-only; (c) 500-mM gemcitabine-only; and (d) no treatment to serve as a control. Cell viabilities were assayed using trypan blue exclusion. Each experiment was repeated six times. For in vivo evaluation, cells were subcutaneously implanted into the flanks of 24 nu/nu nude mice. When the tumor size reached approximately 5mm in diameter, 25mg/kg of gemcitabine was injected into the tumor followed by RFH at approximately 42°C for 20 min. Whole body fluorescent optical imaging and 14T MRI, including T2WI and diffusion-weighted imaging were used to follow up therapeutic effects at 1, 7, and 14 days after treatment. HE staining and confocal microscopy were performed to establish image/histology correlation. Results The IC50 of gemcitabine for Mz-ChA-1 cells at 96hrs is 500 μM. The in vitro experiments demonstrate that RFH-enhanced chemotherapy can significantly inhibit tumor cells growth, compared with chemotherapy only and the RFH only group (0.58±0.10 vs 0.72±0.8 and 0.58±0.10 vs 0.65±0.11, p Conclusion RFH can enhance the killing effect of chemotherapy on cholangiocarcinomas, which may open new avenues to effectively manage pancreatobiliary malignancies.
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