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一种用于膀胱癌大鼠模型的可扩展高热腔内化疗(HIVEC)装置。

A scalable hyperthermic intravesical chemotherapy (HIVEC) setup for rat models of bladder cancer.

机构信息

Department of Urology, Amsterdam University Medical Centers, University of Amsterdam, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands.

Department of Medical Biology, Amsterdam University Medical Centers, Cancer Center Amsterdam, University of Amsterdam, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands.

出版信息

Sci Rep. 2022 Apr 29;12(1):7017. doi: 10.1038/s41598-022-11016-y.

Abstract

Hyperthermic intravesical chemotherapy (HIVEC)-whereby the bladder is heated to ± 43 °C during a chemotherapy instillation-can improve outcomes of non-muscle invasive bladder cancer (NMIBC) treatments. Experiments in animal models are required to explore new hyperthermia based treatments. Existing HIVEC devices are not suitable for rodents or large-scale animal trials. We present a HIVEC setup compatible with orthotopic rat models. An externally heated chemotherapeutic solution is circulated in the bladder through a double-lumen catheter with flow rates controlled using a peristaltic pump. Temperature sensors in the inflow channel, bladder and outflow channel allow temperature monitoring and adjustments in real-time. At a constant flow rate of 2.5 mL/min the system rapidly reaches the desired bladder temperature of 42-43 °C with minimal variability throughout a one-hour treatment in a rat bladder phantom, as well as in euthanised and live rats. Mean intraluminal bladder temperatures were 42.92 °C (SD = 0.15 °C), 42.45 °C (SD = 0.37 °C) and 42.52 °C (SD = 0.09 °C) in the bladder phantom, euthanised, and live rats respectively. Thermal camera measurements showed homogenous heat distributions over the bladder wall. The setup provides well-controlled thermal dose and the upscaling needed for performing large scale HIVEC experiments in rats.

摘要

热腔内化疗(HIVEC)——即在化疗灌注期间将膀胱加热至±43°C——可以改善非肌肉浸润性膀胱癌(NMIBC)的治疗效果。需要在动物模型中进行实验来探索新的基于热疗的治疗方法。现有的 HIVEC 设备不适合用于啮齿动物或大规模动物试验。我们提出了一种与原位大鼠模型兼容的 HIVEC 设备。一种外部加热的化疗溶液通过带有双腔导管在膀胱中循环,通过蠕动泵控制流速。在流入通道、膀胱和流出通道中的温度传感器允许实时监测和调整温度。在恒定的流速为 2.5 mL/min 的情况下,该系统在大鼠膀胱模型中以 42-43°C 的目标膀胱温度快速达到稳定,在大鼠膀胱模型中治疗 1 小时内,以及在安乐死和活的大鼠中,其温度变化很小。在膀胱模型、安乐死和活大鼠中,腔内膀胱的平均温度分别为 42.92°C(SD=0.15°C)、42.45°C(SD=0.37°C)和 42.52°C(SD=0.09°C)。热像仪测量显示膀胱壁上的热量分布均匀。该设备提供了良好控制的热剂量,并且可以扩大规模,以便在大鼠中进行大规模 HIVEC 实验。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb82/9054747/9fcec31997b4/41598_2022_11016_Fig1_HTML.jpg

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