Mauroy B, Bonnal J L, Prevost B, Chive M, Lhotellier V, Sozanski J P, Vanseymortier L, Stefaniak X
Service Universitaire d'Urologie, CHU de Lille-Roubaix, France.
Prog Urol. 1999 Feb;9(1):69-80.
Preliminary clinical studies of the combination of hyperthermia and intravesical chemotherapy indicated very encouraging results in favour of multidisciplinary treatment of recurrent superficial bladder tumours. The authors studied the in vitro and early in vivo effects of this treatment.
An intravesical catheter equipped with a microwave antenna was used for hyperthermia in vivo in dogs. The temperature was controlled by two intravesical thermocouples and 4 transducers on the bladder wall. 0, 40 or 80 mg of mitomycin were instilled in 60 ml of physiological saline. Dogs were sacrificed after each one-hour session, and histological intravesical lesions were defined as grade 0, 1 or 2 corresponding to absence of lesions, or the presence of inflammatory lesions or urothelial lesions, respectively. In vitro, the first step consisted of creation of an immortalized tumour cell line from a grade II bladder papilloma. This HVT 196 cell line was incubated between 37 degrees C and 44 degrees C with increasing mitomycin concentrations of 0 to 10 micrograms per ml. The cytotoxicity was measured by the MTT quantitative colorimetric method.
In vivo, in 8 dogs, histological analysis of the comparative cytotoxicity of the various treatments confirmed the synergistic effect of heat and mitomycin C. In dogs treated at 45 degrees C, marked urothelial lesions were observed, regardless of the mitomycin C concentration. The in vitro comparative toxicity study on our cell line showed a much more intense cytotoxic effect with combined treatment than with cytostatic treatment alone. Expressed as the percentage of cytotoxicity compared to a control cell pool for a concentration of 1 microgram per ml. the temperature rise of the medium between 37 degrees C and 44 degrees C was accompanied by a cytotoxic effect of 8.4% and 98.41% respectively.
A possible clinical application is potentiation of the action of mitomycin C by hyperthermia in the prevention of recurrent superficial bladder tumours, achieving increased efficacy and/or a decreased number of instillations.
热疗与膀胱内化疗联合应用的初步临床研究表明，在复发性浅表性膀胱肿瘤的多学科治疗方面取得了非常令人鼓舞的结果。作者研究了这种治疗的体外和早期体内效果。
使用配备微波天线的膀胱内导管对犬进行体内热疗。温度由两个膀胱内热偶和膀胱壁上的4个换能器控制。将0、40或80毫克丝裂霉素滴注到60毫升生理盐水中。每次治疗1小时后处死犬，膀胱内组织学病变分为0级、1级或2级，分别对应无病变、存在炎性病变或尿路上皮病变。在体外，第一步是从II级膀胱乳头状瘤建立永生化肿瘤细胞系。将该HVT 196细胞系在37℃至44℃之间培养，丝裂霉素浓度从0增加到每毫升10微克。通过MTT定量比色法测量细胞毒性。
在体内，对8只犬进行的各种治疗的比较细胞毒性组织学分析证实了热和丝裂霉素C的协同作用。在45℃治疗的犬中，无论丝裂霉素C浓度如何，均观察到明显的尿路上皮病变。对我们细胞系的体外比较毒性研究表明，联合治疗比单独的细胞抑制治疗具有更强的细胞毒性作用。以每毫升1微克浓度下与对照细胞池相比的细胞毒性百分比表示，培养基温度从37℃升高到44℃时，细胞毒性作用分别为8.4%和98.41%。
热疗增强丝裂霉素C的作用在预防复发性浅表性膀胱肿瘤方面可能具有临床应用价值，可提高疗效和/或减少灌注次数。
