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高热联合腹腔化疗治疗腹膜转移癌:一项实验研究。

Hyperthermia and intraperitoneal chemotherapy for the treatment of peritoneal carcinomatosis: an experimental study.

机构信息

Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands.

出版信息

Ann Surg. 2011 Jul;254(1):125-30. doi: 10.1097/SLA.0b013e3182197102.

Abstract

OBJECTIVE

Hyperthermic intraperitoneal chemotherapy (HIPEC) with mitomycin C can improve survival if used as an adjunct to cytoreductive surgery (CS) for treatment of peritoneal carcinomatosis (PC). It remains unclear if both hyperthermia and chemotherapy are essential for the reported survival benefit.

METHODS

Eighty WAG/Rij rats were inoculated intraperitoneally with the rat colon carcinoma cell line CC-531. Animals were randomly assigned to 1 of the 4 treatment groups (n = 20): CS only, CS followed by HIPEC (mitomycin 35 mg/m(2) at 41°C), CS followed by intraperitoneal mitomycin perfusion at 37°C, CS followed by intraperitoneal saline perfusion at 41°C. Survival was the primary outcome with a maximum follow up of 126 days.

RESULTS

Median survival was 62 days in rats treated with CS only and 57 days in rats treated with CS followed by hyperthermic saline perfusion. Rats receiving HIPEC had a median survival of 121 days (P = 0.022 when compared with CS only). In the group treated with chemotherapy at 37°C, 13 of 20 animals were still alive at the end of the experiment so median survival was not reached. (CS vs. IPEC: P = 0.002, hazard ratio 0.36, 95% CI 0.19-0.69) Rats treated with hyperthermic saline perfusion did not have an increased survival as compared with CS only.

CONCLUSIONS

The effectiveness of intraoperative intraperitoneal perfusion after CS is highly dependent on the presence of chemotherapeutic agents in the perfusate but not on hyperthermia. The need to include hyperthermia in the adjuvant intraoperative treatment after CS for PC should be further investigated.

摘要

目的

含丝裂霉素 C 的腹腔热灌注化疗(HIPEC)联合细胞减灭术(CS)治疗腹膜癌转移(PC)可提高患者生存率。但目前仍不清楚高热和化疗对改善生存率是否都至关重要。

方法

将大鼠结肠癌细胞系 CC-531 接种于 80 只 WAG/Rij 大鼠腹腔内。动物随机分为 4 个治疗组(n = 20):单纯 CS 组、CS 后 HIPEC 组(41°C 时给予丝裂霉素 35mg/m²)、CS 后 37°C 时腹腔内丝裂霉素灌注组、CS 后 41°C 时腹腔内生理盐水灌注组。主要观察终点为生存情况,随访时间最长 126 天。

结果

单纯 CS 组大鼠中位生存时间为 62 天,CS 后行热生理盐水灌注组大鼠中位生存时间为 57 天。接受 HIPEC 治疗的大鼠中位生存时间为 121 天(与单纯 CS 组相比,P = 0.022)。在 37°C 时接受化疗的大鼠中,20 只动物中有 13 只在实验结束时仍存活,因此未达到中位生存时间。(CS 组与 HIPEC 组相比,P = 0.002,风险比 0.36,95%CI 0.19-0.69)CS 后行热生理盐水灌注组与单纯 CS 组相比,生存时间未延长。

结论

CS 后术中腹腔内灌注的有效性高度依赖于灌注液中是否存在化疗药物,但与高温无关。对于 PC 的 CS 术后辅助性术中治疗,是否需要包括高温,需要进一步研究。

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