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PIPAC 与 HIPEC 比较:顺铂在猪模型中的空间分布和扩散。

PIPAC versus HIPEC: cisplatin spatial distribution and diffusion in a swine model.

机构信息

Department of Digestive Surgery, Hospices Civils de Lyon, Lyon-Sud University Hospital, Lyon, France.

EMR 3738, Lyon 1 University, Lyon, France.

出版信息

Int J Hyperthermia. 2020;37(1):144-150. doi: 10.1080/02656736.2019.1704891.

Abstract

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel approach for delivering intraperitoneal chemotherapy and offers perspective in the treatment of peritoneal carcinomatosis. Concept is based on a 12 mmHg capnoperitoneum loaded with drug changed in microdoplets. It was postulated to guarantee a more homogeneous drug distribution and tissular uptake than hyperthermic intraperitoneal chemotherapy (HIPEC). The aim of this study was to compare cisplatin peritoneal distribution and pharmacokinetic between HIPEC and PIPAC procedures in a healthy swine model. Two groups of eight pigs underwent either HIPEC with cisplatin (70 mg/m) at 43 °C for 60 min, or PIPAC with cisplatin (7.5 mg/m) for 30 min. Postoperatively, peritoneal areas were biopsied allowing peritoneal cavity cartography. Tissular and plasmatic cisplatin concentrations were analyzed. Cisplatin distribution was heterogeneous in both the groups with higher concentrations obtained closed to the delivery sites. Median total platinum peritoneal concentration by pig was higher in the HIPEC group than in the PIPAC group (18.0 μg/g versus 4.3 μg/g,  < .001) but the yield was 2.2 times better with PIPAC. Platinum concentrations were higher in the HIPEC group in all stations. At each time-point, cisplatin plasmatic concentrations were higher in the HIPEC group ( < .001) but beneath the toxicity threshold. With doses used in clinical practice, HIPEC guaranteed a higher cisplatin peritoneal uptake than PIPAC in this swine model. Spatial drug distribution was heterogeneous with both technics, with hotspots closed to the drug delivery sites. Nevertheless, considering the dose ratio, IP drug uptake yield was better with PIPAC.

摘要

腹腔内加压气溶胶化疗(PIPAC)是一种将腹腔内化疗递送至腹腔的新方法,为腹膜癌病的治疗提供了新视角。该方法的理念基于将载有药物的 12mmHg 二氧化碳气腹转变为微滴。与腹腔内热化疗(HIPEC)相比,它被认为可以保证更均匀的药物分布和组织摄取。本研究旨在健康猪模型中比较 HIPEC 和 PIPAC 过程中顺铂的腹膜分布和药代动力学。两组 8 头猪分别接受 HIPEC(43°C 下 60 分钟,顺铂 70mg/m2)或 PIPAC(30 分钟,顺铂 7.5mg/m2)治疗。术后,对腹膜区进行活检,以允许对腹膜腔进行绘图。分析组织和血浆中顺铂的浓度。两组腹膜内顺铂分布均不均匀,靠近给药部位的浓度较高。HIPEC 组每头猪总铂腹膜浓度中位数高于 PIPAC 组(18.0μg/g 比 4.3μg/g,<.001),但 PIPAC 组的产量高 2.2 倍。HIPEC 组所有部位的铂浓度均较高。在每个时间点,HIPEC 组的顺铂血浆浓度均较高(<.001),但低于毒性阈值。在临床实践中使用的剂量下,在该猪模型中,HIPEC 比 PIPAC 保证了更高的顺铂腹膜摄取。两种技术的药物空间分布均不均匀,热点靠近药物给药部位。然而,考虑到剂量比,PIPAC 的 IP 药物摄取产率更高。

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