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经皮孤立胰腺灌注化疗期间顺铂全身泄漏最小化:一项初步研究。

Minimizing Systemic Leakage of Cisplatin during Percutaneous Isolated Pancreas Perfusion Chemotherapy: A Pilot Study.

机构信息

From the Departments of Radiology and Center for Advanced Medical Technology (S.M., S.O., T.M., T.U., F.S., D.Y., S.K.) and Analytic Human Pathology (A.S.), Nippon Medical School, 1-1-5 Sendagi, Bunkyou-ku, Tokyo 113-8602, Japan; and Department of Diagnostic Radiology, National Cancer Center East, Kashiwa, Chiba, Japan (M.S.).

出版信息

Radiology. 2015 Jul;276(1):102-9. doi: 10.1148/radiol.15141596. Epub 2015 Feb 27.

Abstract

PURPOSE

To evaluate the feasibility of percutaneous isolated pancreas perfusion (PIPP) by using a pig model.

MATERIALS AND METHODS

All experiments were approved by the institutional Animal Experiment Ethics Committee. Fifteen pigs were assigned to five groups, and PIPP was performed. Angiographic and dye injection studies were performed to confirm the patency of the PIPP system (group 1). Blood that contained cisplatin (1.5 mg per kilogram of body weight) in an extracorporeal circuit was circulated through the pancreas at three infusion rates (40, 60, and 80 mL/min) to determine the optimal infusion rate in terms of safety and pharmacologic effectiveness (groups 2, 3, and 4, respectively). Chronological laboratory data and histologic findings were assessed in group 5, which received the optimal infusion rate. Maximum platinum concentration (Cmax) and area under the platinum concentration-time curve were compared by using the Kruskal-Wallis and Mann-Whitney U tests.

RESULTS

Angiography and dye injection confirmed the patency of the PIPP system. Histopathologic examinations showed no abnormalities in the pancreas or other organs at a 40 mL/min infusion rate of cisplatin. However, edematous changes in the pancreas were observed at higher infusion rates. The pharmacologic effectiveness did not differ significantly among groups; therefore, the optimal infusion rate of 40 mL/min was selected. The median pancreatic-to-systemic exposure ratios were 71.8 for Cmax and 54.8 for the area under the curve. All laboratory data remained normal or returned to pretreatment levels within 1 week.

CONCLUSION

PIPP at a 40 mL/min infusion rate appears to be safe and feasible for perfusion of the pancreas.

摘要

目的

通过猪模型评估经皮孤立胰腺灌注(PIPP)的可行性。

材料与方法

所有实验均获得机构动物实验伦理委员会批准。将 15 头猪分为 5 组,进行 PIPP 操作。进行血管造影和染料注射研究,以确认 PIPP 系统的通畅性(第 1 组)。将含有顺铂(每公斤体重 1.5 毫克)的血液在体外循环中以 3 种灌注率(40、60 和 80 毫升/分钟)循环流过胰腺,以确定在安全性和药效学方面的最佳灌注率(分别为第 2、3 和 4 组)。第 5 组接受最佳灌注率,评估其随时间变化的实验室数据和组织学发现。采用 Kruskal-Wallis 和 Mann-Whitney U 检验比较最大铂浓度(Cmax)和铂浓度-时间曲线下面积。

结果

血管造影和染料注射证实了 PIPP 系统的通畅性。组织病理学检查显示,以 40 毫升/分钟的顺铂灌注率,胰腺或其他器官无异常。然而,在更高的灌注率下观察到胰腺水肿性改变。各组间药效学无显著差异,因此选择最佳灌注率为 40 毫升/分钟。Cmax 的胰腺与系统暴露比中位数为 71.8,曲线下面积为 54.8。所有实验室数据在 1 周内保持正常或恢复至预处理水平。

结论

以 40 毫升/分钟的灌注率进行 PIPP 似乎安全且可行,适用于胰腺灌注。

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