[转移性肺癌局部化疗的实验研究——肺隔离灌注与肺动脉灌注]

[An experimental study of local chemotherapy for metastatic lung tumor--isolated lung perfusion and pulmonary artery infusion].

作者信息

Omiya H, Machida H, Saito Y, Imamura H, Okamura A

机构信息

Department of Thoracic and Cardiovascular Surgery, Kansai Medical University, Osaka, Japan.

出版信息

Jpn J Thorac Cardiovasc Surg. 1998 Oct;46(10):976-82. doi: 10.1007/BF03217858.

DOI:10.1007/BF03217858

PMID:9847573

Abstract

PURPOSE

We evaluated the efficacy of local chemotherapy using isolated lung perfusion (ILP) and pulmonary artery infusion (PAI) in vivo to improve prognosis for patients with metastatic lung diseases.

MATERIAL AND METHODS

Male F344 rats were used. The left lung was isolated and chemotherapeutic agents were administrated to the isolated lung by the ILP or PAI technique. Agents used were cisplatin (CDDP) and fluorouracil (5-FU), and their levels in the perfused lung and serum were measured (renal levels were also measured in CDDP groups). The results were compared with those obtained following intravenous administration (i.v.). In the ILP group, the left pulmonary artery and vein were clamped during perfusion. The agents were infused from the pulmonary artery, and the perfusate was collected from the pulmonary venotomy site following flushing with saline before declamping. In the PAI group, the left pulmonary artery was clamped and perfused with 0.2 ml of the agents, pulmonary arterial flow was occluded for 20 minutes, and perfusate was not collected. Rats were sacrificed 5 minutes after declamping in both groups, and the perfused lung and blood (and also kidneys in the CDDP group) were collected for pharmacokinetic examination. Histological examination of the perfused lung was also performed.

RESULTS

In the ILP group treated with 1 mg of CDDP and PAI group treated with 0.1 mg of CDDP administration, the lung CDDP levels were significantly higher and the serum and renal CDDP levels were significantly lower than those in the IV group. In the ILP group treated with 150 mg of 5-FU and PAI group treated with 10 mg of 5-FU, the lung 5-FU levels were significantly higher than those in all IV groups and the serum 5-FU levels were lower than those in the IV group treated with 10 mg and 15 mg of 5-FU. The bronchopulmonary construction was histologically maintained in the perfused lung in each group.

CONCLUSION

We concluded that local chemotherapy using ILP or PAI could be a safe and effective choice of therapy, and this method may be clinically applicable.

摘要

目的

我们评估了采用离体肺灌注（ILP）和肺动脉灌注（PAI）进行局部化疗在改善转移性肺部疾病患者预后方面的体内疗效。

材料与方法

使用雄性F344大鼠。分离左肺，并通过ILP或PAI技术将化疗药物注入离体肺。使用的药物为顺铂（CDDP）和氟尿嘧啶（5-FU），并测量其在灌注肺和血清中的水平（在CDDP组中还测量了肾脏中的水平）。将结果与静脉注射（i.v.）后获得的结果进行比较。在ILP组中，灌注期间夹闭左肺动脉和静脉。从肺动脉注入药物，在松开夹子前用盐水冲洗后，从肺静脉切开部位收集灌注液。在PAI组中，夹闭左肺动脉并用0.2 ml药物进行灌注，阻断肺动脉血流20分钟，不收集灌注液。两组在松开夹子5分钟后处死大鼠，收集灌注肺和血液（在CDDP组中还包括肾脏）进行药代动力学检查。还对灌注肺进行了组织学检查。

结果

在接受1 mg CDDP治疗的ILP组和接受0.1 mg CDDP给药的PAI组中，肺CDDP水平显著高于静脉注射组，血清和肾脏CDDP水平显著低于静脉注射组。在接受150 mg 5-FU治疗的ILP组和接受10 mg 5-FU治疗的PAI组中，肺5-FU水平显著高于所有静脉注射组，血清5-FU水平低于接受10 mg和15 mg 5-FU治疗的静脉注射组。每组灌注肺的支气管肺结构在组织学上得以维持。