Department of Thoracic and Vascular Surgery, Antwerp University Hospital, Edegem, Belgium.
Eur J Cardiothorac Surg. 2012 Aug;42(2):341-7; discussion 347. doi: 10.1093/ejcts/ezs017. Epub 2012 Feb 15.
Isolated lung perfusion (ILuP) and selective pulmonary artery perfusion (SPAP) are experimental surgical techniques to deliver high-dose chemotherapy selectively to the lung for the treatment of lung metastases. ILuP with melphalan (MN) has shown to be feasible in clinical studies but can only be used once because it is invasive. SPAP as an endovascular technique can be repeated several times, but no results have been reported so far. Pharmacokinetics and efficacy of SPAP with MN were studied in a rodent lung metastasis model and compared it with ILuP and intravenous (IV) therapy.
Pharmacokinetics: forty-five Wag-Rij rats were randomized into three groups: IV 0.5 mg MN, ILuP 0.5 mg MN and SPAP 0.5 mg MN. Every treatment group was again randomized in three groups: 15 min treatment, 30 min treatment and 30 min treatment with 30 min reperfusion. Blood and tissue samples were taken for MN concentrations.
twenty-five Wag-Rij rats were randomized into five groups: control, sham thoracotomy, IV 0.5 mg MN, ILuP 0.5 mg MN and SPAP 0.5 mg MN. At day 0, bilateral lung metastases were induced, and treatment followed at day 7. At day 28, rats were sacrificed and pulmonary metastases counted. Survival: thirty Wag-Rij rats were randomized into five groups: control, sham ILuP, IV 0.5 mg MN, ILuP 0.5 mg MN, SPAP 0.5 mg MN. At day 0, left-sided lungmetastases were induced with treatment at day 7. Endpoints were death due to disease or survival up to 90 days.
Pharmacokinetics: SPAP and ILuP resulted in significantly higher left lung MN concentrations compared with IV (P = 0.05).
SPAP (30 ± 22 nodules) and ILuP (20 ± 9 nodules) resulted in significantly less nodules compared with IV (113 ± 17 nodules; P < 0.01). Survival: median survival of SPAP (74 ± 8 days) was equal to ILuP MN (71 ± 10 days) but significantly longer compared with IV (54 ± 7 days; P < 0.01 both).
SPAP with MN for the treatment of sarcoma lung metastases in rats is equally effective to ILuP but resulted in a significantly better survival compared with IV MN. As SPAP can be applied as a minimally invasive endovascular procedure, continued research with this technique is warranted.
肺隔离灌注（ILuP）和选择性肺动脉灌注（SPAP）是将高剂量化疗药物选择性输送到肺部以治疗肺转移的实验性外科技术。在临床研究中已经证明 MN 肺隔离灌注是可行的，但由于它是侵入性的，因此只能使用一次。SPAP 作为一种血管内技术，可以重复多次，但迄今为止尚未有结果报告。本研究在鼠肺转移模型中对 MN 的 SPAP 药代动力学和疗效进行了研究，并将其与 ILuP 和静脉（IV）治疗进行了比较。
药代动力学：45 只 Wag-Rij 大鼠随机分为三组：IV 0.5mg MN、ILuP 0.5mg MN 和 SPAP 0.5mg MN。每个治疗组再次随机分为三组：15 分钟治疗、30 分钟治疗和 30 分钟治疗后再灌注 30 分钟。采集血样和组织样本以测定 MN 浓度。
25 只 Wag-Rij 大鼠随机分为五组：对照组、假开胸组、IV 0.5mg MN 组、ILuP 0.5mg MN 组和 SPAP 0.5mg MN 组。在第 0 天，双侧肺转移被诱导，然后在第 7 天进行治疗。在第 28 天，处死大鼠并计数肺转移瘤。生存：30 只 Wag-Rij 大鼠随机分为五组：对照组、假 ILuP 组、IV 0.5mg MN 组、ILuP 0.5mg MN 组、SPAP 0.5mg MN 组。在第 0 天，通过治疗诱导左侧肺部转移，第 7 天开始治疗。终点是因疾病导致的死亡或生存至 90 天。
药代动力学：SPAP 和 ILuP 使左肺 MN 浓度明显高于 IV（P = 0.05）。
SPAP（30±22 个结节）和 ILuP（20±9 个结节）与 IV（113±17 个结节；P<0.01）相比，肺转移瘤明显减少。生存：SPAP（74±8 天）和 ILuP MN（71±10 天）的中位生存时间相等，但与 IV（54±7 天；P<0.01）相比明显延长。
SPAP 联合 MN 治疗大鼠肉瘤肺转移与 ILuP 同样有效，但与 IV MN 相比，生存率显著提高。由于 SPAP 可作为一种微创血管内操作，因此需要继续对此技术进行研究。
