Demmy Todd L, Tomaszewski Garin, Dy Grace K, Yendamuri Sai, Nwogu Chukwumere, Pendyala Lakshmi, Ramnath Nithya, Adjei Alex A
Department of Thoracic Surgery, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
Ann Thorac Surg. 2009 Aug;88(2):385-90; discussion 390-1. doi: 10.1016/j.athoracsur.2009.04.101.
After promising preclinical studies using a thoracoscopic regional lung chemotherapy technique less morbid than open perfusion methods, we initiated a Phase I clinical study.
Four performance status 0 to 1 patients with oligometastatic stage IV lung cancer underwent unilateral thoracoscopic lung suffusion targeting the bulk of primary disease and regional lymph nodes. We used the term suffusion (permeation of an organ) to describe the total lung distribution of chemotherapy afforded by venous distention akin to retrograde cardioplegia physiology. This was obtained by temporary thoracoscopic pulmonary vein occlusions and fluoroscopy-guided transfemoral intravascular balloon occlusion, drainage, and cisplatin distention of the main pulmonary artery. Single-lung ventilation allowed atelectasis that helped to drain the blood under pulmonary artery occlusion, then cisplatin (5% systemic dose) was instilled during venous occlusion and lung reexpansion. Chemotherapy dwelled for 30 minutes before lung reperfusion.
All four suffusions were successful (three right, one left). Cisplatin remained concentrated in the pulmonary circulation by the end of the dwell (1,124 versus 236 ng/mL systemic). There were no changes in the postsuffusion pulmonary function tests or lung perfusion scans. All patients were discharged early (24 to 48 hours) without chest tubes, began standard chemotherapy without delay, and completed follow-up. After two systemic chemotherapeutic cycles primary tumors had volume reductions of 96%, 88%, 64%, and 14%, with the latter showing a 100% volume increase in a nonsuffused osseous metastasis.
Our initial clinical experience of thoracoscopic lung suffusion suggests that this approach is safe and merits future study with higher dose levels.
在使用一种比开放性灌注方法创伤性更小的胸腔镜区域肺化疗技术进行了前景良好的临床前研究之后，我们开展了一项I期临床研究。
4例体能状态为0至1级的寡转移IV期肺癌患者接受了单侧胸腔镜肺灌注，靶向主要病灶和区域淋巴结。我们使用“灌注”（器官的渗透）一词来描述类似于逆行心脏停搏生理学的静脉扩张所实现的化疗药物在全肺的分布。这是通过临时胸腔镜肺静脉闭塞以及荧光透视引导下经股血管内球囊闭塞、引流，并对主肺动脉进行顺铂扩张来实现的。单肺通气使肺萎陷，有助于在肺动脉闭塞时引流血液，然后在静脉闭塞和肺复张期间注入顺铂（全身剂量的5%）。化疗药物在肺再灌注前停留30分钟。
所有4次灌注均成功（3例右侧，1例左侧）。在停留结束时，顺铂仍集中在肺循环中（全身浓度为1124 ng/mL，而全身浓度为236 ng/mL）。灌注后肺功能测试或肺灌注扫描均无变化。所有患者均在无胸管的情况下提前出院（24至48小时），立即开始标准化疗，并完成随访。经过两个周期的全身化疗后，原发肿瘤体积分别缩小了96%、88%、64%和14%，后者在未灌注的骨转移灶中体积增加了100%。
我们胸腔镜肺灌注的初步临床经验表明，这种方法是安全的，值得在更高剂量水平上进行进一步研究。
