INSERM Unit 866, Equipe Avenir, Dijon, France.
World J Surg Oncol. 2012 Feb 6;10:29. doi: 10.1186/1477-7819-10-29.
The usual treatments for pleural malignancies are mostly palliative. In contrast, peritoneal malignancies are often treated with a curative intent by cytoreductive surgery and intraperitoneal chemotherapy. As pressure has been shown to increase antitumor efficacy, we applied the concept of high-pressure intracavitary chemotherapy to the pleural space in a swine model.
Cisplatin and gemcitabine were selected because of their antineoplasic efficacy in vitro in a wide spectrum of cancer cell lines. The pleural cavity of 21 pigs was filled with saline solution; haemodynamic and respiratory parameters were monitored. The pressure was increased to 15-25 cm H2O. This treatment was associated with pneumonectomy in 6 pigs. Five pigs were treated with chemotherapy under pressure.
The combination of gemcitabine (100 mg/l) and cisplatin (30 mg/l) was highly cytotoxic in vitro. The maximum tolerated pressure was 20 cm H20, due to haemodynamic failure. Pneumonectomy was not tolerated, either before or after pleural infusion. Five pigs survived intrapleural chemotherapy associating gemcitabine and cisplatin with 20 cm H2O pressure for 60 min.
High-pressure intrapleural chemotherapy is feasible in pigs. Further experiments will establish the pharmacokinetics and determine whether the benefit already shown in the peritoneum is also obtained in the pleura.
胸膜恶性肿瘤的常用治疗方法多为姑息性。相比之下，腹膜恶性肿瘤通常采用细胞减灭术和腹腔内化疗进行根治性治疗。由于压力已被证明可以提高抗肿瘤疗效，我们在猪模型中将这一概念应用于胸膜腔。
选择顺铂和吉西他滨是因为它们在体外对广泛的癌细胞系具有抗肿瘤作用。21 头猪的胸腔内充满生理盐水；监测血流动力学和呼吸参数。将压力增加到 15-25cmH2O。在 6 头猪中，这种治疗与肺切除术同时进行。5 头猪在压力下接受化疗。
吉西他滨（100mg/l）和顺铂（30mg/l）联合具有高度细胞毒性。由于血流动力学衰竭，最大耐受压力为 20cmH20。在进行胸膜灌注之前或之后，肺切除术均无法耐受。5 头猪在胸膜内化疗中存活下来，联合使用吉西他滨和顺铂，压力为 20cmH20，持续 60 分钟。
在猪中进行高压胸膜内化疗是可行的。进一步的实验将建立药代动力学，并确定在腹膜中已显示出的益处是否也在胸膜中获得。
