High intra-abdominal pressure enhances the penetration and antitumor effect of intraperitoneal cisplatin on experimental peritoneal carcinomatosis
High intra-abdominal pressure enhances the penetration and antitumor effect of intraperitoneal cisplatin on experimental peritoneal carcinomatosis
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DOI：
10.1097/01.sla.0000218089.61635.5f
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发表时间：
2006-07-01
影响因子：
9
通讯作者：
Chauffert, Bruno
中科院分区：
文献类型：
--
作者：
Esquis, Philippe;Consolo, David;Chauffert, Bruno
目的：探讨腹内压增高（IAP）对晚期腹膜癌大鼠瘤内蓄积的影响及腹腔注射顺铂的抗肿瘤作用。评估猪对 IAP 的耐受性，因为它是一种体型与人类相当的大型动物。背景数据摘要：在大鼠晚期腹膜癌病模型中，研究由阳性 IAP 驱动的主动对流是否会增加顺铂的渗透和抗肿瘤效果。实验设计：患有宏观腹膜肿瘤的 BDIX 大鼠接受静脉注射 (IV)、常规腹膜内注射 (IP) 或持续注射的顺铂给药方式腹腔注射大量溶剂中的顺铂，维持 IAP 1 小时。通过原子吸收光谱（AAS）测量铂组织浓度，并通过特定诱导X射线发射（PIXE）方法评估铂在肿瘤结节中的分布。在生存实验中评估了抗肿瘤效果。在大白猪中评估了使用或不使用顺铂的 IAP 的血流动力学、局部和全身耐受性。结果：在非通气大鼠中，最大耐受 IAP 为 22 mm Hg，持续 1 小时。与 IV 或传统 IP 注射相比，IAP 导致铂扩散到隔膜和腹膜肿瘤结节的浓度和深度增加。因此，IAP 治疗可延长晚期癌病大鼠的生存期。在 7 头 50 至 70 公斤的通气猪中，40 毫米汞柱 IAP 在稳定保持 2 小时后具有良好的耐受性。总剂量为200和400 mg顺铂联合IAP的猪出现肾衰竭，但100 mg剂量的耐受性良好。 结论：与传统腹膜内或静脉注射化疗相比，增加IAP的腹腔化疗可改善晚期腹膜癌大鼠的肿瘤积累和顺铂的抗肿瘤作用。在临床前条件下，通气猪对持续 IAP 的耐受性是可控的。
Objective: To investigate the role of increased intra-abdominal pressure (IAP) on the intratumoral accumulation and the antitumor effect of intraperitoneal cisplatin in rats with advanced peritoneal carcinomatosis. To evaluate the tolerance of IAP in pigs, as it is a large animal with a body size equivalent to humans.Summary Background Data: To investigate if an active convection, driven by a positive IAP, increases cisplatin penetration and antitumor effectiveness in a model of advanced peritoneal carcinomatosis in rats.Experimental Design: BDIX rats with macroscopic peritoneal tumors received cisplatin administered as intravenous injection (IV), conventional intraperitoneal injection (IP), or sustained intraperitoneal injection of cisplatin given in a large volume of solvent for maintaining IAP for 1 hour. Platinum tissue concentration was measured by atomic absorption spectroscopy (AAS), and platinum distribution into the tumor nodules was assessed by the particular-induced x-ray emission (PIXE) method. The antitumor effect was assessed in a survival experiment. The hemodynamic, local, and systemic tolerance of IAP, with or without cisplatin, was evaluated in Large White pigs.Results: The maximum tolerated IAP was 22 mm Hg for 1 hour in nonventilated rats. IAP, in comparison with IV or conventional IP injections, resulted in the increased concentration and depth of diffusion of platinum into diaphragm and peritoneal tumor nodules. Consequently, IAP treatment induced an extended survival of rats treated at an advanced stage of carcinomatosis. In 7 50- to 70-kg ventilated pigs, a 40-mm Hg IAP was well tolerated when maintained stable for 2 hours. Renal failure occurred in pigs receiving a total dose of 200 and 400 mg of cisplatin with IAP, but a dose of 100 mg was well tolerated.Conclusions: Intraperitoneal chemotherapy with increased IAP, in comparison with conventional IP or IV chemotherapy, improved the tumor accumulation and the antitumor effect of cisplatin in rats bearing advanced peritoneal carcinomatosis. In preclinical conditions, the tolerance of sustained IAP was manageable in ventilated pigs.