Rotational intraperitoneal pressurized aerosol chemotherapy in a porcine model.

Abstract

Peritoneal carcinomatosis (PC) commonly represent drug resistance to intravenous (IV) chemotherapy in advanced or recurrent disease of solid tumors. For improving the prognosis of PC, intraperitoneal (IP) chemotherapy has been introduced in the clinical setting, and phase III trials proved the superiority of IP chemotherapy to IV chemotherapy, in particular, in advanced ovarian cancer. However, increased toxicities by IP chemotherapy lead to reduced cycles of chemotherapy, which does not guarantee its effectiveness. Moreover, hyperthermic IP chemotherapy after cytoreductive surgery also showed improved survival compared to IV chemotherapy in advanced ovarian cancer. Nevertheless, limited distribution and diffusion of drugs, and grade 3 or 4 renal and hepatic toxicity of 20% preclude the expansion of its application. On the other hand, pressurized intraperitoneal aerosol chemotherapy (PIPAC) is known to show the effect by delivering drugs to the parietal and visceral peritoneum in the form of aerosol under the abdominal pressure of 12 mmHg induced by laparoscopic system. Although low dose equivalent to about 1% dose of resistant drugs for IV chemotherapy and normothermia are used in PIPAC, it may improve tumor response and quality of life by repetitive application of PIPAC due to the increased distribution and penetration depth of drugs. However, the heterogeneous distribution of drugs is still the major limitation of PIPAC because the nozzle is placed at the possible outlying position to the tumor-bearing tissues during laparoscopic surgery. Therefore, we developed a novel prototype for PIPAC, rotational intraperitoneal pressurized aerosol chemotherapy (RIPAC) system because rotation of the nozzle and change of spray direction can contribute to homogenous distribution of drugs, and compared the distribution of drugs between PIPAC and RIPAC in a porcine model mimicking human body. As a result, RIPAC was more effective than PIPAC in terms of the distribution of drugs into the visceral and parietal peritoneum.