Mun Jaehee, Park Soo Jin, Kim Hee Seung
Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea.
Gland Surg. 2021 Mar;10(3):1271-1275. doi: 10.21037/gs-2019-ursoc-11.
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.
腹膜癌病（PC）通常表现为实体瘤晚期或复发性疾病对静脉内（IV）化疗产生耐药性。为改善PC的预后，临床已引入腹腔内（IP）化疗，III期试验证明IP化疗优于IV化疗，尤其是在晚期卵巢癌中。然而，IP化疗导致的毒性增加会使化疗周期减少，这无法保证其有效性。此外，在晚期卵巢癌中，减瘤手术后的热灌注IP化疗与IV化疗相比也显示出生存改善。尽管如此，药物的分布和扩散有限，以及20%的3级或4级肾和肝毒性阻碍了其应用的扩大。另一方面，已知加压腹腔内气溶胶化疗（PIPAC）通过在腹腔镜系统诱导的12 mmHg腹腔压力下以气溶胶形式将药物输送至壁层和脏层腹膜而发挥作用。尽管PIPAC使用的剂量相当于IV化疗耐药药物剂量的约1%且为常温，但由于药物分布和渗透深度增加，通过重复应用PIPAC可能会改善肿瘤反应和生活质量。然而，药物分布不均仍然是PIPAC的主要限制，因为在腹腔镜手术期间喷嘴放置在距肿瘤组织可能较远的位置。因此，我们开发了一种新型的PIPAC原型，即旋转腹腔内加压气溶胶化疗（RIPAC）系统，因为喷嘴的旋转和喷雾方向的改变有助于药物均匀分布，并在模拟人体的猪模型中比较了PIPAC和RIPAC之间的药物分布。结果，在药物向脏层和壁层腹膜的分布方面，RIPAC比PIPAC更有效。
