Electrostatic precipitation is a valuable adjunct to pressurized intraperitoneal aerosol chemotherapy : an in vitro study

BACKGROUND: Peritoneal metastasis (PM) is a frequent manifestation of gastro-intestinal and gynaecological cancer. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) was recently introduced for the treatment of irresectable PM, with promising anticancer activity and adequate tolerance. Adding electrostatic force (i.e. 7.5 – 9.5 kV; a current of ≤ 10 µA) to aerosolized particles could further enhance the pharmacologic properties of PIPAC. This procedure is termed electrostatic precipitation PIPAC or ePIPAC. This in vitro study investigated if ePIPAC could lead to a more homogeneous distribution of the drug and an increased penetration depth, enhancing the efficacy of PIPAC. MATERIALS AND METHODS: Black ink was nebulized (PIPAC n=6; ePIPAC n=6) in an in vitro box model containing fresh swine omentum on four different locations: on the bottom of the box (A), under a bilaterally open plastic tunnel (B), on the side wall of the box (C) and on the top of the box (D). The proportion (%) black ink in each specimen was macroscopically measured by ImageJ. The specimens were then embedded and cryosections (20 µm) were made. Each cryosection was scored by three independent observers for the amount of ink visible on the tissue surface using a light microscope: 0 = no ink visible; 0.5 = hardly visible line; 1 = clear line visible. To evaluate the penetration depth after PIPAC and ePIPAC, carboxylate-modified red fluorescent microspheres of 0.1 µm were nebulized (PIPAC n=6; ePIPAC n=6) in the in vitro box. The penetration depth of the microspheres was measured by confocal fluorescence imaging. RESULTS: No significant differences of the stained proportion of the specimens were found at location A (99 ± 1% vs. 98 ± 2%) and B (98 ± 2% vs. 96 ± 4%) in PIPAC and ePIPAC, respectively. Strikingly, a significant (p=0.015) increase was found in location C (68 ± 27% vs. 93 ± 9%) and D (23 ± 35% vs. 84 ± 30%) after ePIPAC, indicating a more homogeneous distribution pattern. These findings were in accordance with the mean cryosection scores: histological ink staining did not differ on location A (0.89 ± 0.17 vs. 1 ± 0.00) and B (0.89 ± 0.20 vs. 0.94 ± 0.09) after PIPAC and ePIPAC, respectively. However, specimens on locations C (0.39 ± 0.33 vs. 0.94 ± 0.09; p=0.0065) and D (0.22 ± 0.36 vs. 0.78 ± 0.20; p=0.022) were significantly more stained after ePIPAC than after PIPAC. Results regarding the penetration depth of the fluorescently labelled microspheres will also be presented. CONCLUSIONS: The addition of electrostatic precipitation to PIPAC significantly enhances aerosol distribution pattern in an in vitro box model. Consequently, ePIPAC may allow more homogeneous and efficient drug uptake, and improve the management of irresectable PM. At the same time, ePIPAC may allow to use a lower drug dose, and lead to less side effects.

Jaar van publicatie:2020

Toegankelijkheid:Closed