Abstract
Background
Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel approach to delivering intraperitoneal chemotherapy (IPC) as a pressurized aerosol. One of the assumed advantages is the homogeneous drug distribution in the intraperitoneal cavity compared with conventional liquid in situ chemotherapy. However, to date, the spatial drug distribution pattern of PIPAC has not been investigated in detail.
Methods
Doxorubicin was aerosolized in an ex vivo PIPAC model containing native fresh tissue samples of swine peritoneum at a pressure of 12 mmHg CO2 at 36 °C. In the center of the top cover of the PIPAC chamber, a PIPAC micropump was installed. Tissue specimens were placed as follows: (A) bottom of the plastic box, (B) margin of the aerosol jet covered with a bilaterally open tunnel, (C) side wall, and (D) top cover, respectively. In-tissue doxorubicin penetration was measured using fluorescence microscopy on frozen thin sections.
Results
The depth of doxorubicin penetration was found to be significantly higher in tissues directly exposed to the aerosol jet (A: 215 ± 79 µm) compared with the side wall (C: 77 ± 18 µm; p < 0.01) and the top of the box (D: 65 ± 17 µm; p < 0.01). The poorest penetration was observed for peritoneal tissue covered under a bilaterally open plastic tunnel (B: 34 ± 19 µm; p < 0.001).
Conclusions
The study data suggest that the spatial drug distribution pattern of ex vivo PIPAC is heterogeneous.
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Author Contribution
Khosrawipour Veria: Study design, laboratory analysis, data acquisition and drafting of the manuscript. Khosrawipour Tanja: Laboratory analysis, data acquisition and manuscript drafting. Diaz-Carballo David: Supervision of the experiments, statistical analysis, data interpretation and manuscript drafting. Förster Eckart: Labor analysis, data acquisition and drafting of the manuscript. Zieren Jürgen: Supervision of the study, drafting and critical revision for important intellectual content of the manuscript. Giger-Pabst Urs: Study design, supervision of the study, data interpretation, drafting and critical revision for important intellectual content of the manuscript.
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This study was financed by institutional funds. There are no conflict of interest or financial ties to disclose.
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Khosrawipour Veria and Khosrawipour Tanja have equally contributed to this study, and both authors should be considered first author.
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Khosrawipour, V., Khosrawipour, T., Diaz-Carballo, D. et al. Exploring the Spatial Drug Distribution Pattern of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC). Ann Surg Oncol 23, 1220–1224 (2016). https://doi.org/10.1245/s10434-015-4954-9
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DOI: https://doi.org/10.1245/s10434-015-4954-9