Abstract
Background
Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel approach delivering intraperitoneal chemotherapy by means of a pressurized aerosol. This study was conducted to evaluate the distribution pattern of doxorubicin in the abdominal cavity after PIPAC in a postmortem swine model.
Methods
Doxorubicin was aerosolized through a Micropump© (MIP) into the peritoneal cavity of two swines at a pressure of 12 mm Hg CO2 and 32 °C. To measure the distribution of the drug, 9 different positions within the abdominal cavity were sampled. In-tissue doxorubicin penetration was evaluated using fluorescence microscopy on frozen thin sections.
Results
A maximum of drug penetration was observed in the area around the MIP. The penetration in the small intestine reached a depth of 349 ± 65 µm. Penetration depth in the right upper abdomen and left upper abdomen were 349 ± 65 and 140 µm ± 26 µm, respectively. Distant areas to the MIP showed variable penetration rates between 50 and 150 µm.
Conclusions
Doxorubicin reached all areas within the peritoneum. Highest penetration rates were measured in the area around the Micropump. Further studies are warranted to evaluate and optimize the distribution and penetration of cytotoxic agent into the tissue after PIPAC.
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Abbreviations
- CO2 :
-
Carbon dioxide
- CRS:
-
Cytoreductive surgery
- HIPEC:
-
Hyperthermic intraperitoneal chemotherapy
- IAP:
-
Intra-abdominal pressure
- IPC:
-
Intraperitoneal chemotherapy
- PC:
-
Peritoneal carcinomatosis
- PCI:
-
Sugarbaker’s peritoneal cancer index
- PIPAC:
-
Pressurized intraperitoneal aerosol chemotherapy
- MIP® :
-
Micropump (Reger Medizintechnik, Rottweil, Germany)
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Funding
This study was funded by institutional funds (Department of Surgery, Marien Hospital Herne, Ruhr University Bochum).
Authors’ contribution
Veria Khosrawipour contributed to study design, laboratory analysis, data acquisition and drafting of the manuscript; Tanja Khosrawipour contributed to laboratory analysis, data acquisition and drafting of the manuscript; Alexander Jens Peter Kern contributed to laboratory analysis, data acquisition and drafting of the manuscript; Aras Osma contributed to laboratory analysis and data acquisition; Burak Kabakci contributed to experimental and study design, laboratory analysis and data acquisition; David Diaz-Carballo contributed to supervision of the experiments and critical revision for important intellectual content of the manuscript; Eckart Förster contributed to study design, drafting and critical revision for important intellectual content of the manuscript; Jürgen Zieren contributed to supervision of the study, drafting and critical revision for important intellectual content of the manuscript; Khashayar Fakhrian contributed to study design, supervision of the study, data interpretation, drafting and critical revision for important intellectual content of the manuscript.
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All authors declare that they have no conflict of interest.
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The swines were used and killed for a laparoscopic course at a local training center (Aesculap Akademie Bochum) prior to the experiment. This article does not contain any studies with human participants performed by any of the authors.
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An approval of the Local Board on Animal Care was obtained.
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Khosrawipour, V., Khosrawipour, T., Kern, A.J.P. et al. Distribution pattern and penetration depth of doxorubicin after pressurized intraperitoneal aerosol chemotherapy (PIPAC) in a postmortem swine model. J Cancer Res Clin Oncol 142, 2275–2280 (2016). https://doi.org/10.1007/s00432-016-2234-0
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DOI: https://doi.org/10.1007/s00432-016-2234-0