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Distribution pattern and penetration depth of doxorubicin after pressurized intraperitoneal aerosol chemotherapy (PIPAC) in a postmortem swine model

Journal of Cancer Research and Clinical Oncology volume 142, pages 2275–2280 (2016)Cite this article

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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Affiliations

  1. Department of General Surgery and Therapy Center for Peritonealcarcinomatosis, Marien Hospital Herne, Ruhr University Bochum, Hölkeskampring 40, 44625, Herne, Germany

    Veria Khosrawipour, Tanja Khosrawipour & Jürgen Zieren

  2. Basic Research Laboratory, Department of General Surgery, Marien Hospital Herne, Ruhr University Bochum, Herne, Germany

    Veria Khosrawipour, Tanja Khosrawipour, Alexander Jens Peter Kern, Aras Osma, Burak Kabakci & David Diaz-Carballo

  3. Department of Radiation Oncology, Marien Hospital Herne, Ruhr University Bochum, Herne, Germany

    Khashayar Fakhrian

  4. Department of Neuroanatomy and Molecular Brain Research, Ruhr University Bochum, Bochum, Germany

    Eckart Förster

Authors
  1. Veria Khosrawipour
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  2. Tanja Khosrawipour
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  3. Alexander Jens Peter Kern
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  4. Aras Osma
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  5. Burak Kabakci
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  6. David Diaz-Carballo
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  7. Eckart Förster
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  8. Jürgen Zieren
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  9. Khashayar Fakhrian
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Corresponding author

Correspondence to Veria Khosrawipour.

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Conflict of interest

All authors declare that they have no conflict of interest.

Human and animals rights

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.

Ethical approval

An approval of the Local Board on Animal Care was obtained.

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Cite this article

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

Keywords

  • Ex vivo swine
  • Whole abdominal radiation
  • Intraperitoneal chemotherapy
  • PIPAC
  • Peritoneal carcinomatosis