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Technical description of the microinjection pump (MIP®) and granulometric characterization of the aerosol applied for pressurized intraperitoneal aerosol chemotherapy (PIPAC)

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Abstract

Background

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is gaining acceptance in clinical practice, but detailed information about the microinjection pump (MIP®), the generated aerosol and drug distribution is missing.

Analytical methods

Ex vivo granulometric analyses by means of laser diffraction spectrometry were performed for MIP® aerosol characterization. Beside the standard operation conditions, the impact of the volumetric liquid flow rate on the aerosol characteristics was investigated with different liquids. Granulometric results as well as the local drug distribution were verified by ex vivo gravimetric analyses. On the basis of determined MIP® characteristics, the aerosol droplet size, which is necessary for a homogenous intra-abdominal drug distribution, was calculated.

Results

Granulometric analyses showed that the MIP® aerosol consists of a bimodal volume-weighted particle size distribution (PSD3) with a median droplet diameter of x 50,3 = 25 µm. Calculations reveal that the droplet size for a homogenous intra-abdominal drug distribution during PIPAC therapy should be below 1.2 µm. We show that >97.5 vol% of the aerosolized liquid is delivered as droplets with ≥3 µm in diameter, which are primarily deposited on the surface beneath the MIP® by gravitational settling and inertial impaction. These findings were confirmed by ex vivo gravimetric analyses, where more than 86.0 vol% of the aerosolized liquid was deposited within a circular area with a diameter of 15 cm.

Conclusions

The granulometric aerosol properties, as well as the aerodynamic conditions achieved by standard MIP® operation, do not support the idea of widespread or homogenous drug distribution in the abdominal cavity.

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Abbreviations

A D :

Cross-sectional area (m²)

d D :

Diameter of nozzle orifice (m)

h O :

Operation distance between MIP® outlet and target surface (m)

IPC:

Intraperitoneal chemotherapy

HELOS:

Helium–neon laser for optical spectrometry

HIPEC:

Heated intraperitoneal chemotherapy

LIPC:

Liquid intraperitoneal chemotherapy

MIP® :

Microinjection pump (Reger Medizintechnik, Rottweil, Germany)

p C :

Overpressure in capnoperitoneum (Pa)

p MIP :

System pressure of MIP® (Pa)

PC:

Peritoneal carcinomatosis

PSD:

Particle size distribution

PSD0 :

PSD, weighted by number

PSD3 :

PSD, weighted by volume

PIPAC:

Pressurized intraperitoneal aerosol chemotherapy

q *0 :

Transformed distribution density, weighted by number (−)

q 3 :

Distribution density, weighted by volume (1/m)

q *3 :

Transformed distribution density, weighted by volume (−)

Q 3 :

Cumulative distribution/function of PSD3 (−)

Q L :

Volumetric liquid flow rate (L/s)

Stk:

Stokes number (−)

x :

Particle/droplet diameter (m)

x 50,3 :

Median diameter of PSD3 (m)

v D :

Droplet velocity (m/s)

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Authors’ contributions

Daniel Göhler performed study design, laboratory analysis, data interpretation, drafting and critical revision for important intellectual content of the manuscript. Veria Khosrawipour carried out study design, laboratory analysis, data acquisition, drafting and critical revision for important intellectual content of the manuscript. Tanja Khosrawipour and David Diaz-Carballo were involved in drafting and critical revision for important intellectual content of the manuscript. Thomas Albert Falkenstein took part in laboratory analysis. Jürgen Zieren contributed to study design, supervision of the study, drafting and critical revision for important intellectual content of the manuscript. Michael Stintz performed data interpretation and critical revision for important intellectual content of the manuscript. Urs Giger-Pabst conducted study design, supervision of the study, laboratory analysis, data interpretation, drafting and critical revision for important intellectual content of the manuscript.

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    Authors and Affiliations

    1. Research Group Mechanical Process Engineering, Institute of Process Engineering and Environmental Technology, Technische Universität Dresden, Dresden, Germany

      Daniel Göhler & Michael Stintz

    2. Department of General Surgery and Therapy Center for Peritonealcarcinomatosis, St. Mary’s Hospital Herne, Ruhr University Bochum, Hölkeskampring 40, 44625, Herne, Germany

      Veria Khosrawipour, Jürgen Zieren & Urs Giger-Pabst

    3. Basic Research Laboratory Department of Surgery, St. Mary’s Hospital Herne, Ruhr University Bochum, Bochum, Germany

      Veria Khosrawipour, Tanja Khosrawipour, Thomas Albert Falkenstein & Urs Giger-Pabst

    4. Department of Hematology and Medical Oncology, St. Mary’s Hospital Herne, Ruhr University Bochum, Bochum, Germany

      David Diaz-Carballo

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    1. Daniel Göhler
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    Correspondence to Urs Giger-Pabst.

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    Disclosure

    This study was funded by institutional funds. Daniel Göhler, Veria Khosrawipour, Tanja Khosrawipour, David Diaz-Carballo, Thomas Albert Falkenstein, Jürgen Zieren, Michael Stintz and Urs Giger-Pabst have no conflicts of interest or financial ties to disclose.

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    Daniel Göhler and Veria Khosrawipour equally contributed to the study and both should be considered as first authors.

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    Göhler, D., Khosrawipour, V., Khosrawipour, T. et al. Technical description of the microinjection pump (MIP®) and granulometric characterization of the aerosol applied for pressurized intraperitoneal aerosol chemotherapy (PIPAC). Surg Endosc 31, 1778–1784 (2017). https://doi.org/10.1007/s00464-016-5174-5

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    • DOI: https://doi.org/10.1007/s00464-016-5174-5

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