J Cancer 2020; 11(24):7209-7215. doi:10.7150/jca.48519

Research Paper

Intraperitoneal chemotherapy of the peritoneal surface using high-intensity ultrasound (HIUS): investigation of technical feasibility, safety and possible limitations

Hien Lau1, Tanja Khosrawipour1,2✉, Agata Mikolajczyk3, Piotr Frelkiewicz4, Jakub Nicpon4, Mohamed Arafkas5, Alessio Pigazzi1, Wolfram Trudo Knoefel2, Veria Khosrawipour1,3

1. Division of Colorectal Surgery, Department of Surgery, University of California Irvine, Orange, USA
2. Department of Surgery (A), University-Hospital Düsseldorf, Heinrich-Heine University Düsseldorf, Germany
3. Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, Wroclaw, Poland
4. The Center of Experimental Diagnostics and Innovative Biomedical Technology, Wroclaw University of Environmental and Life Sciences, Wroclaw, Poland
5. Department of Plastic Surgery, Ortho-Clinic Dortmund, Dortmund, Germany

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Citation:
Lau H, Khosrawipour T, Mikolajczyk A, Frelkiewicz P, Nicpon J, Arafkas M, Pigazzi A, Knoefel WT, Khosrawipour V. Intraperitoneal chemotherapy of the peritoneal surface using high-intensity ultrasound (HIUS): investigation of technical feasibility, safety and possible limitations. J Cancer 2020; 11(24):7209-7215. doi:10.7150/jca.48519. Available from https://www.jcancer.org/v11p7209.htm

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Abstract

Introduction: The penetration of chemotherapeutic drugs into peritoneal nodules remains at levels well below 1 mm, thus significantly limiting the antitumor effect of intraperitoneal chemotherapy (IPC). Recently, high-Intensity ultrasound (HIUS) has been discovered as a potential tool to significantly improve peritoneal diffusion rates. Despite promising preliminary data, basic aspects regarding its technical feasibility, safety and possible limitations remain unclear. This study aims to enhance our current understanding of HIUS and test its applicability using an ex-vivo swine model.

Methods: Three postmortem swine were subject to laparotomy and consecutive lavage with 0.9%NaCl saline and HIUS application. For this purpose, a large HIUS radiating pen was introduced into the abdominal cavity and HIUS was applied on two of the four abdominal quadrants for 300 seconds each at an output power of 70 W, 50 % amplitude and 20 kHz frequency. Following the procedure, small intestinal tissue samples were retrieved for further analyses.

Results: Peritoneal and subperitoneal layers showed structural changes only visible on a microscopic level. The peritoneal layer was transformed into a mesh-like structure while the subperitoneal layer (depth of 142 +/- 28 µm) exhibited microcavities and vascular detachment from surrounding tissues. No bowel rupture or vascular perforations were observed.

Conclusions: Our data indicate that HIUS is a technically feasible and safe add-on procedure for intraperitoneal chemotherapy (IPC) with measurable microscopic changes on the peritoneal surface. Pretreatment of the abdominal cavity with HIUS could significantly improve IPC efficacy. Further studies are required to optimize and evaluate this novel approach.

Keywords: Intraperitoneal chemotherapy, high-intensity ultrasound, HIUS, peritoneal, surface