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Increasing the efficiency of hyperthermic intraperitoneal chemotherapy (HIPEC) by a combination with a photosensitive drug in pediatric rhabdomyosarcoma
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  • Benedikt Wagner,
  • Anna Adamus,
  • Laura Hempfling,
  • Reza Vahdad,
  • Antje Haap-Hoff,
  • Benedikt Heinrich,
  • Olalla Vázquez,
  • Paul Jank,
  • Carsten Denkert,
  • Guido Seitz
Benedikt Wagner
University Hospital of Giessen and Marburg Campus Marburg

Corresponding Author:bennewe@gmx.de

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Anna Adamus
University Hospital of Giessen and Marburg Campus Marburg
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Laura Hempfling
University Children's Hospital Marburg
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Reza Vahdad
University Hospital of Giessen and Marburg Campus Marburg
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Antje Haap-Hoff
Karl Storz SE and Co KG
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Benedikt Heinrich
Philipps-Universität Marburg
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Olalla Vázquez
Philipps-Universität Marburg
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Paul Jank
University Hospital of Giessen and Marburg Campus Marburg
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Carsten Denkert
University Hospital Marburg Center for Pathology
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Guido Seitz
University Children's Hospital Marburg
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Abstract

Background: Cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) is an option in advanced peritoneal sarcomatosis. Nevertheless, CRS and HIPEC are not successful in all patients. An enhancement of HIPEC using photodynamic therapy might be beneficial. Therefore, a combination of the photosensitizer Hypericin (HYP) with HIPEC was evaluated in an animal model. Procedure: An established HIPEC animal model for rhabdomyosarcoma (NOD/LtSz-scid IL2Rγnullmice, n=80) was used. All groups received HYP (100 µg/200 µl) intraperitoneally with and without cisplatin-based (30 or 60 mg/m2) HIPEC (37 or 42 °C, for 60 min) (five groups, each n=16). Tumor dissemination was documented visually and by using HYP-based fluorescence guidance. HYP-based photodynamic therapy (PDT) of the tumor was performed. Finally, tissue samples were evaluated regarding proliferation (Ki-67) and apoptosis (TUNEL). Results: HYP uptake even in smallest tumor nodes (< 1 mm) was found. HYP-based fluorescence guidance allowed a better tumor detection in comparison to visual inspection. Immunohistochemistry revealed HYP penetration across the tumor surface. HYP-based PDT without HIPEC induced marginal apoptotic effects at the tumor surface. Combining HYP with HIPEC revealed cisplatin concentration dependent decrease in proliferation capacity and induction of apoptosis across determined cell layers of the tumor surfaces. Conclusion: HYP as fluorescent photosensitizer offers an intraoperative diagnostic advantage detecting intraperitoneal tumor dissemination. The combination of HYP and cisplatin-based HIPEC was feasible in vivo showing enhanced effects on tumor proliferation and apoptosis induction across the tumor surface. Further studies combining HYP and HIPEC will follow to establish a clinical application.
13 Dec 2021Submission Checks Completed
13 Dec 2021Assigned to Editor
13 Dec 2021Submitted to Pediatric Blood & Cancer
21 Dec 2021Reviewer(s) Assigned
10 Jan 2022Review(s) Completed, Editorial Evaluation Pending
29 Jan 2022Editorial Decision: Revise Major
24 Apr 2022Submission Checks Completed
24 Apr 2022Assigned to Editor
24 Apr 20221st Revision Received
14 May 2022Reviewer(s) Assigned
01 Jun 2022Review(s) Completed, Editorial Evaluation Pending
09 Jun 2022Editorial Decision: Accept
22 Jun 2022Published in Pediatric Blood & Cancer. 10.1002/pbc.29864