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Successful in vivo tumor visualization using fluorescence laparoscopy in a mouse model of disseminated alveolar rhabdomyosarcoma

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Abstract

Background

Surgery for rhabdomyosarcoma is challenging due to a lack of clear delineation between tumor and surrounding tissue. Mutilating surgery can be necessary in difficult tumor localizations. Therefore, novel diagnostic and therapeutic modalities are required. The aim of this study was to evaluate the in vivo tumor detection of RMS using fluorescence laparoscopy and to analyze the efficacy of hypericin-induced photodynamic therapy in a mouse model.

Methods

Seventeen NOD/LtSz-scid IL2Rγnull-mice were divided into four groups. In group 1, mCherry-expressing tumor cells and in group 2–4 non-transfected tumor cells were xenotransplanted. Three weeks later, one fluorochrome per group (ICG, ICG-cetuximab, hypericin) was injected. Fluorescence laparoscopy was carried out and tumors were resected using fluorescence guidance. In the hypericin group, photodynamic therapy was performed using blue light and apoptosis was evaluated by TUNEL test.

Results

A clear discrimination between healthy and tumor tissue was feasible by fluorescending properties with mCherry expressing tumor cells and after injection of hypericin. No fluorescence was detected in mice injected with ICG and ICG-labeled cetuximab. Hypericin photodynamic therapy induced apoptosis of tumor cells after exposure to blue light.

Conclusions

Intraoperative photodynamic diagnosis was feasible using mCherry-transfected tumor cells or hypericin. Additionally, intraoperative photodynamic therapy was possible and effective.

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Acknowledgments

This work was supported by KARL STORZ GmbH & Co. KG, Tuttlingen, Germany, which provided us the laparoscopic equipment and the technical assistance. We also thank Hannes Schramm (Department of Photography, University Hospital Tübingen, Tübingen, Germany) for his support in realization of the figures.

Disclosures

Cristian Urla, Sorin Armeanu-Ebinger, Jörg Fuchs, and Guido Seitz have no conflicts of interest or financial ties to disclose.

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Authors and Affiliations

  1. Department of Pediatric Surgery and Pediatric Urology, University Children’s Hospital Tübingen, Hoppe-Seyler-Strasse 3, 72076, Tübingen, Germany

    Cristian Urla, Sorin Armeanu-Ebinger, Jörg Fuchs & Guido Seitz

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  1. Cristian Urla
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  2. Sorin Armeanu-Ebinger
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  3. Jörg Fuchs
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  4. Guido Seitz
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Corresponding author

Correspondence to Sorin Armeanu-Ebinger.

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Cristian Urla and Sorin Armeanu-Ebinger have contributed equally to the authorship of this paper.

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Urla, C., Armeanu-Ebinger, S., Fuchs, J. et al. Successful in vivo tumor visualization using fluorescence laparoscopy in a mouse model of disseminated alveolar rhabdomyosarcoma. Surg Endosc 29, 1105–1114 (2015). https://doi.org/10.1007/s00464-014-3770-9

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