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The Collagenase of the Bacterium Clostridium histolyticum in the Treatment of Irradiation-Induced Capsular Contracture

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  • Basic Science/Experimental
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Abstract

Background

Irradiation therapy is an important pillar in the treatment of breast cancer. However, it can trigger capsular fibrosis, the most significant complication of implant-based breast reconstruction. As collagen is the main component of fibrotic capsules, the collagenase of the bacterium Clostridium histolyticum poses a potential treatment option for this pathological condition.

Methods

Thirty-six rats received miniature silicone implants on their backs. On day 1, the implant sites of two groups were irradiated with 10 Gy. On day 120, one irradiated group received collagenase injections into the implant pockets (n = 12). Non-irradiated (n = 12) and irradiated capsules (n = 12) were injected with plain solvent solution serving as controls. Data were analyzed by means of in vivo imaging, histology, immunohistochemistry and gene expression analysis.

Results

Compared with both controls, the injection of collagenase led to significantly thinner capsules. This was verified by in vivo imaging and histology. Although irradiation provoked alterations in capsule collagen structure and vessel wall thickness, the application of collagenase resulted in a significant reduction of collagen density. This was accompanied by an up-regulation of VEGF-A gene expression. Of note, hematoma formation inside the implant pocket occurred in two cases after collagenase injection.

Conclusions

The collagenase of the bacterium Clostridium histolyticum is effective in degrading irradiation-induced capsular fibrosis around silicone implants. Hematoma formation occurred most likely because of irradiation-induced alterations in vessel wall architecture and capsule vascularization. Further studies need to be performed to address the clinical safety of this novel treatment option.

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Acknowledgements

We want to acknowledge funding support through an Educational Research Grant from Endo Pharmaceuticals. We would like to thank Polytech (Dieburg, Germany) for providing the miniature silicone implants.

Funding

This study was funded by Endo Pharmaceuticals Inc., Malvern, USA, through an Educational Research Grant. Funders did not influence study design, the collection, analysis and interpretation of data, the writing of the manuscript and the decision to submit the manuscript for publication.

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Authors and Affiliations

  1. Department of Hand-, Plastic and Reconstructive Surgery, Burn Trauma Center, BG Trauma Center Ludwigshafen, University of Heidelberg, Ludwig-Guttmann-Strasse 13, 67071, Ludwigshafen, Germany

    Yannick F. Diehm, Christoph Hirche, Dimitra Kotsougiani, Ulrich Kneser & Sebastian Fischer

  2. Division of Plastic Surgery, Department of Surgery, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis St, Boston, 02115, USA

    Yannick F. Diehm, Bohdan Pomahac & Sebastian Fischer

  3. Toxicology and Chemotherapy Unit, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120, Heidelberg, Germany

    Martin R. Berger

  4. Department of Gynecology and Obstetrics, University of Heidelberg, Im Neuenheimer Feld 440, 69120, Heidelberg, Germany

    Jörg Heil & Michael Golatta

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  1. Yannick F. Diehm
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Correspondence to Sebastian Fischer.

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The authors declare that they have no conflict of interest.

Ethical Approval

All applicable institutional and national guidelines for care and use of animals were followed (AEP No.: 05086).

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Diehm, Y.F., Hirche, C., Berger, M.R. et al. The Collagenase of the Bacterium Clostridium histolyticum in the Treatment of Irradiation-Induced Capsular Contracture. Aesth Plast Surg 43, 836–844 (2019). https://doi.org/10.1007/s00266-018-1267-y

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  • DOI: https://doi.org/10.1007/s00266-018-1267-y

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