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@ARTICLE{Diehm:163679,
      author       = {Y. F. Diehm and Y. Jost and D. Kotsougiani-Fischer and V.
                      Haug and M. Splinter$^*$ and P. Häring$^*$ and M. R.
                      Berger$^*$ and J. Debus and U. Kneser and S. Fischer},
      title        = {{T}he {T}reatment of {C}apsular {C}ontracture {A}round
                      {B}reast {I}mplants {I}nduced by {F}ractionated
                      {I}rradiation: {T}he {C}ollagenase of the {B}acterium
                      {C}lostridium {H}istolyticum as a {N}ovel {T}herapeutic
                      {A}pproach.},
      journal      = {Aesthetic plastic surgery},
      volume       = {45},
      number       = {3},
      issn         = {1432-5241},
      address      = {Berlin},
      publisher    = {Springer},
      reportid     = {DKFZ-2020-01956},
      pages        = {1273-1281},
      year         = {2021},
      note         = {2021 Jun;45(3):1273-1281},
      abstract     = {Irradiation therapy limits the utilization of silicone
                      implants for breast reconstruction due to a significant risk
                      for capsular contracture. The injection of the collagenase
                      of the bacterium Clostridium histolyticum (CCH) might
                      trivialize this risk by providing a minimal-invasive
                      treatment option by capsular contracture degradation.
                      However, efficacy in degrading breast implant capsules
                      induced by fractionated irradiation remains
                      unclear.Twenty-four rats in three groups received miniature
                      silicone implants in a submuscular pocket. After 3D dose
                      calculation and treatment field definition, rats of two
                      groups underwent fractionated radiotherapy (6 × 8 Gy)
                      using a linear accelerator. A third group served as control.
                      On day 120, one irradiated group received injections of
                      0.3 mg/ml collagenase. Administration of plain solvent
                      solution served as control in the two other groups. Outcome
                      parameters included CT-imaging, histology, vessel wall
                      analysis, immunohistochemistry, chemical collagen
                      quantification and gene expression analysis.Fractioned
                      irradiation leads to a significant increase in collagen
                      deposition around silicone implants with higher capsule
                      thickness and collagen density when comparing all groups.
                      Additionally, significant alterations of collagen fiber
                      deposition were evident. Vessel wall thickness was
                      significantly increased after radiotherapy. The injection of
                      collagenase led to a significant reduction of capsule
                      thickness, collagen density and content. However, the
                      collagenase application induced a significant overexpression
                      of TGFβ1. No side effects were monitored.The CCH proved to
                      be a safe and effective approach to degrade capsule tissue
                      induced by fractionated irradiation in an animal model. This
                      may pave its way for clinical application in implant-based
                      breast reconstruction patients.This journal requires that
                      authors assign a level of evidence to each submission to
                      which Evidence-Based Medicine rankings are applicable. This
                      excludes Review Articles, Book Reviews, and manuscripts that
                      concern Basic Science, Animal Studies, Cadaver Studies, and
                      Experimental Studies. For a full description of these
                      Evidence-Based Medicine ratings, please refer to the Table
                      of Contents or the online Instructions to Authors
                      www.springer.com/00266 .},
      cin          = {E040 / G401},
      ddc          = {610},
      cid          = {I:(DE-He78)E040-20160331 / I:(DE-He78)G401-20160331},
      pnm          = {315 - Bildgebung und Radioonkologie (POF4-315)},
      pid          = {G:(DE-HGF)POF4-315},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:32968820},
      doi          = {10.1007/s00266-020-01970-1},
      url          = {https://inrepo02.dkfz.de/record/163679},
}