title: Radiation-induced microenvironments--the molecular basis for free flap complications in the pre-irradiated field?
abstract: OBJECTIVE
  The effect of preoperative radio- or radiochemotherapy on the survival of free flaps used for head and neck reconstruction is reported in a contradictory way. Although there is a lot of knowledge on radiation-induced wound healing disorders from animal models there are no investigations on human patients so far. Our prospective study aimed at clarifying the effect of radiotherapy on clinically apparent free flap complications and on correlating them with radiation-induced extracellular matrix (ECM) remodeling.
  
  
  METHODS
  Healing of 114 free flaps was monitored in a prospective study and correlated with different anamnestic features, such as diabetes and radio- or radiochemotherapy using multivariate regression. During the operation connective tissue biopsies were harvested from the graft beds and analyzed for Transforming Growth Factor (TGF)-beta(1)-expression by means of Western blotting as well as Tissue Inhibitor of Matrix-Metallo-Proteinase (TIMP)-1 and Matrix-Metallo-Proteinase (MMP)-1 by immunohistochemistry.
  
  
  RESULTS
  History of radio- or radiochemotherapy was the only factor significantly predicting free flap complications. Radiochemotherapy resulted in a significant increase in TGF-beta(1)- and TIMP-1-expression, while MMP-1-expression was not significantly altered. Radiotherapy alone significantly increased TIMP-1-expression without detectable effects on TGF-beta(1) and MMP-1.
  
  
  CONCLUSIONS
  Radio- and radiochemotherapy alter graft bed ECM organization prior to surgery. This alteration impacts significantly on free flap survival in the pre-irradiated field.
authors.affiliation: Department of Oral- and Cranio-Maxillofacial Surgery/Plastic Surgery, University of Jena, Germany. cornelia.mueller1@med.uni-jena.de
authors.forename: Cornelia Katharina
authors.initials: CK
authors.lastname: Mueller
authors.forename: Stefan
authors.initials: S
authors.lastname: Schultze-Mosgau
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy* / Q000601:surgery; D005260:Female; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000532:radiotherapy* / Q000601:surgery; D011829:Radiation Dosage; D013524:Surgical Flaps / Q000009:adverse effects* / Q000473:pathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014945:Wound Healing / Q000528:radiation effects
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; D020781:Matrix Metalloproteinase 1