title: Vascularization in the transition area between free grafted soft tissues and pre-irradiated graft bed tissues following preoperative radiotherapy in the head and neck region.
abstract: BACKGROUND
  The healing of free vascular grafts in a pre-irradiated graft bed is characterized by an increased risk of wound healing disorders. For that reason, the aim of this study was to examine quantitative vascularization pattern between free vascular grafts and the pre-irradiated graft bed as a function of the preoperative irradiation dose.
  
  
  METHODS
  A total of 217 free microvascular hard and soft tissue grafts were used within 199 patients in the head and neck region to cover defects after ablative tumor surgery. Seventy-six patients (group 1) had no prior radiation (RT), 50 patients (group 2) were treated with preoperative radiochemotherapy using 40 to 50 Gy and 5-FU/cisplatin, and 73 patients (group 3) had prior RT (60-70 Gy) between 1 and 7 years before surgery. After healing of the grafts, samples were taken from 42 patients from the graft, the irradiated graft bed, and the transition area between graft and irradiated graft bed. Samples were analyzed as follows: capillary sprouting, structural changes, and distribution patterns were analyzed by immunohistochemical staining (CD34 labeling of capillary endothelium). Three histological sections (2-4 microm) per sample were examined histomorphometrically (ratio capillary area/total area, capillary lumen, and the number of capillaries) by (National Institute of Health) NIH-image-digitized measurements. A statistical analysis was performed using the Kruskal-Wallis and Mann-Whitney test (two-tailed p <.05).
  
  
  RESULTS
  The success rate of vascular grafts in group 1 (0 Gy) was 94%, in group 2 (40-50 Gy/5-FU/cisplatin) 90%, in group 3 (60-70 Gy) 84%. In contrast to groups 1 and 2, group 3 showed qualitatively reduced and more irregular capillary distribution with more marked pericapillary fibrosis in the irradiated tissue. Quantitatively, the ratio capillary area/total area, as a marker of improved capillarization, was significantly reduced in group 3 (median 0.01; IQR 0.02) compared with group 1 (median 0.53; IQR 0.32) and group 2 (median 0.44; IQR 1.40) (p <.001).
  
  
  CONCLUSIONS
  After preoperative RT, vascularization of the graft bed decreased continuously as a function of the total dose and time after RT. The results strongly advocate the use of a primary reconstruction after a time interval between 4 and 6 weeks following preoperative RT and suggest the use of a total radiation dose of 40 to 50 Gy.
authors.affiliation: Department of Oral and Maxillofacial Surgery, University of Erlangen-Nuremberg, Erlangen, Germany. stefan.schultze-mosgau@mkg.imed.uni-erlangen.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Schultze-Mosgau
authors.forename: Gerhard G
authors.initials: GG
authors.lastname: Grabenbauer
authors.forename: Martin
authors.initials: M
authors.lastname: Radespiel-Tröger
authors.forename: Joörg
authors.initials: J
authors.lastname: Wiltfang
authors.forename: Jutta
authors.initials: J
authors.lastname: Ries
authors.forename: Friedrich Wilhelm
authors.initials: FW
authors.lastname: Neukam
authors.forename: Franz
authors.initials: F
authors.lastname: Rödel
mesh_terms: D000328:Adult; D000368:Aged; D001707:Biopsy, Needle; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy* / Q000601:surgery*; D046508:Culture Techniques; D005260:Female; D006084:Graft Rejection; D006085:Graft Survival; D006258:Head and Neck Neoplasms / Q000532:radiotherapy* / Q000601:surgery*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011300:Preoperative Care; D011336:Probability; D011446:Prospective Studies; D011829:Radiation Dosage; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects; D019651:Plastic Surgery Procedures / Q000379:methods; D012016:Reference Values; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D013524:Surgical Flaps / Q000098:blood supply* / Q000473:pathology*; D013997:Time Factors; D014945:Wound Healing / Q000502:physiology / Q000528:radiation effects*