[Vascularization of free myocutaneous gracilis flaps in replacement  transplantation after preoperative radiotherapy. An experimental study].
BACKGROUND
Following preoperative radiotherapy prior to ablative surgery of squamous epithelial carcinomas of the head and neck region, inflammatory changes to the connective tissue and vascular endothelium are observed. These processes may lead to a delay in healing of free flaps in the irradiated transplant bed. The aim of the study was to investigate qualitative and quantitative changes in vascularization in irradiated and regular transplant beds.


METHODS
In Wistar rats (male, weight 300 to 500 g) undergoing preoperative irradiation of the neck region with 3 times 10 Gy (30 animals) and 5 times 10 Gy (30 animals) and non-irradiated rats (42 animals), a free myocutaneous gracilis flap taken from the groin was transplanted to the irradiated region of the neck. The time interval between irradiation and transplantation was 4 weeks. On day 3, 4, 5, 7, 14 and 28 post operation, the capillary sprouting, structural changes and the distribution patterns were analyzed by H & E and immunohistochemical staining (goat-F[ab]-2-anti-von Willebrand factor antibody). Three histological sections (2 to 4 microns) per sample were investigated histomorphometrically, qualitatively and quantitatively (ratio capillary area/total area, and capillary lumen) by NH-image-digitized measurement. A statistical analysis was performed using the Mann-Whitney test.


RESULTS
In contrast to non-irradiated rats, irradiated animals showed a qualitatively reduced and a more irregular capillary distribution with more marked pericapillary fibrosis in the irradiated transplant bed. Quantitatively, the ratio capillary area/total area, as a marker of improved capillarization was significantly reduced in the transition area transplant/irradiated transplant bed and in irradiated transplant bed tissues in contrast to the non-irradiated control group (p = 0.004). Also, from day 14 to 28 a significant decrease was found in the transition area between transplanted tissues and irradiated transplant bed tissues in irradiated animals (p = 0.005). The median capillary lumen size also decreased significantly in the transition area and transplant bed in 30 Gy and 50 Gy irradiated animals (p < 0.001 and p = 0.003).


CONCLUSIONS
Following irradiation, vascularization of the soft tissue flaps is both reduced and delayed. This is evidence of delayed healing of soft tissue transplants in transplant beds irradiated prior to surgical interventions. Further optimization of the time interval between radiotherapy and surgery and the total radiation dose are therefore needed.
Schultze-Mosgau
S
S
Klinik und Poliklinik für Mund-, Kiefer-, Friedrich-Alexander-Universität Erlangen-Nürnberg. stefan.schultze-mosgau@mkg.imed.uni-erlangen.de
Rödel
F
F
Keilholz
L
L
Grabenbauer
G G
GG
Wiltfang
J
J
Radespiel-Tröger
M
M
Sauer
R
R
Neukam
F W
FW
D000818:Animals; D002196:Capillaries / Q000166:cytology / Q000502:physiology*; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy* / Q000601:surgery*; D006258:Head and Neck Neoplasms / Q000532:radiotherapy* / Q000601:surgery*; D007150:Immunohistochemistry; D008297:Male; D018919:Neovascularization, Physiologic; D051381:Rats; D017208:Rats, Wistar; D013524:Surgical Flaps; D014841:von Willebrand Factor
D014841:von Willebrand Factor