Radiotherapy as a risk factor for free flap failure has been widely debated. The purpose of this study was to investigate vascular complications in free flap surgery at a center advocating preoperative radiotherapy. On the basis of previous experimental studies, we also aimed to investigate temporal aspects of vascular complications in both arteries and veins. Furthermore, we aimed to study the effect of tissue plasminogen activator (tPA), because irradiated microvascular recipient vessels are associated with impaired fibrinolysis.A retrospective review was conducted for 344 consecutive head and neck microvascular reconstructions. Radiotherapy was administered previously in 283 (82%) of the cases, median dose 64 Gy. Flap outcome, vascular complications, and salvage attempts were identified, along with time elapsed from completed radiotherapy, described as early (<6 weeks), delayed (6-15 weeks) and late (>15 weeks) reconstructions.Total flap loss was more common in irradiated cases (P = 0.035), among which flap failure increased with time elapsed from the last radiotherapy session to surgery (P = 0.021). Among 30 registered vascular complications, venous thrombosis was the most common type and increased in delayed, compared to early, reconstructions (P = 0.012). Increased salvage rates were observed when tPA was administered intraoperatively (P = 0.015).The present study indicates that previous radiotherapy is a risk factor for head and neck free flap failure, especially in delayed reconstructions. This may be linked to previous findings of impaired fibrinolysis in irradiated microvascular recipient veins, which is further supported by the beneficial effect of tPA during salvage surgery. We emphasize the importance of early reconstruction after radiotherapy and suggest that there is a role for fibrinolytic agents during free flap salvage surgery in previously irradiated subjects.

BackgroundClinical studies have shown that radiotherapy increases the risk of cardiovascular disease at irradiated sites years after exposure. However, there is a lack of biological explanations in humans. We therefore examined human blood vessels exposed to radiotherapy and studied C-reactive protein (CRP) and pentraxin 3 (PTX3), a new marker for adverse cardiovascular outcome dependent on TNF- alpha (TNFα) or interleukin-1beta (IL-1β) expression.MethodsPairs of irradiated and non-irradiated human conduit arteries and veins were harvested from the same patient during autologous free tissue transfer for cancer-reconstruction at a median time of 48 weeks after radiotherapy. Differential gene expression was studied using qRT-PCR, confirmed by immunohistochemistry and cellular origins determined by immunofluorescence.ResultsGene expression in irradiated arteries compared to non-irradiated showed a consistent up-regulation of PTX3 in all patients and in a majority of veins (p < 0.001). Both TNFα and IL-1β were increased in irradiated compared to non-irradiated arteries (p < 0.01) and IL-1β correlated to the PTX3 expression (p = 0.017). Immunohistochemical and immunofluorescence staining confirmed an increased expression of PTX3 in endothelial cells, macrophages and smooth muscle cells.ConclusionsThe sustained expression of PTX3 in arteries and veins tie biological evidence in humans to clinical studies and encourage further exploration of innate immunity in the pathogenesis of a radiation-induced vasculopathy.