ABSTRACT
The clinically beneficial effect of low frequency pulsed electromagnetic fields (ELF-PEMF) on bone healing has been described, but the exact mechanism of action remains unclear. A recent study suggests that there is a direct autocrine mitogenic effect of ELF-PEMF on angiogenesis. The hypothesis of this study is that ELF-PEMF also has an indirect effect on angiogenesis by manipulation of vascular endothelial growth factor (VEGF)-A-based paracrine intercellular communication with neighboring osteoblasts. Conditioned media experiments measured fetal rat calvarial cell (FRC) and human umbilical vein endothelial cell (HUVEC) proliferation using tritiated thymidine uptake. We demonstrate that ELF-PEMF (15 Hz, 1.8 mT, for 8 h) has an indirect effect on the proliferation rate of both endothelial cells and osteoblasts in vitro by altering paracrine mediators. Conditioned media from osteoblast cells stimulated with ELF-PEMF increased endothelial proliferation 54-fold, whereas media from endothelial cells stimulated with ELF-PEMF did not affect osteoblast proliferation. We examined the role of the pro-angiogenic mediator VEGF-A in the mitogenic effect of ELF-PEMF-stimulated osteoblast media on endothelial cells. The production of VEGF-A by FRC as measured by ELISA was not changed by exposure to PEMF, and blocking experiments demonstrated that the ELF-PEMF-induced osteoblast-derived endothelial mitogen observed in these studies was not VEGF-A, but some other soluble angiogenic mediator.
Subject(s)
Electromagnetic Fields , Endothelium, Vascular/cytology , Osteoblasts/radiation effects , Vascular Endothelial Growth Factor A/physiology , Animals , Cell Proliferation/drug effects , Cell Proliferation/radiation effects , Cells, Cultured , Culture Media, Conditioned/pharmacology , Culture Media, Conditioned/radiation effects , Humans , Osteoblasts/drug effects , Osteoblasts/metabolism , Rats , Umbilical Veins/cytologyABSTRACT
BACKGROUND: A major source of morbidity after abdominoperineal resection (APR) after external beam pelvic radiation is perineal wound complications, seen in up to 66% of cases. Our purpose was to determine the effect of rectus abdominus myocutaneous (RAM) flap reconstruction on perineal wound morbidity in this population. METHODS: The study group consisted of 19 patients with anorectal cancer treated with external beam pelvic radiation followed by APR and RAM flap reconstruction of the perineum. A prospectively collected database was queried to identify a control group (n = 59) with anorectal cancer treated with similar radiation doses that subsequently underwent an APR without a RAM flap during the same time period. Comparison of percentages was performed with a two-sided Fisher's exact test, and comparison of means was performed with Wilcoxon's test. RESULTS: Perineal wound complications occurred in 3 (15.8%) of the RAM flap patients and 26 (44.1%) of the control patients (P = .03). The incidence of other complications was not different between groups (42.1% vs. 42.4%; P = .8). Despite an increased number of anal squamous tumors, an increased vaginectomy rate, increased use of intraoperative radiotherapy, and an increased proportion of cases with recurrent disease, the flap group had a significantly lower rate of perineal wound complications relative to the control group. CONCLUSIONS: Perineal closure with a RAM flap significantly decreases the incidence of perineal wound complications in patients undergoing external beam pelvic radiation and APR for anorectal neoplasia. Because other complications are not increased, RAM flap closure of the perineal wound should be strongly considered in this patient population.
