Vascular Endothelial Growth Factor in Response to Drug Therapy in Patients with Infantile Hemangioma

Abstract

Infantile hemangioma (IH) is the most common form of benign vascular tumors of infancy that arises from the abnormal proliferation of endothelial cells and enhanced angiogenesis. Vascular endothelial growth factor A (VEGF-A) has been proved to be a master regulator of angiogenesis and vasculogenesis with a higher levels in IH tumors in the proliferating phase compared to the regression phase. About 10% of infantile hemangiomas require intervention during infancy because the lesion poses a threat to life or function or causes tissue distortion or destruction. Current treatments for IH include: steroids either systemic, intralesional or topical steroids, interferon- alpha, vincristine, laser therapy, cryotherapy, surgery and beta blockers (propranolol). Pharmacologic effect of propranolol on IHs is not well understood, may be involving the three following different molecular mechanisms: vasoconstriction, inhibition of angiogenesis and induction of apoptosis. We aimed to study the effect of drug therapy on the level of vascular endothelial growth factor (VEGF) in patients with infantile hemangioma and to compare its level in patients with IH in regressive phase. A prospective study was performed at Pediatric combined clinic of vascular anomalies at Pediatric Department; Ain Shams University from December 2013 to June 2015. Full history was taken from parents including gender, birth weight, number of gestation, maternal age, age of presentation), then general and system examination. Local examination of lesions for determination of phase, types according to its depth, complications and dimensions of the hemangioma based on direct measurement and photographic analysis. Our patient group were treated with oral propranolol (70.8%), oral propranolol with oral steroids (12.5%), intralesional steroids (12.5%) and intralesional steroids with oral propranolol (4.2%). Clinical response to therapy was measured by blinded volume estimation at first visit and 3 month later by using estimated surface area in superficial flat lesions and serial hemispheric measurements of tumor volume for deep and mixed lesions. Serum blood samples were taken for all patients in the first visit for VEGF analysis before treatment. Patients were given drug therapy for 3 months. The studied patient group comprised 47 patients, aged between 2 months to16 months, with IH in proliferative phase (13 males, 34females).They were compared to patients with IH in regression phase; they included 9 children (4 boys and 5 girls). Patients were diagnosed between 2 months after birth to 16 months of age (median 4 months); 89.4% of the studied patients had single lesions, 51.1% of them had superficial type and 48.9% had lesions in the face of non-parotid site.