Angiogenesis and vascular malformations: Antiangiogenic drugs for treatment of gastrointestinal bleeding

Treatment of gastrointestinal bleeding in patients with angiodysplasias and Osler's disease (hereditary hemorrhagic teleangiectasia) is clinically challenging. Frequently, vascular malformations occur as multiple disseminated lesions, making local treatment an unfavorable choice or impossible. After local therapy, lesions often recur at other sites of the intestine. However, as there are few therapeutic alternatives, repeated endoscopic coagulations or surgical resections are still performed to prevent recurrent bleeding. Hormonal therapy has been employed for more than 50 years but has recently been shown to be ineffective. Therefore, new therapeutic strategies are required. Understanding of the pathophysiology of angiogenesis and vascular malformations has recently substantially increased. Currently, multiple inhibitors of angiogenesis are under development for treatment of malignant diseases. Experimental and clinical data suggest that antiangiogenic substances, which were originally developed for treatment of malignant diseases, may also represent long-awaited specific drugs for the treatment of vascular malformations. However, antiangiogenics display significantly different actions and side-effects. Although antiangiogenics like thalidomide seem to inhibit gastrointestinal bleeding, other substances like bevacizumab can cause mucosal bleeding. Therefore differential and cautious evaluation of this therapeutic strategy is necessary.